7 Pharmacology Main Handout Oct 2022 Kevin Bolinget 1

TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN HANDOUT BY DR.
YNS PEREYRA-BORLONGAN, MD-MBA

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Histamine, Serotonin, Ergot Alkaloids 26
IMPORTANT LEGAL INFORMATION Prostaglandins and Other Eicosanoids 28
Bronchodilators & Other Drugs Used in Asthma 28
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Skeletal Muscle Relaxants 41
Drugs Used in Parkinsonism 42
Antipsychotic Agents and Lithium 44
DISCLOSURE Antidepressants 45
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THIS HANDOUT IS NOT FOR SALE! 54
Gout
Endocrine Pharmacology 57
INSTRUCTIONS Hypothalamic and Pituitary Hormones 57
To scan QR codes on iPhone and iPad Thyroid and Antithyroid drugs 59
1. Launch the Camera app on your IOS device
2. Point it at the QR code you want to scan
Corticosteroids and Antagonists 61
3. Look for the notification banner at the top Gonadal Hormones and Inhibitors 63
of the screen and tap Pancreatic Hormones, Antidiabetic agents, Drugs
66
To scan QR codes on Android for Obesity and Glucagon
1. Install QR code reader from Play Store Drugs that affect Bone and Mineral Homeostasis 69
2. Launch QR code app on your device
Antibiotic Agents 70
3. Point it at the QR code you want to scan
4. Tap browse website Antibacterial agents 70
Antifungal drugs 78
Antiviral drugs 79
This handout is only valid for the October 2022 PLE batch. Antiprotozoal drugs 81
This will be rendered obsolete for the next batch Anthelmintic drugs 83
since we update our handouts regularly. COVID drugs 84
Cancer Chemotherapy 85
Gastrointestinal Pharmacology 89
PHARMACOLOGY – Toxicology 91
MAIN HANDOUT
By Maria Yña Eluisia T. Pereyra-Borlongan, BASIC PRINCIPLES OF
RPh, MD-MBA PHARMACOLOGY
Contributors:
Julianne Cristy B. Lopez, MD-MBA
INTRODUCTION
Eric E. Calderon Jr., MD DEFINITION OF TERMS
Martin C. Magadia, MD • DRUGS
Tiffany Grace Uy, MD o any substance that brings about a change in biologic function
Imran Rodriguez RPh, MD-MBA through its chemical actions
NATURE OF DRUGS
Approach to Topnotch
• The effects of drugs depend on their characteristics explained as
Pharmacology follows:
https://qrs.ly/7mdvdpq
• SIZE AND MOLECULAR WEIGHT
o vary from MW 7 (lithium) to over MW 50,000 (alteplase)
INTERACTIVE BOX: § MW <100 – rarely sufficiently selective in their actions
We will be using the yellow box as an interactive box in some areas of the § MW 100 to 1000 – most drugs
handout to make the concepts stick better and make the handout more § >1000 – poorly absorbed and poorly distributed; too large to
enjoyable! Good luck <3
Dr. Rodriguez, Im cross membranes
TOPIC PAGE
• DRUG-RECEPTOR BONDS
Basic Principles of Pharmacology 1 o Drugs bind to receptors with a variety of chemical bonds
Pharmacodynamics 2 o They may differ by strength: Covalent > Electrostatic >
Pharmacokinetics 3 Hydrophobic
Drug Evaluation and Regulation 8 § Electrostatic bonds: ionic bonds, hydrogen bonding, van der
Autonomic Pharmacology 9 Waals (permanent/induced dipoles)
Cholinergic Pharmacology 9 o Strength of bond formed by drugs determines reversibility of
Cholinoreceptor-Activating and Cholinesterase-
10
effects
Inhibiting Drugs § Organophosphate bond with AChE: initially weak and
Cholinoreceptor Blockers 12 reversible-> after 24-48 hrs, forms strong covalent bones
Adrenergic Pharmacology 13 (‘aging’), cannot be reversed by Pralidoxime
Sympathomimetics 14
Adrenoreceptor Blockers 15 For size and MW remember that because they are too big, it’s difficult for them
Treatment of Glaucoma 16 to cross different membranes. Kaya mahirap silang ma-distribute.
For drug receptor interaction, think of it simply as “The stronger the bond to
Cardiovascular Drugs 17
the receptor, the more difficult it is to remove it. Hence the action becomes
Drugs for Hypertension 17
essentially irreversible.”
Drugs Used in the Treatment of Angina Pectoris 19 Dr. Rodriguez
Drugs Used in Heart Failure 20 IMPORTANT DRUG PRINCIPLES
Anti-Arrhythmic Drugs 21
• PHARMACODYNAMICS
Diuretics 23
o actions of a drug on the body
Other Cardiovascular Drugs 24
Drugs used in the treatment of Dyslipidemia 25
o receptor interactions, dose-response phenomena, and
Drugs with Important Actions on Smooth Muscles 26 mechanisms of therapeutic and toxic action
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY MARIA YNA PEREYRYA-BORLONGAN, MD-MBA Page 1 of 95
This handout is only valid for the October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN HANDOUT BY DR. YNS PEREYRA-BORLONGAN, MD-MBA
• PHARMACOKINETICS
o actions of the body on the drug
o concerned with:
§ Absorption
§ Distribution
§ Metabolism
§ Excretion
§ Elimination: metabolism and excretion
MNEMONIC: Pharmacokinetics vs Pharmacodynamics

pharmacoKineTics pharmacoDynaMics
(Katawan → Tableta) (Drugs → Man)
PHARMACODYNAMICS
DEFINITION OF PHARMACODYNAMIC TERMS
RECEPTORS
• Receptor: specific molecules in a biologic system with which
drugs interact to produce changes in the function of the system
o Receptor site or recognition site: specific binding region of the
macromolecule
• Effector: translate the drug-receptor interaction into a change
in cellular activity
EFFICACY
• Maximal efficacy or Emax : maximal effect an agonist can
produce if the dose is taken to very high levels
o determined mainly by: nature of the receptor and its
associated effector system
POTENCY When you consider the effect in a POPULATION, the curve is then known as
• Potency: denotes the amount of drug needed to produce a given effect quantal dose response curve. For example, the response that you want to
achieve is to lower the BP by 5 mmHg; so given a dose for example 10mg, ilan
o Determined mainly by: affinity of the receptor for the drug
sa population yung magkakaroon ng BP lowering by 5 mmHg.
o Measurement of potency:
§ If using graded dose-response curves, it is the EC50 or ED50 Recall, what was the previous curve discussed again? What is observed?
(concentration/dose required to produced 50% of the Answer: Graded-dose response; clinical effect. E.g. “Anong dosage ang
maximal effect) mag magbibigay ng increased heart rate”
§ If using quantal dose-response curves, three potency Versus if it’s Quantal you note ilan sa populasyon ang nagkaroon ng desired
variables are measurable (ED50, TD50, LD50) response, sa anong dose naging toxic; or namatay (lethal).
Dr. Rodriguez
§ See next section for further discussion of the curves
THERAPEUTIC INDEX
Efficacy ay yung pinakamataas na effect na kayang abutin ng isang drug.
12!"
Potency ay kung gaano kadami/kakonti ang kailangang dose para !"#$%&#'()* ,-.#/ =
magkaroon ng effect. Meaning if the drug has a higher potency, konting dose 32!"
lang, magkakaroon ka na ng effect.
Dr. Rodriguez
• A measure which relates the
dose of a drug required to
produce a desired effect to
RESPONSE-CURVES
that which produces an
GRADED DOSE-RESPONSE RELATIONSHIP undesired effect
• Dose-response curve: graph of
dose (drug concentration)
versus response FACTORS AFFECTING DOSE RESPONSE CURVES
o Efficacy (Emax) and potency
(EC50) are derived from this
curve
§ Emax: Maximal effect
achievable, with increasing
concentration of a drug
§ EC50: Concentration of the
drug, wherein half of the
maximal effect is achieved
Recall the definitions of efficacy and potency discussed earlier. Can you note in
the graph above which point denotes efficacy and which denotes potency?
Answer Emax = efficacy. EC50 is the potency
Please also note that in graded dose response curve when you reach the Emax,
you’ll notice that it plateaus. Meaning even if taasan mo pa yung dose, same
pa rin magiging effect na makukuha mo.
Dr. Rodriguez
Adapted from Katzung BG. Pharmacology Board Exam Review
QUANTAL DOSE-RESPONSE RELATIONSHIP

DEFINITION OF TERMS
• minimum dose required to produce a specified response is • Receptor: A molecule to which the drug binds to, in order to create
determined in each member of a population
a change in function of a biologic system
• Quantal dose-response curve: graph of dose (drug • Effector: When a receptor is activated, effectors are components of
concentration) versus fraction of the population that
the system that accomplished the biologic effect (e.g. a channel, a
responds at each dose against the log of the dose administered transporter)
median effective (ED50): dose at which 50% of the population responds
• Constitutive activity: receptor activity in the absence of a ligand (it
• Can be used to graph toxic/ lethal effect of the drug
can be related to “ano yung usual niyang gawain or activity”)
o median toxic (TD50) and median lethal (LD50) doses are derived
AGONISTS Try to answer the following. I’ll be giving you keywords only, then try to recall
• Full Agonist: drug capable of fully activating the effector system the important concepts in section.
1. Acts as inhibitor in the presence of an agonist: ________
when it binds to the receptor
2. Binds to different receptor; produces opposite effect: ________
• Partial Agonist: drug produces less than the full effect, even 3. Binds to different receptor; alters the configuration of the agonist
when it has saturated the receptors receptor: __________
o IN THE PRESENCE OF AN AGONIST, A PARTIAL AGONIST ACTS 4. Inhibition by direct interaction with a drug: ___________
AS AN INHIBITOR / ANTAGONIST. 5. Histamine and Epinephrine: _________
6. Atenolol and Salbutamol:________
ANTAGONISTS 7. Dose that produces in 50% of the max effect: ________
8. Max effect an agonist can produce:____________
• Do not provoke a biological response upon binding to a receptor 9. Graph of dose versus effect
• Blocks or dampens drug response in the presence of an agonist 10. Graph of dose versus response in a population
• Classifications of Antagonist (to be discussed next)
o Pharmacologic ___________________COVER ANSWERS BELOW THIS LINE !!!________________________
§ competitive (reversible) 1) Partial agonist 2. Physiologic antagonist 3. Non-competitive inhibitor 4.
§ non-competitive (irreversible) Chemical antagonist 5. Physiologic antagonist 6. Competitive antagonist 7.
Potency 8. Efficacy 9. Graded dose response 10. Quantal dose response
o Physiologic
o Chemical Dr. Rodriguez
It’s very important to understand the Antagonists. Kindly look at the graphs VARIATIONS IN DRUG RESPONSE
below as you study the upcoming section.
Dr. Rodriguez TACHYPHYLAXIS
• frequent or continuous exposure to agonists often results in
short-term diminution of the receptor response.
• Many mechanisms may be responsible:
o Blocking access of G protein to activated receptor (ß-arrestin)
o Receptor molecules may be internalized by endocytosis (to
prevent exposure to extracellular molecules)
o Tolerance: Depletion of substrates required for downstream
effects (EXAMPLE: depletion of thiol cofactors in nitroglycerin
tolerance, reversible with administration of glutathione)
• e.g. Theophylline, Salbutamol. Nitrates, Dobutamine
MNEMONIC: Tachyphylaxis
What drugs display tachyphylaxis?
MEDical students Love to watch CNN in HD!
Pharmacologic Antagonists Metoclopramide Nitroglycerin
• Competitive or Reversible Antagonists: bind to receptor very Ephedrine Nicotine
close to the agonist receptor site, without activating the effector Dobutamine Hydralazine
system LSD Desmopressin
§ Dose-response curve: shift to the right (increased ED50) Calcitonin
§ Effects overcome by adding more agonist • Downregulation: Long term reduction in receptor number
§ Examples: β-blockers (Propranolol) and β-agonists due to continuous exposure to agonist
(Isoproterenol) • Upregulation: Increase in receptor number, which occurs when
• Non-competitive or Irreversible Antagonists: acts at an receptor activation is blocked for prolonged periods
allosteric site of the receptor
§ Dose-response curve: downward shift of the Emax IDIOSYNCRATIC DRUG RESPONSE
(decreased Emax) • one that is infrequently observed in most patients.
§ NOT overcome by adding more agonist • EXAMPLES:
§ example: Norepinephrine and Phenoxybenzamine o aplastic anemia with chloramphenicol
o cataracts with allopurinol
For competitive antagonism, look at the graph, maachieve mo pa rin yung
maximum efficacy, as long as you increase the dosage (concentration) of the PHARMACOKINETICS
drug. Yun nga lang need mo ng mas malaking dose to get 50% of the
As a guide in this section, we will be discussing first the properties of drugs
effectiveness. Now let me ask you “What happened to the potency? How about
(solubility and dissociation principles). Then followed by the ADME of
efficacy?”
pharmacokinetics (Absorption, Distribution, Metabolism, Excretion)
Answer: Potency bumaba (shift to the right yung ED50). Why? Kasi you Dr. Rodriguez
needed a greater dose just to achieve 50% effectiveness. If shift to the left,
potency increases. Why? Kasi look at the x-axis, you just needed a smaller WATER AND LIPID SOLUBILITY OF DRUGS
dose/concentration to achieve 50% of the effect. • aqueous solubility is directly proportional to electrostatic charge
But in competitive antagonism, efficacy mo is still the same. (ionization, polarity)
o ionized and polar drugs are more water-soluble, hence
For Noncompetitive inhibition, may allosteric drug ka na nagbind sa ibang
increased clearance (less absorption)
site. Because of this binding, naiba yung shape na kung saan dapat magbbind
yung drug. If that’s the case, the drug can’t bind to the receptor dahil iba yung • lipid solubility is inversely proportional to electrostatic charge
shape, and it’s irreversible because iba na yung shape, hence in totality baba (ionization, polarity)
din yung effectiveness (look at the graph). o non-ionized and non-polar drugs are more lipid-soluble,
Dr. Rodriguez hence increased absorption (less clearance)
Physiologic Antagonists In absorption REMEMBER the mnemonic LUNA
• Binds to a different receptor that has the capacity of producing Lipid soluble , Unionized, Neutral molecules, are Absorbed.
an effect opposite to that produced by the drug it is antagonizing Recall that cell membranes are made up of lipids; and like dissolves like –
• Examples: Histamine and Epinephrine (Histamine binds to therefore, drugs that are lipid soluble, unionized and neutrally charged will
histamine receptors causing, vasodilation. Epinephrine binds to pass through the lipid membrane
Dr. Rodriguez
alpha receptors causing vasoconstriction). This is the reason
why you use epinephrine in anaphylaxis.
PERMEATION
• Propranolol and thyroid hormone This is the movement of drug molecules into and within biologic
environments. It involves the ff. processes:
Chemical Antagonists
• Interact directly with the drug being antagonized to remove it1. AQUEOUS DIFFUSION
or to prevent it from reaching its target. (i.e. Directly attacks the
• Passive movement of small drugs through small water-filled
drug) pores between the blood and extravascular space (exceptions:
• does NOT depend on interaction with receptors brain, testes, and eye barriers that have no pores)
• examples: Dimercaprol for lead poisoning, Pralidoxime for • Affected by drug concentration and charge
organophosphate poisoning • Governed by Fick’s Law of Diffusion; to be discussed below.
2. LIPID DIFFUSION DISSOCIATION OF WEAK BASES
• Movement of drugs through lipid membranes between body
compartments, and from the ECF to the ICF
• Most important limiting factor for permeation
• Governed by Fick’s law of diffusion
• Very important for the diffusion of weak acids and weak bases • Protonated (BH+) form is more water-soluble and undergoes
better clearance
3. TRANSPORT BY SPECIAL CARRIERS o Weak base is better excreted in acidic environment
• Drugs that do not readily cross through membranes may be (Amphetamine is better excreted in acidic urine)
transported across barriers by mechanisms that carry similar • Unprotonated (B) form is more lipid-soluble and more likely to
endogenous substances cross biological membranes
o ions through Na+/K+ pump o Weak base is better absorbed in basic environment
o neurotransmitter through reuptake transporters (Allopurinol is better absorbed in the basic environment of the
o metabolites such as glucose through GLUT small intestines)
o carriers for foreign molecules or xenobiotics To simplify the concept, the pH characteristic of the drug same to the
• NOT governed by Fick’s law of diffusion and is capacity-limited environment to which it will be absorbed. In other words, ang weakly acidic
na drug ay ma-absorb sa acidic environment (e.g. Aspirin is acidic; it’s
4. ENDOCYTOSIS AND PINOCYTOSIS absorbed in relatively acidic parts of the GIT). Weakly basic drug ma-absorb
sila sa relatively basic portions of the GIT.
• Endocytosis: large drugs bind to receptors, are internalized and
released after vesicle breakdown (reverse: exocytosis) On the opposite, if gusto mo sila tanggalin sa body, expose them in an
• Small polar drugs combine with special proteins to form environment na opposite sa pH characteristic nila. Example, to excrete a
weakly acidic drug, alkalinize it’s environment with a basic agent. Let’s apply
complexes which undergo endocytosis:
this to the examples below.
o vitamin B12 bound to intrinsic factor Dr. Rodriguez
o iron bound to transferrin
BASIC PHARMACOKINETIC PROCESSES
FICK’S LAW OF DIFFUSION For you to remember the pharmacokinetic processes please remember the
• Predicts the rate of movement of molecules across a barrier mnemonic ADME. It stands for absorption, Distribution, Metabolism and
Permeability Coefficient Excretion. Please also remember that Elimination is different from excretion.
!"#$ = ('! − '" ) × × "?@A Elimination = Metabolism and Excretion.
Thickness
• Pharmacologic implications: Dr. Rodriguez
o absorption is faster in organs with larger SA (intestinal > A. ABSORPTION

stomach) • Transfer of a drug from its site of administration to the
o absorption is faster in organs with thinner membranes (lung > bloodstream
skin) • Affected by 3 major factors
1. Route of administration
WEAK ACIDS AND BASES 2. Blood flow
3. Concentration
• Many drugs are weak acids and weak bases which dissociate into
Classically, absorption is defined as the process by which the drug reaches the
ionized and non-ionized forms SYSTEMIC CIRCULATION. Different routes have different sets of barriers
• pH determines the fraction of drug molecules charged (ionized) that the drug needs to pass through, thus affecting absorption. More blood
versus uncharged (non-ionized) flow in a site of absorption means higher absorption also. For concentration,
• Predicted by Henderson-Hasselbach equation remember the Fick’s law of diffusion, where is (C1-C2) found in the
o relationship between pH, pKa (dissociation constant) and equation? _____________ Go back to the previous page. It’s found in the
concentration of charged and uncharged forms numerator, hence bigger difference in concentration would have a directly
proportional effect to the rate of movement of molecules through a barrier.
Dr. Rodriguez
HENDERSON-HASSELBACH EQUATION
ROUTES OF DRUG ADMINISTRATION
1. Oral Route
• Most common route of drug administration
• Absorption is slower
• Subject to first-pass effect (a significant amount of the drug is
metabolized in the gut wall, portal circulation and liver before it
reaches the systemic circulation)
2. Buccal and Sublingual

• Direct absorption into the systemic venous circulation (bypasses
the first pass effect).
DISSOCIATION OF WEAK ACIDS o Buccal (pouch between the gums and cheek) -> Facial vein ->
Internal jugular vein
o Sublingual (under the tongue) -> Lingual vein → Internal
jugular vein (IJV) → brachiocephalic (innominate) vein → superior
vena cava → right atrium
• Protonated (HA) form is more lipid soluble and more likely to
cross biological membranes 3. Intravenous
o Weak acid is better absorbed in acidic environment • Instantaneous and complete absorption that bypasses first-
(Phenobarbital is better absorbed in the acidic environment of pass effect (100% bioavailability)
the stomach) • Potentially more dangerous: Inadvertent systemic introduction
• unprotonated (A-) form is more water-soluble and undergoes of bacteria through the IV line (line sepsis); Difficult to reverse
better clearance effects
o Weak acid is better excreted in basic environment
(Aspirin is better excreted in a basic urine) 4. Intramuscular
Again, same principle “LUNA.” • Absorption is faster and more complete than oral (bypasses
U = uncharged. Uncharged is absorbed. Look at the equations above HA has first-pass effect, higher bioavailability)
no charge, so it is the one absorbed. HA is called protonated dahil meron • Large volumes may be delivered if drug is not too irritating (i.e. 5g
siyang H; H in basic chemistry is a proton, hence “protonated” of MgSO4)
Dr. Rodriguez
• Anticoagulants cannot be given by this route because they may
cause bleeding (hematomas)
• IM Injections to Buttocks This graph shows us the classic “Area under the curve” of the of the plasma vs.
o Which quadrant of the buttocks is safest for IM drug time graph – very important for measuring bioavailability. It is a graph of
administration? plasma concentration (blood stream) versus time. Look first at the graph on
the left, and focus on the solid-colored graph for IV. You’ll notice na mataas
§ superolateral = safe
na siya agad, kasi direcho siya sa dugo. And in time the dose decreases
§ superomedial = gluteus medius gait because the drug gets eliminated. Next look at the curve with grids for Oral
§ inferomedial = sciatica AUC. As you can see, pataas muna siya, kasi shempre wala pa siya agad sa
dugo. But as more and more drug gets absorbed the concentration in the
5. Subcutaneous
blood increases. Now the greater the area under the curve is, the higher the
• Bypasses the first pass effect bioavailability.
• Slower absorption than intramuscular route (NO blood But notice that this is only for single dose. And as you can see, in time, bumababa
vessels in the subcutaneous space) concentration Paano mo ma-maintain that drug has high concentration or high
• Large volume doses are less feasible bioavailability or high AUC? Give multiple doses. Look at the next graph. Try to
• Anticoagulants do NOT cause hematomas when administered apply this by studying the computation below.
Dr. Rodriguez
via this route
6. Rectal Suppository CLINICAL APPLICATION: MAINTENANCE DOSE CALCULATION
-.&"/"$'& × )&+#/&1 2."+3" '*$'&$%/"%#*$
• Partial avoidance of the first-pass effect !"#$%&$"$'& )*+& =
4#*"5"#."6#.#%7
• Useful for large amounts of drugs with unpleasant tastes and for
patients who are vomiting • Equal to the rate of elimination at steady state.
• VENOUS DRAINAGE OF THE RECTUM. • Important to maintain concentration above minimum therapeutic level:
o Superior Rectal Vein: IMV → PV (first-pass) o give large doses at long intervals
o Middle Rectal Vein: IIV → IVC o smaller doses at more frequent intervals
o Inferior Rectal Vein: IPV → IIV → IVC As you see in the graphs discussed above, the concentration of the drug in the
blood stream will always go down because the kidneys try to clear it. Hence
7 Inhalational clearance is factored in the computation of maintenance dose. Next ask
• Offers delivery closest to the respiratory tissues yourself “ano ba yung target kong level sa katawan ng pasyente” – this is
• Very rapid absorption with minimal systemic effects factored in by the desired plasma concentration. Now try to recall the
• Convenient for drugs that are gases at room temperature definition of Bioavailability. Take time to recall… As you already know the
(nitrous oxide, nitric oxide) or easily volatilized (anesthetics) higher the bioavailability, meaning mas madaming naaabsorb sa systemic
circulation. Hence if madaming na-absorb, kakailanganin mo lang ng
8. Topical smaller maintenance dose. Kaya siya nasa denominator para maging
smaller yung maintenance dose mo in the case na high yung bioavailability
• Topical: application to skin, mucous membranes of the eye, ear,
mo.
nose, throat, airway, or vagina for local effect Maintenance dose is equal to the elimination at steady state meaning, equal
• Slowest route of drug administration lumalabas sa katawang and equal din pumapasok. Hence maintained yung
o Absorption varies with the area of application and drug level.
formulation Dr. Rodriguez
• Ordered by Increasing ability to retard evaporation: STEADY STATE

o (more evaporation) tinctures > wet dressings > lotions > gels • Condition in which the average total amount of drug in the body
> aerosols > powders > pastes > creams > foams > ointments does not change over multiple dosing intervals
(less evaporation) • Rate of drug administration equals the rate of elimination
• Using dermatologic drug preparations for skin inflammation: • Reached in 3-4 half-lives of the drug
o Acute inflammation = drying agents (tinctures, wet dressings,
lotions) THERAPEUTIC WINDOW
o Chronic inflammation = lubricating agents (creams,
• safe range between the minimum effective concentration and the
ointments)
minimum toxic concentration of a drug
9. Transdermal o minimum effective concentration: determines the desired
• Application to the skin for systemic effect trough levels of a drug given intermittently
• Absorption occurs very slowly but bypasses the first-pass effect o minimum toxic concentration: determines the permissible
peak plasma concentration
SUPPLEMENT:
What routes of administration undergo significant First-Pass Effect?
ORAL
Partially bypass? RECTAL
Completely bypass? IV, IM, SC, SL, INHALATIONAL, TOPICAL,
TRANSDERMAL
UNIQUE BARRIERS TO
DISTRIBUTION
https://qrs.ly/dhdveeu
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
BIOAVAILABILITY In giving multiple doses it is very important to take note of the therapeutic
• This is an important parameter of absorption window. So as to give the right amount of drug to achieve the minimum
• It is the fraction of administered drug that reaches the systemic effective concentration, but not too high to exceed the minimum toxic
concentration.
circulation Dr. Rodriguez
• 100% bioavailability for IV; because it’s already in the B. DISTRIBUTION
bloodstream.
• Process wherein drug reversibly leaves the bloodstream and enters
• Determined by computing the area under the plasma
the target organ (earlier absorption was to the bloodstream, this
concentration curve (AUC)
time, leaving the bloodstream going to the organ)
• Depends on 4 major factors:
1. SIZE OF THE ORGAN

• Determines concentration gradient between blood and the organ
o Skeletal muscles are a very large organ
§ large doses are required to actually change the
concentration gradient
o Brain is a small and compact organ
§ only a small amount of drug is required to change
concentration gradient
2. BLOOD FLOW C. DRUG METABOLISM
• Important determinant of the rate of drug uptake (but not the • Process by which drugs are chemically altered in the body
amount of drug in tissue equilibrium) • Drugs may undergo 3 metabolic fates:
• well-perfused organs will achieve high tissue concentrations o Termination of drug action (drugs are metabolized into
sooner than poorly perfused tissues biologically inactive derivatives)
o Drug activation: prodrugs are metabolized in the body to
3. SOLUBILITY become active (Desmethyldiazepam – an active metabolite of
• Influences the concentration of the drug in the extracellular fluid Diazepam, Chlordiazepoxide and Flurazepam)
surrounding blood vessels o Elimination without metabolism (some drugs are not modified by
• Brain which is high in lipid content will dissolve high the body and continue to act until they are excreted).
concentration of lipid soluble drugs
o non-ionized, non-polar drugs are more lipid-soluble Ang goal ng body dito ay to make the drug more polar. Remember when
you’re polar, you’re more readily excreted kasi you are more water
and undergo more extensive distribution
soluble. Unlike if you’re lipid soluble, remember sa previous topic on
4. PROTEIN BINDING distribution, ‘di ba mas nadidistribute sila?
Dr. Rodriguez
• Binding to macromolecules in blood or tissue will tend to TYPES OF METABOLIC REACTIONS
increase the drug’s concentration in that compartment PHASE 1
PHASE 2
o (A)cidic drugs: bound to (A)lbumin BIOTRANSFORMATION/
SYNTHESIS/ CONJUGATION
o Basic drugs: bound to Orosomucoid and a1-acid FUNCTIONALIZATION
glycoprotein • Reactions that convert the • Reactions involve conjugation
• If a drug is bound to proteins it CANNOT cross membranes and parent drug to a more polar of subgroups to –OH, –NH2,
exert their effect. Remember proteins are big molecules (water-soluble) or more and –SH functions on the drug
(macromolecules). They can’t readily cross membranes reactive product by molecule
• Therefore, only unbound drugs CAN cross membranes and exert unmasking or inserting a • makes the drug more polar
their effect polar functional group
o ONLY THE FREE (UNBOUND) DRUG CAN BE ABSORBED, • Hydrolysis Conjugation with:
DISTRIBUTED, METABOLIZED, EXCRETED AND EXERT • Oxidation • Glucuronic acid
PHARMACOLOGIC EFFECT o Majority by cytochrome • Acetic acid
o Examples: Phenytoin, Valproic acid P450 enzymes • Glutathione
• Reduction • Glycine
Okay, skill keeper. Tell if increased or decreased • Deamination • Sulfate/methyl group
1. More protein binding will lead to ___________ distribution
2. Lipid soluble drug will lead to __________ distribution There is no specific sequence between the 2 phases. Drugs may undergo Phase
3. Lower blood flow will lead to _________ distribution II metabolism before or after Phase I. Basta tandan, and kakasabi lang a few
4. Higher blood flow will lead to _________ absorption bullet points earlier, goal ng metabolism is to make the drug POLAR.
Answer: Inc. Inc. Dec, Inc. Remember LUNA earlier? So if Polar na ngayon yung drug, what happens to
Dr. Rodriguez it? Absorbed or excreted mga bhie?
APPARENT VOLUME OF DISTRIBUTION Kamay sa ilalim ng baba (chz) Write your answer: ________________
Dr. Rodriguez
• This parameter is very important in measuring the distribution CYTOCHROME P450 ENZYMES
of a drug
• Involved in the oxidation reactions of Phase I metabolizing
• It is the volume at which drug would need to be uniformly
reactions
distributed to produce an observed blood concentration.
CDEFGH EI JKFL MG HNO PEJQ • Also called mixed-function oxidases
B# = • High concentrations in the smooth endoplasmic reticulum of the liver
RSTUDT JKFL VEGVOGHKTHMEG
• Can be altered by liver and kidney disease • Not highly selective in their substrates
• Approximately 75% are metabolized by: CYP3A4 or CYP2D6
Volume of Distribution
Low Vd Distributed in blood 1. Enzyme Induction
Distributed in extracellular space or body • Results from increased synthesis of cytochrome P450 enzymes
Medium Vd and heme
water
High Vd Distributed in tissues • Several days are usually required to reach maximum induction
• Most common strong inducers are Carbamazepine,
Vd is just a hypothetical value that estimates the volume needed to
Phenobarbital, Phenytoin, and Rifampin
dissolve a drug to reach a certain concentration. Meaning gaano
kadaming volume yung kailangan para madissolve yung isang dose ng
gamut para maachieve yung certain concentration. MNEMONIC: CYTOCHROME P450 INDUCERS
Dr. Rodriguez “Ethel Booba takes Phen-Phen
and Refuses Greasy Carb Shakes”
CLINICAL APPLICATION: LOADING DOSE CALCULATION Ethanol (Chronic ingestion) Griseofulvin
.#8)$#. ;<%8=% >5-*#-($%()5- Barbiturates exc. SECOBARBITAL Carbamazepine
45%.)-6 758# = 9# × Phenytoin St. John’s Wort/Smoking
?)5%@%)<%A)<)(B Rifampicin
• If therapeutic concentration must be achieved rapidly you give a OTHER ENZYME INDUCERS:
loading dose Glutethimide
• You also give a loading dose if the volume of distribution is Phenylbutazone
high Ritonavir (on chronic or repeated administration)
• However if the LD is very large, dose should be given slowly to **SECOBARBITAL is an INHIBITOR **
prevent toxicity
o due to excessively high plasma levels during the distribution 2. Enzyme Inhibition
phase • Most significant inhibitors are Amiodarone, Cimetidine,
Furanocoumarins present in grapefruit juice, azole antifungals,
Now drugs with high volume of distribution would need a greater dose. Bakit? and the HIV protease inhibitor ritonavir
Where is the drug distributed if the Vd is high? ______________.
• Drug metabolism may be decreased by reduction in blood flow
Correct, it’s distributed in the tissues. So think of it na parang naipon lang sila
doon “i.e. na-distribute.” So dahil naipon sila sa other areas of the body you to the metabolizing organ
would need a higher loading dose in order to have more drug that can o EXAMPLE: Propranolol reduces hepatic blood flow
interact with the receptor rather than just being distributed in the
peripheral tissues. (Hence the formula above). Now to make it stick more, Suicide Inhibitors
note the difference between the formulas of Loading dose and Maintenance • bind irreversibly to metabolizing enzymes
dose, what is the only difference? _____________________ o EXAMPLES: ethinyl estradiol, norethindrone, spironolactone,
Answer: Vd for LD, Clearance for MD. secobarbital, allopurinol, fluroxene, PTU
Dr. Rodriguez
MNEMONIC: CYTOCHROME P450 INHIBITORS Lastly, for you to fully understand why zero-order is called saturable kinetics,
“Inhibitors Stop Cyber Kids from Eating GRApefruit QV” imagine exiting an LRT/MRT train. The people will serve as the drug and the
Isoniazid Grapefruit Juice exits will serve as the receptors. There are 100 people exiting but there are only
Sulfonamides Ritonavir (on acute ingestion) 5 exit doors/turnstile allowing only 5 people to exit per second. Therefore sa
Cimetidine Amiodarone bawat segundo, kahit na may 100 na taong gustong-gusto na makalabas
Ketoconazole Quinidine (maeliminate), eh 5 lang yung exit doors/turnstile, 5 lang ang makakalabas
Erythromycin Valproic Acid (eliminate) per second. Kahit iassume mong milyon milyon pa gusto
OTHER CYP450 INHIBITORS makalabas; saturated na yung exit, therefore per second 5 lang din
Allopurinol Chloramphenicol makakalabas.
Dr. Rodriguez, Im
Chlorpromazine Dicumarol
Disulfiram Ethanol (acute toxicity)
Itraconazole Nortriptyline MNEMONIC: Zero Order Kinetics
Oral contraceptives Phenylbutazone What drugs display zero order
Saquinavir Secobarbital elimination kinetics?
Spironolactone Troleandromycin WHAT PET
Warfarin
Heparin
While it is important to know which drugs are inducers and inhibitors of
Aspirin
metabolism, it is also equally important to apply this knowledge. Recall, what
Tolbutamide
is the main function of metabolism again: You make the drug more _______?
Phenytoin
Hence is it readily excretable or not? It’s more excretable
Ethanol
So now let’s assume we have a drug, then we add the following: Theophylline
+ Enzyme Inducers =
- What happens to the drug level in the body?
CLEARANCE
- Risk of toxicity is increased or decreased?
+ Enzyme Inhibitors = • Relates the rate of elimination to the plasma concentration
- What happens to the drug level in the body? • Depends on the drug, blood flow and condition of the organs of
- Risk of toxicity is increased or decreased? elimination
o for a drug that is very effectively extracted by an organ,
___________________COVER ANSWERS BELOW THIS LINE !!!________________________ clearance is flow-limited
Inducers: Decreased, Decreased (kasi you excrete it further)
o for drugs eliminated with first-order kinetics, clearance is a
Inhibitors: Increased, Increase (kasi you let the drug stay, because it’s not constant proportion
metabolized) o for drugs eliminated with zero-order kinetics, elimination rate
EXCEPTION if the drug mentioned is a PRODRUG (inactive state). If you is a constant amount
induce its metabolism, you create more of the DRUG (active state). Hence • Most important pharmacokinetic parameter to be
more active drug circulating and increased possibility toxicity. considered in defining a rational steady state during dosage
Dr. Rodriguez
regimen
E%(# 5F #<)=)-%()5-
><#%$%-*# (>4) =
;<%8=% *5-*#-($%()5- (>&)
BIOTRANSFORMATION
I hope by this time, you’ll appreciate why clearance is important in the
https://qrs.ly/2udvdpr computation of the maintenance dose. Ito ay dahil kailangan mo mapantayan
yung kung gaano kabilis tinatanggal yung gamot sa katawan. Can you recall
the formula for maintenance dose? How about loading dose? Go back to the
D. ELIMINATION sections if necessary.
For clearance, it is the volume removed per time. The numerator here is
• Elimination: termination of drug action (may involve removed drug per time. The denominator is drug per volume. If you divide the
metabolism into inactive state and/ excretion out the body) two values you’ll be left with the units “Volume per time.” Kaya ang clearance
Elimination = Metabolism + Excretion ay, gaano kadaming volume yung natatanggal sa bawat oras.
• Excretion: release of drugs/metabolites out the body (via urine, Dr. Rodriguez
stool, bile, exhaled air)

• Duration of drug action is determined by: OTHER PHARMACOKINETIC CALCULATIONS
o Dose administered Now that you are familiar with the different calculations per pharmacokinetic
o Rate of elimination following the last dose parameter, let’s try to integrate and compute for the other important
Rate of elimination is parameters
First-Order Elimination proportionate to the
Dr. Rodriguez
HALF-LIFE
concentration W. YZ[ × BESFDO EI JMUHKMPFHMEG
• concentration decreases H$& =
exponentially over time
% \SOTKTGVO
• Constant for drugs following first-order kinetics
Characteristic half-life of
elimination: concentration • Disease, age, and other variables usually alter clearance of a drug
decreases by 50% for every half- much more than Vd
life
ADJUSTMENT OF DOSAGE IN RENAL IMPAIRMENT
Most common type of >$#%()-)-# ><#%$%-*#
elimination >5$$#*(#. 758# = GHIJKLI 2MNI ×
OPP =4/=)-
Zero-Order Elimination / Rate of elimination is
• if a drug is cleared partly by the kidney and partly by other
Saturable / constant regardless of
routes, apply the equation only to the part of the dose that is
Michaelis-Menten concentration
eliminated by the kidney
Kinetics • concentration decreases linearly
over time
• Constant amount of drug being Cockcroft-Gault Equation
excreted over time • to calculate the patient’s creatinine clearance, use the Cockcroft-
Occurs when drugs have Gault equation
saturated their elimination (ORP − T6#) × U#)6"(&'
><$% = (× P. Z[ )- F#=%<#8)
mechanisms VW × X#$'= >$#%()-)-#('/#*
SUPPLEMENT:
First order kinetics is easier to understand because the rate of elimination is Amount of drug in the body at any time is computed as:
just halved every half-life. So for example if the rate of elimination of a drug ]' × ^_AàA bcdb@de?Aefcd
starts at 10 units/hour, after 1 half-life it would be 5 units /hour (10 divided Steady State Concentration during the ff t½:
by 2). After 2 half-lives it would be 2.5 units/hour (5 divided by 2) and so on. 1st t½ : 50%
For Zero order elimination, it’s constant for every half-life. If for example its 2nd : 75%
elimination rate is 5 units/hour, after 1 half-life it’s _________; after 2 half-lives 3rd : 87.5%
it’s __________. If you answered 5 units/hour for both, good job! 4th : 93.75%
TERATOGEN EFFECT
DRUG EVALUATION AND REGULATION Tetracycline Tooth discoloration
Prior to the release of every drug in the market. Keep in mind that it has to
Streptomycin Ototoxicity
undergo (1) PRE-CLINICAL TESTS – those that involve non-human subjects
such as animals. Then followed by the (2) CLINICAL TRIALS. Which involves
Methimazole Aplasia cutis congenita
human subjects. We will divide this section per the two major categories of Sulfonamides Kernicterus
drug evaluation and regulation Fluoroquinolones Cartilage damage
Dr. Rodriguez Warfarin 1st trimester Chondrodysplasia
ANIMAL STUDIES 2nd trimester CNS malformations
• These studies are needed prior to the implementation of testing 3rd trimester Bleeding diatheses
in humans.
• However in cases when a drug is needed urgently such as REPRODUCTIVE TOXICITY STUDIES
anticancers and antivirals and thus approved in an accelerated • involves the study of the fertility effects of the candidate drug
schedule and its teratogenic and mutagenic toxicity
• The following are examples of studies conducted pre-clinically • FDA uses a 5-level descriptive scale to summarize information
regarding the safety of drugs in pregnancy
ACUTE TOXICITY STUDIES
FDA Drug Categories: and Pregnancy
• Required for all new drugs PREGNANT PREGNANT
• Involve administration of single doses of the agent up to the CLASS HUMAN ANIMAL EXAMPLES
lethal level in at least 2 species (e.g., 1 rodent and 1 non-rodent). STUDIES STUDIES
Folic acid, Thyroid
A Safe Safe
SUBACUTE AND CHRONIC TOXICITY STUDIES hormones
• Required for most agents, especially those intended for chronic No studies Safe Zidovudine
B
use – maintenance medications Safe Unsafe
• duration: 2–4 weeks (subacute) or 6–24 months (chronic), in No studies Unsafe Aspirin
C
at least 2 species No studies No studies
ACE inhibitors,
D Unsafe Unsafe
Anticonvulsants
TYPES OF ANIMAL STUDIES Statins, OCPs, Clomiphene,
MUTAGENESIS X Unsafe Unsafe Misoprostol,
• induction of changes in the genetic material of animals of any High-dose Vitamin A
age and therefore induction of heritable abnormalities This is important! As a guide for recall:
o EXAMPLES: aflatoxin, cancer chemotherapeutic drugs, and A: Easy to remember, may study sa pareho. At parehong proven na safe.
other agents that bind to DNA D and X are both unsafe in humans or animals. Difference ay:
D: Unsafe and proven teratogen. Pero may be given if benefits outweigh risk
• Ames Test in some situation
o In vitro test for mutagenicity (using special strain of X: Kenat be! RISKS outweighs any benefits
Salmonella that naturally depends on specific nutrients) B or C: Madalas ito yung pwedeng tanong, since ito yung medyo nakakalito.
o Loss of this dependence signals a mutation For B basta may isang safe either human or animal, then minimum ay B na.
• Dominant Lethal Test For letter C, most of them have no studies, or proven na unsafe only in
o In vivo test for mutagenicity (carried out in mice) animals.
Dr. Rodriguez
o Male animals are exposed to the test substance before mating
o Abnormalities in the results of subsequent mating signal a
mutation in the male's germ cells CLINICAL TRIAL
• Requires approval by institutional committees that monitor the
CARCINOGENESIS ethical (informed consent, patient safety) and scientific aspects
• Induction of malignant characteristics in cells (study design, statistical power) of the proposed tests
• Difficult and expensive to study
• High degree of correlation between mutagenicity in the Ames INVESTIGATIONAL NEW DRUG (IND)
test and carcinogenicity in some animal tests • Includes all the preclinical data collected up to the time of
o EXAMPLES: coal tar, aflatoxin, nitrosamines, urethane, vinyl submission and the detailed proposal for clinical trials.
chloride, polycyclic aromatic hydrocarbons in tobacco smoke
(benzo-α-pyrene) NEW DRUG APPLICATION (NDA)
• Constitutes the request for approval of general marketing of
TERATOGENESIS the new agent for prescription use and includes all the results of
• Induction of developmental defects in the somatic tissues of the preclinical and clinical testing
fetus
• Studied by treating pregnant female animals of at least 2 species
at selected times during early pregnancy when organogenesis is
known to take place
o EXAMPLES: thalidomide, isotretinoin, valproic acid, ethanol,
glucocorticoids, warfarin, lithium, and androgens
COMMON TERATOGENS
TERATOGEN EFFECT
ACE inhibitors Fetal renal damage
Antiepileptic Drugs Neural tube defects
Phenytoin Fetal hydantoin syndrome
Oral hypoglycemic agents Neonatal hypoglycemia
Barbiturates Neonatal dependence
Diethylstilbestrol (DES) Vaginal clear cell adenocarcinoma Adapted from Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
Ethanol Fetal alcohol syndrome PHASE 1 TRIAL

Lithium Ebstein anomaly
• Careful evaluation of the dose-response relationship and
Isotretinoin Craniofacial malformations
lodide Congenital hypothyroidism
pharmacokinetics among normal human volunteers (25–100
usually, only 20-50 for chemotherapeutic and other toxic drugs)
Misoprostol Mobius sequence
Penicillamine Cutis laxa
o EXCEPT in cancer and highly toxic agents (volunteer patients
Thalidomide Phocomelia
with target disease)
Smoking IUGR • Acute effects of the agent are studied over a broad range of
dosages
PHASE 2 TRIAL
• Evaluation of a drug in a moderate number of patients (e.g.
100–200) with the target disease
• Placebo or positive control drug is included in a single-blind or
double-blind design
• Under carefully controlled conditions with close monitoring https://qrs.ly/rldvdpv https://qrs.ly/7qdvdr3
usually in a hospital ward SYMPATHETIC PARASYMPATHETIC
• Determine whether the agent has the desired efficacy at doses Spinal Roots of Thoraco-Lumbar
Cranio-Sacral
that are tolerated by sick patients (CN 10,9,7,3
Origin (T1-12; L1-5)
and S2-4)
Location of
PHASE 3 TRIAL Near the spinal cord Near the organ
Ganglia
• Large design involving many patients, including those Preganglionic
considered as “special population” (1000–5000) Short Long
fibers
• Would be done by many clinicians in different Postganglionic
Long Short
centers/hospitals/countries fibers
• Include placebo and positive controls in a double-blind
Receptors in the Autonomic Nervous System
crossover design
ORGAN Sympathetic Parasympathetic
• Explore further the spectrum of beneficial actions of the new Iris radial
drug, to compare it with older therapies, and to discover Mydriasis (ɑ1) No effect
muscle
infrequent toxicities not seen in Phase 2 Iris circular
Eye
No effect Miosis (M3)
muscle
PHASE 4 TRIAL Contraction (M3) for near
Ciliary muscle Relaxes (β)
• Post-marketing surveillance phase vision or accommodation
Tachycardia
• Detects toxicities that occur very infrequently SA node Bradycardia (M2)
Heart
(β1> β2)
INTERACTIVE BOX: Increased
1. Mainly tests efficacy: ____________ Contractility Decreased (atria) (M2)
(β1> β2)
2. Post marketing surveillance: ____________ Skin, splanchnic Vasoconstriction
3. Mainly tests Safety: ____________ vessels (ɑ1> ɑ2)
4. Safety and efficacy: ____________ Vasodilation
5. Normal healthy volunteers: ____________ No effect
Blood vessels
Skeletal muscle (β2 and less

6. Small population with disease: ____________ vessels importantly,
___________________COVER ANSWERS BELOW THIS LINE !!!________________________ M3**
Endothelium of
(1) Phase 2, (2) Phase 4 (3) Phase 1 (4) Phase 3 (5) Phase 1 (6) Phase 2 Synthetizes and releases
vessels in heart, ---
Dr. Rodriguez EDRF (M3,M5)
SUPPLEMENT: brain and viscera
Bronchiolar Bronchodilation Bronchoconstriction
Bioequivalence smooth muscle (β2) (M3)
• Two related drugs are bioequivalent if they show comparable Smooth muscle Relaxation Contraction
bioavailability and similar times to achieve peak blood walls (ɑ2, β2) (M3)
concentrations. Digestion
GIT
Smooth muscle Relaxation

Contraction (ɑ1)
• Used in determining safety and efficacy of generic drugs sphincters (M3)
Secretion --- Increased (M3)
Can you recall which pharmacokinetic parameter does bioavailability Bladder wall Contraction
Relaxation (β2)
measure again? _____________________ (detrusor) (M3)
Urination
Basta kapag sinabing bioequivalence, pinagcocompare mo yung dalawang Trigone and Relaxation
Contraction (ɑ1)
bioavailability ng dalawang gamot. Yan yung reason kung bakit pag bladder sphincter (M3)
GUT
tinanong dapat kayo about generic drugs, dapat sagot niyo ay pareho lang Uterus, Contraction (M3) - not
Relaxation (β2)
ang end effect ng branded sa. generic drug. Because need nila pumasa sa pregnant sensitive
bioequivalence studies before siya ma-approve sa isang bansa for use. Ang Ejaculation (ɑ) Erection (M)
Penis, Seminal
difference lang siguro ng branded sa generic would be other parameters Shoot for Point for
vesicles
(example dissolution or disintegration), hence nagiiba sila ng onset of Sympathetic Parasympathetic
action. Kasi iba-ibang ingredient (excipients) ang gamit ng bawat Sweat, salivary,
Glands
companies in creating their own drug formulations. Example si biogesic, lacrimal,

No effect Increased secretion (M)
claim niya na mas mabilis mag-effect than other brands of paracetamol. nasopharyngeal
Probably because it has a better ingredient that helps it to disintegrate glands
faster. But in the end, both will achieve the same outcome of analgesia – Pilomotor
difference is time. Contracts (ɑ)
smooth muscle
Answer: Absorption Increases (M)
Eccrine sweat
Skin
Dr. Rodriguez
Sympathetic,
glands
mediated by Ach
AUTONOMIC PHARMACOLOGY Apocrine (stress)
sweat glands
Increases (ɑ)
No effect
Gluconeogenesis
Autonomic Nervous System (β2, ɑ)
Liver
• Major involuntary, unconscious, automatic portion of the Glycogenolysis
Others
nervous system (β2, ɑ)

• Concerned primarily with visceral functions (i.e. cardiac output, Fat cells Lipolysis (β3)
Renin release
blood flow distribution, digestion) Kidney
(β1)
• Major divisions:
o Parasympathetic ANS (PANS) CHOLINERGIC PHARMACOLOGY
o Sympathetic ANS (SANS) As a guide, we will first discuss the primary neurotransmitter, acetylcholine
and its biosynthesis. Then followed by the receptors in cholinergic system.
Enteric nervous system (ENS) Then at this point try to picture out two main division:
• Primarily controlled by the ANS parasympathoMIMETIC and parasympathoLYTIC. Mimetic means “like” or
“same” while parasympathetic should make you recall “Acetylcholine.” So
• Consists of myenteric plexus (plexus of Auerbach) and bringing them together it’s like Acetylcholine-like effects. On the other hand
submucous plexus (plexus of Meissner) “lytic” means “to stop.” So parasympatholytic, is like stopping the effects of
Acetylcholine.
One of the most important topic in pharmacology that you have to know by To make things simpler, memorize niyo muna yung effects ng acetylcholine,
heart is Autonomic Pharma. A lot of systems will be encompassed by this by using DUMBELLS as a guide. Anything opposite to this should be
section so please take time to know it by heart Parasympatholytic.
Dr. Rodriguez Dr. Rodriguez
A. ACETYLCHOLINE AND ITS BIOSYNTHESIS TYPICAL RESULT OF

RECEPTOR NAME
LOCATION LIGAND BINDING
• Primary transmitter in all autonomic ganglia and at the
Opening of K+
synapses between parasympathetic postganglionic neurons
M2 Myocardium channels, inhibition
and their effector cells
of cAMP production
• Primary transmitter at the somatic (voluntary) skeletal muscle
Exocrine glands,
neuromuscular junction
vessels ↑ IP3 and DAG,
M3
(Smooth muscle, ↑ intracellular Ca2+
endothelium)
inhibition of cAMP
M4
production
CNS
↑ IP3 and DAG,
M5
↑ intracellular Ca2+
Let’s recall in physio the G-protein receptors that are associated with the
different muscarinic receptors. If the mnemonic for Alpha-1, Alpha-2, Beta-1,
and Beta -2 receptors is “QISS” respectively, recall the mnemonic for M1, M2
and M3. That would be “QIQ” which stands for M1= Gq, M2=Gi and M3=Gq.
Remember that Gq increases IP3 and DAG, while Gi inhibits CAMP production.
Now look again at the table above, take note of the third column. J
Dr. Rodriguez
C. PARASYMPATHOMIMETICS
STEP 1 – TRANSPORT AND SYNTHESIS

• Choline transferase (CHT): Na+/Choline symporter that
transports choline inside
o Rate-limiting step
o Choline transport inhibited by Hemicholinium Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2019
• Choline acetyltransferase (ChAT): enzyme uses free acetyl CoA Let’s start first with Cholinergic drugs, specifically the AGONIST. Later na yung
and choline to synthesize Acetylcholine mga antagonist.
When you hear CHOLINERGIC AGONIST same lang with:
STEP 2 – STORAGE Cholinomimetic = “Choline” + “Mimetic” = Mimics Choline (Mimics
• ACh is actively transported into vesicles for storage by vesicle- Acetylcholine) So any Cholinomimetic, think Ach! Think DUMBBELLS!
Diarrhea (and diaphoresis) and abdominal cramps
associated transporter (VAT)
Urination
o Inhibited by Vesamicol Miosis
STEP 3 – RELEASE Bradycardia (muscarinic) or tachycardia (nicotinic)
Emesis
• Entry of calcium -> Calcium interaction with SNARE proteins Lacrimation
(VAMPs and SNAPs) -> triggers fusion of vesicle membrane with Lethargy
terminal membrane Salivation
o Botulinum toxin alter synaptobrevins to prevent release of They are divided into:
ACh through the enzymatic removal of 2 amino acids from one • DIRECT: Acts sa receptor mismo (Muscarinic or Nicotinic receptor)
or more of the fusion proteins • INDIRECT: Prevents breakdown of ACh; hence more parasympathetic
stimulation
STEP 4 – TERMINATION Go through each section one by one, returning back to this box as a guide as
• Degradation of ACh into choline and acetate by you read.
acetylcholinesterase (AChE) Dr. Rodriguez
o Inhibited by INDIRECT-ACTING CHOLINOMIMETICS DIRECT ACTING CHOLINERGIC AGONISTS

(Carbamates & Organophosphates) ACETYLCHOLINE
MOA Activates BOTH nicotinic and muscarinic receptor
Heads up! Take note of these steps and their inhibitors. Keep in mind as early
as now that there will be similar inhibitors of steps in the sympathetic Use/s Miotic eyedrop (constricts iris) during ocular surgery
nervous system. P’kin Short-lived (5-30 secs) – due to fast hydrolysis by AChE
Dr. Rodriguez SE DUMB BELLS
Remember that it’s the prototype cholinergic drug/NT. So it stimulates both
B. CHOLINORECEPTORS nicotinic and muscarinic receptor. Remember in the autonomic nervous
system anatomy, what is the primary neurotransmitter in all preganglionic
VISUALIZATION TIME! Get a scratch paper. Then write down the two main
fibers? _______________. So as you go downstream, acetylcholine in the
cholinoreceptors: (1) Nicotinic receptors and (2) Muscarinic receptors. In
preganglionic fiber should meet what receptor at the ganglion?
however method you want to visualize, write down below Nicotinic
_________________. Then as you follow the path of a parasympathetic fiber down
receptors the two types Nicotinic-Neural and Nicotinic Muscular. While
to the neuro muscular junction, what receptor does it meet? ____________________.
under Muscarinic receptors, there are M1 to M5 receptors. Fill out your
Answer: Ach, Nicotinic-neural, Nicotinic-muscular or in other locations
paper following the details in the next table in your own ways. You may
Muscarinic receptors.
draw if you want. Trust me this will help you J
Dr. Rodriguez This exercise should help you remember that Ach is NON-SELECTIVE because
it can stimulate both NICOTINIC and MUSCARINIC receptors.
TYPICAL RESULT OF Dr. Rodriguez
RECEPTOR NAME
LOCATION LIGAND BINDING DIRECT ACTING (MUSCARINIC)
Nicotinic NON-SELECTIVE
Ganglion
Neural (Nn) Opening of Na+ and Bethanechol, Carbachol
Skeletal muscle K+ channels causing
Nicotinic MOA Being classified as non-selective, it stimulates M1 to M3
neuromuscular depolarization
Muscular (Nm) Bowel and bladder atony, (post-surgery or spinal cord
junction Use/s
injury), congenital megacolon.
↑ IP3 and DAG,
M1 Nerves SE Think DUMB BELLS
↑ intracellular Ca2+
M3 SELECTIVE INDIRECT ACTING CHOLINERGIC AGONISTS
Pilocarpine, Cevimeline
• Bind to acetylcholinesterase (AChE) and undergo prompt
MOA Only M3
hydrolysis
Acute angle closure glaucoma, Sjögren syndrome,
Use/s
Sicca syndrome
o Prevents the binding and hydrolysis of endogenous
Miosis, Blurring of vision (due to cyclospasm), acetylcholine → amplify acetylcholine effects
SE Pilocarpine - Hypertension Acetylcholinesterase inhibitors: indirect acting cholinomimetics act by
For others, again think DUMB BELLS raising Ach concentrations in the synaptic cleft by inhibiting the action of
Hypertension is an interesting exception to the rule for promuscarinics; it the enzyme that metabolizes Ach.
Dr. Uy
may be seen after a brief period of hypotension due to the activation of
sympathetic postganglionic M1 receptors in pilocarpine Indirect acting cholinomimetics will be divided into 4: Alcohol,
Dr. Rodriguez Carbamates, Organophosphates and some drugs for Alzheimer’s .
Table guide: just want to emphasize that among the muscarinic agonist, To generalize, this section will have the same MOA and SE
Pilocarpine has a Selective action to M3. Most are Non-selective and have MOA: Inhibits acetylcholinesterase.
“CHOL” in their name; which reminds you of AcetylCHOLine. Sometimes in the SE: Encompassed by DUMB BELLS, but will just note some must knows.
boards they give the less common drugs we encounter, so it’s best to tackle We will not repeat each per section to simplify.
Dr. Rodriguez
some based on their etymology.
At this point, it is wise to recall the locations of M1 to M5. Can you try to
ALCOHOL: EDROPHONIUM
practice recall without looking back at the tables? Diagnosis of MG (Tensilon test)
Dr. Rodriguez Depolarizing NMJ blocker, Muscle relaxation
TOXICITY WITH MUSCARINIC AGONISTS Use/s Differentiation of cholinergic crisis and myasthenic
• This is seen in overdosage of muscarinic agonists and certain crisis.
types of mushrooms (genus: Inocybe) Reversal of neuro-muscular blockade.
o CNS stimulation
o EYE: miosis, spasm of accommodation
CARBAMATES (-STIGMINES)
o LUNGS: bronchoconstriction Neostigmine, Pyridostigmines, Ambenonium,
o GIT/GUT: excessive gastrointestinal and genitourinary smooth Treatment of MG
muscle activity Neostigmine: Bladder and bowel atony
Use/s
o Increased secretory activity (sweat glands, airway, Reversal of nondepolarizing neuromuscular blockage
gastrointestinal tract, lacrimal glands) (by curiums and curoniums)
o Vasodilation Physostigmine, Demecarium, Echothiophate
• Treatment: Atropine (Cholinergic antagonist) Reversal of Atropine Poisoning
* Note that the symptoms of muscarinic poisoning are essentially the same Use/s
Acute glaucoma
with organophosphate poisoning minus symptoms of nicotinic excess.
SE Physostigmine: CNS effects SEIZURES
DIRECT ACTING (NICOTINIC)
NICOTINIC NEURAL AND NICOTINIC MUSCULAR AGONIST ORGANOPHOSPHATES
Nicotine, Varenicline, Lobeline Parathion, Malathion
Activates: Nn and Nm Insecticide
Use/s
MOA Nicotine: Full agonist Scabicide (Malathion)
Varenicline: Partial agonist SE Dangerous cholinergic crisis
Use/s Smoking cessation
Tabun, Sarin, Soman
Generalized ganglionic stimulation (hypertension,
SE Use/s War nerve gases
tachycardia, nausea, vomiting, diarrhea)
SE Rapidly lethal
NICOTINIC MUSCULAR AGONIST
Succinylcholine DRUGS FOR ALZHEIMERS
MOA Activates: Nicotinic (more selective to Nm) Rivastigmine, Donepezil, Galantamine, Tacrine
Use/s Depolarizing NMJ blocker, Muscle relaxation Alzheimer’s Disease
Initial muscle spasms and postoperative pain, prolonged Use/s Rivastigmine (as transdermal patch)
SE Donepezil + Memantine: Alzheimer’s Dementia
action in persons with abnormal butylcholinesterase
Table guide: In these two tables, appreciate that all the drugs for smoking SE Nausea and vomiting
cessation will both stimulate Nn and Nm and notice that they also rhyme. Section guide
Recall where are Nn receptors found? How about Nm receptors? All inhibits acetylcholinesterase kaya sila tinawag na indirect agonist
Great!, now that you know that Nm receptors are found at the NMJ, this should Take note which is used for diagnosis versus treatment of MG.
somehow help you recall that Succinylcholine is a neuromuscular blocker. But Don’t think much of the SE for each, since they are cholinomimetic, think
why is it called a blocker if it’s called an AGONIST? Pause and answer. As anything DUMBBELLS! Then add the additional notes if there are any. The
agonist, it should stimulate the Nm receptor. Pero dahil ayaw niya umalis sa uses are very distinct. Improve recall with repetition.
Dr. Rodriguez
pagkakabind sa Nm receptor, continuous muscle depolarization will result to MYASTHENIA GRAVIS
paralysis. Kasi ghorl sobrang napagod yung muscle sa too much stimulation.
Remember muscles need to relax in order have another contraction. Hence in • An autoimmune destruction of nicotinic ACh receptors,
a way, nagiging “blocker” yung end effect niya dahil na-paralyze yung muscle. characterized by:
Dr. Rodriguez o Fluctuating muscle
NICOTINIC TOXICITY o Weakness
• Largely due to the nonspecific ganglionic stimulation (affecting o Ocular symptoms
sympathetic, parasympathetic and neuromuscular junctions) o Bulbar symptoms
• Blockade of neuromuscular end plate depolarization o Proximal muscle weakness
o Leading to fasciculations and paralysis • May be worsened by the ff drugs:
o CNS toxicity: stimulation (convulsions) followed by CNS o Nondepolarizing neuromuscular blockers (because the
depression mechanism of the disease and its MOA are similar)
• Treatment: symptom directed (atropine for muscarinic excess, o Aminoglycoside antibiotics (because these drugs interfere
diazepam & anticonvulsants for CNS stimulation, mechanical with neuromuscular transmission)
ventilation if with neuromuscular blockade) Differentiating MYASTHENIC CRISIS VS CHOLINERGIC CRISIS
Notice that Nicotinic toxicity is like a mixture of Sympathetic reactions and
Parasympathetic reactions. Why? Clue, it lies in the location of the nicotinic
• Myasthenic Crisis: acute worsening of symptoms due to
receptors. infection, stress or UNDERmedication
Ans. Because remember nicotinic neural receptors are found in the ganglion o Edrophonium IMPROVES muscle strength
either in sympathetic and parasympathetic nervous system. So meaning if • Cholinergic Crisis: excessive activation of cholinoceptors
nastimulate yung Nn both systems are stimulated. Try to look at the SE of (skeletal muscle weakness and parasympathetic signs) due to
Nicotine above. ‘di ba? Hypertension and tachycardia is sympathetic, nausea OVERmedication
vomiting and diarrhea are parasympathetic. o Edrophonium WEAKENS muscle strength
Dr. Rodriguez
Go back to the section under the use of edrophonium, to make more sense of Ipratropium, Tiotropium,
this section Umeclidinium, Glycopyrronium, Aclidinium
Dr. Rodriguez
MOA Blocks muscarinic receptors in bronchial smooth muscles
ORGANOPHOSPHATE POISONING
Acute Asthma, COPD
• Accidental exposure to toxic amounts of pesticides Use/s
Tiotropium: More selective for M3
• Clinical manifestation: DUMBBELLS SE Antimuscarinic effects; dry mouth, blurred vision
Treatment of Organophosphate Poisoning
• Atropine: addresses only MUSCARINIC symptoms Scopolamine
o Notorious for causing hyperthermia in susceptible patients MOA Blocks All Muscarinic receptors
(because Atropine suppresses thermoregulatory sweating) Motion Sickness
• Pralidoxime: addresses BOTH Nicotinic and Muscarinic Use/s Decrease acid secretion in GIT
symptoms Nausea and Vomiting
o Must be administered before 6-8 hours of organophosphate SE Antimuscarinic effects;
bond with cholinesterase occurs (before the bond has AGED or
turned covalent, which is a stronger bond) M3 RECEPTOR BLOCKERS
o has oxime group which has high affinity for phosphorus Dicyclomine, Hyoscyamine, Glycopyrrolate
Diarrhea
Atropine Use/s
IBS, decrease acid secretion in GIT
MOA Blocks all Muscarinic receptors. SE Tachycardia, confusion, urinary retention, increased IOP
• 1st choice: Organophosphate poisoning
Use/s Added in general anesthesia: for Bradycardia, Oxybutynin, Darifenacin, Solifenacin
hypersalivation, decrease airway secretion. Fesoterodine, Tolterodine, Trospium, Imidafenacin
SE Antimuscarinic effects MOA Modest M3 Selectivity; reduces detrusor muscle tone
Use/s Urinary urgency, incontinence
Pralidoxime SE Excess parasympatholytic effects
Binds phosphorus of organophosphate. Breaks
MOA organophosphate bond with cholinesterase. M1 SELECTIVE BLOCKER
(Regenerates active acetylcholinesterase) Pirenzepine, Telenzepine
• Antidote for early stage cholinesterase inhibitor poisoning Use/s Peptic disease (not available in USA)
Use/s (organophosphate poisoning and nerve gas poisoning) SE Excess parasympatholytic effects
• Can relieve skeletal muscle and endplate block Pirenzep1ne and Telenzep1ne. Change “i” to 1 to remember the drugs for M1
SE Muscle weakness blocker
Dr. Rodriguez
Good job! You’re done with Parasympathomimetics! Okay tara quick
synthesis. Parasympathomimetics are divided mainly into two: Direct acting Section guide
and indirect acting. Direct acting will act on the receptors mismo; what are Just in case you’ll forget the drugs that might come out; take this as a clue that
these receptors? ____________ and _____________. Prototype direct acting drug is drugs related to Atropine may have TROP in their name. Take note of the
__________. For for the muscarinic agonists, carbachol is nonselective, while drugs that have selectivity to M1 and M3. This would also help in remembering
pilocarpine is selective for _____ muscarinic receptor. their uses. Again for the SE, study smart by knowing the effects of ATROPINE
Indirect acting parasympathomimetics will increase the levels of Ach by (Alice in Wonderland) because Atropine would be our prototype cholinergic
preventing its degradation by the enzyme ______________. “-Stigmines” are antagonist (see the toxic effects below)
Dr. Rodriguez
known examples of this and used mainly for treatment of ___________. ATROPINE TOXICITY
Answers: muscarinic, nicotinic, Ach, M3, AChE, MG
Dr. Rodriguez • Atropine: prototype nonselective muscarinic blocker, found in
Atropa belladonna plant
D. PARASYMPATHOLYTICS • Features of Atropine Toxicity:
o Atropine fever (hyperthermia) - due to inhibition of sweating
o Atropine flush (cutaneous vasodilation)
o Decreased secretions
o Tachycardia
o Arrhythmias (intraventricular conduction block)
o Constipation
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2019 o Blurred vision
Parasympatholytics in other words are known as CHOLINERGIC o CNS toxicity
ANTAGONIST. Quick recall before going forward, what are the two receptors • Atropine Toxicity Mnemonic:
ulit under cholinergic? Nicotinic and muscarinic. Therefore, o HOT as a hare (hyperthermia)
parasympatholytics or cholinergic antagonists may be expounded further to
muscarinic antagonist and nicotinic antagonist. Okie lezzgo, you’re ready
o DRY as a bone (decreased secretion)
for the next sections. o RED as a beet (cutaneous vasodilation)
Dr. Rodriguez o BLIND as a bat (cycloplegia)
o MAD as a hatter (CNS toxicity)
MUSCARINIC ANTAGONISTS • Treatment: Symptomatic
Again for this part, I won’t be repeatedly mentioning the SE to simplify your o Temperature control: use of cooling blankets
thought process and save brain space. Haha. Basta SE ng mga ‘to ay o Seizure control: Diazepam
ANTIMUSCARINIC effects – Alice in Wonderland.
o HOT as a hare (hyperthermia)
o To reverse antimuscarinic effect: Physostigmine
o DRY as a bone (decreased secretion) CONTRAINDICATIONS TO MUSCARINIC BLOCKERS
o RED as a beet (cutaneous vasodilation)
o BLIND as a bat (cycloplegia) • Cautious use in infants (since they are sensitive to the
o MAD as a hatter (CNS toxicity) hyperthermic effects of atropine)
Dr. Rodriguez • Acute angle-closure glaucoma (since mydriasis can block the
normal drainage of aqueous humor)
NON-SELECTIVE BLOCKERS • Benign prostatic hyperplasia (can precipitate further urinary
Atropine, Homatropine, Cyclopentolate, Tropicamide retention already present in this subgroup because muscarinic
MOA Blocks all Muscarinic receptors. antagonists will relax smooth muscle of the ureters and bladder wall)
Mydriatic, Cycloplegic
• 1st choice: Organophosphate poisoning
NICOTINIC ANTAGONISTS
Use/s Recall again where are the nicotinic receptors found? _____________
Added in general anesthesia: for Bradycardia,
hypersalivation, decrease airway secretion. In the ganglion what nicotinic receptor is found? ___________
How about in the NMJ? ___________
SE Antimuscarinic effects
Answer: Ganglion and Neuromuscular junction. Nn Nm
If you remember your ophtha rotation, you might have been requested to So since they are found in these area, our next topic will be about Ganglionic
dilate your patient prior to an eye surgery. These drugs are being used for that. blockers and Neuromuscular blockers. Getchieee?
GANGLIONIC BLOCKERS STEP 2 – STORAGE

• Competitive pharmacologic antagonists at nicotinic • Norepinephrine and dopamine are transported into vesicles
acetylcholine receptors (NN) of both sympathetic and o Inactivated by monoamine oxidase in the cytoplasm
parasympathetic autonomic ganglia o Monoamine oxidase inhibitors (MAOi) increase stores of NE
• First successful agents for the treatment of hypertension but and dopamine
were abandoned due to severe adverse effects • Inhibitor: Reserpine
o The transfer of DOPA into vesicles is BLOCKED by the drug
Hexamethonium, Trimethaphan, Mecamylamine o
MOA Competitive Nn blocker STEP 3 – RELEASE
Uses Hypertension (Obsolete), Hypertensive emergencies • entry of calcium -> calcium interacts with SNARE proteins
Postural Hypotension, Dry mouth, Blurred vision, (VAMPs and SNAPs) -> vesicle fuses with membrane
SE
Constipation, Sexual dysfunction, Tachycardia o Inhibited by: Guanethidine
Let’s use this section as a learning point to help you remember an important o Promoted by: Amphetamines and Tyramine
neurotransmitter. What is the important neurotransmitter for (1) pre-ganglionic * Release of NE via these agents is calcium INDEPENDENT.
sympathetic nerve fiber? (2) post-ganglionic para-sympathetic nerve fiber?
Answer: You should answer ACh for both. This would make sense again, because the
receptors in the ganglion are Nn which is a type receptor for Ach. Hence if you can STEP 4 – TERMINATION
notice sabi na mabblock niya both sympathetic and parasympathetic ANS kasi Nn
is seen in the ganglion of both sympa or parasympa.
• diffusion and reuptake via NET and DAT in synaptic cleft
Dr. Rodriguez o inhibited by Cocaine and TCAs
• metabolized by MAO and COMT into metanephrines and VMA
NEUROMUSCULAR BLOCKERS o inhibited by MAOi and COMTi
The curare compounds “-curiums” and “curoniums”
Tubocurarine, Pancuronium, Atracurium, Vecuronium, Remember earlier, we asked you to remember the inhibitors for cholinergic
NT synthesis. Now notice the inhibitors for the adrenergic nervous system. Can
MOA Nm blocker you try to fill out the table below in order to synthesize the idea?
Uses Skeletal muscle relaxation prior to surgery Dr. Rodriguez
SE Tachycardia, confusion, urinary retention, increased IOP
SECTION SYNTHESIS
Quick synthesis. Kindly fill out the table below. Name as much drug as you
can. Try to push this exercise further by recalling the use.
Dr. Rodriguez
DESCRIPTION DRUGS
CHOLINERGIC AGONISTS: DIRECT ACTING
Non-selective
M3 selective
Nn and Nm Agonist
Selective Nm agonist
CHOLINERGIC AGONIST: INDIRECT ACTING
An alcohol
Carbamates
Organophosphates
Drugs for Alzheimer’s
CHOLINERGIC ANTAGONIST: MUSCARINIC BLOCKERS
Non-selective blockers Adapted from Katzung BG. Pharmacology Board Exam Review
M3 receptor blockers
M1 selective blockers INHIBITORS
STEPS
CHOLINERGIC ANTAGONIST: NICOTINIC BLOCKERS CHOLINERGIC ADRENERGIC
Synthesis A F
Ganglionic blockers
Storage B G
Neuromuscular blockers
Release C H
Answers: On purpose won’t be placing here the answers for this table. Termination
Because I want this to be a learning opportunity for you. The table is made in
Metabolism D I
the same chronology as how we discussed it and I want you to go back to the
previous pages to complete this table J Reuptake E J
Dr. Rodriguez
VISUALIZATION TIME! Get a scratch paper. And try to create a concept map Answer: A. Hemicholinium. B. Vesamicol C. Botulinum D. Neostigmine. E. None
for the whole cholinergic Pharmacology by following the table you F. Metyrosine G. Reserpine H. Guanethidine I. MAOis, and COMTs, J. Cocaine
completed above. Use this as your go-to notes when you review and TCA
ADRENERGIC PHARMACOLOGY B. ADRENERGIC RECEPTORS

A. CATECHOLAMINE SYNTHESIS Receptor Location G
2nd
Function
NOREPINEPHRINE Msgr
Effector
• Primary transmitter at the sympathetic postganglionic neuron- tissues, ↑Ca2+, causes
effector cell synapses in most tissues Alpha 1 ↑IP3,
Smooth Gq contraction,
o EXCEPTIONS: (ɑ1) DAG
muscle, secretion
§ Accrine sweat glands (uses ACh) Glands
§ Vasodilator sympathetic fibers in skeletal muscle Nerve
• It is the immediate precursor of epinephrine Alpha 2 endings, ¯transmitter release,
Gi ¯cAMP
(ɑ2) Smooth causes contraction
STEP 1 – SYNTHESIS muscle
Cardiac
• Tyrosine is hydroxylated by tyrosine hydroxylase to DOPA
Beta 1 muscle, ↑heart rate, force
o Rate-limiting step (β1) JG
Gs ↑cAMP
↑renin release
o Inhibitor: Metyrosine apparatus
• DOPA is decarboxylated to dopamine
• Dopamine is hydroxylated to norepinephrine
2nd Dopamine
Receptor Location G Function
Msgr D1, ⍺1, ⍺2, β1, β3 agonist
Smooth MOA Dose-dependent actions:
Relax smooth muscle Low dose: D1 Mod dose: β1 Higher dose: ⍺1
muscle,
Beta 2 (β2) Gs ↑cAMP ↑glycogenolysis • First line: Septic shock especial if with renal shutdown
Liver,
↑heart rate, force • Cardiogenic shock
Heart Uses
• Acute heart failure (especially if with accompanied severe
Adipose hypotension
Beta 3 (β3) Gs ↑cAMP ↑lipolysis
cells SE Cardiovascular disturbance, arrhythmia
Smooth Relax renal vascular
Dopamine 1 (D1) Gs ↑cAMP Try to answer the following important points (all the answers are in the tables
muscle smooth muscle
above)
Memorize these receptors by heart, mind and soul, their locations and their 1. Has negligible B2 effect: ___________
actions. Remember the mnemonic QISS and QIQ (read as Kiss and Kick!). 2. First line for anaphylaxis: ___________
Q =Alpha 1, I=Alpha 2; S=Beta 1; S = Beta 2, Q=M1, I=M2 Q=M3. Highlighted in 3. First line for septic shock ___________
green are the important differences 4. First line for shock with renal failure: ___________
Dr. Rodriguez
Kindly take note also that all the ENDOGENOUS neurotransmitters are all
non-selective. Take a look at the heading of each in the table.
C. SYMPATHOMIMETICS Dr. Rodriguez, Im
(ADRENERGIC AGONISTS) DOPAMINE: DOSE DEPENDENT ACTIONS

• LOW DOSE (0.5 to 3 mcg/kg/min)
o Stimulates D1 and D2 receptors
o Leading to vasodilation, decreased arterial blood pressure and
increased renal and splanchnic blood flow (natriuresis and
diuresis will occur)
• MEDIUM DOSE (3-10 mcg/kg/min)
o Stimulates β1 receptors (high chronotropy and contractility)
o Results in increased cardiac output
• HIGH DOSE (>10 mcg/kg/min)
o Stimulates α1 receptors
o Leads to arterial and venous vasoconstriction, increased
systemic vascular resistance, increased blood pressure
o Reflex bradycardia may be seen at this point
CLINICAL APPLICATIONS OF SYMPATHOMIMETICS
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2019 CLINICAL DESIRED SYMPATHOMIMETIC
Section guide: This section will be divided into: Non-selective agonists, CONDITION PARAMETER OF CHOICE
followed by the selective agonists for each for the adrenergic receptors in the Acute heart
Increased cardiac
table above. failure b1 & D1 agonists
Dr. Rodriguez output
Septic chock
MOA OF SYMPATHOMIMETICS Hemostasis Vasoconstriction
Decongestion Temporary a1 agonist
• Direct activation of adrenoceptors
Spinal shock maintenance of BP
o a1: vasoconstriction, increases BP, increase pulmonary Bronchodilation
vascular resistance Bronchospasm
Uterine smooth b2 agonist
o b1: increased HR, conduction and contractility of heart Premature labor
muscle relaxation
o b2: bronchodilation in lungs Hypertension
Decrease BP a2 agonist
o D1: vasodilation in splanchnic and renal blood vessels Glaucoma
o These can be divided into non-selective and selective agonist.
• INDIRECT activation by increasing concentration of available BETA NON-SELECTIVE
catecholamines in the synapse Isoproterenol
o Release of stored catecholamines (amphetamine & tyramine) MOA β1, β2 β3 agonist
o Inhibition of reuptake (cocaine & TCA) • Asthma (as adjunct to B2 agonist)
Uses • Drug for sustained increases in HR (during pacemaker
NON-SELECTIVE ADRENERGIC AGONIST insertion for bradydysrhythmia)
ENDOGENOUS CATECHOLAMINES SE Cardiovascular disturbance, arrhythmia
Endogenous catecholamines are the neurotransmitters found in the Okay at this point, we are still under Adrenergic AGONISTS. But we just
sympathetic nervous system. Endogenous, meaning ginawa sila ng finished non-selective AGONISTS. Review, when you hear Non-selective
katawan. And they have action on all the receptors of the SNS – alpha, beta, adrenergic agonist, what drugs should come to mind again? ____________
dopamine. That’s right, the endogenous catecholamines NE, E, D.
Dr. Rodriguez, Im Now we move on to SELECTIVE Adrenergic Agonists (i.e. Alpha Agonist and
Epinephrine Beta Agonists)
Dr. Rodriguez, Im
MOA β 1 = β 2 > Alpha
• Anaphylaxis, Cardiac arrest, Hemostasis SELECTIVE ADRENERGIC AGONISTS
• Added to local anesthetics to decrease systemic absorption
Uses ALPHA-1 AGONIST
(increases duration of action)
• Severe asthma/COPD Phenylephrine, Pseudoephedrine,
Hypertension, arrhythmia, stroke, MI, pulmonary edema, (-ZOLINES) Oxymetazoline, Tetrahydrozoline,
SE
Hyperglycemia, Tachycardia, Mydriasis Naphazoline Xylometazoline, Midodrine
• Decongestant
Norepinephrine
Uses • Mydriatic, Neurogenic hypotension, drug-induced
MOA a > b1 >> b2 almost negligible hypotension, orthostatic hypotension
• First line: Septic shock • Rebound nasal congestion (Rhinitis medicamentosa)
Uses • Shock SE • Hypertension, stroke, MI, Piloerection, urinary retention,
• Cardiogenic shock reflex bradycardia.
Extreme vasospasm, tissue necrosis, excessive increase in • Ocular administration causes mydriasis WITHOUT cycloplegia;
BP, arrhythmia, MI, ischemia → decreased organ perfusion, also used intranasally to produce local vasoconstriction as a
SE
reflex bradycardia, metabolic acidosis (due to decreased decongestant.
tissue blood flow) • 1st trimester: avoid Pseudoephedrine because it may be associated
with possible risk of gastroschisis
• Midodrine: treatment of orthostatic hypotension
• High doses may cause Alpha-1 agonist overdose
o DOC: Phentolamine (adrenergic blocker)
ALPHA-2 AGONIST Phenoxybenzamine

Clonidine IRREVERSIBLY alpha blocker (forms covalent bond)
MOA
(a1>a2) receptors
Uses Hypertension, cancer pain, opioid withdrawal
Uses • Pheochromocytoma (pre-surgical)
Rebound hypertension (due to abrupt
SE SE Myocardial ischemia
discontinuation). Sedation, Dry mouth (common)
⍺2: decreases central sympathetic outflow → INHIBITION of sympathetic Phenoxybenzamine also blocks histamine (H1), Ach and serotonin receptors.
Dr. Uy
tone and reduced blood pressure
Dr. Uy
Phentolamine
• Taper use prior to discontinuation to avoid rebound hypertension. If
rebound hypertension occurs, administer Phentolamine (reversible REVERSIBLE alpha blocker
MOA
alpha antagonist) (a1 = a2) receptors
• When taken PO, there is initial increase in BP then will go down once • Pheochromocytoma (pre-surgical), Antidote to a1
drug enters the CNS Uses agonist overdose, Rebound Hypertension, reversal of
• If Clonidine is given to patients with pure autonomic failure, clonidine local anesthetics in soft tissue sites
may INCREASE BP because the central sympatholytic effect of clonidine Phentolamine has minor inhibitory effects at serotonin receptors and
becomes irrelevant whereas peripheral vasoconstriction remains intact agonist effects at muscarinic, H1 and H2 receptors.
• TCAs can reduce the antihypertensive effect of clonidine (due to alpha Dr. Uy
blocking effects of TCAs)

Dr. Uy SELECTIVE ALPHA BLOCKERS
• Pharmacologic advantage of a1 selectivity: Reflex Tachycardia is
Methyldopa,
(Others: Guanfacine, Guanabenz, Dexmedetomidine, Tizanidine) LESS common and less severe.
Uses Pre-eclampsia, Gestational hypertension ALPHA-1 BLOCKERS (-ZOSINS)
Sedation (most common), Hemolytic anemia (Positive Prazosin, Doxazosin, Terazosin, Tamsulosin, Silodosin, Alfuzosin
Coombs test) Lactation (due to ↑ prolactin secretion),
SE Uses • Benign prostatic hyperplasia, Hypertension
CNS effects (mental depression, vertigo, nightmares,
impaired mental concentration) Orthostatic hypotension (especially the first dose),
but little reflex tachycardia (compared to non-
SE
Apraclonidine, Brimonidine selective a antagonists),
Uses Glaucoma (decreases secretion of aqueous humor) Increased HDL (Prazosin), Dizziness, Drowsiness, Headache
Blurring of vision, Dry mouth, hyperemia and pruritus, • Tamsulosin: most selective for prostatic smooth muscle
SE Oral tamsulosin may precipitate Intraoperative Floppy Iris Syndrome
eye discomfort
(IFIS) in patients undergoing cataract surgery. This is characterized by
BETA-1 AGONIST billowing of flaccid iris, propensity for iris prolapse and progressive
intraoperative pupillary constriction
Dobutamine Dr. Uy
Cardiogenic shock. Acute heart failure, Cardiac stress Doxazosin, Tamsulosin, Silodosin and Alfuzosin: not indicated for use
Uses testing (Pharmacologic agent to induce ischemia in the in females or for the treatment of hypertension
myocardium.)
ALPHA-2 BLOCKERS
Hypertension, Tachycardia, Arrhythmias, Premature
SE ventricular beats, Angina, Dyspnea, Tachyphylaxis, Yohimbine (Obsolete)
Eosinophilic myocarditis, Fever, Headache, Nausea Uses • Benign prostatic hyperplasia, Hypertension
• Dobutamine effect on alpha receptors increases at higher dose, Increased skeletal muscle activity, tremors, tachycardia,
SE
which explains why peripheral resistance doesn’t decrease hypertension, rhinorrhea, paresthesia
significantly with dobutamine use Note that blocking alpha-2 stops the negative feedback, ultimately
increasing catecholamine release!
Dr. Uy
BETA-2 AGONIST Yohimbine can greatly elevate BP if administered to patients
Salbutamol (Albuterol), receiving NE-transport blocking drugs
Terbutaline, Ritodrine, Isoxsuprine, Metaproterenol
• Acute asthma attacks (DOC) BETA BLOCKERS
Uses • Tocolysis for preterm labor (terbutaline, ritodrine, • Generalizations:
Isoxsuprine) o SE: Bronchospasm (less in selective), AV Block, HF,CNS
Tachycardia, Tremors, Nervousness, Restlessness, sedation, erectile dysfunction,
SE Arrhythmias when used excessively, Loss of o Increased VLDL and decreased HDL Increased plasma potassium
responsiveness (tolerance) (sometimes used clinically for hypokalemia)
SUPPLEMENT: OTHER SYMPATHOMIMETICS
NON-SELECTIVE BETA BLOCKERS
ISOXUPRINE [C]
B2-adrenoceptor agonist that causes direct relaxation of uterine and PROPANOLOL, Pindolol, Timolol, Nadolol, Levobunolol,
vascular smooth muscle; used in the treatment of premature labor and Metipranolol, Carteolol, Sotalol, Labetalol, Carvedilol
as vasodilator for cerebral vascular insufficiency and Raynaud’s MOA Blocks b1 AND b2 receptors.
phenomenon; Angina prophylaxis, Hypertension, Arrhythmias,
Migraine, Performance anxiety, Hyperthyroidism and
Uses
D. SYMPATHOLYTICS Thyroid storm (Propranolol), Glaucoma, Esophageal
(ADRENERGIC ANTAGONISTS) varices (Propranolol)
For this section, there will be two main divisions: (1) alpha blockers and Blocks sympathetic effects on heart and BP. Reduces renin release.
Dr. Uy
(2) beta-blockers. For each divisions, there will be (a) non-selective and • Masks symptoms of hypoglycemia in diabetics (tachycardia,
(b) selective.
Dr. Rodriguez
tremor, anxiety), may impair hepatic glucose mobilization
• Beta blockers are used for the treatment for hyperthyroidism by
ALPHA BLOCKERS blocking the sympathomimetic effects of thyroid hormones and
NON-SELECTIVE ALPHA BLOCKERS inhibition of peripheral conversion of thyroxine to triiodothyronine
• Generalizations: (more active form)
o SE: Orthostatic hypotension, Reflex tachycardia, GI irritation. • Interaction with verapamil (calcium antagonist): severe
Recall in the big table of receptors, alpha receptors are found in the hypotension, bradycardia, heart failure and cardiac conduction
blood vessels. If you block them it will cause vasodilation hence the SE abnormalities.
mentioned above. Vasodilation = babagsak BP (Orthostatic • Carvedilol and Labetalol has combined a and b blockade (may be
hypotenstion) = as a compensation, bibilis tibok ng puso para mapataas used in pheochromocytoma)
ang BP (Reflex tachycardia) • Sotalol lacks local anesthetic action and has marked class III
Dr. Uy
antiarrhythmic effects
• Propranolol: High first pass effect, highly protein bound
• Principal Contraindication to BB use: preexisting atrioventricular
heart block or cardiac failure NOT caused by tachycardia
SELECTIVE BETA BLOCKERS Beta-2 agonists

• Beta-1 blockers (Cardio-selective betablockers) – ADRENERGIC BLOCKERS
(Mnemonic: BEAM NC) Non-selective alpha blockers
ATENOLOL, Acebutolol, Alprenolol, Betaxolol, Bisoprolol, Alpha-1 blockers
ESMOLOL, METOPROLOL, NEBIVOLOL, Celiprolol Alpha-2 blockers
MOA Blocks b1 receptors. Non-selective beta blockers
Angina, Hypertension, Heart failure, Selective beta blockers
Uses
Supraventricular tachycardia (Esmolol only) VISUALIZATION TIME! Pause. Get a scratch paper. And try to create a
• Beta 1 selective agents are also termed as cardio-selective drugs concept map for the whole adrenergic Pharmacology by following the table
(because 75% of beta receptors in the myocardium are beta 1) you completed above. Use this as your go-to notes when you review
Dr. Rodriguez
• Beta 1 selective agents are better suited for patients with
asthma or restrictive airway disease (less chance of GLAUCOMA DRUGS
bronchospasm)
• Also, better suited for patients with essential hypertension as
these drugs lack inhibition of peripheral beta 2 receptors that
produce vasodilation
• Esmolol has shortest half-life
EFFECTS NOT RELATED TO BETA BLOCKADE

Intrinsic Sympathomimetic Activity
• Partial agonist activity
• Effective for hypertension and angina and ideal because they’re
less likely to cause bradycardia and abnormalities in plasma
lipids
• Advantage in treating patients with asthma because these drugs
are less likely to cause bronchospasm
• Acebutolol, Pindolol, Carteolol, Labetalol, Celiprolol,
Penbutolol, Bopindolol, Oxprenolol
Figure 6-9. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
Local Anesthetic Activity DRAINAGE SYSTEM OF THE EYE: FLOW OF AQUEOUS HUMOR
• Also known as “membrane-stabilizing activity” (means inhibition Ciliary body ® posterior chamber ® anterior chamber angle ®
of action potential propagation across the cell membrane similar pupil ® anterior chamber ® trabecular meshwork ®
to Na channel blockers that are class I anti-arrhythmic) canal of Schlemm ® uveoscleral veins
• disadvantage when beta-blockers are used topically in the eye
o decreases protective reflexes TYPES OF GLAUCOMA
o increases the risk of corneal ulceration OPEN ANGLE CLOSED ANGLE
• absent in Timolol and Betaxolol making them useful in • Sudden complete block of
glaucoma • Partial block of normal
drainage system of the eye,
drainage system of the
causing rapid pressure buildup in
MAJOR SUBGROUPS OF BETA-BLOCKERS eye, causing gradual
the eye
pressure buildup inside
Non-selective PROPRANOLOL, TIMOLOL • Associated with: shallow anterior
the eye
ACEBUTOLOL, BETAXOLOL, ESMOLOL, chamber and dilated iris (can
Beta 1-selective • Sx: gradual loss of
ATENOLOL, METOPROLOL OCCLUDE outflow drainage
Partial agonist PINDOLOL, ACEBUTOLOL peripheral vision,
pathway)
Lacking local anesthetic “halos” around lights,
TIMOLOL • Sx: severe eye pain and pressure,
effect gradually increasing
corneal cloudiness, halos around
Low lipid solubility ATENOLOL eye pain
lights, nausea/vomiting
ESMOLOL Treatment:
Shortest-acting Treatment: Iridectomy
ESMOL (small) lang ang half-life Pharmacologic
NADOLOL
Longest-acting
NADOLOL = NAsa DOLO ang half-life
PHARMACOLOGIC TX OF GLAUCOMA IS TWO PRONGED:
Combined g and β
NEBIVOLOL, CARVEDILOL, LABETALOL • REDUCTION of aqueous humor Production
blockade
It’s important to be able to have a mind map of the different drugs in the • ENHANCEMENT of aqueous humor OUTFLOW
previous section that you read. To help you, let’s try to classify the following DRUG CLASS EXAMPLES MECHANISM
drugs. We won’t be giving out the answers here, but try to go back to the Pilocarpine
Ciliary muscle
tables so that there will be help from visual retention. (Selective muscarinic
CLASSIFY THE ACTION if agonist/antagonist and to which receptor. Be as contraction,
agonist),
specific as possible if it’s selective or non-selective opening of
Cholinomimetics Physostigmine &
1. Epinephrine 8. Methyldopa trabecular
Echothiopate
2. Isoproterenol 9. Xylometazoline meshwork →
(Acetylcholinesterase
3. Phenylephrine 10. Salbutamol Increased outflow
inhibitor)
4. Phenoxybenzamine 11. Phentolamine
Increased outflow
5. Dopamine 12. Prazosin Prostaglandin Latanoprost,
via
6. Dobutamine 13. Propranolol analogue Brimatoprost
7. Clonidine 14. Esmolol canal of Schlemm
Dr. Rodriguez Non selective a Increased outflow
Epinephrine
agonists via uveoscleral veins
SECTION SYNTHESIS Timolol, Levobunolol,
Beta Carteolol, Metipranolol,
Quick synthesis. Kindly fill out the table below. Name as much drug as you
antagonists (nonselective),
can. Try to push this exercise further by recalling the use.
Dr. Rodriguez Betaxolol (b1 selective)
Decreased
DESCRIPTION DRUGS Osmotic agents Mannitol
production of
ADRENERGIC AGONIST Brimonidine,
a2 agonists aqueous humor
Non-selective Apraclonidine
from ciliary
Carbonic Acetazolamide, epithelium
Beta-Nonselective
anhydrase Dorzolamide
Alpha 1 agonists inhibitors
Alpha 2 agonists
Beta-1 agonists
CARDIOVASCULAR DRUGS
DRUGS FOR HYPERTENSION DIURETICS
https://qrs.ly/92dvdrc
SYMPATHOPLEGICS
• Drugs interfere with sympathetic control of cardiovascular
function. By reducing: venous tone, heart rate, contractile force
of the heart, cardiac output and total peripheral resistance.
Drugs in this section were all discussed under autonomics. As a guide let’s
look at the term Sympathoplegics. Sympa means, sympathetic system.
Plegic from Plegia means “paralyze” so in this case parang stop or put an
end to sympathetic effects – tachycardia, vasoconstriction etc. which all
contributes to high BP.
Dr. Rodriguez
• Generalizations:
o Indication:
§ Hypertension: Clonidine, Alpha-1 blockers (-zosin) and
Beta blockers (-olols)
§ Pre-eclampsia: Methyldopa
§ Hypertension (obsolete use): Ganglionic blockers
o Side effects:
§ Sedation: Alpha 2 agonists, Ganglionic blocker (both due to
DRUGS STRATEGY FOR decreased sympathetic stimulation)
HYPERTENSION § In general, note that in the SE section of each, the side effects
https://qrs.ly/86dvdr9 are due to blockade of adrenergic receptors.
In the MOA per each drug chart later, we won’t be indicating the
mentioned indications above. Instead, we will give out the other uses. But
DIURETICS please focus on the indications under the generalization above.
• Diuretics lower BP by decreasing volume and a direct vascular Dr. Rodriguez
effect that is not yet fully understood CENTRALLY ACTING ALPHA 2 AGONIST
There are two main diuretics for hypertension: (1) Thiazide and (2) Loop.
The other diuretics will be discussed at a later section. • General MOA: Blocks alpha-2 receptor. And if you remember
Dr. Rodriguez earlier, alpha-2 is regulatory in nature. If you stimulate it further,
it will decrease central sympathetic outflow.
THIAZIDE DIURETICS
Hydrochlorothiazide, Chlorthalidone, Indapamide, Metolazone Clonidine
Inhibit Na+/Cl- transporter in DCT Uses • Other uses: cancer Pain, Opioid withdrawal
MOA Other: cause moderate diuresis and reabsorption of SE Rebound hypertension, dry mouth (anti-cholinergic)
calcium (see use below) • Taper before discontinuing to avoid rebound hypertension
• Hypertension, Heart failure, Hypercalciuria, Renal
Uses Methyldopa
calcium stones, Nephrogenic diabetes insipidus
Hypokalemic metabolic alkalosis, Dilutional SE Hemolytic anemia (POSITIVE COOMBS TEST)
hyponatremia, Sulfa allergy, K+ wasting, • Most commonly used maintenance meds for hypertension in
SE
HYPER-GLUC: HyperGlycemia, HyperLipidemia, pregnancy
HyperUricemia, HyperCalcemia
• Metolazone appears in cord blood and crosses placenta and may ADRENERGIC BLOCKERS
cause hypokalemia, hyponatremia, hypoglycemia, jaundice and Alpha-blockers (-zosin)
thrombocytopenia. Prazosin, Doxazosin, Terazosin, Tamsulosin, Silodosin, Alfuzosin
• Less effective in edematous states compared to Loop diuretics. Uses BPH
• For diuretics remember that they can cause acid-base imbalances, both First dose syncope/orthostatic hypotension (give at
acidosis and alkalosis.
SE bedtime). Reflex tachycardia (less chance), Dizziness,
• Always remember that “Where Na+ goes, water follows” and “Where
Drowsiness, Headache, Weakness, Asthenia, Nausea, Edema
Na+ goes, HCO3- follows too” (This will be useful also for explaining
acidosis caused by Carbonic Anhydrase inhibitors). Tamsulosin: most selective for prostatic smooth muscle
• Also remember that “Where K+ goes, H+ follows” Notes Doxazosin, Tamsulosin, Silodosin and Alfuzosin: not for
• So for diuretics that cause K+ wasting, they are expected to cause use in females or for treatment of hypertension.
HYPOkalemic Metabolic ALKALOSIS since H+ is also lost in the urine. While Beta-blockers (-olol)
for K+ sparing diuretics, since you retain K+, you will also retain H+, leading to
Other: Angina prophylaxis, Arrhythmias, Migraine,
HYPERkalemic metabolic ACIDOSIS. The mechanism of acidosis caused by Uses
Carbonic Anhydrase inhibitors is further discussed in the diuretics chapter. Performance anxiety, Hyperthyroidism, Glaucoma
Dr. Uy Bronchospasm, AV block, Heart failure, CNS sedation,
SE
Erectile dysfunction
LOOP DIURETICS • DO NOT GIVE in acute heart failure. But this is used
Furosemide, Bumetanide, Torsemide, Ethacrynic acid in chronic HF to decrease demand
Notes
Inhibit Na/K/2Cl transporter in thick ascending limb of loop • Carvedilol and Labetalol: has combined a and b
MOA of Henle. (See the difference between thiazide) blockade (may be used in pheochromocytoma)
Others: Powerful diuresis, increased calcium excretion Sympathoplegics (Must Knows):
• Heart failure, pulmonary edema 1. Class of drugs used for BPH: ______________
Uses 2. Causes Hemolytic anemia: _____________
• Hypertension, Hypercalcemia, Acute renal failure, Anion overdose
“OH DANG” 3. Tapered use prior to discontinuation to avoid rebound
SE O-totoxicity, H-ypokalemia, D-ehydration, A-llergy to sulfa, hypertension: ______________
N-ephritis, G-out 4. Beta blockers can be given in Acute or Chronic HF? _______________
5. Safe antihypertensive drug for pregnant women: _____________
• Ethacrynic acid: NOT a sulfur-derivative, and therefore, can be
6. Obsolete use for hypertension management: ______________
given to Px with sulfur allergy. 7. First dose phenomenon: _____________
• Very effective in edematous and states of fluid overload.
• Also known as the high ceiling diuretics
• Inhibition of a different isoform of NKCC1 in the inner is thought to be responsible
for the ototoxicity that is rarely seen with high dose IV loop diuretics
• Hypercalciuria may cause nephrocalcinosis
Dr. Uy
PARENTERAL VASODILATORS
Nitroprusside
Relaxes venous and arteriolar smooth muscle by
MOA
increasing NO → ↑ cGMP → smooth muscle relaxation
• Hypertensive emergency,
Uses • Acute heart failure, Cardiogenic shock, Controlled
hypotension
SE Cyanide toxicity, Hypotension, Headache
Very light sensitive, short duration of action
Notes MOST EFFECTIVE VASODILATOR. Both arteriolar and
a venodilator.
D1 Receptor Agonist: Fenoldopam

Arteriolar vasodilation of afferent and efferent
MOA
arterioles. Increases renal blood flow
Uses Hypertensive emergency
Modified from Figure 11-2. Katzung BG. Basic and Clinical Pharmacology 14 ed. 2018.
th
SE Hypotension, hypokalemia
KEY LEARNING POINTS Pheochromocytoma Short duration of action: 10 mins. Not commonly used
Notes
What drugs are used to control blood pressure in pheochromocytoma? due to its very short half-life.
Phenoxybenzamine, Phentolamine or Labetalol
Although all of the drugs in this section are vasodilators they differ in the way
they cause vasodilation. Some affects intracellular calcium metabolism
VASODILATORS ________. Others causes hyperpolarization by activating potassium channels
• Generalization: ________________. While CCBs, based on their name affect the calcium channels,
o MOA: Look at the MOA of each, they all differ. Memorize this by heart one group has a better action to the heart than the vessels, like in the case
o SE: Notice that when you vasodilate BP drops (SE: hypotension), of __________ types of CCBs – take note of the type of CCB that has this effect.
hence as a compensation to make the BP higher, tachycardia happens Also important are the well-known SEs of these vasodilators, can you name
(reflex tachycardia) can be a SE. Also when you vasodilate, fluid the drug that causes the following SEs? Drug induced lupus: ________.
goes down to dependent portions (edema). Vasodilation may also Hirsutism: ________. Gingival hyperplasia: ________ Cyanide toxicity: _________
cause (headache). Later on in the drug charts, we won’t be Dr. Rodriguez
mentioning all these repeatedly. We’ll focus on the other buzzwords

M
Dr. Rodriguez
RAAS ANTAGONIST
Generalization:
OLDER ORAL VASODILATORS • Indication: These are used mainly for hypertension, heart failure, and
Hydralazine diabetic nephropathy.
Alters intracellular Ca2+ metabolism. • SE: Note the since aldosterone is affected: Potassium excretion is
MOA impaired (Hyperkalemia). Since aldosterone is inhibited, there is no
Vasodilates ARTERIOLES = decreased AFTERLOAD
Pre-eclampsia, hypertension sodium reabsorption, volume is depleted, and so BP is decreased
Uses (Hypotension). ACE and ARBs are Teratogens.
+ISDN = for HEART FAILURE
• Other SE and indications will be added in the drug cards.
SE Severe psychiatric depression, suicidal ideation
Notes Drug induced lupus, Myocardial ischemia ARBS and ACEi:
• Heart failure: Slows ventricular remodeling and increases survival in
Minoxidil, Diazoxide heart failure
Opens K+ channels in vascular smooth muscle = • Kidney disease: Delays progression of diabetic nephropathy.
MOA hyperpolarization = smooth muscle relaxation = Decreases albumin excretion and slow progression from micro- to
vasodilation macroalbuminuria (renoprotective effect)
o Not for patients with AKI and Hyperkalemia
Uses Alopecia, Hypertension
• Contraindicated: Pregnancy
Hirsutism, Angina, pericarditis, pulmonary o Use in 2nd and 3rd trimester = reduced renal function = fetal/neonatal
SE
hypertension morbidity and mortality
Notes Drug induced lupus, Myocardial ischemia o Discontinue as soon as pregnancy is detected (fetal hypotension,
• Minoxidil stimulates hair follicles (telogen phase) to neonatal skull hypoplasia, anuria, renal failure, renal dysplasia)
differentiate into growth follicles (anagen phase) o Never combine ACEi and ARBs together (Increased adverse reaction
since they have the same effect on the RAAS pathway and possible
increased incidence of cancer)
CALCIUM CHANNEL BLOCKERS Dr. Rodriguez
Both mechanism block the L-type calcium channels. But look at the
difference per drug class.. Both types are used for Angina and ACE INHIBITORS (-PRILS)
Hypertension. Additional uses are indicated below. CCBs may also cause
the following SE: Constipation, Pretibial edema (common), Nausea, Captopril, Enalapril, Benazepril, Fosinopril, Lisinopril, Quinapril,
Flushing, Dizziness, Heart failure, AV block, Sinus node depression Ramipril, Trandolapril, Moexipril, Perindopril, Imidapril
Dr. Rodriguez Inhibits ACE and formation of Angiotensin II.
M
MOA
Decreases aldosterone secretion
Non-dihydropyridine CCB: VERAPAMIL and DILTIAZEM Uses Other use: Post myocardial infarction
Block L-type Ca channels (Cardiac > Vascular) SE Cough, Angioedema, Taste disturbance, Teratogen
MOA
More cardioselective (hence for arrhythmia) Short duration of action: 10 mins. Not commonly used
Uses Supraventricular tachycardia, Migraine Notes
due to its very short half-life.
SE Gingival hyperplasia (Verapamil) • Captopril has a short half-life, necessitating 2-4x a day
• NOT for ACUTE HEART FAILURE: will further depress the heart. administration
• Inhibits ACE (aka kininase II and peptidyl dipeptidase) →
Dihydropyridine CCB (-DIPINES) increase in endogenous vasodilators of the kinin family
Nifedipine, Amlodipine, Felodipine, Nicardipine, Nisoldipine, (bradykinin) may cause cough and angioedema
Clevidipine, Isradipine, Levamlodipine, Lacidipine, Lercanidipine • 5-20% of patients experience dry cough. Remedy: decrease
Block L-type Ca channels (Vascular > Cardiac) dose or shift to ARBs
MOA
More selective for blood vessel (hence for hypertension) • Do not give to patients with bilateral Renal Artery stenosis since
Uses Hypertension, Angina ACEi can decrease the GFR of the stenotic kidney (due to removal of
Gingival hyperplasia (Amlodipine). Please don’t forget angiotensin II-induced renal vasoconstriction)
SE
the SE’s mentioned in the generalization above.
ANGIOTENSIN RECEPTOR BLOCKERS (-SARTANS) ANGINA PECTORIS

Losartan, Candesartan, Valsartan, Telmisartan, Irbesartan, • Atherosclerotic Angina
Eprosartan, Azilsartan, Olmesartan o angina of effort or classic angina
Blocks Angiotensin (AT1 receptors) in vascular smooth o associated with atheromatous plaques that partially occlude 1
MOA muscle and adrenal cortex. or more coronary arteries
Decreases aldosterone secretion o constitutes about 90% of angina cases
Uses ARBS are as effective as ACEi but has less cough • Vasospastic Angina
SE Other SE: Hypoglycemia, Anemia, diarrhea o rest angina, variant angina, or Prinzmetal angina
Short duration of action: 10 mins. Not commonly used o involves reversible spasm of coronaries, usually at the site of
Notes an atherosclerotic plaque
due to its very short half-life.
• 1.6-6.6% of Px may experience cough as well. o responsible for less than 10% of cases
• Has lower rates of cough and angioedema but higher rates of o may deteriorate into unstable angina
hypotension • Unstable Angina
o unstable/crescendo angina, acute coronary syndrome
RENIN INHIBITORS o increased frequency and severity of attacks that result from a
combination of atherosclerotic plaques, platelet aggregation
Aliskiren
and vasospasm
Inhibits renin.
MOA o immediate precursor of a myocardial infarction
Prevents conversion of angiotensinogen to angiotensin I.
Uses Hypertension
THERAPEUTIC STRATEGIES IN ANGINA
Headache, diarrhea, cough, rash, hyperkalemia, increase
SE
in serum creatinine, renal impairment, angioedema • Defect that causes anginal pain is inadequate coronary oxygen
delivery relative to the myocardial oxygen requirement
Notes Contraindicated in pregnancy
• Can be corrected in 2 ways:
Aliskiren sounds like alis ka renin!
Dr. Rodriguez o increasing oxygen delivery (by vasodilation)
o reducing oxygen requirement (by decreasing HR)
M
SUPPLEMENT: HYPERTENSION IN PREGNANCY

• NO CLEAR CONSENSUS ON THE MANAGEMENT OF MILD TO NITRATES
MODERATE HTN IN PREGNANCY. Nevertheless, drugs that have been • Nitrates decrease angina by reducing cardiac work (reducing
listed as acceptable oral antihypertensive agents in pregnant women preload) and increasing the blood flow through partially
are as follows: occluded epicardial coronary vessels
o Methyldopa
o Labetalol
o Nitrates are more of a venodilator than an arteriolar
o Nifedipine vasodilator
o Hydralazine • Nitrates PLUS Sildenafil: a dangerous combination
• Methyldopa is a drug of first choice. It does not alter maternal cardiac o Nitrates release nitric oxide, which activates the guanylyl
output or blood flow to the kidneys or uterus cyclase and increases the cGMP
• The combined alpha and beta blockade of labetalol makes it a o Sildenafil also increases cGMP (by inhibiting its degradation).
peripheral vasodilator which has been shown to be effective in pre- This could lead to a very dangerous hypotension if both are
eclamptic and non-proteinuric hypertension in pregnancy. However, used together.
because the safety record of labetalol in pregnancy in not well
established as that of methyldopa, labetalol should be considered a 2nd
line agent for pregnant women with chronic hypertension requiring
long-term drug therapy.
• Oral CCBs have been shown to reduce maternal blood pressure in
pregnant women, but little is known about the effects of long-term
administration in the 1st trimester. Among the CCBs, Nifedipine has
been the best studied and has been used extensively in later pregnancy.
• Oral HYDRALAZINE is effective as monotherapy or as add-on to
methyldopa in chronic hypertension in pregnancy. In general,
hydralazine often requires combination therapy with a sympatholytic
agent (Methyldopa or BB) to help attenuate the reflex tachycardia
associated with hydralazine
• ACEi and ARBs are NOT recommended during pregnancy
• Diuretics are also avoided since it can reduce maternal plasma volume
and can cause electrolyte disturbance
RAAS AND PREGNANCY
https://qrs.ly/dndvdrh NITRATE POISONING
• Nitrates → meningeal blood vessel vasodilation → ↑ ICP → headache
• Monday Disease:
o Due to occupational exposure to nitrates
DRUGS FOR ANGINA PECTORIS o Alternating development of tolerance (during the work
week) and loss of tolerance (over the weekend) every
Monday (every Monday with headache)
CYANIDE POISONING: NITRATES AS A PART OF THE ANTIDOTE

• Cyanide affects Complex IV (cytochrome oxidase) of the
Electron Transport Chain
• Antidote: Lilly Cyanide Kit: inhaled amyl nitrite + IV sodium
nitrite + IV sodium thiosulfate
o Short acting nitrite to cause oxidation of Fe2+ in Hemoglobin to Fe3+ in
methemoglobin (nitrate is used to make Methemoglobin)
o Methemoglobin combines with cyanide (cyanomethemoglobin), thus
releasing cytochrome oxidase enzyme
o Sodium thiosulfate reacts with cyanomethemoglobin (converts to
nontoxic thiocyanate and methemoglobin)
SUPPLEMENT: Effects of Drug Combinations In angina, the problem is mababa yung oxygen supply to the myocardium. The
Combined approach to these drugs is to know that you want to increase the delivery of
oxygen (Vasodilate to increase blood flow) to the heart or decrease niyo
Nitrates BB or CCB Nitrates
yung usage of oxygen by decreasing demand (slow down heart rate with
alone alone and BB or CCBs or BB). CCBs and BB were already discussed previously. So focus on the
CCB nitrates in this table. Note the special use of amyl nitrite: _____. Recall, can you use
Reflex CCBs and BBs in acute heart failure? _____
Heart rate DECREASE DECREASE
increase Dr. UY
Arterial
Decrease DECREASE DECREASE
pressure METABOLISM MODIFIERS
End-diastolic
pressure
DECREASE Increase DECREASE • Metabolism modifiers decrease myocardial oxygen demand in
Reflex No effect or general since they try make use of pathways that utilize less
Contractility DECREASE ATP, hence, less amount of work for the myocardium.
increase decrease
Reflex
Ejection time Increase No effect
decrease Trimetazidine
Net myocardial • Inhibit Beta oxidation of fatty acid by inhibiting 3-
DECREASE DECREASE DECREASE
O2 requirement ketoacyl-CoA thiolase which enhances glucose
MOA
As mentioned, the end strategy is to make sure oxygen is still oxidation.
available/enough for the cardiac cells. There are two strategies: (1) • Prevents decrease in ATP in ischemic/ hypoxic states.
increase the delivery of oxygen by vasodilating the arteries going to the Uses Angina pectoris, Tinnitus, Dizziness
heart (NITRATES) and (2) Decrease the utilization of oxygen by relaxing
the heart (CCBs and Beta-blockers)
SE EPS, gait instability, restless leg syndrome
Dr. Rodriguez Notes Interacts with MAO inhibitors
NITRATES Ranolazine
• Generalizations: • Reduces a late, prolonged Na+ current in myocardial
o MOA: Releases nitric oxide (NO), increases cGMP (cyclic cells.
guanosine monophosphate), and relaxes smooth muscle, Decreased intracellular Na+
MOA
especially vascular → increased Ca2+ expulsion via Na+-Ca2+ exchanger
o SE: Reflex tachycardia, Orthostatic hypotension, Headache, →Intracellular Ca2+
→decreased cardiac force and work.
Tolerance (transdermal) Methemoglobinemia
Tx for Methemoglobinemia? Low dose Methylene blue Uses Angina prophylaxis
SE QT prolongation, nausea, constipation, dizziness
Amyl Nitrite (Ultrashort acting) • CYP3A4 inhibitors increase Ranolazine concentration
Notes
Uses Cyanide poisoning (Inhalational) May also modify fatty acid oxidation
Notes Part of the Lilly Cyanide Kits
Ivabradine
Nitroglycerin (NTG) • Inhibits If Na current in SA node → decreases
ISDN – Isosorbide dinitrate hyperpolarization-induced inward pacemaker current →
MOA
ISMN – Isosorbide mononitrate decrease HR and cardiac work
Decreases HR without decreasing the BP
• Angina, Acute Coronary Syndromes
Uses Angina prophylaxis, Heart Failure
Uses ISMN: M for matagal since it has longer half-life, and M for
Bradycardia, Hypertension,
Matibay since it does not undergo first pass effect SE
Atrial Fibrillation
+Sildenafil: Cause dangerous hypotension
Notes First pass effect: ~90% (NTG)
NTG: Decreases platelet aggregation DRUGS USED IN HEART FAILURE
CALCIUM CHANNEL BLOCKERS
These were already discussed earlier. Recall tayo: What type of calcium
channel are blocked? _______________. Which type are more
cardioselective?____________ Which group is more used for arrhythmia?
___________ Which group is used more for hypertension? ______________. Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2019
Go back to the CCB section for the answers.
Dr. Rodriguez
CONGESTIVE HEART FAILURE: PATHOPHYSIOLOGY
Non-dihydropyridine CCB (Verapamil and Diltiazem) • Fundamental physiologic defect: decrease in cardiac output
Uses DOC for Prinzmetal angina: Diltiazem relative to the needs of the body
o frequently associated with chronic hypertension, valvular
disease, coronary artery disease, and cardiomyopathies
Dihydropyridine CCB (-dipines)
• Clinical Manifestations:
Uses Angina, Hypertension
o Left-sided heart failure: Orthopnea, PND, Pulmonary Congestion
Recall that they can cause reflect tachycardia; may also
SE o Right-sided heart failure: Hepatomegaly, Edema, Engorged
have pro-arrhythmogenic effect.
Neck Veins
CHF: THERAPEUTIC STRATEGIES

BETA-BLOCKERS • Positive inotropic drugs: Direct augmentation of depressed
PROPRANOLOL, Pindolol, Timolol, Labetalol, Carvedilol, Nadolol, cardiac contractility
Levobunolol, Metipranolol, Betaxolol, Bisoprolol, Nebivolol • Vasodilators: Reduction of preload or afterload
Angina prophylaxis, Hypertension, Arrhythmias, • Diuretics: removal of retained salt and water
Migraine, Performance anxiety, Hyperthyroidism,
• ACE inhibitors: reduction of afterload and salt and water retention
Uses Glaucoma
Used in Chronic heart failure to control HR but NOT acute • Beta-blockers: reduction of excessive sympathetic stimulation
heart failure for it may further depress the heart
Bronchospasm (B1), AV block (B1 in AV node), Heart THERAPEUTIC
SE STRATEGY
failure, CNS sedation, Erectile dysfunction
• Masks symptoms of hypoglycemia in diabetics FOR HEART FAILURE
Notes • Carvedilol and Labetalol: has combined a and b https://qrs.ly/3idvdrs
blockade (may be used in pheochromocytoma)
CHF TREATMENT: MNEMONIC: Narrow Therapeutic Index
• ACUTE HEART FAILURE What drugs have narrow therapeutic index?
o Should be treated with a loop diuretic WALA na Cyang PaPa! VasTeD na!
Warfarin Phenobarbital
o if very severe, use prompt-acting positive inotropes (beta-
Aminoglycosides Phenytoin
agonists or PDE inhibitors) and vasodilators Lithium Vancomycin
• CHRONIC HEART FAILURE Amphotericin B Theophylline
o treated with diuretics (often loop plus spironolactone) plus Carbamazepine Digoxin
an ACE inhibitor and, if tolerated, a beta-blocker
o digitalis may be helpful if systolic dysfunction is prominent
DIGOXIN
POSITIVE INOTROPES https://qrs.ly/qldvds3
Cardiac Glycoside: Digoxin, Digitoxin
Inhibits Na+/K+ ATPase; Increases intracellular Ca2+,
MOA OTHER DRUGS FOR CHF
increasing cardiac contractility
Uses Heart failure, Nodal arrhythmias VASODILATORS
Narrow therapeutic index • NITROPRUSSIDE or NITROGLYCERIN for acute severe failure
SE
Arrhythmias, Vomiting, Diarrhea, Visual changes with congestion
• Reduced clearance with quinidine, amiodarone, • Dramatically effective in CHF due to increased afterload (e.g.
cyclosporine, diltiazem and verapamil.
Notes continuing hypertension in an individual who has just had an
Arrhythmogenesis increased by hypokalemia,
infarct)
hypomagnesemia and hypercalcemia.
• HYDRALAZINE and ISOSORBIDE DINITRATE: reduce
mortality in African Americans
Dobutamine
• CCBs: NO value in CHF
MOA β1 agonist
Acute heart failure, Cardiogenic shock, Cardiac stress
Uses
testing DIURETICS
Hypertension, Tachycardia, Arrhythmias, Premature • First-line therapy for both systolic and diastolic failure
ventricular beats, Angina, Dyspnea, Tachyphylaxis • FUROSEMIDE for immediate reduction of the pulmonary
SE
(common with dobutamine), Eosinophilic myocarditis, congestion and severe edema associated with acute heart failure
Fever, Headache, Nausea • SPIRONOLACTONE and EPLERENONE have significant long-
DOBUTAMINE and DOPAMINE are useful in acute heart term benefits and can reduce mortality in chronic failure
failure
Notes Not appropriate for chronic failure because of tolerance,
lack of oral efficacy and significant arrhythmogenic
BETA-BLOCKERS
effects. • CARVEDILOL, LABETALOL, BISOPROLOL, NEBIVOLOL and
METOPROLOL reduce progression of chronic heart failure
PDE inhibitor: Milrinone Inamrinone • NOT OF VALUE in acute failure and may be detrimental if
Increase cAMP by inhibiting its breakdown by PDE3 → systolic dysfunction is marked
MOA
increase in cardiac intracellular calcium.
Heart failure, pulmonary hypertension, intraoperative ANGIOTENSIN ANTAGONIST
Uses
cardiac support • Reduce aldosterone secretion, salt and water retention and
SE Arrhythmias, hypotension vascular resistance
should not be used in chronic failure because they • Decrease ventricular remodeling (cardioprotective)
Notes
increase morbidity and mortality • Reduce morbidity and mortality in chronic heart failure
• FIRST-LINE DRUGS FOR CHRONIC HEART FAILURE
It’s important to note for Digoxin the electrolyte derangements that
• ARBs have the same benefits as ACE-inhibitors
causes toxicity. Remember the mnemonic “Kamukha” “KMO2 C@” When
you write the letter “K” the last stroke points downwards, same with “M.”
Also when you write O2 with curl in the 2 it points downwards When you NEPRILYSIN INHIBITOR: SACUBITRIL
write Ca write the letter a as “@” the last stroke you did while writing this • In combination with Valsartan for Heart Failure
points upwards. The direction of stroke corresponds to the level of the
• It is prodrug that is activated to Sacubitrilat, which inhibits the
electrolyte that causes the toxicity. HYPOkalemia, HYPOmagnesemia,
LOW Oxygen. HYPERcalcemia. enzyme Neprilysin
Dr. Rodriguez • Neprilysin enzyme
o Responsible for the degradation of atrial and brain natriuretic
CARDIAC GLYCOSIDES: DIGITALIS peptide – two BP lowering peptides that work mainly by
Digitalis Toxicity reducing blood volume
• increased by hypokalemia, hypomagnesemia, and hypercalcemia o Degrades Bradykinin – an inflammatory mediator exerting
o loop diuretics and thiazides may significantly reduce serum potent vasodilatory action
potassium and precipitate digitalis toxicity (causes HypoK, There is a combination therapy of Sacubitril with Valsartan (Brand
HypoMg, HyperCa) Names include Entresto and Vymada) that has been proven to improve
o digitalis-induced vomiting may deplete serum magnesium ejection fraction among patients with chronic heart failure with reduced
and similarly facilitate toxicity EF.
MNEMONIC: Survival in CHF
The most common ECG change seen in Digoxin toxicity is Premature
Ventricular Contractions (PVCs) What drugs have been shown to improve survival in cases of heart failure?
Dr. Pereyra-Borlongan ABA! Buhay ka pa!
Treatment of Digitalis Toxicity ACE inhibitors
• Correction of potassium/magnesium deficiency Beta-blockers
Aldosterone Antagonists
• Antiarrhythmic drugs
o drug of choice is LIDOCAINE
o electronic pacemaker may be required in severe cases ANTIARRHYTHMIC DRUGS
• Digoxin antibodies
o digoxin antibodies (Fab fragments; Digibind)
If digoxin antibodies are not available, Bile Acid binding resins can be
given as a substitute. Since these agents are substances that look like
cholesterol (meaning they also have the CPPP ring), then they can also
bind Digoxin since digoxin is also a sterol. (All glycosides are sterol
derivatives)
Dr. Pereyra-Borlongan
Before moving to each of the sections, kindly take time to memorize the main CLASS 1C
mechanism of the different groups of antiarrhythmics. Once you’re done, try Propafenone, Flecainide, Encainide, Moricizine
to answer the following by giving the class without looking:
Refractory arrhythmias
1. Beta blockers: 3. Sodium Channel blocker
2. CCB: 4. Potassium channel blocker
Uses Most arrhythmogenic among the class 1 anti-arrhythmics
Now go through each section one by one. Give importance to those who are (that’s why they’re only used for refractory arrhythmias)
emphasized in bold in each table. At the end of this topic, we will try to • Increased arrhythmias (proarrhythmic effect), CNS
synthesize with questions SE excitation
Dr. Rodriguez • Contraindicated for post-MI arrhythmias.
ARRHYTHMIAS: MECHANISMS OF ARRHYTHMIAS
• ABNORMAL AUTOMATICITY
CLASS 2 ANTIARRHYTHMICS
o pacemaker activity that originates anywhere other than in the
sinoatrial node (BETA BLOCKERS)
• ABNORMAL CONDUCTION • Acts on: Phase 4
o conduction of an impulse that does not follow the defined path • Primarily cardiac beta-adrenoceptor blockade and reduction in cAMP
or reenters tissue previously excited o reduction of both sodium and calcium currents
o Slows down of abnormal pacemakers and pacemaker activity
TORSADES DE POINTES
• AV node is particularly sensitive to blockers
• Often induced by antiarrhythmics and other drugs that change
o PR interval is usually prolonged
the shape of the action potential and prolong the QT interval
• Sotalol and Amiodarone also have group 2 effects
• ECG morphology: polymorphic ventricular tachycardia
• General SE:
(waxing and waning QRS amplitude)
o Bronchospasm, Cardiac depression, AV block, Hypotension
• Associated with long QT syndrome (heritable abnormal
prolongation of the QT interval caused by mutations in the IK or
Propranolol, Metoprolol, Atenolol
INa channel proteins)
Post-MI prophylaxis against sudden death,
Uses
Thyrotoxicosis
SINGH-VAUGHAN WILLIAMS CLASSIFICATION Notes
• In CHF, reduces progression and decreases incidence of
• Based loosely on the channel or receptor affected potentially fatal arrhythmias
o CLASS 1. Sodium channel blockers
o CLASS 2. Beta-adrenoceptor blockers Esmolol
o CLASS 3. Potassium channel blockers Thyrotoxic arrhythmias,
Uses
o CLASS 4. Calcium channel blockers Acute perioperative arrhythmias, SVT
CLASS 3 ANTIARRHYTHMICS
(POTASSIUM CHANNEL BLOCKERS)
• Acts on: Phase 3
• Hallmark is prolongation of the AP duration
o Caused by blockade of IK potassium channels that are
responsible for the repolarization of the AP
o Results in an increase in ERP and reduces the ability of the
heart to respond to rapid tachycardias
• ECG morphology: increase in QT interval (compare later with
Class 4)
AMIODARONE, Dronedarone, Vernakalant

Strong IK block produces marked prolongation of action
MOA
CLASS 1 ANTIARRHYTHMICS potential and refractory period
(SODIUM CHANNEL BLOCKERS Refractory arrhythmias, Used off-label in many arrhythmias
Uses Dronedarone is less toxic but less effective than
• Generalization: Amiodarone. It is used in Afib and Atrial flutter
o Differentiation on MOA: Microcrystalline deposits in cornea and skin
§ 1A: Prolong action potential SE Thyroid dysfunction (hyper- or hypo-)
§ 1B: Shorten duration of action potential Paresthesia, Tremor, Pulmonary fibrosis
§ 1C: No effect on action potentiation • Most efficacious of all antiarrhythmic drugs
o Hyperkalemia: Exacerbates toxicity • Has the longest t½
Notes
Can cause fetal harm (cardiac, thyroid, neurodevelopmental,
neurological and growth defects in neonates)
CLASS 1A
SOTALOL
Disopyramide, Quinidine, Procainamide MOA Potassium channel blockade (IK) + BETA BLOCKADE
Atrial and ventricular arrhythmias post MI
Uses Uses Ventricular arrhythmias, AFib, SVT
For Malaria (Quinidine)
Torsade de pointes (Dose related), Sinus bradycardia,
Procainamide: Lupus-like syndrome SE
SE asthma (due to beta blockade)
Quinidine: Cinchonism (headache, vertigo, tinnitus)
Sodium lactate: Reverses drug-induced arrhythmias
Notes due to Class 1A overdose. Give pressor Ibutilide, Dofetilide
sympathomimetics if with drug induced hypotension. Selective IK block; prolonged action potential & QT
MOA
interval
Uses Afib (Tx and prophylaxis)
CLASS 1B
SE Torsades de pointes
Lidocaine, Phenytoin, Tocainide, Mexiletine KEY LEARNING POINTS: Amiodarone Toxicity
DOC for ventricular arrhythmias post-MI AMIODARONE TOXICITY
Uses Digoxin-induced arrhythmias Pulmonary fibrosis Thyroid dysfunction
Mexiletine: used for neuropathic pain Paresthesia Corneal deposits
Tocainide: Agranulocytosis Tremors Skin deposits
SE CNS stimulation, Cardiovascular depression,
Arrhythmias, Allergy
Lidocaine: Least cardiotoxic; significant first pass effect AMIODARONE
Notes Phenytoin: Malformations (orofacial clefts, cardiac https://qrs.ly/qldvds3
defects, fetal hydantoin syndrome)
CLASS 4 ANTIARRHYTHMICS DIURETICS

(CALCIUM CHANNEL BLOCKERS)
• Effective in arrhythmias that must traverse calcium-dependent
cardiac tissue (e.g. the AV node)
• cause a state- and use-dependent selective depression of Ca2+
currents
• AV conduction velocity is decreased and effective refractory
period increased
• ECG morphology: PR interval is consistently increased
Dihydropyridine CCBs: not useful as antiarrhythmics because
dihydropyridine CCBs evoke compensatory sympathetic discharge which
facilitates arrhythmias rather than terminating them
NON-DHP CCBs (Verapamil, Diltiazem)

SITES OF ACTION OF THE DIURETICS AND ADH DRUGS
Block L-type calcium channels
MOA
(cardiac > vascular)
Supraventricular tachycardia
Uses
Angina, Hypertension, Migraine
Constipation, Pretibial edema, Nausea, Flushing, Dizziness,
SE Gingival hyperplasia (Verapamil), Heart failure, AV block,
Sinus node depression
Excessive cardiac depression may occur
Notes
Should be avoided in Ventricular tachycardia
MISCELLANEOUS ANTIARRHYTHMICS
Adenosine
Increase in diastolic IK of AV node that causes marked
MOA
hyperpolarization and conduction block; reduced Ica
Uses DOC Paroxysmal SVT, AV nodal arrhythmias
SE Flushing, Hypotension, Transient chest pain, Dyspnea
Notes Very short half life (15 sec)
Potassium Ion
Depresses ectopic pacemakers, including those caused by
MOA
digitalis toxicity.
When treating arrhythmias, serum potassium should be • Generalizations:
measured and normalized if abnormal. o Sites of action:
Hypokalemia is associated with an increased incidence of Transporters and ions
Uses Location Diuretic
arrhythmias, especially in patients receiving digitalis exchanged
Excessive potassium levels depress conduction and can Carbonic Anhydrase Amino acid, glucose, Na, Cl
PCT
cause reentry arrhythmias. inhibitors HCO3, Uric acid
Na/K/2Cl transporter
LOH Loop diuretics
Magnesium Ion Mg and Calcium reabsorption
Poorly understood, possible increase in Na+/K+ ATPase DCT Thiazide diuretics Na/Cl carrier
MOA activity, slows the rate of SA node impulse formation in CD Potassium-sparing ENaC
the myocardium and prolongs conduction time.
Digitalis induced arrhythmias (similar to depressant MNEMONIC Potassium-Sparing Diuretics
Uses :
effects of potassium)
The K STAEs (stays) with K sparing diuretics!
SE Some cases: TORSADES DE POINTES Spironolactone
Sudden and large increase in Mg may cause severe respiratory paralysis Triamterene
Dr. Uy
Amiloride
Eplerenone
Summary of the Effects of Antiarrhythmic Drugs
Effect on Which drugs can cause GYNECOMASTIA?
CLASS PROTOTYPE AP Effect on ECG Some Drugs Create Awesome Knockers
Spironolactone Alcohol
Duration
Digoxin Ketoconazole
PROLONGS PR interval, Cimetidine
1A Procainamide PROLONGS
PROLONGS QRS duration
1B Lidocaine SHORTENS NO EFFECT on normal cells MNEMONIC: Metabolic Acidosis
1C Flecainide NO EFFECT PROLONGS QRS duration ACIDazolamide causes ACIDosis
2 Propranolol NO EFFECT PROLONGS PR interval What are the causes of HAGMA? NAGMA
3 Dofetilide PROLONGS PROLONGS QT interval Methanol Hyperalimentation
4 Verapamil NO EFFECT PROLONGS PR interval Uremia Acetazolamide
DKA RTA
Summary: Paraldehyde Diarrhea
Class ____, also known as the sodium channel blockers are divided to three Isoniazid, Iron Ureteral diversion
subclasses differentiated by their effect on AP duration. Which one Lactic Acid Pancreatic fistula
prolongs? Which one shortens? And which one has no effect? Some Ethanol, Ethylene glycol
important side effects that you have to remember includes cinchonism, Salicylates
associated with _______ and lupus-like syndrome with ________. Both these
drugs are classified under what subclass?__________ DIURETIC DRUGS
Class 2 aka ______ and class 3 aka ___________ act on phase ____ and ____ • Generalization:
respectively. Beta blockers end in -olol so they are easy to classify but you o SE:
should remember that Sotalol is also a beta blocker however it can also
§ Potassium wasting (except for: Potassium sparring – causes
block what channel? _______. Classified together with sotalol we have
amiodarone, the most efficacious of all antiarrhythmic and is used in what hyperkalemia);
endocrine disorders? ____________. § Hyperchloremic Metabolic acidosis: CAIs and Aldosterone
Lastly class 4 are ___________ blockers. However not all types of CCBs have antagonist
antiarrhythmic effect, and is only associated with the class __________ § Hypokalemic metabolic acidosis: Metabolic alkalosis:
Loop and Thiazide
Dr. Rodriguez
CARBONIC ANHYDRASE INHIBITORS OSMOTIC DIURETIC

AcetaZOLAMIDE, Dorzolamide, Brinzolamide, Dichlorphenamide Mannitol, Glycerin, Isosorbide, Urea
Key Ends in ZOLAMIDES or AMIDES Increase osmotic gradient in PCT and descending LOH
MOA
Inhibits: carbonic anhydrase. (the water permeable areas)
MOA In proximal tubule, bicarbonate reabsorption is Uses Edema, Increased ICP
blocked and Na+ excreted with HCO3. Hypovolemic hypernatremia, dehydration, pulmonary
SE
Glaucoma: Secretion of aqueous humor is reduced edema
Mountain sickness: Metabolic acidosis increases Initially dahil malakas humatak ng fluid ang mannitol babagsak yung
Uses
respiration. volume agad, kasama ng water, but in the long run, since more water is
Edema with alkalosis excreted, sodium concentration increases kasi mas nasasaturate.
Dr. Rodriguez
Hyperchloremic metabolic acidosis
SE Drowsiness, Paresthesia, Sulfa allergy, Renal calcium
Go through each of the drugs in order of the anatomy of the whole nephron. It
stones.
would be easier to remember that way.
Don’t forget, lagi tinatanong yung metabolic acidosis dito.
Dr. Rodriguez
CAIs end in -zolamides. Among the different diuretics these drugs, ___________,
are known for causing Metabolic Acidosis. Check out the row of MOA
because they should stand out among the rest. Loops and Thiazide cause
LOOP DIURETICS Hypokalemia because they throw potassium out of the tubules, but
FUROSEMIDE, Bumetanide, Torsemide, Ethacrynic acid potassium sparing doesn’t. Because by its name, it spares potassium hence
Key Ends in IDE but not AMIDES causing ____________. Potassium sparing diuretics can be memorized by the
word SEAT. The first two letter are aldosterone antagonist, the last two
Inhibit Na+/K+/2Cl- transporter in thick ascending letters are Epithelial sodium channel inhibitors. For side effects remember
MOA limb of loop of Henle. HyperGLUC for the Thiazides (see above). Gynecomastia is important to
Cause powerful diuresis and increased Ca2+ excretion. note in the potassium sparing diuretic, _____________. And lastly, Mannitol is
Heart failure, Pulmonary edema, Hypertension, an example of an __________ diuretic which draws water into the tubules.
Uses
Hypercalcemia, Acute renal failure, Anion overdose Dr. Rodriguez
Synergistic ototoxicity with AMINOGLYCOSIDES

SE
Efficacy decreased by NSAIDs ANTIDIURETIC HORMONE
Note the difference in calcium excretion of loop in comparison to Thiazides
below. So that you’ll remember, look at the corresponding usage due to this
AGONIST/ANTAGONIST
effect. ADH AGONIST: Vasopressin, Desmopressin, Terlipressin
PGs vasodilate the afferent arteriole (which regulates and ↑ GFR). NSAIDs MOA V1 and V2 ADH receptor AGONIST
inhibit PG production → ↓ GFR. Central diabetes insipidus, Von Willebrand’s disease
Dr. Rodriguez Uses
Nocturnal enuresis, Hemophilia
SE Hyponatremia, Hypertension
THIAZIDE DIURETICS Terlipressin: uterine contractions (not recommended during
HYDROCHLOROTHIAZIDE Notes
pregnancy)
Chlorthalidone, Indapamide, Metolazone Increases FACTOR VIII activity of patient with mild Hemophilia A or Von
Bendroflumethiazide, Hydroflumethiazide, Methyclothiazide, Polythiazide, Willebrand disease.
Quinethazone, Trichlormethiazide For the SE, due to fluid retention, sodium is diluted (hyponat); fluid inc. = inc.
Key End in -ide but with -th- somewhere in the name cardiac output = hypertension.
Dr. Rodriguez
Inhibit Na+/Cl- transporter in distal convoluted
tubule.
MOA ADH ANTAGONIST: Conivaptan, Tolvaptan, Lixivaptan,
Cause moderate diuresis and reduced excretion of
Demeclocycline, Lithium
calcium.
MOA Antagonist at V1a & V2 receptors
Hypertension, Heart failure, Nephrogenic diabetes
Uses insipidus SIADH, Hyponatremia
Uses
*Conivaptan (parenteral), Tolvaptan (oral)
Hypercalciuria, Renal calcium stones
Infusion site reactions, Hyperkalemia,
Hypokalemic metabolic alkalosis, Dilutional
Nephrogenic diabetes insipidus,
hyponatremia, Potassium wasting, Hyperglycemia, Renal failure (lithium, demeclocycline),
SE
Hyperlipidemia, Hyperuricemia, Hypercalcemia, Sulfa Bone and teeth abnormalities (demeclocycline),
allergy Central pontine myelinosis may occur with rapid
Again, in addition the diuretic use, look at the effect on calcium. If reduced SE
correction of hyponatremia
excretion ng calcium, then gagamitin siya for hypercalciuria (mataas Hypotension (Conivaptan; V1 and V2 inhibitor): due to V1
calcium sa wiwi). antagonism
Dr. Rodriguez
Tolvaptan: No hypotension (V2 selective); Causes
hepatotoxicity (use 1-2 months only)
POTASSIUM-SPARING DIURETICS
ALDOSTERONE ANTAGONIST: Spironolactone, Eplerenone OTHER CARDIOVASCULAR DRUGS
Steroid inhibitors of cytoplasmic aldosterone
MOA Bosentan
receptor in cortical collecting ducts.
Hyperaldosteronism, Hypertension, MOA Endothelin receptor antagonist
Uses Uses Pulmonary artery hypertension
Heart failure, Hypokalemia
Gynecomastia (spironolactone only) SE Teratogen
SE Impotence, Benign prostatic hyperplasia, Notes Do NOT use in hepatically impaired patients
Hyperchloremic metabolic acidosis
Eplerenone: reduces progression of DM nephropathy
Notes Citicoline
and reduces mortality post-MI
Stabilizes cell membranes and reduces free radicals
If you inhibit aldosterone receptors, you inhibit sodium reabsorption and
potassium secretion = hence hyperkalemia.
Also stimulate dopamine in the brain (stimulate cholinergic
MOA
Dr. Rodriguez system – hence for AD also)
Also increases ACTH. TSH, GH and LH
Sodium Channel Inhibitors: Amiloride, Triamterene Traumatic brain injuries, stroke, vascular dementia,
Inhibitor of ENaC epithelial sodium channels (CD) Uses Parkinson’s disease, brain aging
MOA Alzheimer Disease (AD)
Reduces Na reabsorption and K excretion
Uses Hypokalemia
Triamterene: Renal stone formation Cinnarizine
SE An anti-histamine and CCB; promotes cerebral blood
Metabolic acidosis, ARF (with indomethacin) MOA
Notes Do not give with potassium supplements flow
Treat cerebral apoplexy, post-trauma cerebral
symptoms and cerebral arteriosclerosis.
Uses
More common use: nausea and vomiting due to motion
sickness, chemotherapy, vertigo or Meniere’s disease
DRUGS FOR DYSLIPIDEMIA CHOLESTEROL ABSORPTION INHIBITORS

EZETIMIBE
NPC1L1 transporter inhibitor decreasing intestinal
MOA
absorption of cholesterol and other phytosterols
Uses Adjunct to statins (hypercholesterolemia)
SE Hepatotoxicity (increased with statin use), Myositis
• Synergistic LDL-lowering effect with statins
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2019 Notes • May be given as combination therapy with statins
• Considered a prodrug
Pathogenesis of Hyperlipoproteinemia
• Premature atherosclerosis is strongly associated with elevated
concentrations of lipoproteins Sitosterol
o elevated level of low-density lipoproteins (LDL) Cholesterol analog, takes the place of dietary and
o depressed level of high-density lipoproteins (HDL) MOA biliary cholesterol, decreasing intestinal absorption of
cholesterol and other phytosterols.
o hypertriglyceridemia
Uses Adjunct to statins (hypercholesterolemia)
• Hyperchylomicronemia is associated with a high incidence of
acute pancreatitis Gastrointestinal upset, Bloating, Impotence (rare),
SE
Coronary events
Treatment Strategies: DIET
• Cholesterol and saturated fats are the primary dietary factors NIACIN
that contribute to elevated plasma lipoproteins Decreases catabolism of apoA-I. Decreases VLDL
• Dietary measures constitute the first method of management MOA synthesis and secretion from the liver. Decreases LDL
o May be sufficient to reduce lipoprotein levels to a safe range cholesterol concentrations. Increases HDL cholesterol
• Alcohol raises triglyceride and VLDL levels: should be avoided Uses Alternative for hypertriglyceridemia (FIBRATES)
by patients with hypertriglyceridemia Flushing, Pruritus, Rashes, Acanthosis nigricans,
Treatment Strategies: DRUGS Gastrointestinal irritation, Hepatotoxicity (mild),
SE
Hyperuricemia, Impaired glucose tolerance,
• Lowers LDL cholesterol
Arrhythmias, Amblyopia
o statins, resins, ezetimibe, niacin
Give aspirin to reduce flushing.
• Lowering TGs, VLDL and raising HDL
Avoid in PUD
o niacin, fibrates Notes Potentiates effects of antihypertensives (vasodilators,
ganglion blockers)
Decreases fibrinogen and increases t-PA
FIBRATES
FENOFIBRATE, GEMFIBROZIL, BEZAFIBRATE
Activates PPAR-a stimulating expression of lipoprotein
MOA
lipase
DOC for hypertriglyceridemia, hypercholesterolemia
Uses
(low HDL, high LDL), Fat redistribution syndrome
Cholesterol gallstones (esp. if with resins),
SE Rhabomyolysis (+statins)
Clofibrate: hepatobiliary cancer (withdrawn)
PCSK9 INHBITORS
ALIROCUMAB, EVOCUMAB
Human monoclonal antibody that binds to proprotein
convertase subtilisin kexin type 9 (PCSK9). PCSK9 binds
Figure 35-1. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018. to the low-density lipoprotein receptor (LDLR) on
hepatocyte surfaces to promote LDLR degradation with
STATINS the liver. LDLR is the primary receptor that clears
MOA
SIMVASTATIN, Atorvastatin, Rosuvastatin, circulating LDL. Therefore, the decrease in LDLR levels
Fluvastatin, Pravastatin, Lovastatin, Pitavastatin by PCSK9 results in higher blood level of LDL. By
MOA Inhibits: HMG-COA Reductase inhibiting the binding of PCSK9 to LDLR, there is now an
DOC Hypercholesterolemia (high LDL), Acute increase in LDLRs available for binding by LDL, hence
Uses coronary syndromes / Atherosclerotic vascular disease lower LDL levels.
(primary and secondary prevention), Ischemic stroke Adjunct to statins (for those with
Hepatotoxicity, Myopathy, Rhabdomyolysis, hypercholesterolemia who do not meet treatment
SE Uses
Gastrointestinal distress, Teratogen goals), may be given for secondary prevention of
cardiovascular events
• + Fibrates = myopathy and rhabdomyolysis
Local injection site reaction, diarrhea, hypersensitivity
• Give at bedtime: Cholesterol synthesis predominantly SE
reaction, transaminitis
occurs at night
• Prodrugs: Simvastatin and Lovastatin (all the rest in Notes Given subcutaneously once every 2weeks
Notes
their active form)
• Give at least 1hr before or 4hrs after resin administration COMBINATION THERAPY
(resins decrease the absorption of statins). • All patients with hyperlipidemia are treated first with dietary
• Get baseline liver function test (due to hepatotoxicity) modification
Compare the use of STATIN versus the FIBRATES later. That is a very • Certain drug combinations provide advantages whereas others
important difference in the use. present specific challenges
Dr. Rodriguez
BILE ACID BINDING RESINS Antihyperlipidemic Combinations to watch out for!

CHOLESTYRAMINE, COLESEVELAM, COLESTIPOL Combination Risk
Binds bile acids, preventing their reabsorption and Fibrate + Resin Increased risk of cholelithiasis
MOA increasing cholesterol utilization for replacement → Statin + Resin Impaired statin absorption
Upregulates LDL receptors → Modestly lowers LDL levels.
Statin + Fibrate Increased risk of myopathy, rhabdomyolysis
Adjunct to statins (hypercholesterolemia)
Uses For dyslipidemia drugs, it’s important to know first their mechanism of
Pruritus in cholestasis, Digitalis toxicity actions, then take note of the differences in usage and important side-effects
Steatorrhea (and bloating), Gallstones (rare)
SE
Malabsorption (vitamin K)
MECHANISMS OF ACTION DESCRIPTION DRUGS
1. Activates PPAR-a : _____________ Inotrope: PDE inhibitor
2. Binds bile acids: _____________
Vasodilators
3. Inhibits HMG-CoA Reductase: __________
4. Inhibits NPC1L1 transporter: _____________ Diuretics
INDICATIONS Beta-blockers
All of your dyslipidemia drugs are used for hyperCHOLESTEROLEMIA, Neprilysin Inhibitor
while one stands out for its use for hyperTRIGLYCERIDEMIA,
_____________ ANTI-ARRHYTHMIC DRUGS
SIDE-EFFECTS Class IA, IB, IC
Risk for Myopathy and rhabdomyolysis is increased when __________ and Class 2
__________ are combined. Class 3
Due to prevention of reabsorption of cholesterol, bile acid binding resins
present with ____________ in stools. Class 4
Flushing and pruritus is associated with ___________ DIURETICS
Dr. Rodriguez
Inhibits: carbonic anhydrase.
Inhibit: Na/K/2Cl transporter
DYSLIPIDEMIA Inhibit Na/Cl tranporter
https://qrs.ly/a1dvds6 Aldosterone antagonist
Epithelial sodium channel inh.
Osmotic diuretics
LIPID Primary Secondary DRUGS FOR DYSLIPIDEMIA
CONDITION & CAUSE
PROFILE Tx Tx HMG-COA Reductase inhibitors
Primary hyper- Binds to bile acids
chylomicronemia chylomicrons Low-fat Niacin
NPC1L1 transporter inhibitor
Deficiency in LPL or triglycerides diet Fibrate
ApoC-II Cholesterol Analog
Familial Increases HDL cholesterol
LDL Niacin
hypercholesterolemia Activates PPAR-alpha
(N) VLDL Ezetimibe
Defect in LDL receptors A gentle reminder for VISUALIZATION TIME!
Niacin Dr. Rodriguez
Familial combined VLDL Statin Fibrate
hypercholesterolemia
LDL
Overproduction of
VLDL VLDL
Niacin
Ezetimibe
DRUGS ON SMOOTH MUSCLES
LDL
Familial dysbetalipo- VLDL
proteinemia remnants Statin
Deficiency in ApoE chylomicrons
Familial hyper- Triglycerides
triglyceridemia Increased
Decreased clearance of VLDL Fibrate
VLDL ¯/N LDL Niacin
Familial combined
triglycerides
hyper-
chylomicrons
triglyceridemia
VLDL
Decreased clearance of
VLDL ¯/N LDL
SECTION SYNTHESIS Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 13th ed. 2021
DESCRIPTION DRUGS AUTACOIDS

DRUGS FOR HYPERTENSION • Endogenous molecules with powerful pharmacologic effects that
Diuretics
do not fall into traditional autonomic groups
• Histamine and serotonin are the most important amine autacoids
Na/Cl transport inh. In DCT
For this topic, focus on being to classify the drugs to the receptor involved
Na/K/2cl transport inh. in LOH and the uses. Expect different numbers for the receptor subtypes, but
Sympathoplegics repetition is the key to be able to recall them all. J
Dr. Rodriguez
Central alpha 2 agonists
Ganglion blockers
Post-ganglionic neuron blocker HISTAMINE, SEROTONIN, AND ERGOT
Alpha blockers ALKALOIDS
Beta blockers SEROTONERGIC AGENTS
Vasodilators Serotonin (5 Hydroxytryptamine or 5-HT)
Oral Vasodilators • produced from the amino acid tryptophan, metabolized by
Calcium channel blockers monoamine oxidase
Parenteral vasodilators • physiologic roles
RAAS Antagonists o neurotransmitter in CNS and enteric nervous system
o local hormone that modulates gastrointestinal activity
ACE inhibitors
SUMMARY OF SEROTONERGIC AGENTS
Angiotensin receptor blocker
5-HT1A Partial agonist Buspirone (to be discussed in CNS)
Renin Inhibitors
5-HT1D Agonist -Triptans (Sumatriptan, Naratriptan)
DRUGS FOR ANGINA PECTORIS
5-HT2A agonist Ergot compounds (Ergotamine, ergonovine)
Ultrashort acting nitrate
5-HT3 antagonist -Setrons
Non-DHP CCBs
5-HT4 partial agonist Tegaserod
DHP CCBs
Beta blockers
Metabolism modifiers (3) SEROTONIN RECEPTORS
DRUGS FOR HEART FAILURE https://qrs.ly/vzdvds9
Inotrope: Na/K ATPase inhibitor
Inotrope: B1 agonist
SEROTONERGIC DRUGS HISTAMINE RECEPTORS AND EFFECTS

PROTOTYPE
5-HT1D Receptor Agonists (TRIPTANS) TYPE LOCATION MECHANISM EFFECTS
ANTAGONIST
SUMATRIPTAN, Almotriptan, Eletriptan, Frovatriptan, Naratriptan, Pain and itching,
Rizatriptan, Zolmitriptan broncho-
Smooth Gq,
H1 Diphenhydramine constriction,
MOA Causes vasoconstriction; Modulate NT release muscle ↑IP3, DAG
vasodilation,
Uses DOC for acute migraine, Cluster headache local edema
Paresthesia, Dizziness, Chest pain, Stomach, Gastric acid
Gs,
SE H2 heart, mast Cimetidine secretion, cardiac
Coronary vasospasm, Injection site reaction cells
↑cAMP
stimulation
All are per orem (except: Sumatriptan – Intranasal; Nerve Gi, Modulation of
Notes H3 Clobenpropit
Shortest DOA) endings, CNS ↓cAMP other NTs
Gi, Leukocyte
H4 Leukocyte ----
↓cAMP chemotaxis
5-HT3 Receptor ANTAGONIST (SETRONS)
ONDANSETRON, Granisetron, Dolasetron, Palonosetron, Alosetron
Pharmacologic antagonist of 5-HT3 receptors in the H1 RECEPTOR ANTAGONIST
MOA
chemoreceptor trigger zone and enteric nervous system FIRST GENERATION
Chemotherapy and postoperative vomiting,
Uses
Irritable bowel disease (Alosetron only)
• Generalization:
Paresthesia, Dizziness, Chest pain, o MOA:
SE § Competitive pharmacologic block of peripheral and CNS H1
Coronary vasospasm, Injection site reaction
Diarrhea, Headache, Malaise, receptor blockade
Notes QRS and QT prolongation (Dolasetron only), § Plus alpha and muscarinic-receptor blocker (compare to
Constipation (Alosetron only) second gen)
o SE:
5-HT4 Partial agonist TEGASEROD § COMMON: Sedation
§ Drowsiness, Blurred vision, Dry mouth, Urinary retention,
MOA Causes increased intestinal motility
Anorexia, Orthostatic hypotension
Uses Irritable bowel syndrome with prominent constipation
§ Sedating antihistamines may enhance the sedative effects of
CNS depressants including alcohol, barbiturates, hypnotics,
SUPPLEMENT: DRUGS USED FOR MIGRAINE opioid analgesics, anxiolytic sedatives, and antipsychotics
Selective Calcium Entry blocker with calmodulin INDICATIONS
binding properties and H1 antagonistic activity;
Allergic reactions, Hay fever, Angioedema,
FLUNARIZINE effective in the prophylaxis of migraine, Diphenhydramine
occlusive peripheral vascular disease, vertigo,
Insomnia
and as adjuvant for epilepsy Brompheniramine,
Cold mediations
Chlopheniramine
Anti-emetic; decrease secretions during
ERGOT ALKALOIDS Promethazine
anesthetic induction
Ergot Alkaloids Cyproheptadine Serotonin syndrome
• complex molecules are produced by a fungus found in wet or CYCLIZINE,
Dimenhydrinate used for nausea, vomiting
spoiled grain Meclizine,
and dizziness caused by motion sickness;
o responsible for the epidemics of "St. Anthony's fire" Buclizine,
Cyclizine used to motion sickness
(ergotism) described during the Middle Ages Dimenhydrinate
• Most are partial agonists at alpha receptors and 5HT receptors
but some are potent agonist at dopamine receptors SECOND GENERATION
• Classification • Generalization:
o VASOSELECTIVE o Competitive pharmacologic block of peripheral H1 receptors.
o UTEROSELECTIVE o No autonomic or anti-motion sickness effects
5-HT2 Receptor ANTAGONIST (VASOSELECTIVE) o Does NOT cross BBB; sole indication is for allergy
ERGOTAMINE, Dihydroergotamine, METHYLSERGIDE
o Fatal arrhythmias from interaction between
In addition, also has partial alpha and dopamine agonist
MOA azoles/erythromycin and Terfenadine/Astemizole
effect
o No sedation, antimuscarinic effects
Uses Migraine, Cluster headache
CETIRIZINE, Levocetirizine, LORATADINE, Desloratadine, FEXOFENADINE,
Gastrointestinal upset, Vasospasm, Gangrene, Uterine Terfenadine, ASTEMIZOLE, Azelastine, Ebastine, Bilastine, Rupatadine
SE
spasm, Retroperitoneal fibrosis (methylsergide only)
5-HT2 Receptor ANTAGONIST (UTEROSELECTIVE) H2 RECEPTOR ANTAGONIST

ERGONOVINE, Methylergonovine CIMETIDINE, Ranitidine, Famotidine, Nizatidine
Partial agonist at a and 5-HT2 receptors, some have MOA Competitive pharmacologic block of H2 receptors
MOA
potent agonist effect at Dopamine receptors Peptic ulcer disease,
Uses Postpartum bleeding, Migraine Uses
Zollinger-Ellison syndrome, Gastroesophageal reflux
Gastrointestinal upset CYP450 inhibitor and antiandrogen effects
SE
(Nausea, Vomiting, Diarrhea), Uterine spasm, Abortion SE like gynecomastia (cimetidine only),
Decreased hepatic flow (cimetidine)
HISTAMINERGIC AGENTS Reduction of nocturnal acid secretion in gastric and
Notes
duodenal ulcer, accelerate healing and prevent recurrences
Histamine
• formed from the amino acid histidine, metabolized by the
enzymes monoamine oxidase and diamine oxidase PUD
• important pathophysiologic roles https://qrs.ly/b6dvdsv
o seasonal rhinitis (hay fever), urticaria, and angioedema
o control of acid secretion in the stomach
Triple Response of Lewis (wheal, flush and flare)
• classic demonstration of histamine effect SUPPLEMENT: DRUGS USED FOR VERTIGO
• mediated mainly by H1 and H2 receptors Strong antagonist of H3 receptor (leads to
• involves a small red spot at the center of an intradermal injection increased levels of neurotransmitters histamine,
acetylcholine, norepinephrine, serotonin and
of histamine surrounded by a red edematous wheal GABA) and a weak agonist of H1 receptor (causes
BETAHISTINE
local vasodilation and increased permeability in
the inner ear); used for balance disorders or to
HISTAMINE RECEPTORS alleviate vertigo symptoms associated with
https://qrs.ly/rndvdt7 Meniere’s disease
SUPPLEMENT: DRUGS USED FOR VERTIGO PGE2 ANALOG
An anti-histamine and CCB; promotes cerebral DINOPROSTONE, Sulprostone
blood flow (used to treat cerebral apoplexy, post-
trauma cerebral symptoms and cerebral Low concentrations contract, higher concentrations relax
CINNARIZINE MOA uterine and cervical smooth muscle, soften cervix at term
arteriosclerosis); more commonly prescribed for
nausea and vomiting due to motion sickness, before induction with oxytocin
chemotherapy, vertigo or Meniere’s disease Uses Induction of labor (Cervical ripening), Abortifacient
SE Cramping, Fetal trauma
• Approved abortifacient in the 2nd trimester
ANTIHISTAMINES Notes • Although effective in inducing labor, it produces more
https://qrs.ly/ygdvdu6 SE than other oxytocics
PGF2a ANALOG
PROSTAGLANDIN AND OTHER EICOSANOIDS Carboprost
MOA Uterine contraction
Control of postpartum hemorrhage, for refractory
Uses
postpartum bleeding, abortifacient
SE Vomiting, diarrhea, transient bronchoconstriction
Latanoprost
Activates FP receptors. Increases outflow of aqueous
MOA
humor, reduces intraocular pressure
Uses Glaucoma
SE Alters color of the iris, causing permanent eye color change
Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 13th edition, 2021.
May cause vomiting, diarrhea, transient broncho-
EICOSANOIDS Notes
constriction if given systemically
• Important group of endogenous fatty acid derivatives that are
produced from arachidonic acid PGI2 ANALOG
• Major families of eicosanoids include EPOPROSTENOL
o straight-chain derivatives (leukotrienes) Beratoprost, Iloprost, Treprostinil
o cyclic derivatives (prostacyclin, prostaglandins, and thromboxane) Activates IP receptors. Causes vasodilation. Reduces
MOA
platelet aggregation
Cyclooxygenase Isoforms Pulmonary hypertension, Reduces platelet aggregation in
Uses
• CYCLOOXYGENASE-1 (COX-1) dialysis machines
o Found in many tissues SE Hypotension, Flushing, Headache
o Important for a variety of normal physiologic processes
OTHER DRUGS USED FOR ERECTILE
• CYCLOOXYGENASE-2 (COX-2) SUPPLEMENT:
DYSFUNCTION
o found primarily in inflammatory cells
Drugs SILDENAFIL [B], TADALAFIL [B], VARDENAFIL [B]
o major role in tissue injury (e.g. inflammation)
Class Phosphodiesterase 5 inhibitor
o synthesis of prostacyclin in the vascular endothelium and of Inhibits PDE5 which degrades cGMP to inactive GMP →
prostaglandins important in renal function MOA
vasodilation
EFFECTS OF IMPORTANT EICOSANOIDS Erectile dysfunction, Pulmonary Arterial Hypertension,
Uses
Raynaud’s Phenomenon
G- Headache, flushing, priapism, hearing loss, optic
Eicosanoid Effects SE
Prot neuropathy
LTB4 Gq Leukocyte chemotaxis Do not take with Nitrates (ISDN, ISMN, NTG) because it
LTC4 Gq Bronchoconstriction, slow-reacting Notes
may lead to fatal hypotension
LTD4 Gq, Gi substance of anaphylaxis
Vascular smooth muscle relaxation,
PGE1 Gs, Gq protective effects on gastric mucosa,
maintains PDA
Vascular smooth muscle relaxation,
PGE2 Gs, Gq
maintains PDA, increases uterine tone
Vascular smooth muscle relaxation
PGI2 Gs
(peripheral, pulmonary, coronary)
PGF2( Gq Increases uterine tone, decreases IOP
TXA2 Gq Platelet aggregation
For the following drugs, remember that they are analogs of prostaglandin, so
they will activate the respective receptor (e.g. E1 or I2 receptors etc.). Under
the MOA section are the effects of stimulating the subreceptor. To make it
easier, immediately correlate the MOA with the use.
Dr. Rodriguez
PGE1 ANALOG For the Autacoids and Eicosanoid drugs it is essential that you can
Misoprostol, Gemeprost identify which autacoid/eicosanoid it mimics or antagonize. Moreover
you have to know which subtype (i.e. 5-HT1D, 5-HT3 etc.) Let’s try by
Causes increased HCO3- and mucus secretion in stomach.
MOA identifying the receptor and the action of following (i.e. 5-HT3
Uterine contraction
antagonist). If you can give the use then better.
Peptic Ulcer Disease, Prevention of NSAID-induced 1. Cimetidine 6. Misoprostol
Uses
gastric mucosal injury, abortifacient 2. Cetirizine 7. Alprostadil
Abdominal pain, Diarrhea, Uterine cramping, Miscarriage, 3. Dinoprostone 8. Carboprost
SE
Teratogenic effect (Moebius sequence) 4. Ondansetron (SETRONS) 9. Epoprostenol
• Misoprostol's intended use is for NSAID-induced gastritis 5. Sumatriptan (TRIPTANS)
Notes • May also be used together with Mifepristone or
Methotrexate as safe abortifacient ___________________COVER ANSWERS BELOW THIS LINE !!!________________________
Answers: (1) H2 blocker – PUD (2) H1-blocker -2nd gen – allergies (3)
PGE2 Analog – Cervical ripening, (4) 5HT3 Antagonist – PONV, be careful
Alprostadil
if its agonist or antagonist (5) 5HT1D Agonist – Migraine; this is the only
MOA Vascular smooth muscle relaxation and vasodilation agonist in the table, to help you remember. (6) PGE1 – PUD, abortifacient
Maintenance of patent ductus arteriosus (PDA), (7) PGE1 Analog – keep ductus arteriosus patent (8) PGF2a – control
Uses
Erectile dysfunction postpartum hemorrhage. (9) PGI2 – Pulmonary hypertension. Note that
SE Apnea, Hypotension, Arrhythmia, Priapism, Lightheadedness PG analogs have PROST in their names. Histaminergic drugs end in MINE,
DINE, ZINE because they rhyme with histamine.
Notes Given as injection into the cavernosa for erectile dysfunction Dr. Rodriguez
TREATMENT STRATEGIES
EICOSANOIDS
IN ASTHMA CONTROL
https://qrs.ly/8rdvdub
https://qrs.ly/drdvduc
BRONCHODILATORS AND OTHER DRUGS RELIEVERS

USED IN ASTHMA When you activate beta 2 receptors found in the lungs, it will cause
bronchodilation. This also potentiates the use of corticosteroids. Side effects
include Tachycardia, Tremors, Nervousness, Restlessness, Arrhythmias (In
excess), Loss of responsiveness (tolerance, tachyphylaxis). Tremors happen
due to activation of the beta-2 receptors in the skeletal muscles.
Dr. Rodriguez
SHORT ACTING BETA-2 AGONIST

SALBUTAMOL (Albuterol),
Levalbuterol, Terbutaline, Metaproterenol, Pirbuterol,
Procaterol , Fenoterol, Bitolterol
Uses Acute asthma attacks (drug of choice)
• May precipitate arrhythmias in patient with
concurrent COPD and heart disease
• Usual DOA: 2-4hrs
Notes
• All are given inhalational
• Salbutamol, terbutaline (PO)
• Terbutaline (IV) (especially as tocolytic)
LONG-ACTING BETA-2 AGONIST
ASTHMA
SalmeTEROL, Formoterol, Clenbuterol, Bambuterol, Arformoterol,
• Characterized by airway inflammation and episodic, reversible
Vilanterol, Indacaterol, Olodaterol
bronchospasm All are Preg Cat C
• Major risk factor of asthma: atopy Asthma prophylaxis (compare with SABA above)
Uses
Given together with ICS
Pathophysiology of Asthma • Increase asthma mortality when used alone;
• Bronchoconstriction caused by release of several mediators • Usual DOA: 12hrs
from IgE-sensitized mast cells Notes • Vilanterol, Indacaterol and Olodaterol are Ultra Long-acting
• Chemotactic mediators attract inflammatory cells to the LABAs. They have a 24-hour activity for once daily
airways, leading to chronic inflammation treatment for COPD and Asthma
Strategies of Asthma Therapy MUSCARINIC RECEPTOR ANTAGONIST

• Acute attacks of bronchospasm (relievers) When you block the muscarinic receptors in the bronchial smooth muscles
o Use bronchodilators or relievers what happens? _______________
o Short-acting b2 agonists Ans: prevents vagal stimulated bronchoconstriction.
o Muscarinic antagonists Notice the ending of the names they end in -TROPIUM (from aTROPIne)
o Methylxanthines Dr. Rodriguez
o Intravenous corticosteroids
IpraTROPIUM, TioTROPIUM,
• Long-term prevention and prophylaxis (controllers)
UmeclidiNIUM, GlycoyrroNIUM
o Use anti-inflammatory drugs or controllers
Acute Asthma, COPD
o Corticosteroids Glycopyrronium: monotherapy as maintenance for
o Long-acting b2 agonists Uses
COPD, also used as anti-spasmodic and reduce salivation
o Mast cell stabilizers with some anesthetics.
o Anti-IgE, IL5, IL5R, IL4R antibodies Dry mouth, blurred vision etc.
o leukotriene antagonists SE
(Anti-cholinergic effects)
• Less toxic than B-agonists in patients with COPD
Notes • Tiotropium and Umeclidinium have longer DOA than
Ipratropium
METHYLXANTHINES
THEOPHYLLINE, Aminophylline,
Pentoxifylline, Doxofylline
Phosphodiesterase inhibition &
MOA
Adenosine receptor antagonist à bronchodilation
Asthma (prophylactic against nocturnal attacks)
Uses
Intermittent claudication (pentoxifylline only)
CNS stimulation (Insomnia, seizure, Anorexia),
SE Cardiac stimulation (Arrhythmias),
Tremors, increased BP, diuresis, increased GI motility
• Antidote in overdosage is Beta blockers
• Higher clearance in adolescents and smokers
Notes • Narrow therapeutic window
Causes bronchodilation and increased strength of
contraction of diaphragm
CONTROLLERS • biological agents that interfere in different steps of the TH2

inflammatory cascade and are licensed in severe asthma
CORTICOSTEROIDS
FLUTICASONE, Beclomethasone, BUDESONIDE, Anti-IL5 and anti-IL5R (All are given SC)
Ciclesonide, Flunisolide, Mometasone, Triamcinolone • Mepolizumab: anti-IL5, given SC to > 6 years old
Inhibits: Phospholipase A2 • Reslizumab: anti-IL5, given IV to > 18 years old
MOA
Activates: Glucocorticoid response elements o Acts by neutralizing effects and blocking activation of
Asthma prophylaxis (drug of choice), eosinophils by IL5
COPD, Allergic rhinitis, first line treatment for moderate to • Benralizumab: anti-IL5 receptor, given SC to >12 years old
Uses severe BA, COPD, also used as anti-inflammatory for other o Targets the effector cells itself circulating and tissue eosinophils)
conditions such as autoimmune diseases and cancer, also
for immune suppression Anti-IL4R
Oropharyngeal candidiasis (Advise to gargle every after • Dupilumab: anti-IL4 receptor, given SC to >12 years old
SE use), Minimal systemic steroid toxicity (e.g. adrenal binds to the α-subunit of the IL-4 receptor, with resulting blockage
suppression), Mild growth retardation of both the IL-4 and IL-13 pathways
• For status asthmaticus: use IV prednisolone or hydrocortisone For anti-asthma drugs, you need to be able to know which can be given for
Notes • Prednisolone: active metabolite of prednisone acute attacks versus for control. Among them beta-agonists are used for
• Ciclesonide: lowest systemic steroid toxicity acute exacerbation. Especially the SABAs. Can you give one SABA?
Arachidonic acid synthesis is hindered pag inhibited si PA2. Therefore no ___________. Antimuscarinics can also have immediate action like SABA, and
COX and LOX; it also , increases responsiveness of Beta receptors in the airway. usually end in what syllable again?: _________. Recall that these drugs are
By activating GRE (in the nucleus; intracellular) = synthesis of substances that derivatives of what prototype antimuscarinic drug? ______________- kaya
prevent full expression of inflammation and allergy. naging TROPIUM yung ending nila.
Dr. Rodriguez
On the other hand LABAs such as, (give one: ___________) are used together with
corticosteroids for control of future exacerbation. Remember in Asthma
LEUKOTRIENE SYNTHESIS INHIBITOR there is bronchoconstriction and inflammation, which are addressed by the
Zileuton bronchodilators and corticosteroids respectively. In the clinics, when you
MOA Inhibits: 5-lipoxygenase (LOX) prescribe corticosteroids, advice the patient to gargle to avoid : _____________.
Asthma prophylaxis, Exercise-, Antigen- and Aspirin- In the pathophysiology of asthma, mast cells release histamine, you can
Uses control this by using what drug? Among the drugs which has a narrow
induced bronchospasm
therapeutic index?
Flulike syndrome, Headache, Drowsiness, Dyspepsia, Hepatitis,
Some students get confused with LT synthesis inhibitor and LT receptor
Elevation of liver enzymes
SE antagonist, can you tell which drug is which?
Similar side effects with LTRA, but also associated with
Answers: All are in the tables above so that it will help you recall visually.
transaminitis. So need to monitor liver profile Dr. Rodriguez
Without LOX = no Leukotrienes there by preventing airway inflammation
and bronchoconstriction.
DRUGS FOR COUGH
Dr. Rodriguez Mucolytics: Muco means sipon; lytic means “sirain” so in essence, imagine
sisirain niya yung sipon haha. Expectorants ay para mailabas yung
LEUKOTRIENE RECEPTOR ANTAGONIST plema. Antitussive: Anti means pigilan, “tussis” means pag-ubo – so
MONTELUKAST, Zafirlukast, Pranlukast pigilan ang pag-ubo. Usually for patients na dry cough kasi magagasgas
MOA Blocks Leukotriene receptor pa lalo lalamuna if ubo nang ubo.
Dr. Rodriguez
Asthma prophylaxis, Exercise-, Antigen- and Aspirin-
Uses MUCOLYTICS
induced bronchospasm
Gastrointestinal upset, Insomnia, Neuropsychiatric effects, N-Acetylcysteine, Carbocisteine, Ambroxol, Bromhexine, Erdosteine
SE
Churg-Strauss syndrome (rare) Reduces: disulfide bridges that bind glycoproteins to
MOA
Leukotriene synthesis inh. and receptor antagonists have no other proteins such as albumin
bronchodilator actions and therefore hindi pwede sa acute asthma attack Uses Cough (available as IV, PO, IM and inhalational forms)
Dr. Rodriguez
Chest tightness, Disagreeable odor, Drowsiness, Fever,
MAST CELL STABILIZER Hemoptysis, Increased volume of bronchial secretions,
SE
Irritation of tracheal or bronchial tract, Nausea,
CROMOLYN, Nedocromil, LODOXAMIDE
Rhinorrhea, Stomatitis, Vomiting
MOA Stabilizes mast cells Orally available drugs are well-tolerated; but of little
Asthma prophylaxis, Notes
Uses benefit in acute respiratory condition
Allergies (ophthalmic, nasopharyngeal, gastrointestinal) Mucolytics have cysteine in their name. Recall in biochem that these are sulfur
Cough, Airway irritation containing amino acids – go check niyo structure sa net dali. J This sulfur is
SE
Not normally used because may induce cough important to break the disulfide bridges that makes your plema at sipon sticky.
• No bronchodilator action but can prevent So if broken bridges, then di na sticky yung mucus – easier to expel
bronchoconstriction caused by antigens (both in the early Dr. Rodriguez
Notes and late BA responses) • N-acetylcysteine is also used in the management of

• May be given as ophthalmic solution for allergic conjunctivitis acetaminophen toxicity to prevent fulminant hepatitis
• May be given (Off-label) for Food allergy and IBD o NAC converts back the oxidized glutathione to the reduced form of
It prevents calcium influx kaya hindi nadedepolarize yung mast cell; glutathione that works as antioxidant to counteract the reactive
hence hindi magrerelease ng histamine na nakatago sa loob. metabolite of acetaminophen known as NAPQ1 (free radical)
Dr. Rodriguez
ANTI-IGE ANTIBODIES
Omalizumab
MOA Binds IgE antibodies on mast cells
Prophylaxis of severe, refractory asthma not responsive to
Uses
all other drugs
Fever, Angioedema, Anaphylactic reactions, Idiopathic severe
SE
thrombocytopenia, nasopharyngitis, upper abdominal pain
Notes Very expensive (humanize murine monoclonal antibody)
Kapag nagbind sa IgE yung gamot, then hindi masstimulate na EXPECTORANT
magdegranulate yung mast cell = no histamine. So kahit maka-inhale ka
Guiafenesin
ng allergen, most likely hindi magrerelease ng histamine
Dr. Rodriguez Irritant to gastric vagal receptors, and recruit efferent
NEW ASTHMA DRUGS: BIOLOGIC ANTIBODIES MOA parasympathetic reflexes that cause glandular exocytosis of a
less viscous mucus mixture
Uses Cough
Drowsiness, Incomplete or Infrequent Bowel
Movements, Inducing of a Relaxed Easy State, Stomach
SE
Cramps, dizziness or headache, a rash, or. nausea,
vomiting, or stomach upset
Notes Are often emetics (ipecac, guaifenesin)
Source: Benralizumab: A unique IL-5 inhibitor for severe asthma. Tan et al., 2016
If you irritate the vagal receptors (parasympathetic) – may feeling na FOR ASTHMA
gusto mong mag-suka. This way parang nasstimulate yung cough reflex also. Relievers
Dr. Rodriguez
SABAs
ANTITUSSIVES LABAs
• Used for dry painful cough of neoplasia or pleural disease; Irritative Muscarinic Antagonist
cough in inflammation of the respiratory tract (epiglottitis); in Methylxanthines
hemoptysis Controllers
• DO NOT suppress cough in bacterial lung infections, asthma,
Corticosteroids
bronchiectasis (suppurating bronchial inflammation) or chronic
LT synthesis inhibitor
bronchitis where antitussives can cause harmful sputum
thickening & retention LT receptor antagonist
As a guide, pwede silang centrally acting or peripherally acting. Mast cell stabilizer
Dr. Rodriguez
Anti-IgE Antibody
CENTRALLY ACTING (OPIOID) FOR COUGH
Dextromethorphan, Codeine Mucolytics
Decreased sensitivity of the medullary/ CNS cough Expectorant
MOA centers to peripheral stimuli and decreased mucosal Antitussive (Central)
secretion Antitussive (Peripheral)
Uses Cough A gentle reminder for VISUALIZATION TIME!
Decreases secretions in the bronchioles, thickens Dr. Rodriguez
SE sputum & inhibits ciliary activity, reducing clearance of

thickened sputum, Constipation CNS DRUGS
• Morphine: indicated only in intractable cough from SEDATIVE-HYPNOTIC DRUGS
bronchial carcinoma
Notes Dextromethorphan has no addictive potential, no
analgesic effect, produces less constipation and
inhibition of mucociliary clearance
CENTRALLY ACTING (NON-OPIOID)

Butamirate Citrate
MOA act through receptors in the brainstem to inhibit cough
Uses Cough
Somnolence, nausea, vomiting, diarrhea, dizziness and
SE
hypotension Katzung and Trevor’s Pharmacology Examination and Board Review. 13TH Edition, 2021.
Centrally acting antitussive but is neither chemically or
Notes • SEDATIVES (ANXIOLYTICS)
pharmacologically related to opioids
o drugs that reduce anxiety and exert a calming effect
PERIPHERALLY ACTING o degree of CNS depression should be the minimum consistent
Levodropropizine with therapeutic efficacy
Non-opioid drug with a peripheral action by inhibiting • HYPNOTICS
MOA the afferent pathways that generate the cough reflex o drugs that produce drowsiness and encourage the onset and
(modulates C-fiber activity) maintenance of a state of sleep
Uses Cough o involve more pronounced CNS depression than sedation
Nausea, vomiting, heartburn, diarrhea, fatigue,
SE
weakness, drowsiness, dizziness, headache, palpitations CNS Effects of Sedative-Hypnotics with increasing dose
Does not cause side effects such as constipation or
Notes respiratory depression which can be produced by opioid
antitussive
Please know the difference between expectorants and antitussive. Expectorant
ay papa-ubuhin ka para mailabas ang plema. Antitussive prevents yung pag-
ubo especially if it’s dry cough. Baka magasgas na lalamunan if papaubuhin
mo pa yung pasyente mo.
Dr. Rodriguez
SUPPLEMENT: OTHER DRUGS USED FOR COUGH

LAGUNDI (VITEX NEGUNDO)
• Inhibits PDE III and inhibits Ca2+ entry (acts as CCB), which partly
explain its bronchodilatory effect
• Considered a potent anti-inflammatory agent and acts via inhibition
of COX2 without much interfering COX1 pathways
• traditionally used in hyperactive respiratory disorder, has medicinal
importance in asthma
Figure 22-2. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
SECTION SYNTHESIS • Barbiturates (linear slope): with increasing dose higher than
DESCRIPTION DRUGS
needed for hypnosis, it can cause general anesthesia and even
depression of respiratory and vasomotor centers in the medulla,
Serotonergic Agents
leading to coma and death.
5-HT1D Agonists
• Benzodiazepine (plateauing curve): only causes CNS
5-HT3 Antagonist depression at proportionately greater doses (“ceiling effect”),
5-HT4 Partial Agonist featuring comparatively better safety profile.
5-HT2 Antagonists The GABA-A receptor: Site of Action of Sedative-Hypnotics
Histaminergic Agents • GABA-A receptor: site of action of benzodiazepines, barbiturates
H1 Blockers and other related drugs (i.e. Zolpidem, Zaleplon, Eszopiclone)
H2 Blockers This is different from GABAB receptor, of which the agonist is the drug
Prostaglandin Analogs Baclofen).
PGE1
• Functions as a chloride ion channel, which is activated by the
PGE2
inhibitory neurotransmitter GABA
PGF2a
PGI2
SHORT ACTING BENZODIAZEPINES

MIDAZOLAM, TRIAZOLAM, OXAZEPAM,
BROTIZOLAM, , ETIZOLAM
Midazolam Pre-op sedation, anesthesia induction
Uses
Triazolam Insomnia
Rapid tissue redistribution (NOT rapid elimination)
Notes
accounts for the short duration of action of these agents
INTERMEDIATE ACTING BENZODIAZEPINES

LORAZEPAM, ALPRAZOLAM, ESTAZOLAM, CLONAZEPAM,
LORMETAZEPAM, NITRAZEPAM, TEMAZEPAM
Alprazolam and For anxiety disorders even panic
Clonazepam: disorders
Estazolam: Insomnia
Figure 22-6. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018. Uses Tranquilizers, bipolar disorder,
Clonazepam: myoclonic and infantile spasm,
muscle relaxant, seizure disorder
SEDATIVE HYPNOTIC DRUGS
https://qrs.ly/rxdvduv Lorazepam: STATUS EPILEPTICUS
High dose BZD and Barbs may suppress seizure but at
Notes the expense of marked sedation EXCEPT Clonazepam
and Phenobarbital
BENZODIAZEPINES
What are the 5 principle pharmacologic effects LONG-ACTING BENZODIAZEPINES
of your benzodiazepines? DIAZEPAM, CHLORAZEPATE, CHLORDIAZEPOXIDE,
1. Anxiolysis FLURAZEPAM, QUAZEPAM, FLUNITRAZEPAM
2. Sedation and hypnosis
Flurazepam: Insomnia
3. Anticonvulsant actions
4. Spinal cord mediated skeletal muscle relaxation Cerebral palsy – muscle relaxation,
seizure disorder, tranquilizers,
5. Anterograde amnesia Uses Diazepam:
STATUS EPILEPTICUS, adjunct to
This effect is very specific to benzodiazepines
Dr. Pereyra-Borlongan anesthesia
Diazepam,
Alcohol withdrawal
CLINICAL USES OF BENZODIAZEPINES Chlordiazepoxide:
CLINICAL USE PREFERRED BENZODIAZEPINE Flunitrazepam: DATE RAPE DRUG
Anticonvulsant Notes Decreases REM sleep (abnormal sleeping patterns)
Clonazepam Chlordiazepoxide: LONGEST half life
maintenance
Status epilepticus Lorazepam, Diazepam
Skeletal muscle relaxation BARBITURATES
Diazepam
(e.g. cerebral palsy) CORRELATION: Biochemistry - Porphyria
Panic Disorders, Phobia Alprazolam, Clonazepam What enzyme is deficient in acute intermittent porphyria?
Insomnia Estazolam, Flurazepam, Triazolam HMB Synthase
Anesthesia induction Midazolam, Diazepam What is the most catastrophic symptom of sedative-hypnotic
Bipolar disorder Clonazepam withdrawal?
Rebound Suicide
Alcohol withdrawal Chlordiazepoxide, Diazepam
GENERALIZATION
BENZODIAZEPINE OVERDOSE • MOA: Bind to GABAA receptor sites (distinct from
• DOSAGE benzodiazepines); increases duration of chloride channel
o toxic dose is 1000x the therapeutic dose opening; block glutamic acid neurotransmission, at high doses
• CLINICAL PRESENTATION can block NA channels
o slurred speech, ataxia, altered (decreased) mental status, • SE:
respiratory depression o Extension of CNS depressant actions, Tolerance, Dependence
• TREATMENT liability (greater than benzodiazepines)
o antidote is flumazenil, a BZD receptor antagonist o Contraindicated in porphyria: patients with a history of
o activated charcoal is useless acute intermittent porphyria, variegate porphyria, hereditary
porphyria and symptomatic porphyria
Flumazenil o Additive CNS depression with ethanol
Competitive Antagonist at benzodiazepine sites on o Potent inducer of CYP450 enzymes (true for all barbiturates)
MOA
GABA-A receptor
Uses Benzodiazepine overdose ULTRASHORT-ACTING
Agitation, confusion, and precipitates benzodiazepine THIOPENTAL, METHOHEXITAL, THIAMYLAL
SE
withdrawal for those with benzodiazepine dependence Thiopental Anesthesia induction
Seizures and arrhythmias may occur when administered Uses Seizure induction for epileptic patients
Notes Methohexital
in patient who took both TCAs and benzodiazepines undergoing temporal lobe resection
Thiopental: highest lipid solubility (rapid entry to brain
GENERALIZATION Notes
<1 min and rapid awakening
• USE: Since they are sedative hypnotics, use nila ay for anxiety
disorders, pampatulog/sedation, some are relaxant for some INTERMEDIATE-ACTING
seizures; while others are for alcohol withdrawal PENTOBARBITAL, SECOBARBITAL, AMOBARBITAL,
• MOA: Binds to GABA-A receptor subunits to increase BUTALBITAL, BUTABARBITAL, TALBUTAL, APROBARBITAL
FREQUENCY of chloride channel opening. Uses Secobarbital: Insomnia and pre-op sedation
Pag pumasok si chloride (which is negatively charged) mas magiging
negative yung loob ng cell = HYPERPOLARIZED. Compare niyo ito later LONG-ACTING
with BARBITURATES PHENOBARBITAL, MEPHOBARBITAL, PRIMIDONE
Dr. Rodriguez
• SE: Anterograde amnesia, Unwanted daytime sedation, Phenobarbital: Seizure disorder, status epilepticus,
Respiratory depression, Tolerance, Dependence liability, Uses Hyperbilirubinemia (Gilbert’s syndrome); DOC for
rebound insomnia or anxiety, seizures in infant
• Decreased psychomotor skills (especially Diazepam and High dose BZD and Barbs may suppress seizure but at
Notes the expenses of marked sedation EXCEPT Clonazepam
Flurazepam), Painful on injection (diazepam)
and Phenobarbital
NEWER HYPNOTICS ALCOHOLS

• Methanol (wood alcohol): creates toxic formate, which causes
IMIDAZOPYRIDINE visual disturbance, come, seizures
ZOLPIDEM, ZALEPLON, ESZOPICLONE • Ethylene glycol (antifreeze): creates toxic aldehydes and
Bind selectively to a subgroup of GABAA receptors, acting oxalate, which causes kidney damage and severe acidosis
like benzodiazepines to enhance membrane • Ethanol: multiple effects on neurotransmitters, CNS
MOA
hyperpolarization, only interact with GABAA receptors depression; antidote in methanol and ethylene glycol poisoning
with alpha-1 subunit
Uses Insomnia; sleep disorder when sleep onset is delayed
Modest day-after psychomotor depression, Few
SE
amnestic effects, Tolerance, Dependence liability
Reversing agent: FLUMAZENIL
• NO anti-convulsant, anti-anxiety and muscle relaxant effects
• Very rapid onset of action
Notes • May decreased REM sleep
• Rebound insomnia on withdrawal from chronic use
• Has minimal effects on the sleep pattern and cause less
daytime cognitive impairment as compared to BZD
zzZZzzZZzzZZzz (sleep)
Zolpidem, Zaleplon = Zleep disorders
ANXIOLYTICS
BUSPIRONE
2 MAJOR PATHWAYS FOR ALCOHOL METABOLISM
MOA 5HT1A Partial agonist; also D2 agonist
Uses Generalized anxiety disorder EFFECTS OF ALCOHOL
SE Tachycardia, gastrointestinal distress, paresthesia ACUTE EFFECTS OF ETHANOL
• No anticonvulsant / muscle relaxant properties • CNS EFFECTS
• Minimal CNS depressant effects o sedation, loss of inhibition, impaired judgment, slurred speech,
• Minimal abuse liability ataxia
Notes • Minimal tolerance and withdrawal “BLACKOUTS” (i.e. periods of memory loss that occurs with high levels of alcohol
• Slow onset of action (>1week) – hence not for acute anxiety intoxication) are a result of inhibition of NMDA activation (since ethanol inhibits
• Metabolized by CYP3A4 the ability of glutamate to open the cation associated with NMDA receptors).
• Safe for pregnant patients • EFFECTS ON OTHER ORGAN SYSTEMS
o slight cardiac depression, vasodilation, hypothermia, uterine
RAMELTEON muscle relaxation
Activates melatonin receptors (MT1 and MT2 receptors)
MOA in the suprachiasmatic nuclei in the CNS --> decreased Blood Alcohol Concentration (BAC)
latency of sleep onset BAC
Effects
Insomnia, Sleep disorders, especially those (mg/dL)
Uses characterized by difficulty in falling asleep. 50-100 Sedation, subjective “high”, slower reaction times
Not a controlled substance 60-80 Impairment of driving ability (DUI)
Dizziness, fatigue, endocrine changes (decreased 100-200 Impaired motor function, slurred speech, ataxia
SE 200-300 Emesis, stupor
testosterone, increased prolactin)
300-400 Coma
• Rapid onset of sleep with minimal rebound insomnia
>500 Respiratory depression, death
or withdrawal symptoms
• Minimal rebound insomnia or withdrawal symptoms CHRONIC EFFECTS OF ETHANOL
Notes
• Minimal abuse liability • TOLERANCE AND DEPENDENCE
• Metabolized by CYP450 (increased levels in the o result of CNS adaptation and increased ethanol metabolism
presence of CYP1A2 or CYP2D6 inhibitors) o cross-tolerance with benzodiazepines and barbiturates
o marked psychological and physical dependence
SECTION SYNTHESIS • LIVER DISEASE
Again the name of the drug gives a clue to its classification. BenzodiAZEpine o most common complication of chronic alcohol abuse
have -AZE- in their name. Barbiturates have BARBs in their name except for o reduced gluconeogenesis leads to hypoglycemia
the ultrashort acting. Try to look at the table again. o progressive loss of liver function (reversible fatty liver to
Benzodiazepine induces hyperpolarization by activating what GABA irreversible hepatitis, cirrhosis and liver failure)
Receptor? A or B? If this receptor is activated, what electrolyte passes o increased severity in females and those with hepatitis B and C
through? Do Barbiturates act on the same receptor? Yes or No? What is an
important difference that you need to note between barbs and benzos?
• GASTROINTESTINAL SYSTEM
Among the benzos which can be given for alcohol withdrawal: o irritation, inflammation, bleeding and scarring of gut wall
_________________________; which among them is used as a date rape drug: o absorption defects and exacerbation of nutritional deficiencies
_________________________. Toxicity with benzodiazepines can be reversed with o increased risk of pancreatitis
what drug: _____________________ • CENTRAL NERVOUS SYSTEM
Barbiturates: Due to its high lipid solubility, this barbiturate was previously o peripheral neuropathy (described as generalized, symmetric)
used for the induction of anesthesia: ________________. Ultrashort acting is the most common neurologic abnormality in chronic alcoholics
barbiturates have Thio/Thia in their names. For Intermediate acting, sing
“ Amobarbital, Butabarbital” – in I’m a barbie doll tune.
• ENDOCRINE SYSTEM
Dr. Rodriguez o gynecomastia, testicular atrophy and salt retention due to
ALCOHOLS altered steroid metabolism in the cirrhotic liver
• CARDIOVASCULAR SYSTEM
o increased incidence of hypertension, anemia and dilated
cardiomyopathy
o binge drinking can cause arrhythmias
o ingestion of modest quantities of ethanol (10–15 g/day) raises
HDL levels and may protect against CAD
• FETAL ALCOHOL SYNDROME
o Mental retardation (most common)
o growth deficiencies, microcephaly
Katzung and Trevor’s Pharmacology Examination and Board Review. 12 ed. 2018
th
o characteristic underdevelopment of midface region
o associated with heavy consumption of alcohol during the first
trimester of pregnancy
• NEOPLASIA § Before giving glucose in a patient with hypoglycemia, we must
o increased incidence of neoplastic diseases in GIT restore the dehydrogenase enzyme necessary for carbohydrate
o small increase in the risk of breast cancer metabolism, do give thiamine to resurrect the level of dehydrogenase.
Otherwise, it will just cause more osmotic pull in the cell.
• IMMUNE SYSTEM
correction of electrolyte imbalance and hydration – since patients
o enhances inflammation in the liver and pancreas
maybe dehydrated and vomiting
o inhibits immune function in other tissues
o heavy use predisposes to infectious pneumonia
DELIRIUM TREMENS
ALCOHOL INTOXICATION VS.
• Seen in chronic alcoholics when forced to reduce or discontinue alcohol
ALCOHOL WITHDRAWAL • a withdrawal syndrome (characteristic of motor agitation,
anxiety, insomnia and reduction of seizure threshold)
WERNICKE-KORSAKOFF SYNDROME
• Ataxia, confusion, paralysis of the extraocular muscles
• Seen in intoxication states
• Associated with thiamine deficiency (Vitamin B1)
• Rarely seen in the absence of alcoholism
• Ocular signs and ataxia improve with thiamine administration
• Left with a disabling chronic memory disordered known as
Korsakoff’s psychosis (irreversible memory loss)
MNEMONIC: Wernicke-Korsakoff Syndrome
Weird ACO
Wernicke-Korsakoff Syndrome: Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
Ataxia, Confusion, Ophthalmoplegia MNEMONIC: Delirium Tremens
What changes in the brain are seen in Wernicke-Korsakoff syndrome? H-A-D 48
hemorrhagic necrosis of the mamillary bodies Hallucinations Delirium
Autonomic instability 48-72 hours post-discontinuation
• Treatment:
• Treatment of Delirium Tremens:
o maintenance of vital signs
o substituting a long-acting sedative-hypnotic drug as a
o prevention of aspiration after vomiting
replacement for alcohol and then gradually reducing
o intravenous dextrose – for hypoglycemia
("tapering") the dose of the long-acting drug.
o thiamine administration to protect against Wernicke-
§ DOC is long-acting benzodiazepine (e.g. diazepam,
Korsakoff syndrome
chlordiazepoxide)
PHARMACOLOGIC MANAGEMENT
OF CHRONIC ALCOHOLISM
Drugs NALTREXONE [C], NALOXONE [C], Nalmefene [B], Alvimopan [B], Methylnaltrexone [B] DISULFIRAM
Opioid antagonist (systemic and long acting):
MOA Aldehyde dehydrogenase inhibition
Competitively blocks µ, d and k receptors. Rapidly reverses effects of opioid agonists.
Opioid and alcohol dependence (naltrexone only)
Uses Naloxone: DOC for opioid overdose Alcohol dependence
Naltrexone: DOC for opioid dependence and chronic alcoholism
Pruritus, Nausea, Vomiting, Hepatotoxic
SE Nausea, headache, flushing and hypotension
Don’t combine with disulfiram: both drugs are hepatotoxic
• Precipitate abstinence syndrome in patients with opioid dependence • Drug interactions: decreases metabolism of
• Naltrexone reduces craving in alcohol, nicotine and opioid dependence Diazepam, Phenytoin, Oral anticoagulants
• Naltrexone & Nalmefene have longer DOA and isoniazid
Notes
• Naloxone and Nalmefene is IV (DOA: 12-24 hrs) while Naltrexone is PO (DOA: 48h) • Disulfiram is absorbed rapidly (peak effect is
• Alvimopan & Methylnaltrexone have poor CNS penetrability → antagonize peripheral 12 hours) but eliminated slowly (action may
effects such as constipation persist for days)
MNEMONICS: Disulfiram Reaction

What drugs can cause disulfiram reaction?
Clara took the Pre-Medical Test in the PM
Chlorpropamide Procarbazine
Cefo Perazone Metronidazole
Mandole
Tetan
MNEMONIC:
DRUGS THAT CAUSE
DISULFIRAM REACTION
https://qrs.ly/7tdvduy
ALCOHOL AND
ALCOHOL METABOLISM Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
https://qrs.ly/xhdvdv3
OTHER ALCOHOLS
Drugs METHANOL POISONING ETHYLENE GLYCOL POISONING
• Methanol is metabolized by ADH to formaldehyde, which is then oxidized • Ethylene glycol forms toxic aldehyde and oxalic acid
to formic acid (toxic) • Industrial exposure (by inhalation or skin absorption)
Sources
• Wood alcohol, windshield cleaners, “canned heat,” commercial solvents, • Self-administration (e.g. by drinking antifreeze
photocopier toner products)
Visual dysfunction, gastrointestinal distress, shortness of breath, loss of
Clinical consciousness, coma
Severe acidosis and renal damage
features • accumulation of formaldehyde and formic acid causes severe acidosis,
retinal damage, and blindness
Drugs METHANOL POISONING ETHYLENE GLYCOL POISONING
ETHANOL ETHANOL
• retards formation of formaldehyde • competes for oxidation by alcohol dehydrogenase
• acts as a preferred substrate for alcohol dehydrogenase FOMEPIZOLE
Tx
• competitively inhibits the oxidation of methanol • slows or prevents formation of oxalic acid
FOMEPIZOLE
• inhibitor of alcohol dehydrogenase
SECTION SYNTHESIS
For the toxic alcohols Ethylene glycol and Methanol, they both have the same ANTISEIZURE DRUG MOAs
treatment but differ in the metabolites formed. Ethylene glycol forms: https://qrs.ly/dedvdv5
________________ after the action of alcohol dehydrogenase, while Methanol
forms _______________ after the action of the same enzyme. Both toxicities are
prevented by giving __________ to inhibit the enzyme alcohol dehydrogenase
or given ___________________ to compete with the usage of the enzyme. MOA of the Antiseizure Drugs (• major MOA, ° minor MOA)
Answers: are in the diagram above. Antiseizure
Na+ Ca2+ K+ GABA Glutamate Others
Dr. Rodriguez Drug (AED)
NE,
ANTISEIZURE DRUGS Phenytoin • ° ° °
Ach
Carbamazepine • °
Valproic acid • ° ° °
Phenobarbital ° ° • °
Ethosuximide • °
Benzodiazepine •
Gabapentin • °
Pregabalin • •
Lamotrigine • ° °
Levetiracetam • • • SV2A
Topiramate • • • •
Perampanel AMPA
Retigabine •
Tiagabine •
Katzung and Trevor’s Pharmacology Examination and Board Review. 12TH ed. 2018 Felbamate • NMDA
SUPPLEMENT: Seizures Lacosamide •
Seizures Rufinamide •
• finite episodes of brain dysfunction resulting from abnormal Vigabatrin •
discharge of cerebral neurons
Zonisamide •
• classification based on seizure characteristics
o simple or complex Clobazam •
o partial, generalized or partial with secondary generalization
Types of Seizures ENHANCE GABA SYNAPTIC TRANSMISSION
• SIMPLE PARTIAL SEIZURES
o Characterized by minimal spread of abnormal discharge
§ consciousness and awareness is preserved (patient can describe
in full detail the attack)
§ convulsive jerking, paresthesia, psychic symptoms (altered
sensory perception, illusions, hallucinations, affect changes) and
autonomic dysfunction
• COMPLEX PARTIAL SEIZURES
o Localized discharge → becomes more widespread/ bilateral
o usually arise from temporal lobe
§ impaired consciousness
§ demonstrate automatisms (lip smacking, swallowing, scratching,
walking about)
• GENERALIZED TONIC-CLONIC SEIZURES (GRAND MAL)
o tonic phase (< 1 min): abrupt loss of consciousness, muscle rigidity
and respiration arrest
o clonic phase (2–3 min): jerking of body muscles, with lip or tongue
biting, and fecal and urinary incontinence
• ABSENCE SEIZURES (PETIT MAL)
o begin in childhood and usually cease by age 20 yrs
§ impaired consciousness (abrupt onset, brief)
§ automatisms, loss of postural tone, or enuresis
• MYOCLONIC SEIZURES
o Sudden, brief, shock-like contractions of musculature (myoclonic jerks)
• ATONIC SEIZURES
o Sudden loss of postural tone
• INFANTILE SPASMS
o Epileptic syndrome
o 90% of patients have their first attack before the age of 1
• STATUS EPILEPTICUS
o series of seizures (usually tonic-clonic) without recovery of
consciousness between attacks Figure 17-3. Brunton LL. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. 2018
o life-threatening emergency • GABA (primary inhibitory neurotransmitter): when present, the
GABA-A receptor opens, allowing an influx of Cl-, which in turn
MOA OF THE ANTI-SEIZURE DRUGS increases membrane polarization.
• Some Anti-seizure drugs enhance GABA transmission
• Mechanism falls under any of the 3 categories:
o Benzos and barbiturates: act on the receptor itself
o Enhancement of GABAergic (INHIBITORY) Transmission
o Gabapentin: acts presynaptically to promote GABA release
o Diminution of excitatory (usually GLUTAMATERGIC)
o Vigabatrin and Valproate: act by reducing metabolism of GABA
transmission
o Tiagabine, act by inhibiting its reuptake (action on GAT-1)
o Modification of ionic conductance (Na, K, Ca, etc.) and
presynaptic transmitter release (SV2A)
ENHANCE NA+ CHANNEL INACTIVATION IMPORTANT OTHER USES

Trigeminal neuralgia A
Acute mania (Bipolar Disorder) B
Hyperbilirubinemia C
Post herpetic neuralgia D
TERATOGENIC EFFECTS
E Fetal hydantoin syndrome
F Spina-bifida (NTD) and craniofacial anomalies
Figure 17-2. Brunton LL. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. 2018 G Spina-bifida, neural tube defects
• Carbamazepine, Phenytoin, Topiramate, etc: Prolong MOST COMMON SE
inactivation of the Na channels, reducing ability of neurons to Hydantoins (phenytoin),
H
fire at high frequencies Tricyclic (carbamazepine)
I Branched-chain FA (Valproic)
REDUCE CURRENT THROUGH T-TYPE CA2+ CHANNEL
J Barbiturates
MUST KNOW SE
Gingival hyperplasia K
SJS L
Acute intermittent
M
porphyria
CYP450 Effects
N Phenytoin, Carbamazepine, Phenobarbital
Figure 17-4. Brunton LL. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. 2018 O Valproic acid
• Ethosuximide, Valproic acid (DOC for absence seizures); reduce
Ca2+ flux through Thalamic type (T-type) Ca2+ channels, reducing Answers (a) Carbamazepine (b) Valproic acid (c)Phenobarbital (d)
pacemaker current underlying thalamic rhythm Gabapentin. (e) Phenytoin (f) Carbamazepine (g) Valproic acid (h)
diplopia-ataxia (i) GI upset (j) Sedation (k) phenytoin (l) Carbamazepine
FETAL HYDANTOIN SYNDROME: TERATOGENIC EFFECT OF (m) barbiturates (n) Inducers (o) inhibitor
PHENYTOIN Dr. Rodriguez
• Wide set eyes

• upturned nose SODIUM CHANNEL BLOCKERS
• mild midfacial hypoplasia / broad mandible HYDANTOINS
• long upper lip with thin vermilion border PHENYTOIN, FOSYPHENYTOIN, MEPHENYTOIN, ETHOTOIN,
• lower distal digital hypoplasia PHENACEMIDE
MOA Major: Blocks voltage-gated Na+ channels
CLINICAL USES OF ANTISEIZURE DRUGS DOC for generalized tonic-clonic seizures,
Drugs of Uses DOC for partial seizures, status epilepticus, arrhythmias
Seizure Type Alternative Drugs
Choice (Group 1B Action), migraine
Generalized Valproic Acid Phenobarbital, Nystagmus (early),
Tonic-Clonic Phenytoin Lamotrigine, Diplopia and Ataxia (most common),
Seizures Carbamazepine Topiramate Gingival Hyperplasia (favorite to ask in the boards),
SE
Felbamate, Teratogen (fetal hydantoin syndrome), abnormalities in
Carbamazepine Vit D metabolism, Hirsutism, Anemias, Peripheral
Phenobarbital,
Partial Seizures Lamotrigine neuropathy, Osteoporosis,
Topiramate, Valproic
Phenytoin • Potent inducer of CYP450 enzymes
Acid
• Metabolism is NON-LINEAR (elimination shift from 1st
Lamotrigine,
order to zero order at moderate to high dose levels), hence
Ethosuximide Levetiracetam, serum monitoring is necessary,
Absence Seizures Notes
Valproic Acid Zonisamide, • Fosphenytoin: water-soluble prodrug of phenytoin
Clonazepam • Sedating only at very HIGH levels
Clonazepam, • Phenytoin has an affinity for thyroid binding globulin (can
Myoclonic and
Levetiracetam, interfere with thyroid function)
Atypical Absence Valproic Acid
Topiramate,
Syndromes
Zonisamide, Felbamate
Lorazepam
TRICYCLIC
Diazepam CARBAMAZEPINE, OXCARBAZEPINE , ESLICARBAZEPINE
Status Epilepticus --
Phenytoin Blocks voltage-gated Na+ channels, decrease glutamate
MOA
Phenobarbital release
DOC for trigeminal neuralgia,
OTHER CLINICAL USES OF ANTISEIZURE DRUGS DOC for generalized tonic-clonic seizures,
Uses
DOC for partial seizures,
• BIPOLAR AFFECTIVE DISORDERS: valproic acid (first-line for Manic phase (bipolar disorder)
mania), carbamazepine, lamotrigine Stevens-Johnson syndrome,
• TRIGEMINAL NEURALGIA: carbamazepine (DOC), erythematous rash (most common idiosyncratic
oxcarbazepine reaction),
• NEUROPATHIC PAIN (POSTHERPETIC NEURALGIA): Diplopia and ataxia (Most common – just like phenytoin),
gabapentin, pregabalin SE cognitive dysfunction, drowsiness,
blood dyscrasias (i.e., aplastic anemia and agranulocytosis,
• MIGRAINE: gabapentin, phenytoin, topiramate both idiosyncratic reactions),
Teratogen (spina bifida and craniofacial anomalies),
TRADITIONAL ANTISEIZURE DRUGS Hyponatremia (Oxcarbazepine)
At this point don’t be overwhelmed with the amount of information. For the • Potent CYP450 inducer
MOA and clinical uses, there will be several for each drug, but if merong • Can cause auto-induction (induce its own metabolism)
Notes
hindi dapat makalimutan, yun yung mga nabanggit sa dalawang table sa • Oxcarbazepine has less drug interactions
taas (MOA and Clinical Uses). Also focus on those that are in bold per table. • Also, highly protein bound (75%)
Okiiii? Kaya natin ito. J Below is a blank sheet that you can fill out, as you Check out the next two drugs (Branched-chain fatty acid and the
go along the different tables. I hope that this will help lessen the work you phenyltriazines), park in your mind that they too have use for BIPOLAR
need to summarize the contents. Answers will be given below but please DISORDERS.
Dr. Rodriguez
don’t look at them first
Dr. Rodriguez
BRANCHED-CHAIN FATTY ACID GABA ANALOGUE

VALPROIC ACID, SODIUM VALPROATE, DIVALPROEX SODIUM GABAPENTIN [C], PREGABALIN [C]
Blocks Na channel high-frequency firing of neurons Blocks Ca2+ channels. Decrease glutamate release.
(similar to phenytoin and carbamazepine) Inhibits neuronal discharge from seizure foci.
MOA MOA
Blocks NMDA, Increases GABA levels Despite its structural similarity with GABA, it’s MOA
Broad spectrum antiseizure drug doesn’t directly act on GABA receptors
DOC for bipolar disorder (acute mania), Partial seizures,
DOC for generalized tonic-clonic seizures and absence
Uses Uses Neuropathic pain (postherpetic neuralgia) – first
seizure (especially if with GTC component), partial
line, Migraine, Fibromyalgia (Pregabalin)
seizures, myoclonic seizures, migraine prophylaxis
GI upset (Most common, in the form of nausea, vomiting, SE Dizziness, Sedation, Ataxia, Nystagmus, Tremor
SE anorexia), Weight gain • Also have the same effect on Ca currents like
Teratogen (neural tube defects, spina bifida) Ethosuximide
Notes
• CYP450 INHIBITOR (unlike some of its AED relatives Pregabalin is also manufactured as a combination drug
Notes which are more often than not, INDUCERS) with Methylcobalamin for neuropathic pain
• Highly protein bound (90%)
PIRACETAM
PHENYLTRIAZINE LEVETIRACETAM, BRIVARACETAM
LAMOTRIGINE, ZONISAMIDE Selectively binds synaptic vesicular protein SV2A →
Blocks Na and Ca channels, Decreases glutamate, selectively inhibiting hypersynchronization of
MOA MOA
Zonisamide only blocks Na channels epileptiform burst firing; Modifies synaptic release of
Generalized tonic-clonic seizures, glutamate and GABA. Inhibits Ca2+ channels also
Uses DOC for Partial seizures, Myoclonic seizures, Generalized tonic-clonic seizures, Partial seizures,
Absence seizures, bipolar disorder Uses
Juvenile myoclonic epilepsy
Dizziness, ataxia, nausea, rash, headache, SJS / TEN Ataxia, Asthenia, Dizziness, Sedation, Weakness,
(lamotrigine), severe skin reaction (Zonisamide) SE
Irritability, Hallucinations, Psychosis
SE
Zonisamide may also cause cognitive impairment, Drug interactions are minimal (neither an
Notes
confusion and poor concentration inducer/inhibitor)
• Primarily undergoes glucuronidation reaction
Notes Lamotrigine may be used for acute manic phase and as MONOSACCHARIDE DERIVATIVE
prophylaxis in the depressive phase
TOPIRAMATE, FELBAMATE
Multiple actions on synaptic function, probably via
GABAERGIC actions on phosphorylation (Na, K, Ca, GABA, AMPA-
BARBITURATES MOA glutamate, carbonic anhydrase)
Felbamate also facilitate the inhibitory actions of GABA,
PHENOBARBITAL, PRIMIDONE but its exact MOA is still unknown
Bind to GABAA receptor sites (distinct from Generalized tonic-clonic seizures,
MOA benzodiazepines); also has actions on Na (limits sustained
Absence seizures, Partial seizures,
repetitive firing in neurons), Ca and glutamate Uses
Lennox-Gastaut syndrome, West syndrome, Migraine;
Generalized tonic-clonic seizures, Partial seizures, Status
Felbamate is only for severe refractory seizure states
epilepticus, Insomnia, Hyperbilirubinemia
Uses Sleepiness, cognitive slowing, confusion, paresthesias
Barbiturates, particularly phenobarbital, is the DOC for
infants (Katzung) Urolithiasis (because of weak carbonic anhydrase
Sedation (most frequent unwanted SE), SE effect)
Extension of CNS depressant actions, Tolerance, Felbamate causes hepatic failure and hematotoxicity
Dependence liability (greater than benzodiazepines), (can cause ITP, aplastic anemia)
SE Acute intermittent porphyria • Antiseizure drug with the greatest number of
Do not use phenobarbital for absence, atonic and infantile mechanisms of action
spasms. It may worsen these seizure types. • Weak inhibitor of carbonic anhydrase
Notes Potent inducer of CYP450 enzymes • Topiramate can also block Na channels, activate a
Notes
hyperpolarizing K+ current and potentiate action of
GABA and block glutamate receptor (particularly
BENZODIAZEPINES AMPA receptor)
DIAZEPAM, LORAZEPAM, CLORAZEPATE • Felbamate may also block glutamate receptors
Clonazepam, Clobazam
Binds GABAA receptor subunits to increase frequency of
MOA SECTION SYNTHESIS
chloride channel opening; membrane hyperpolarization
DIAZEPAM, Remember in seizure that there is excessive firing of the neurons. To excite a
LORAZEPAM, Status epilepticus neuro remember an action potential should be fired. And that is done
CLORAZEPATE through activation of sodium channel, as well as calcium channels. These
Uses
Absence seizures (second line), are the two main channels blocked by our known anticonvulsants. There are
Clonazepam,
Myoclonic seizures, Infantile spasms, 4 types of sodium channel blockers can you name them again? Among them
Clobazam
Lennox-Gastaut syndrome one is well known for causing gingival hyperplasia: __________________.
Anterograde amnesia, Painful on injection, Decreased Another is known for its usage for trigeminal neuralgia _______________, and
SE psychomotor skills, Unwanted daytime sedation, lastly the other is used for acute mania for bipolar disorder,
Respiratory depression, Tolerance, Dependence liability _____________________. On the other hand, there are drugs that inhibit calcium
Binds GABAA receptor subunits to increase frequency of channels, can you name one? _________________ note that they have the same
Notes suffix to help you remember.
chloride channel opening; membrane hyperpolarization
Later there will be another set of drugs for Lennox Gastaut under
monosaccharide. Paki-park na po sa mind J Aside from preventing the action potential by inhibiting Na and Ca
Dr. Rodriguez channels, we can also hyperpolarize them to inactivate them by
opening GABA channels. This is seen in two important drug classes:
_______________ and ______________. Among them is the drug _______________
CALCIUM CHANNEL BLOCKERS used for status epilepticus.
ETHOSUXIMIDE [C], PHENSUXIMIDE, METHSUXIMIDE Dr. Rodriguez
Decreases Ca2+ currents (T-type) in thalamus

MOA Ethosuximide reduces low threshold T-type Ca2+
currents in the thalamic neurons.
Uses Absence seizures (DOC)
GI complaints (MC; ex. Nausea, vomiting, anorexia),
SE
Lethargy, Headache, Behavioral changes (euphoria)
GENERAL ANESTHETICS GENERALIZATION

• MOA: Facilitate GABA-mediated inhibition; Block brain NMDA
and Ach-N receptors
• Use: General anesthesia
• Side effects:
Side effects D S I E H M
Peripheral vasodilation
Bronchodilation
Bronchospasm
Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2019
Renal Insufficiency A F
Catecholamine-induced arrhythmias
General Anesthesia Myocardial depression
• A neurophysiologic state characterized by unconsciousness, *Note A: Renal insufficiency due to compound A; F: renal insufficiency due to
analgesia, amnesia, skeletal muscle relaxation, and loss of fluorine. Summarized the important side effects in this table. When you go
reflexes through each of the drug below, we won’t be mentioning them again para
hindi kayo overwhelmed, but will place the must knows if there are any.
• An ideal anesthetic should induce rapid, smooth loss of
Otherwise always go back to this table as a refresher for the SE
consciousness, be rapidly reversible upon discontinuation and Dr. Rodriguez
possess a wide margin of safety.
• Goal of anesthesiologist: smooth transition from stage 1 to stage 3 Desflurane
Contraindicated in patients with asthma
Stages of Anesthesia (Guedel’s signs): Notes PUNGENT ODOR: not for induction
Stage Name Events (also causes bronchospasm)
Decreased awareness of pain, sometimes
1 Analgesia with amnesia Sevoflurane
Consciousness is impaired, not lost
Sweet smelling
Patient is delirious or excited Notes
Amnesia occurs, reflexes are enhanced, Best for asthmatic (bronchodilation)
2 Disinhibition
and respiration is typically irregular
Retching and incontinence may occur Isoflurane
Patient is unconscious SE Coronary steal syndrome
Surgical
3 anesthesia
No pain reflexes, regular respiration, and Coronary steal syndrome, the preferential
maintained blood pressure redistribution of blood from ischemic areas to non-
Severe respiratory and cardiovascular Notes
Medullary ischemic areas, is a theoretical possibility for isoflurane
4 depression
depression that requires mechanical and use
pharmacologic support
The general anesthetics are mainly divided into inhalational anesthetics and
intravenous. Enflurane
Dr. Rodriguez Spike-and-wave activity in EEG, muscle twitching,
SE
breath-holding
INHALATIONAL ANESTHETICS Notes PUNGENT ODOR limits its use
Inhalational Anesthetics
• Include nitrous oxide, halothane, desflurane, enflurane, Halothane
isoflurane, sevoflurane, and methoxyflurane HALOTHANE HEPATITIS
SE
(immune mediated response characterized by eosinophilia)
• Partial pressure or "tension” is a measure of concentration of
Sweet smelling
inhaled anesthetics
Highest propensity to cause hepatitis
o Standard pressure of the total inhaled mixture is atmospheric
• Notes Storage: Amber bottles (light sensitive)
pressure (760 mm Hg at sea level) Preservative: Thymol (prevent oxidative
o 50% nitrous oxide in the inhaled air would have a partial decomposition)
pressure of 380 mm Hg
Methoxyflurane
Minimum Alveolar Anesthetic Concentration (MAC)
Highest POTENCY, Lowest MAC
• Best measure of potency of inhaled anesthetics Notes
Very slow onset and recovery
• A 1.0 MAC as the partial pressure of an inhalational anesthetic in
the alveoli of the lungs is 50% of the population of non-relaxed
Nitrous oxide
patients remained immobile at the time of surgical skin incision
Anesthesia for minor surgery and dental procedures,
(standardized painful stimulus) Uses
Balanced anesthesia for major surgery
• When several anesthetic agents are used simultaneously, their Megaloblastic anemia on prolonged exposure,
MAC values are additive Euphoria (laughing gas), bronchodilation,
SE
Partition Expansion of air-filled cavity to NONCOMPLIANT spaces,
Anesthetic MAC Metabolism diffusion hypoxia
Coefficient
Nitrous oxide 0.47 >100 None • Not a SOLE anesthetic agent; combined with other
Desflurane 0.42 6-7 <0.05% inhaled local anesthetics for a more balanced effect
2-5% • Lowest potency (highest MAC) and least
Sevoflurane 0.69 2.0 cardiotoxicity among inhalational anesthetics
(fluoride)
Isoflurane 1.40 1.40 <2% Notes • CNS: Only inhaled anesthetic that INCREASES cerebral
Enflurane 1.80 1.7 8% blood flow and hence INCREASE ICP due to activation
Halothane 2.30 0.75 >40% of sympathetic nervous system
>70% • Cardiac effect: Minimal circulatory depressant (only at
Methoxyflurane 12 0.16 high doses) because it activates the SNS
(fluoride)
Anesthetic Comments EFFECTS OF INHALED ANESTHETICS
Nitrous oxide CNS EFFECTS:
Incomplete anesthetic; rapid onset and recovery
Low volatility; poor induction agent
• Variable effects depending on MAC levels
Desflurane
(pungent); rapid recovery
• Reduction in cerebral metabolic rate is greater than vasodilation
Sevoflurane Rapid onset and recovery, unstable in soda-lime
→ cerebral blood flow is decreased
Isoflurane • Vasodilation is greater than reduction in cerebral metabolic rate
Enflurane Medium rate of onset and recovery → cerebral blood flow is increased
Halothane o Undesirable for patients with increased ICP (remember
Methoxyflurane Very slow onset and recovery Monroe-Kelly Doctrine?) ex. Brain tumor, ICH and head injury
• EXCEPTION: Nitrous OXIDE IMIDAZOLE DERIVATIVE
• REMEMBER: Hyperventilation to decrease PaCO2 → cerebral Etomidate
vasoconstriction → decrease in cerebral blood flow → reduction in ICP
MOA Modulates GABAA receptors containing b3 subunits
General anesthesia (especially in patients with limited
CARDIOVASCULAR EFFECTS Uses
cardiac or respiratory reserve)
• ALL inhaled anesthetic depress normal cardiac contractility → Pain on injection, Myoclonus, Postoperative nausea and
decrease mean arterial pressure via different mechanisms vomiting, Adrenocortical suppression
o EXCEPTION: Nitrous Oxide SE
Etomidate’s propensity to cause adrenocortical
• Inhaled anesthetics have variable effect on baroreceptor reflex suppression limits its use.
• Inhaled anesthetics reduce myocardial oxygen consumption Etomidate, unlike other IV anesthetics, has minimal effects
on CV and respiratory functions upon induction. HENCE, it
Notes
RESPIRATORY EFFECTS can be used as an induction agent of choice for unstable
patients or those with minimal cardiopulmonary reserve
• ALL inhaled anesthetics have BRONCHODILATING properties except
o DESFLURANE (and ISOFLURANE to a lesser extent) – can
cause airway irritability and hence is unsuitable for induction OPIOID ANALGESIC
o Preferred for bronchodilation is sevoflurane and halothane, FENTANYL, MORPHINE, ALFENTANIL, REMIFENTANIL
both sweet smelling Interact with µ (mu), d (delta) and k (kappa) receptors for
MOA
endogenous opioid peptides
MALIGNANT HYPERTHERMIA
Uses Analgesia
• Genetic disorder of susceptible individuals upon exposure to Respiratory depression, chest wall rigidity (which may
volatile anesthetics and succinylcholine SE
cause impaired ventilation) and constipation
• Signs and symptoms: muscle rigidity, hyperthermia, rapid onset of • Antidote is NALOXONE (DOC)/NALTREXONE
tachycardia, hypercapnia, hyperkalemia and metabolic acidosis • Neuroleptanesthesia (analgesia + amnesia) happens when
• Pathophysiology: Mutation in the ryanodine receptor (calcium Notes Fentanyl, Droperidol and Nitrous oxide are given together
release channel in the SR) of the skeletal muscle that results to • Faster recovery: remifentanil
uncontrolled release of Ca2+ from the sarcoplasmic reticulum These drugs have fast onset of action
• Caffeine-Halothane contracture test: most reliable test to
establish susceptibility PROPOFOL
• Treatment: Dantrolene
Propofol, fospropofol, “Milk of Amnesia”
Potentiates GABAA receptors, Blocks Na channels
INTRAVENOUS ANESTHETICS MOA
* Propofol has an antiemetic action
BARBITURATES IV anesthetic induction of choice, General anesthesia,
Uses
Sedation for ICU patients and outpatient procedures
Thiopental, Methohexital, Thiamylal
Pain at injection site, Hypotension (at induction)
Bind to GABAA receptor sites (recall, what does it do to Paresthesia in the perianal region (Fospropofol),
MOA SE
the opening of chloride channels?) Propofol Infusion syndrome
Anesthesia induction (old) CVS depression
Uses For increased ICP • Contains egg lecithin
Methohexital: Identification of epileptic foci • Metabisulfite (an agent to prolong shelf life) can cause
Dependence liability (greater than BZDs) allergic reactions to asthmatic patients and patients
Extension of CNS depressant actions with sulfa allergies
SE
Tolerance, Acute intermittent porphyria, • Fast onset fast recovery due to inactivation
Accidental Intra-arterial injection can lead to gangrene Notes
• REMEMBER: Zero analgesic properties
They do no produce analgesia; rather cause
• Alternative General anesthetic maintenance for patients
HYPERALGESIA
susceptible to malignant hyperthermia
Notes Potent cerebral vasoconstrictors = for px with inc. ICP
• Fospropofol is the water- soluble prodrug form of propofol
Do not mix with acidic drugs (neuromuscular blockers)
but with slower onset and recovery
→ can cause precipitates.
PROPOFOL INFUSION SYNDROME
BENZODIAZEPINES • Seen in prolonged high dose infusions (>75ug/kg/min) for
MIDAZOLAM, BROTIZOLAM, TRIAZOLAM, OXAZEPAM, longer than 24 hours
ETIZOLAM, LORAZEPAM • Cardinal feature: metabolic (lactic) acidosis
Bind to GABAA receptor sites (recall, what does it do to • TRIVIA – Death of Michael Jackson
MOA the opening of chloride channels?) – compare this with o Immediate COD: acute propofol intoxication
Barbiturates o Contributory factors: drug interactions (lorazepam,
Acute anxiety, Panic attacks, Anesthesia induction, midazolam, diazepam)
Uses
Preoperative sedation
Anterograde amnesia, decreased psychomotor skills, SUPPLEMENT: OTHER ANESTHETICS
SE unwanted daytime sedation, Postoperative respiratory a novel sedative-analgesic agent, an alpha-2
depression (Antidote: Flumazenil), Dependence liability, adrenoceptor agonist. Alpha-2 receptor
Midazolam, is a usual adjunct with inhalational agonists decrease sympathetic tone with
DEXMEDETOMIDINE
Notes anesthetics and IV opioids, has a slow onset but longer attenuation of the neuroendocrine and
DOA. hemodynamic responses to anesthesia and
surgery and cause sedation and analgesia
PHENCYLIDINE DERIVATIVE
Ketamine LOCAL ANESTHETIC
MOA NMDA antagonist, weak GABAA modulation
Dissociative anesthesia (analgesia, amnesia, and catatonia
Uses
but with retained consciousness)
Increased ICP, Emergence delirium
(Post-op effects: disorientation, hallucination, excitation)
SE Lacrimation and salivation (pretreatment with
anticholinergics).
Cardiovascular stimulation
• Ketamine produces potent analgesia with little respiratory Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2019.
depression (it is a bronchodilator) making it ideal for

Notes asthmatic patients
You can reduce emergence delirium by pretreatment with
benzodiazepines
Local Anesthesia Benzocaine, Butamben
• Refers to a loss of sensation in a limited region of the body Uses Local anesthesia, Topical anesthesia
accompanied by muscle paralysis and sympathetic blockade. SE Methemoglobinemia (rare but serious)
• Recovery from clinically relevant local anesthetics should be • Topical use only
spontaneous, predictable and without residual effects • Use cautiously when treating sunburns or large areas
of skin
MNEMONICS: Local Anesthetics Notes
• Benzocaine is unique in the sense that it is a weak acid,
How will you distinguish whether local anesthetics are esters or amides? hence it exist predominantly in the non-ionized form at
ESTERS have only 1 i in their names. physiologic pH.
Tetracaine, Procaine, Benzocaine
AMIDES have 2 i’s in their names.
Bupivacaine, Ropivacaine, Lidocaine Cocaine
As long as you know how to count, you can get this right! Local anesthesia, Topical anesthesia. Used for surgeries
MNEMONICS – Half Life of Local Anesthetics Uses involving the ear, nose, and throat procedures
Which local anesthetics have the shortest and longest half-lives? All local anesthetics are vasodilators EXCEPT cocaine
PROCAINE = sLhortest half-life (1-2 mins) Abuse liability, Severe hypertension, Cerebral hemorrhage,
A PRO finishes the race fastest. SE
Cardiac arrhythmias, Myocardial infarction, Stroke
ROPIVACAINE = longest half-life (4.2 hrs) • Topical use only
At the end of the long ROPe.
• Causes mood elevation (dopamine receptor action)
MOA OF LOCAL ANESTHETICS Notes • Has Intrinsic sympathomimetic activity. Causes
vasoconstriction. So, it does NOT need an alpha agonist
(like epinephrine) to limit its systemic absorption
Tetracaine
Local anesthesia, Spinal anesthesia, Epidural
Uses
anesthesia, Topical ophthalmic anesthesia
Notes Long acting
There are 2 na for topical use only: ______________ and ___________
Dr. Rodriguez
Figure 26-1. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
• block voltage-gated Na+ channels, reducing influx of Na+,
Don’t forget the MOA of Ester Local Anesthetics is blockade of sodium channel
thereby preventing depolarization kaya walang action potential na nagaganap sa nerves ninyo. Same as with
• Relationship of local anesthesia with electrolytes the amide local anesthetic below.
o hyperkalemia enhances local anesthetic activity Dr. Rodriguez
o hypercalcemia antagonizes local anesthetic activity AMIDE LOCAL ANESTHETICS

Local Anesthetics as weak bases Anesthetic use L P/M B/L R
• Most are weak bases that undergo dissociation
Local anesthesia
o more lipid-soluble (nonionized, uncharged) form reaches
effective intracellular concentrations more rapidly Dental
§ may hasten onset of block by alkalinizing solution with Epidural
bicarbonate (increasing nonionized form) Intrathecal
o once inside the axon, the ionized (charged) form of the drug is In general, for the side effect of local anesthetics we have: Light-
the more effective blocking entity headedness, Sedation, Restlessness, Nystagmus, Seizures, Respiratory
• CANNOT inject local anesthetics into an abscess during I & D: and cardiovascular depression
o Lidocaine won’t work in an acidic environment, because Dr. Rodriguez
charged form will predominate. This will not be able to cross

the cell membrane and exert its action Lidocaine
Infiltration of Local anesthesia,
LOCAL ANESTHETICS: SYSTEMIC TOXICITY (LAST) Uses Antiarrhythmic (group 1B; used post-MI and for
• Adverse systemic effects following INADVERTENT digitalis toxicity),
INTRAVASCULAR injection or ABSORPTION of LA from site of + Epinephrine: limit systemic absorption
administration Proparacaine: commonly used in ophthalmic
• CNS EFFECTS Notes preparations
o Initial symptom of circumoral and tongue numbness and • Routes: topical, IV, infiltration, spinal, epidural, minor
metallic taste and major peripheral blocks
o light-headedness or sedation, restlessness, nystagmus,
generalized tonic-clonic seizures, respiratory and Prilocaine, Mepivacaine
cardiovascular depression Methemoglobinemia (rare but serious) – Antidote:
SE
• CARDIOVASCULAR EFFECTS Methylene blue
o Most local anesthetics have intrinsic vasodilator quality
EXCEPT cocaine, mepivacaine and ropivacaine Bupivacaine, Levobupivacaine
o use with caution in patients with preexisting cardiovascular Most cardiotoxic
disease because they may develop heart block and • Use with caution in pregnant women and patients with
arrhythmias cardiac disease (may cause heart block, arrhythmia and
Notes
Treatment of LAST hypotension)
• Treatment should be instituted during earliest sign of toxicity • Treat cardiotoxicity with INTRALIPID/LIPOSOMAL
FORMS (fat emulsion used in TPN)
• Ensure oxygenation (supplemental Oxygen) and ventilation
(control airway if necessary)
Ropivacaine
• Treat seizures with benzodiazepines
S(-) enantiomer of bupivacaine (Less cardiotoxic) –
• ANTIDOTE: INTRALIPID (lipid emulsion therapy)
Notes same treatment as above.
LONGEST HALF LIFE
ESTER LOCAL ANESTHETICS
Procaine, Novocaine, Chlorprocaine SECTION SYNTHESIS
Local anesthesia, Extravasation complications from
INHALATIONAL ANESTHETICS:
Uses venipuncture, Inadvertent intraarterial injections. Used
End in -ANE
for very short procedures 1. Known to cause hepatitis
Shortest half-life among local anesthetics 2. Sweet smelling anesthetic
Notes
May also be given with epinephrine 3. Pungent odor
4. Coronary steal phenomenon
5. Highest potency
Answers (1) Halothane (2) Sevoflurane – (S)weet. (3) Enflurane -Eng Beho! • SE (FOR ALL)
(4) Isoflurane (5) Methoxyflurane o Respiratory paralysis (remember your diaphragm is a muscle)
§ +AMINOGLYCOSIDES: potentiates paralysis
INTRAVENOUS ANESTHETICS:
o Apnea
1. Dissociative anesthesia
2. IV anesthetic induction of choice • Reversal agent: NEOSTIGMINE
3. Antidote for barbiturate toxicity
4. Antidote for opioid toxicity Tubocurarine (PROTOTYPE)
Answers (1) Ketamine (2) Propofol (3) Flumazenil (4) Naloxone Uses Poison arrow (curare) – animal hunting
Ganglion block (hypotension),
LOCAL ANESTHETICS
SE Histamine release (moderate) with hypotension – also
1. Remember that all local anesthetics are vasodilators except for?
2. Most cardiotoxic of all the local anesthetics
MIVACURIUM,
3. Associated with methemoglobinemia
4. Can you remember the drug class of lidocaine as an Mivacurium
antiarrhythmic? SE Histamine release (moderate)
Answers (1)Cocaine (2) Bupivacaine (3) Prilocaine/Benzocaine (4) IB • Metabolized by pseudocholinesterase (just like
Dr. Rodriguez
Notes succinylcholine)
• Short DOA (10-20mins)
SKELETAL MUSCLE RELAXANTS
ATRACURIUM, CISATRACURIUM
Histamine release (Cisatracurium < Atracurium),
SE
Bronchospasms
Both undergo HOFFMAN ELIMINATION rapid
spontaneous breakdown) yielding LAUDANOSINE (seizure
Notes
causing).
Ideal for HEPATIC PATIENTS
Vecuronium
Elimination: BILE
Notes
Reverse effects with: SUGAMMADEX
Rocuronium
SKELETAL MUSCLE RELAXANTS
SE Hypersensitivity
• neuromuscular blocking drugs are used to produce muscle
• SUGAMMADEX is a novel reversal agent (chemical
paralysis to facilitate surgery or assisted ventilation antagonist) specifically for rocuronium (but can also reverse
• spasmolytic drugs are used to reduce abnormally elevated tone Notes vecuronium and Pancuronium to a lesser extent)
caused by neurologic or muscle end plate disease • For renal impairment
• Rapid onset (60-120sec)
NEUROMUSCULAR BLOCKERS
TYPES OF NEUROMUSCULAR BLOCKADE Pancuronium
• DEPOLARIZING BLOCKADE Tachycardia (has atropine like effects), Hypertension,
SE
o neuromuscular paralysis that results from persistent Recurarization
depolarization of the end plate (e.g. by succinylcholine) If you watched Moana you’ll see poison arrows being used. Probably they
• NONDEPOLARIZING OR STABILIZING BLOCKADE used curare which contains the prototype NMB which is :
________________________. Isoquinolone and Amino steroid can easily be
o Competitive antagonists at the acetylcholine receptor of the
distinguished from one another by their suffixes. Isoquinoline ends in:
end plate (e.g. by tubocurarine) _______________. Amino-steroids in :_____________________ (check above).
o Increasing doses of Ach can reverse the effect of Among all the NMBs only one has a reversal agent, what is this drug and
nondepolarizing neuromuscular blocker (i.e. use of what is the reversal agent? ______________________.
neostigmine or an indirect acting cholinomimetic) Dr. Rodriguez
SUPPLEMENT: APPLICATIONS – Lethal Injection DEPOLARIZING NEUROMUSCULAR BLOCKERS

What are the drugs used in lethal injection? Succinylcholine
• Thiopental (5 g) Short acting
• Pancuronium (100 mg) Duration
Duration: 6-11 minutes, onset: 60-90 seconds
• Potassium chloride (100 mEq)
Agonist at ACh-N receptors causing initial twitch then
persistent depolarization. Initial depolarization causes
NON-DEPOLARIZING BLOCKERS MOA transient contractions, followed by prolonged flaccid
GENERALIZATIONS paralysis. Depolarization is then followed by
• MOA: repolarization that is also accompanied by paralysis
o Competitive antagonists at skeletal muscle nicotinic Relaxant during intubation and general anesthesia,
Uses
acetylcholine receptors. NMB of choice for rapid sequence induction
o Pancuronium: additional moderate block on cardiac Malignant hyperthermia ((MH) – When given
muscarinic receptors. together with Halothane)), Post-operative muscle pain,
• USES: SE Hyperkalemia (0.5 mEq/L increase), Increased
o Relaxant during intubation and GA intragastric pressure leading to regurgitation
(aspiration), Increased intraocular pressure, Arrhythmia
o Atracurium: also used for Relaxation of respiratory muscles
Metabolized by pseudocholinesterase (just like
to facilitate mechanical ventilation in the ICU setting Notes
mivacurium); Treatment for MH: Dantrolene
o Pancuronium: also used for Euthanasia, Lethal injection,
Strychnine poisoning In the earlier parts of this handout we already mentioned how
succinylcholine causes paralysis by continuously stimulating the Nicotinic
o Cisatracurium, vecuronium, rocuronium: DOC for receptors. Must know for this drug is it’s side effect. Can you recall what
hemodynamically compromised (less changes of histamine this is? _____________. How do you treat this? ___________________
release causing hypotension) Dr. Rodriguez
• Duration of action:
Short acting 15-21 mins Mivacurium PHASES OF DEPOLARIZING BLOCKADE
45 mins Atracurium, Cisatracurium • PHASE I (DEPOLARIZATION)
Intermediate acting 25-40 mins Vecuronium o membrane depolarizes w/ initial electric discharge
36-73 mins Rocuronium o transient fasciculations followed by flaccid paralysis
Pancuronium
• PHASE II (DESENSITIZATION)
85-100 mins
Long acting o membrane repolarizes but receptor is desensitized to the
80 mins Tubocurarine
effects of acetylcholine
CENTRALLY ACTING SPASMOLYTICS o Restore balance between cholinergic and dopaminergic

neural circuitry, hence the value of your antimuscarinic
Baclofen
agents (4) curbing cholinergic excess
MOA GABAB agonist. Facilitates spinal inhibition of motor neurons
The first three will address bradykinesia and number 4 will address
Severe spasticity due to cerebral palsy,
Uses dystonia and resting tremors.
multiple sclerosis, stroke Dr. Pereyra-Borlongan
Sedation. Weakness. Dizziness. Confusion. Nausea,
SE
Headache DRUG-INDUCED PARKINSONISM
• occurrence of reversible Parkinsonian symptoms in patients
Diazepam taking the following drugs:
MOA Facilitates GABAergic transmission in CNS o Typical antipsychotic drugs (MOA: Dopamine antagonist)
Chronic spasm due to cerebral palsy, stroke, spinal cord o RESERPINE (MOA: depletes catecholamine stores)
Uses
injury, acute spasm due to muscle injury o MPTP (methylphenyltetrahydropyridine) (MOA: protoxin
Anterograde amnesia, Decreased psychomotor skills, damaging dopaminergic neurons)
SE Unwanted daytime sedation, Respiratory depression,
Tolerance, Dependence liability
Pramipexole, Bromocriptine,
ropinirole + pergolide
Tizanidine Dopamine +
MOA a2 agonist in the spinal cord receptors
Spasms due to multiple sclerosis, stroke, amyotrophic Salegiline,
Uses
lateral sclerosis rasagiline Tolcapone
SE Weakness, Sedation, Hypotension +
- -
Orphenadrine, Chlorphenesin, Methocarbamol, Cyclobenzaprine
MAO-B COMT
MOA Poorly understood inhibition of muscle stretch reflex DOPAC Dopamine 3-MT
Uses Acute spasm due to muscle injury. Inflammation
SE Strong antimuscarinic effects DOPA decarboxylase
DIRECT ACTING MUSCLE RELAXANT L-DOPA
Dantrolene Brain L-amino acid transporter

Ca Channel blocker - Block RyR1 Ca2+-release Blood Brain Barrier
MOA channels in the sarcoplasmic reticulum of the skeletal
muscle Periphery
Malignant Hyperthermia, Spasm due to cerebral 3-OMD L-DOPA Dopamine
Uses
palsy, spinal cord injury & multiple sclerosis COMT DOPA
decarboxylase
SE Muscle weakness
- -
Eperisone
Entecapone,
Antispasmodic drug which relaxes both skeletal tolcapone Carbidopa Adverse
and vascular smooth muscles and reduces effects
Uses
myotonia, improves circulation and suppresses pain
reflex. Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
DOPAMINERGIC
DRUGS USED IN PARKINSONISM THERAPY
OF PARKINSON’S
DISEASE
https://qrs.ly/w4dvebm
LEVODOPA TREATMENT: PROBLEMS ENCOUNTERED

Fate of Orally administered Levodopa and the effect of Carbidopa
PARKINSON’S DISEASE
• also known as paralysis agitans: neurodegenerative disease
caused by degeneration of dopaminergic neurons in the
substantia nigra
o Dopaminergic neurons: responsible for inhibiting excitatory
cholinergic output from the striatum.
• classic triad of bradykinesia, resting tremors and dystonia
o progressive neurologic disease characterized by shuffling gait,
stooped posture, resting tremor, speech impediments,
movement difficulties and an eventual slowing of mental
processes and dementia
PARKINSON DISEASE: It’s a TRAP! Tremor, Rigidity, Akinesia, Postural
Instability!
• The pathological hallmark of PD is the loss of the pigmented,

dopaminergic neurons of the substantia nigra pars
compacta, with the appearance of intracellular inclusions
known as Lewy bodies.
o The principal component of the Lewy bodies is aggregated α-
synuclein
• Treatment strategies:
o Restore dopaminergic activity in the basal ganglia via:
§ (1) dopamine precursors (increase level of levodopa)
§ (2) dopamine agonists Figure 28-4. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
§ (3) drugs that inhibit its metabolism

• Diminishing effect on chronic therapy: As treatment with NON-ERGOT
levodopa is continued, patients eventually become less Pramipexole, Ropinirole
responsive to L-dopa Partial agonist at dopamine D2 (pramipexole) &
o Begins to diminish after 3-4 years of therapy MOA
D3 receptors (ropinirole) in brain.
o due to progressive destruction of nigrostriatal neurons that Addresses affective symptoms of PD,
occurs with disease progression Restless legs syndrome,
Uses
• ON-OFF PHENOMENA (unrelated to timing of doses) On-Off phenomenon
o alternating periods of improved mobility and akinesia, Compulsive gambling, hypersexuality, overeating
occurring over a few hours to days during treatment Anorexia, nausea, constipation, postural hypotension,
SE
• WEARING-OFF PHENOMENA (related to timing of doses) dyskinesia, mental disturbance
o deterioration of drug effect in between medication doses (off Impulse control problems attributed to the activation of D2/D3 receptors
periods are characterized with marked akinesia which in the mesolimbic pathways of the brain. Mawawala sila pag na-stop yung
pag take ng gamot.
alternate with few hours of on periods characterized by Dr. Rodriguez
improved mobility) OPIOIDS
MNEMONIC Livedo Reticularis Apomorphine
What drugs can cause livedo reticularis? A man reads FHM and GQ! Agonist at dopamine D2 receptors.
MOA
Amantadine Gemcitabine Antagonist at 5-HT and alpha adrenoceptors.
Hydroxyurea Quinidine Rescue treatment for off-periods of Parkinson’s disease
Minocycline (temporary relief),
Uses
SUPPLEMENT: DRUGS FOR HUNTINGTON’S DISEASE Alcoholism, Opiate addiction, Erectile dysfunction,
Deplete amine transmitters especially Alzheimer’s disease
Dopamine from nerve endings by Profound Hypotension, Loss of consciousness,
reversibly inhibiting human vesicular QT prolongation, Severe nausea (tx:
TETRABENAZINE, monoamine transporter type 2 (VMAT2) SE
TRIMETHOBENZAMIDE), Dyskinesias, Drowsiness,
RESERPINE resulting in decreased uptake of Sweating
monoamines; reduces chorea severity; Last mo itong gagamitin kapag di gumana mga dopamine agonists and
SE: hypotension, sedation, depression, mga COMT inhibitors
diarrhea Dr. Rodriguez
SUPPLEMENT: DRUGS FOR TOURETTE’S SYNDROME

DEGRADATION INHIBITORS
Block central D2 receptors, reduce vocal and
motor tic frequency & severity ; SE: MAO-B INHIBITORS
HALOPERIDOL, parkinsonism and other dyskinesias, Selegiline, Rasagiline
PIMOZIDE sedation, blurred vision, dry mouth, GI Selective inhibitors of monoamine oxidase type B →
disturbance, Pimozide may cause MOA decreased degradation of dopamine. Increases response
arrhythmia to levodopa/carbidopa.
Adjunct for waning effect treatment to levodopa for
DRUGS USED IN PARKINSONISM Uses Parkinson’s disease, wearing off or on-and-off
In Parkinson’s dahil kulang sila sa Dopamine, think of giving drugs that can phenomenon
(1) act like dopamine or agonist of dopamine receptors or (2) inhibit niyo Serotonin syndrome (with meperidine, SSRI and TCAs)
yung pagkasira ng Dopamine (remember that it is destroyed by MAO and SE Insomnia, Mood changes, Dyskinesias, Gastrointestinal
COMT). With this in mind let’s talk about those that act like dopamine. We distress, Hypotension
have a drug which acts as a precursor of dopamine known as
___________________. For it to reach the brain it must be given together with COMT INHIBITORS
_________________ , in order to inhibit the peripheral metabolism of levodopa.
Tolcapone, Entacapone
Others have an agonistic effect on dopamine receptors and are divided into (a)
ergot (b) non-ergot and (c) opioid. Note that some are partial agonist to D2, Block L-dopa metabolism by inhibiting catechol-O-
these are _____________ and ____________. While the opioid agonist known as MOA methyltransferase in periphery (both) and CNS
_________________ has agonist effect to D2. (tolcapone only)
For the others, they act by inhibiting the destruction of dopamine. Those that Wearing off phenomena for Parkinson’s
Uses
end in -GILINE- are known as ___________________. While those that end in - Adjunct to Levodopa
CAPONE- are known as ________________. Please don’t forget also an anti-viral Orange urine
drug used for parkinsonism: ____________________. And is related with a known SE Hepatotoxicity (Tolcapone)
side-effect known as ______________. SEs Related to increased levels of L-DOPA
FILL THIS OUT AS YOU GO ALONG. ANTIVIRAL FOR PARKINSONISM

Dr. Rodriguez
Amantadine
DOPAMINE PRECURSOR Potentiate dopaminergic function by influencing the
Levodopa-carbidopa MOA synthesis, release, or reuptake of dopamine. Antagonizes the
Levodopa: Dopamine precursor effects of adenosine at adenosine A2A receptors
MOA Carbidopa: inhibits peripheral metabolism via dopa Uses Can be used for Parkinsons; Influenza
decarboxylase. Livedo reticularis, behavioral changes, GI disturbances,
Uses DOC for Parkinson’s SE urinary retention, postural hypotension, peripheral
GI upsets, dyskinesias, behavioral effects edema
SE On-off phenomena, Wearing off phenomena. May improve bradykinesia, rigidity and tremor
Notes
Arrhythmia Has anti-muscarinic action
GI disturbance is due to the peripheral dopamine effects on the GI system.
Bawal din with psychosis due to the SE (tx: Atypical Antipsychotics – kasi ANTICHOLINERGICS FOR PARKINSONISM
sa D2 affinity nila). Increased dopamine peripherally = arrhythmia. Benztropine, Biperiden, Trihexyphenidyl, Procyclidine
Dr. Rodriguez
Block muscarinic receptors = dec. excitation in
MOA
DOPAMINE AGONISTS cholinergic neurons in striatum
Adjunct for Parkinson’s. For EPS caused by
ERGOT ALKALOIDS Uses
antipsychotics
Bromocriptine, Pergolide, Cabergoline, Piribedil Typical atropine-like side effects, psychological
Partial agonist at dopamine D2 receptors in brain, SE
MOA disturbance
D2 agonism leads to inhibition of prolactin release Improve tremor and rigidity, with little effect on
Uses Levodopa intolerance, Hyperprolactinemia Notes bradykinesia. Exacerbate tardive dyskinesias that result
Erythromelalgia, pulmonary infiltrate from prolonged use of antipsychotic drugs
SE (Bromocriptine), Anorexia, nausea, constipation, Notice that by increasing the dopamine levels you’ll see na medyo related
postural hypotension, dyskinesia, mental disturbance lahat ng adverse events: dyskinesias, GI distress, psychological
Piribedil also has alpha 2 antagonistic action. Additional use for disturbances, sleep disturbance. So if hirap to remember, this can serve as
intermittent claudication. a guide.
OTHER DRUGS FOR PARKINSON’S DISEASE • High potency typical antipsychotics (i.e.
DISORDER TIMING CHARACTERISTIC Tx Haloperidol, droperidol): higher chances
Retrocollis, of causing extrapyramidal symptoms
4hrs- Diphen- (EPS)
Acute Dystonia opisthotonos,
4days hydramine • Low potency typical antipsychotics (i.e.
oculogyric crisis
Tremor, rigidity, Thioridazine, Chlorpromazine): lower
4days- chances of causing EPS, more likely to
Parkinsonism akinesia, postural Benztropine
4mos cause sedation and postural
instability
Rabbit 4mos- hypotension (due to alpha receptor
Perioral tremor Benztropine blockade)
Syndrome 4yrs
Tardive • HETEROCYCLICS (clozapine, loxapine,
Dyskinesia olanzapine, risperidone, quetiapine,
*Supersensitivity Repetitive ziprasidone, aripiprazole)
of the involuntary ATYPICAL
Atypical antipsychotics address both
postjunctional DA 4mo- movement ANTIPSYCHOTICS
positive and negative effects of
None
receptors in the 4yr (tongue schizophrenia
CNS leading to protrusion, lip MOA: Block 5HT2A
receptors > D2 • Atypicals have a lesser propensity to
relative decrease smacking/pursing)
receptors cause EPS compared to its typical
in cholinergic
counterparts, but has a higher propensity
activity
in causing metabolic derangements
Decrease (weight gain, endocrine problems)
Restlessness,
Any Dose,
Akathisia pacing, sitting up
time Diphen-
and down TYPICAL ANTIPSYCHOTICS
hydramine
Neuroleptic Mechanism of action: Block of D2 receptors >> 5-HT2 receptors. This is
Withdraw
Malignant Fever, the main difference compared to the atypical antipsychotics. Check niyo
drug,
Syndrome Encephalopathy, below yung difference.
Any dantrolene, Dr. Rodriguez
extreme Vitals unstable,
time diazepam,
sensitivity to EPS Elevated CPK,
dopamine PHENOTHIAZINES
effects of Rigidity
agonists Chlorpromazine, Levomepromazine, Prochlorperazine,
antipsychotics
Promethazine, Thiothexene (Thioxanthene), Flupentixol
(Thioxanthene)
ANTIPSYCHOTIC AGENTS AND LITHIUM Schizophrenia and other psychotic disorders
Uses Manic phase of BPD
Promethazine & prochlorperazine only Antiemetic
• Postural hypotension (a)
• Marked sedation (H1)
• Extrapyramidal dysfunction (D2)
• Tardive dyskinesia (D2)
• Hyperprolactinemia (D2 in tuberoinfundibular
SE
pathway)
• Failure of ejaculation (a)
Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2018 • Corneal and lens deposits (Chlorpromazine)
• Neuroleptic malignant syndrome
Schizophrenia: Dopamine Hypothesis
• Contact dermatitis, (a)
• Schizophrenia is caused by a relative excess of dopamine in
Remember: Histamine antagonism accounts for relief
specific neuronal tracts in the brain
of pruritus and sedating effect
• Hypothesis not fully satisfactory because antipsychotic drugs
• Chlorpromazine: Prototype of all antipsychotics
are only partly effective in most patients Notes
Levomepromazine blocks a variety of receptors including
• Schizophrenia: involves excess activity of the dopaminergic adrenergic dopamine, histamine, muscarinic and serotonin
neuron in the mesolimbic-mesocortical pathway, causing Hard receptors
symptoms/ Positive (HIDES): Hallucination, Illusion, Delusion,
Excitement and Suspiciousness. PIPERIDINE
• For negative signs, think of social depression (anhedonia,
Thioridazine, Fluphenazine, Perphenazine, Trifluoperazine
avolition, anergia)
Uses Schizophrenia and other psychotic disorders
Dopamine Receptors • Extrapyramidal dysfunction (D2)
• five different dopamine receptors (D1–D5) grouped into 2 • Tardive dyskinesia (D2)
separate families: • Hyperprolactinemia (D2 in tuberoinfundibular
o D1 receptor family: D1, D4, D5 pathway), Anticholinergic effects,
o D2 receptor family: D2 and D3 • Failure of ejaculation (a)
• D2 receptors are found presynaptically and postsynaptically in • Postural hypotension (a)
the caudate putamen, nucleus accumbens, cerebral cortex and SE • Retinal deposits (Thioridazine)
hypothalamus • Cardiotoxicity (QT prolongation – arrhythmias -
o many antipsychotic drugs block brain dopamine receptors Thioridazine)
o dopamine agonist drugs (e.g. amphetamine, levodopa) • Decreased seizure threshold
exacerbate schizophrenia Thioridazine has the most muscarinic blockade
therefore has the least EPS amongst the typical
CLASSIFICATION OF ANTIPSYCHOTICS antipsychotics
• Different classes: PHENOTHIAZINES • Thioridazine: QT Prolongation
(chlorpromazine, thioridazine, fluphenazine), • Fluphenazine and Trifluoperazine: significant
TYPICAL THIOXANTHENES (thiothixene) and Notes Parkinson-like effect
(CLASSICAL) BUTYROPHENONES (haloperidol) • Fluphenazine has less sedation compared to other anti-
ANTIPSYCHOTICS psychotics
Block more D2
receptors > 5HT2A Addresses positive symptoms
(Hallucinations) of schizophrenia
receptors
but not much effect on negative symptoms
(emotional blunting, social withdrawal, lack
of motivation)
BUTYROPHENONE Aripiprazole
Haloperidol, Droperidol MOA Partial agonist at D2 receptor
Additional use: Huntington and Tourette’s syndrome Uses MDD, Autism, Cocaine dependence
Uses
Aside from Schizo or other pscyh disorders SE Gastrointestinal upset, Tremor, Hypersensitivity (rare)
• Extrapyramidal dysfunction (major, D2) Least sedating atypical antipsychotic
• Tardive dyskinesia (D2) Notes No atropine-like effects
• Hyperprolactinemia (D2 in tuberoinfundibular pathway) D2 = 5HT2A > D4 > a1 = H1 >> D1
SE • Neuroleptic Malignant syndrome
Haloperidol (Haldol) is a major tranquilizer given IM. It
NEWER ANTIPSYCHOTICS:
has the highest potential for EPS and neuroleptic
malignant syndrome. Dibenzo-oxepino pyrrole class. Atypical
antipsychotic for treatment of schizophrenia and
• Specific Receptor antagonism binding profile:
acute mania associated with bipolar disorder. It
D2 > a1 > D4 > 5HT2A > D1 > H1
is also for severe post-traumatic stress disorder
Notes • Weakest autonomic effects Asenapine nightmares in soldiers as an off-label use.
• Least sedating among typical antipsychotics Asenapine is a serotonin, dopamine,
Some a-blockade but minimal M receptor blockade noradrenaline, and histamine antagonist in
which asenapine possess more potent activity
ATYPICAL ANTIPSYCHOTICS with serotonin receptors than dopamine
Mechanism of action: Block of 5-HT2 receptors >> D2 receptors. Piperazine derivative. A partial agonist at central
Take note of the additional MOA of aripiprazole indicated below. The rest dopamine D2, dopamine D3, and serotonin 5-
Cariprazine
same sila lahat. HT1A receptors and as an antagonist at serotonin
Lahat ng mga susunod na drugs USE nila ay for: SCHIZOPHRENIA and Other 5-HT2A receptors
Psychotic Disorders AND BIPOLAR DISORDERS. Take note of Clozapine in A dopamine D2 and 5-HT2A receptor antagonist
Iloperidone
the list, please don’t forget this. The rest of the other important uses are and acts as a neuroleptic agent.
indicated below. Used to treat schizophrenia and depressive
Dr. Rodriguez
episodes associated with bipolar I disorder. It is
Clozapine an atypical antipsychotic that is a D2 and 5-HT2A
Uses DOC for refractory and suicidal schizophrenia (mixed serotonin and dopamine activity) to
AGRANULOCYTOSIS, Myocarditis, , Seizures, Ileus, Lurasidone improve cognition. It is thought that antagonism
SE
Hypersalivation (sialorrhea) of serotonin receptors can improve negative
PROTOTYPE ATYPICAL symptoms of psychoses and reduce the
Relapse after d/c is rapid and severe extrapyramidal side effects that are often
HIGHEST WEIGHT GAIN: Clozapine and Olanzapine associated with typical antipsychotics.
Notes
• Specific Receptor antagonism binding profile
(compare with others below) Side effects C O Q R/P Z A
D4 = a1 > 5HT2A > D2 = D1 EPS
Clozapine is not associated with EPS because it blocks the D2C receptor Hyperprolactinemia M
(mesocortical mesolimbic area) not the D2A (nigrostriatal pathway). Postural hypotension
However, it is cumbersome to use this because of the potential life- L L
threatening agranulocytosis which requires the patient to have weekly Weight gain
CBC. Cognizant of this, other atypical antipsychotics were born. Hyperlipidemia
Agranulocytosis !!!
Olanzapine
Remember LESS EPS for atypical antipsychotics. M=Marked. L=Less. !!!=
Uses Anorexia nervosa, Depression
must know!!!
SE Weight gain Dr. Rodriguez
Olanzapine, Quetiapine and Aripiprazole cause

MINIMAL or NO increases in prolactin and has a reduced
Notes SUMMARY OF ANTIPSYCHOTICS
risk of EPS (reflected by minimal D2 antagonism)
https://qrs.ly/r7dveda
5HT2A > H1 > D4 > D2 > a1 > D1
Quetiapine
Uses Bipolar (Manic episode), Sleep promotion and maintenance ANTIDEPRESSANTS
Somnolence, fatigue, sleep paralysis, hypnagogic
SE hallucinations,
CATARACTS, PRIAPISM, QT Prolongation
Quetiapine and Clozapine LEAST LIKELY to cause
Notes tardive dyskinesia (among atypicals)
H1 > a1 > M1,3 > D2 > 5HT2A
QUIET-iapine (for sleeping). For the other side-effects: Diba remember Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2018
sleeping ang keywords sa quetiapine, pag sleeping nakapikit mata –
wala ka makita – tulad sa CATARACT wala ka makita. For Priapism AMINE HYPOTHESIS OF MOOD
naman which is painful erection; so to connect, boys have nocturnal
penile tumescence (nocturnal erection) = sleeping =erection. QT is part • Brain amines, particularly NE and serotonin, are neurotransmitters
of the name QTiapine. in pathways that function in the expression of mood
Dr. Rodriguez o functional decrease of activity results in depression
Risperidone, Paliperidone o functional increase of activity results in mood elevation
Depression, Intractable hiccups, Tourette syndrome Other theories explaining depression
Uses Only approved antipsychotic for SCHIZOPHRENIA IN • decrease in BNDF
THE YOUTH • elevated glutamate levels are seen in depressed patients (which
Insomnia (opposite of Quetiapine), Photosensitivity explains role of ketamine, an NMDA antagonist for the treatment
SE
Marked HYPERPROLACTINEMIA (highest propensity) of refractory depression)
Ziprasidone
Uses Bipolar (acute mania) CLASSIFICATION OF ANTIDEPRESSANTS
SE QT Prolongation (Greatest risk) TRICYCLIC ANTIDEPRESSANTS
imipramine, amitriptyline
(TCAs)
No atropine-like effects
SELECTIVE SEROTONIN
• Little or no tendency to cause hyperglycemia, fluoxetine, escitalopram,
REUPTAKE INHIBITORS (SSRIs)
Notes hyperprolactinemia or weight gain paroxetine, sertraline
– first line
• Increased mortality in elderly patients with dementia-
SEROTONIN-NOREPINEPHRINE
related psychosis duloxetine, venlafaxine
REUPTAKE INHIBITORS (SNRIs)
SEROTONIN (5-HT2) RECEPTOR MNEMONIC: Erectile Dysfunction
nefazodone, trazodone
ANTAGONISTS What drugs can cause erectile dysfunction?
HETEROCYCLIC amoxapine, bupropion, ERECTILE DYSFUNCTION
ANTIDEPRESSANTS maprotiline, mirtazapine A SORE PeniS can’t Fuck Hard!
MONOAMINE OXIDASE phenelzine, tranylcypromine, SSRIs Propranolol
INHIBITORS (MAOIs) selegiline Opiates Spironolactone
Risperidone Finasteride
TRICYCLIC ANTIDEPRESSANTS (TCA) OVERDOSE Ethanol, Estrogen Hydrochlorothiazide
• DOSAGE
o toxic dose: 7 mg/kg MNEMONIC: Priapism
o lethal dose: 15 mg/kg What drugs can cause PRIAPISM?
• CLINICAL PRESENTATION Tigas PeniS Qo, AyaW Bumaba!
o agitation, delirium, neuromuscular irritability Trazodone Alprostadil
o convulsions, and coma Papaverine Warfarin
Sildenafil Bupropion
o respiratory depression and circulatory collapse
Quetiapine
o hyperpyrexia
For the use of all the following drugs, kindly take note that they are all used for
o cardiac conduction defects and severe arrhythmias MAJOR DEPRESSION. We won’t be indicating MDD for each para hindi paulit
§ ECG reveals abnormal morphology of QRS complexes, ulit. J Instead, we’ll be placing additional uses that you need to know
prolonged QRS duration, abnormal size and ratio of R and S Dr. Rodriguez
waves in AVR
MNEMONIC: TCA Toxicity TRICYCLIC ANTIDEPRESSANTS (TCA)
What are the 3 Cs of TCA Overdose? Imipramine, Clomipramine, Desipramine,
Coma Convulsions Cardiotoxicity Amitryptyline, Nortryptiline, Doxepin, Protriptyline , Trimipramine
Inhibits neuronal reuptake of serotonin and
Treatment of TCA Overdose MOA
norepinephrine
• SUPPORTIVE MEASURES
MDD not responsive to SSRI (first line) and SNRI,
o fluid resuscitation for hypotension
Uses Chronic pain
o gastric decontamination with activated charcoal Clomipramine: OCD
o control seizures with benzodiazepines Anticholinergic effects, histamine block effect,
• ADMINISTRATION OF BICARBONATE alpha-blocking effect (may interfere with Clonidine).
o QRS duration >100 msec or ventricular arrhythmias Fatigue, Confusion, , Tremors, Paresthesia,
o reverses cardiotoxicity SE
Amytriptyline: significant muscarinic blocking effect
3Cs of overdose: Coma, Cardiotoxicity
SEROTONIN SYNDROME, NMS, (Cardiomyopathies, Arrhythmias), Convulsions
AND MALIGNANT HYPERTHERMIA Imipramine is metabolized to desipramine while amitriptyline
https://qrs.ly/9xd9qmq is metabolized to nortriptyline.
Additive depression of the CNS with other central
Notes depressants
SEROTONIN SYNDROME Lower seizure threshold
• life-threatening syndrome characterized by severe muscle • Drug levels are easily affected by CYP inducers and
rigidity, myoclonus, hyperthermia, cardiovascular instability, inhibitors
and marked CNS stimulatory effects, including seizures Anticholinergic = alice in wonderland symptoms; Histamine block =
• drugs implicated include MAOIs, TCAs, dextromethorphan, sedation and weight gain; Alpha blockade = orthostatic hypotension
Dr. Rodriguez
meperidine, St. John's wort, and MDMA ("ecstasy")
• antiseizure drugs, muscle relaxants, and blockers of 5-HT
receptors (e.g. Cyproheptadine)
SELECTIVE SEROTONIN REUPTAKE INHIBITOR
Fluoxetine, Paroxetine, Citalopram, Escitalopram, Sertraline,
Fluvoxamine, Vilazodone
KEY LEARNING Differentiate Serotonin Syndrome from
Inhibits neuronal reuptake of serotonin by inhibiting
POINT NMS and Malignant Hyperthermia MOA
Serotonin Transporter (SERT)
MALIGNANT NEUROLEPTIC
SEROTONIN DOC for Major Depressive Disorder
HYPER- MALIGNANT
SYNDROME Anxiety disorders, OCD, PMDD, PTSD, Bulimia,
THERMIA SYNDROME Uses
• Within Fluvoxamine: approved only for OCD
Onset • Within minutes • 1-3 days
Dapoxetine: Premature ejaculation
hours
• SSRIs, Sexual dysfunction, Nausea, vomiting and diarrhea
• Volatile MAOIs, Serotonin Syndrome (if co-administered with MAOi.
Precipitating anesthetics TCAs,
drug (halothane), Meperidine,
• Antipsychotics Discontinue for 4 weeks or longer before initiating use
succinylcholine MDMA, St. SE of MAOi if already on SSRIs)
John’s Wort Paroxetine and Sertraline: Discontinuation syndrome
• Massive calcium • Excess • Dopamine Citalopram: QT prolongation and teratogen (cardiac
Mechanism
release from SR serotonin antagonism septal defects)
• Fever
• Fever • Fever Check niyo side effects, to simplify ang side effect ay due to increased levels
• Agitation
• Acidosis • Encephalo- of serotonin sa GI, hence yung GI symptoms, and in the spinal cord
• Tremor
Clinical • Rhabdomyolysis pathy (diminished sexual interest)
• Clonus
features • Trismus • Vitals unstable Dr. Rodriguez
• Hyper-
• Clonus • Elevated CPK
reflexia
• Hypertension • Rigidity
• Diaphoresis SEROTONIN-NOREPINEPHRINE
• Sedation,
First-line
paralysis,
• Diphen-
REUPTAKE INHIBITOR
• Dantrolene intubation
Venlafaxine, Duloxetine, Desvenlafaxine, Milnacipran
treatment hydramine
and
ventilation Inhibits neuronal reuptake of serotonin and
MOA
• Cooling, • Cooling, norepinephrine
cypro- Dantrolene, Uses Chronic pain, fibromyalgia, menopausal symptoms
Other
• Cooling heptadine, bromocriptine,
treatment
chlorpro- amantadine, Venlafaxine: hypertension
mazine diazepam CNS stimulation (insomnia, anxiety and agitation) due to
SUPPLEMENT: Serotonin Syndrome NE effects
SE
What are the features of Serotonin Syndrome? Duloxetine: Hepatotoxicity
FAT CHD Withdrawal syndrome (even if one missed dose)
Fever Clonus Anticholinergic symptoms
Agitation Hyperreflexia Look at TCA again same sila ng MOA, but the difference is yung mga SNRI
Tremor Diaphoresis walang H1, Muscarinic and alpha-adrenergic receptor blockades
Dr. Rodriguez
SEROTONIN ANTAGONIST OPIOID ANALGESICS AND ANTAGONISTS

Trazodone, Nefazodone, Vortioxetine
Block 5-HT2 receptors
MOA Nefazodone also blocks Serotonin reuptake transporters
while Trazodone can also block 5HT2C receptors
Trazodone: Hypnosis
Uses
Anxiety disorders, Sleeping aid
Nefazodone Hepatotoxicity
Trazodone Priapism
SE
Hyperprolactinemia, Sedation, Gastrointestinal
disturbance, Orthostatic hypotension,
TETRACYCLIC ANTIDEPRESSANT OPIOIDS
Amoxapine, Maprotiline • include natural opiates and semisynthetic alkaloids derived
Strong norepinephrine reuptake inhibitor and weak from the opium poppy, pharmacologically similar synthetic
MOA serotonin reuptake inhibitor. Blocks dopamine D2 surrogates, and endogenous peptides
receptors. Resembles TCA in terms of effects • MOA: has G protein coupled actions on neurons doing the ff:
Uses Major depression 1. Close voltage gated Ca2+ channels on presynaptic nerve
Dopamine blockade: Parkinsonism, amenorrhea, terminals and reduce transmitter release
SE galactorrhea 2. Open K+ channels and hyperpolarize and thus inhibit
Seizures, Cardiotoxicity, Autonomic effects, Akathisia postsynaptic neurons
• Lowers seizure threshold
Notes • Has significant muscarinic receptor blocking effect CLASSIFICATION OF OPIOIDS
• Lowers seizure threshold (Amoxapine) • SPECTRUM OF CLINICAL USES
o analgesics, antitussives, antidiarrheal
Mirtazapine • STRENGTH OF ANALGESIA
Increases amine release from nerve endings by o strong, moderate, weak agonists
MOA antagonism of presynaptic a2 adrenoceptors; Blocks o partial agonists exert less analgesia than full agonists
serotonin 5HT2 receptors. • RATIO OF AGONIST TO ANTAGONIST EFFECTS
Uses Sedation/Sleeping aid o agonists (receptor activators [full or partial])
Weight gain, Marked sedation, Dizziness, Blurred vision, o antagonists (receptor blockers)
SE
Nightmares o mixed agonist-antagonists
• Has significant muscarinic receptor and alpha-2
Notes
blocking effect OPIOID SIDE EFFECTS
• Opioid side effects with minimal or no tolerance (an effect
BUPROPION that does not diminish despite continued use)
Bupropion o Miosis
Inhibits neuronal reuptake of dopamine and o Constipation
MOA o Convulsions
norepinephrine.
Uses Smoking cessation • Side effects of Opioids not mediated by opioid receptors
Weight loss, Agitation, Dizziness, Dry mouth, o Nausea and vomiting – stimulation of CTZ at 4th ventricle
SE o Hypotension – histamine release
Aggravation of psychosis, Seizures, Priapism
Similar to Amphetamine: stimulant feature o Pruritus – histamine release
Mirtazapine, Bupropion and Nefazodone, are among MNEMONIC for Morphine side effect: MORPHINE = Miosis, Out of it,
Notes
the few antidepressants that are not associated with Respiratory depression, Pruritus, Hypotension and Headache,
sexual dysfunction as side effect In frequency, Nausea, and Emesis
OPIOID OVERDOSE
MONOAMINE OXIDASE INHIBITOR • Triad of pupillary constriction, comatose state, and
Phenelzine, Trancylpromine, Isocarboxazid, Selegiline respiratory depression
Inhibits MAO-A and B • Diagnosis confirmed if intravenous injection of naloxone results
MOA
Selegiline (MAO-B Selective) in prompt signs of recovery
MDD unresponsive to other drugs • treatment involves the use of antagonists such as naloxone and
Uses
Significant anxiety, Phobic features and hypochondriasis
other therapeutic measures, especially ventilatory support
Dizziness, Insomnia, Orthostatic hypotension, Blurred
Hypoventilation: Opioids will shut the central drive for breathing
SE vision, Arrhythmias, Diarrhea, hyperthermia, CNS
which is high levels of carbon dioxide. Now giving high levels of
stimulation, seizure
Amphetamine like features
oxygen will shut the peripheral control wherein the main
+ SSRI (Serotonin syndrome) stimulus is low level of oxygen. It will impair the remaining drive
• CYP450 inhibitors to breathe unless you will put the patient under mechanical
• Long-term use may lead to down-regulation of Beta ventilation.
receptors (leading to decrease in BP) KEY LEARNING POINTS
Notes • Lower seizure threshold • By half-life: Which opioids have the shortest and longest half-lives?
• Selegiline may be given as skin patch o REMIFENTANIL = shortest half-life (3-4 mins)
• Hypertensive crisis when taken with tyramine (indirect- o BUPRENORPHINE = longest half-life (4-8 hrs)
acting sympatho-
mimetic in cheese) Mu1 Mu2
• Other tyramine rich food: avocado, Cheese, wine Analgesia (Spinal),
Analgesia (supraspinal
depression of
TCAs end in TRIPTYLINE and PRAMINE + Doxepin. SE can be summarized by and spinal), Euphoria,
ventilation,
HAM blockade. SSRIs should first come to mind for the treatment of Major Low abuse potential,
Effect Physical
depressive disorders. And since these drugs increase the levels of serotonin Miosis, Bradycardia,
dependence,
they can cause Serotonin syndrome. The treatment for this is (1) hypothermia, Urinary
___________________. For SNRI, please take not that they have no HAM blockade Constipation
retention
effect. Compare that with TCA earlier. For Serotonin receptor antagonist, do (marked)
not forget, Trazodone which causes (2) _________________. This is due to the Agonists Endorphins, Morphine, Synthetic opioids
blockade of 5HT2A/2C receptors which causes vasodilation. Antagonists Naloxone, naltrexone
Answers (1) Cyproheptadine (2) Priapism
Dr. Rodriguez
Kappa Delta PARTIAL AGONISTS
Analgesia Hydrocodone, Oxycodone, Dihydrocodeine
Analgesia (supraspinal
(supraspinal and
and spinal), dysphoria, Strong agonist (µ and k)
spinal), depression MOA Binds NMDA receptors;
Effect sedation, addiction and
of ventilation, Antagonizes the effects of glutamate
dependence, Miosis,
physical Moderate to severe pain, Cancer pain, Neuropathic pain
Constipation Uses
dependence, (postherpetic neuralgia, DM neuropathy),
Agonists Dynorphins Enkephalins SE Same as under Morphine + Hypogonadism, Hearing loss
Antagonists Naloxone, naltrexone
Dextromethorphan, Codeine
FULL AGONISTS Decreases sensitivity of cough receptors.
MOA Depressing the medullary cough center through sigma
Note the side effects of morphine listed above. Kapag nag-tanong ng tungkol
receptor stimulation
sa mga side effects ng opioids, yun agad yung unang papasok dapat sa isip
niyo. Then as you go thru the SE below, we will list some additional ones that Uses Cough suppression
you should remember. Increased or decreased pupil size
Dr. Rodriguez SE Hallucinations, Confusion, Excitation, Nystagmus, Seizures,
PHENANTHRENES Coma
MORPHINE (opioid prototype), CYP2D6: Codeine metabolized to Morphine
Notes
Hydromorphone, Oxymorphone, + SSRI/MAOi = Serotonin syndrome
HEROIN (Synthetic derivatives of Morphine)
Strong agonist at µ receptors WEAK AGONISTS
MOA Propoxyphene, Levopropoxyphene, Dextropropoxyphene
Variable activity at d and k receptors.
Severe pain (MI, Cancer, Pulmonary edema) Weak agonist at µ receptors.
Uses MOA
Adjunct to anesthesia Inhibits pain neurotransmission
Miosis, Restlessness, Respiratory depression, Increased Mild to moderate pain, Restless legs syndrome,
Uses
SE ICP, Postural hypotension, Constipation, Urinary Opioid withdrawal
retention, Pruritus, Addiction liability Usual morphine SE, seizures, pulmonary edema, fatal
SE
arrhythmia
Hydromorphone & Oxymorphone: Like morphine in
Propoxyphene: chemically related to methadone but with
efficacy but higher potency.
Notes weaker analgesic activity
Significant first pass
Levopropoxyphene: anti-tussive
Metabolites:
Notes
• Morphine-6-glucoronide: 4-6x analgesic fx of MIXED AGONIST-ANTAGONIST
morphine
Buprenorphine, Nalbuphine, Butorphanol,
• Morphine3-glucoronide: Seizure causing
Pentazocine, Levallorphan
(neuroexcitatory)
Partial µ receptors agonist
MOA Antagonist at k & d receptors.
PHENYLPIPERIDINE Inhibits pain neurotransmission.
Fentanyl, Sufentanil, Alfentanil, Moderate to severe pain, Opioid dependence, Alcohol
Remifentanil, Ohmefentanyl dependence, Balanced anesthesia
Uses
MOA Same as Phenanthrenes Butorphanol: Postoperative shivering
Buprenorphine: Opioid withdrawal states
Uses Same as Phenanthrenes
Less respiratory depression
SE See the list under SE above SE Sedation, Dizziness, Sweating, Nausea, Anxiety, Hallucinations,
• FENTANYL:75-125 x more potent than morphine Nightmares, Tolerance, Dependence liability
• SUFENTANIL: 5-10x more potent than fentanyl • Effects resistant to naloxone reversal
Notes • REMIFENTANIL: same potency as fentanyl • Nalbuphine: strong k agonist and partial µ antagonist; has
Notes
• ALFENTANIL: 1/5th to 1/10th as potent as fentanyl a ceiling effect
• May be given transdermally or via lollipop • Pentazocine: k agonist and weakly µ antagonist
Clue: The drug class is Phenyl. Look at the name of the drugs they have FEN +
NYL/NIL OPIOID ANTAGONIST
Dr. Rodriguez
Naloxone, Naltrexone, Nalmefene, Alvimopan, Methylnaltrexone
Competitively blocks µ, d and k receptors.
PETHIDINE MOA
Rapidly reverses effects of opioid agonists.
MEPERIDINE NALOXONE: DOC for Opioid overdose
Uses
Strong agonist at µ and k receptors. NALTREXONE: Opioid and alcohol dependence
MOA Inhibits pain neurotransmission. SE Pruritus, Nausea, Vomiting
Muscarinic blocking actions. • Precipitates abstinence syndrome in patients with opioid
Moderate to severe pain, Labor analgesia, dependence
Uses
Postoperative Shivering, Preoperative sedation • Naltrexone reduces craving in alcohol, nicotine and opioid
See the list under SE above dependence
SE Notes • Naltrexone & Nalmefene have longer DOA
Seizures, Delirium, Lesser addiction liability
DOES NOT CAUSE MIOSIS, rather it causes MYDRIASIS • Naloxone and Nalmefene is IV (DOA: 12-24 hrs) while
(owing to its atropine like function) Naltrexone is PO (DOA: 48h)
The most pronounced anti-shivering effect (a2 • Alvimopan & Methylnaltrexone: Poor CNS penetrability →
Notes antagonize peripheral effects such as constipation
antagonism)
+ MAOi = Hyperpyrexic Coma
+ SSRI = Serotonin Syndrome
DUAL ACTING
Tramadol, Tapentadol
PHENYLHEPTYLAMINES Weak agonist at µ receptor.
MOA Inhibits neuronal reuptake of serotonin and
Methadone, Levomethadyl Acetate, Levorphanol norepinephrine. Inhibits pain neurotransmission.
Strong agonist at µ receptors. Moderate pain, Chronic pain syndromes, Neuropathic pain,
MOA NMDA antagonist. Uses
Fibromyalgia, Adjuncts to opioid in chronic pain syndromes
Blocks monoamine reuptake transporters. SE Seizures, Nausea, Dizziness, Pruritus, Constipation
Moderate to severe pain (resistant to morphine) • 5-10 x less potent compared to morphine
Uses Opioid dependence (especially for a relapsing chronic • Lowers seizure threshold : Contraindicated in patients
heroin addict), Opioid withdrawal with a history of epilepsy
Same above + Hepatic dysfunction, QT prolongation Notes • Serotonin syndrome when used with SSRIs
SE
(specific to methadone) • SE profile vs other opioids: Low tendency for respiratory
METHADONE MAINTENANCE THERAPY for opioid abuse and low chances for developing tolerance and
Notes dependence dependence
Investigated as novel treatment for leukemia
CONGENERS OF AMPHETAMINE
SUMMARY OF OPIOIDS Dimethoxymethylamphetamine (DOM)
https://qrs.ly/lvdvedm Methylenedioxyamphetamine (MDA)
Methylene dioxymethamphetamine (MDMA/ Ecstasy)
• More selective action on the serotonin transporters in
CNS
DRUGS OF ABUSE Fx • Facilitate interpersonal communication
DRUG ABUSE • Act as sexual enhancers
• use of an illicit drug or the excessive or nonmedical use of a licit • Causes depletion of neurons in serotonergic tracts
drug CM OVERDOSE
• denotes the deliberate use of chemicals that generally are not agitation, hypertension, tachycardia, delusions,
considered drugs by the lay public but may be harmful to the user hallucinations, hyperthermia, seizures, death
• primary motivation is the anticipated feeling of pleasure derived • No specific antidote
from the CNS effects of the drug MGT • control of body temperature
• Protection against cardiac arrhythmias and seizures
DEPENDENCE
• older term is physical OR physiologic dependence
• state characterized by signs and symptoms, frequently the COCAINE
opposite of those caused by a drug, when it is withdrawn from STREET NAMES: “coke”, “super-speed”, “crack”
chronic use or when the dose is abruptly lowered • Inhibition of CNS transporters of dopamine,
norepinephrine, and serotonin
ADDICTION Fx • Marked amphetamine-like effects
• older term is psychological dependence • Short-lasting euphoria, self-confidence and mental
• compulsive drug-using behavior in which the person uses the alertness positively reinforce its continued use
drug for personal satisfaction, often in the face of known risks to OVERDOSE WITHDRAWAL
health hypertension,
vasoconstriction, thrombus
TOLERANCE formation, psychomotor
• decreased response to a drug, necessitating larger doses to agitation, severe apathy, irritability, increased
achieve the same effect CM hyperthermia, dyspnea, sleep time, disorientation,
• etiology of tolerance bowel ischemia, mydriasis, severe depression strongly
crack lung (hemorrhagic reinforces compulsions
o metabolic: increased disposition of the drug
alveolitis),
o behavioral: ability to compensate for the effects of a drug fatalities from arrhythmias,
o functional: changes in receptor or effector systems involved in seizures or respiratory
drug actions depression
ABSTINENCE SYNDROME/ WITHDRAWAL SYNDROME • no specific antidote is • antidepressant drugs may
available be indicated
• signs and symptoms that occur on discontinuation or • supportive care • infants born to mothers who
withdrawal of a drug in a dependent person • cocaine abuse during abuse have possible
SUPPLEMENT: Dopamine Hypothesis of Addiction MGT pregnancy is associated teratogenic abnormalities
• dopamine in the mesolimbic system appears to play a primary role in with increased fetal (cystic cortical lesions),
the expression of "reward" morbidity and mortality increased morbidity and
• excessive dopaminergic stimulation may lead to pathologic mortality and may be cocaine
reinforcement dependent
o behavior may become compulsive and no longer under control—
common features of addiction
• most addictive drugs have actions that include facilitation of the
PHENCYCLIDINE
effects of dopamine in the CNS Phencyclidine (PCP; "angel dust")
Ketamine ("special K")
SUPPLEMENT: OTHER RELATED COMPOUNDS • antagonists at the glutamate NMDA receptor
Chemically related to Amphetamine, A • no actions on dopaminergic neurons in the CNS unlike
METHYLPHENIDATE CNC stimulant used for ADHD. Do not use most drugs of abuse
together with antidepressants Fx
• PCP: most dangerous hallucinogenic agent
ATOMOXETINE A NE reuptake inhibitor; used for ADHD
• Psychotic reactions, impaired judgment leading to
reckless behavior (psychotomimetic effect)
AMPHETAMINES CM OVERDOSE WITHDRAWAL
Methamphetamine (“speed”, “ice”) horizontal and vertical fever, seizures, muscle
Dextroamphetamine nystagmus, marked breakdown,
• Feeling of euphoria and self-confidence that contributes to hypertension, and fatal depression and memory
the rapid development of addiction seizures loss in long-term
• Effects of chronic high-dose abuse • Supportive care (seizures
Fx
• Psychotic state (w/ delusions and paranoia) hypertension)
• Supportive care
development of necrotizing arteritis, → cerebral • Parenteral benzodiazepines
MGT • Benzodiazepines and/
hemorrhage, renal failure (diazepam, lorazepam) are
antipsychotics
CM OVERDOSE WITHDRAWAL used to curb excitation and
agitation, hypertension, apathy, irritability, protect against seizures
tachycardia, delusions, increased sleep time,
hallucinations, hyperthermia, disorientation, HALLUCINOGENS
seizures, death depression Lysergic acid diethylamide (LSD)
• antidepressants Mescaline Psilocybin
• no specific antidote (amineptine, • Psychedelic and mind raveling effects
• control of body temperature mirtazapine) are of • Perceptual and psychological effects accompanied by
MGT Fx
• protection against cardiac limited benefit marked somatic effects (nausea, weakness, paresthesia)
arrhythmias and seizures • acidify urine to • Panic reactions ("bad trips") may also occur
increase elimination
MARIJUANA IRON CHELATORS

Lysergic acid diethylamide (LSD) IRON INTOXICATION
Mescaline Psilocybin Acute Iron Intoxication
Psychoactive constituents in crude extracts of the plant • usually occurs as a result of accidental ingestion of iron
Cannabis sativa (hemp)
supplementation tablets, commonly in children
Active ingredients: tetrahydrocannabinol (THC), cannabidiol • CLINICAL MANIFESTATIONS
(CBD), cannabinol (CBN) o necrotizing gastroenteritis, shock, metabolic acidosis, coma, death
Hashish is a partially purified, more potent form • TREATMENT
Street names: "weed", "pot", "grass", "damo", "dope", "Mary o removal of unabsorbed tablets from the gut
Jane", "hash" o correction of acid-base and electrolyte abnormalities
• Fx • Feeling of being "high," with euphoria, disinhibition, o parenteral administration of DEFEROXAMINE, which chelates
uncontrollable laughter, changes in perception, and circulating iron
achievement of a dream-like state
Chronic Iron Intoxication: Hemochromatosis
• impaired mental concentration
• vasodilation, tachycardia reddened conjunctiva
• state of chronic iron overload that damages the organs that store
• dry mouth excess iron (heart, liver, pancreas)
• impairment of judgment and reflexes • Triad: CIRRHOSIS, DIABETES MELLITUS, SKIN PIGMENTATION
• effects potentiated by concomitant use of sedative- • OCCURRENCE
hypnotics including ethanol o persons with an inherited abnormality of iron absorption
o persons who receive frequent transfusions for treatment of
DRUGS USED TO TREAT hemolytic disorders (e.g. thalassemia major)
• TREATMENT
DISEASES OF THE BLOOD o Phlebotomy
AGENTS USED IN ANEMIAS AND o chronic administration of DEFEROXAMINE or DEFERASIROX
HEMATOPOIETIC GROWTH FACTORS HEAVY METAL CHELATORS
DEFEROXAMINE, DEFERASIROX, DEFERIPRONE
MOA Chelates excess iron
Acute iron poisoning, Hemochromatosis not adequately
Uses treated by phlebotomy
Hypotension, ARDS, Neurotoxicity, Increased susceptibility
SE to infections
Deferoxamine is used for acute intoxication (IV form), while
Notes
Deferasirox and Deferiprone are for chronic (Oral)
Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2018 VITAMINS (FOLATE AND B12)
For this topic, kindly read through the whole section then after, go through the
FOLATE
quizlet we prepared for you. Aside from understanding, active recall and
repetition is the key for pharma. • required for normal DNA synthesis
Dr. Rodriguez Pharmacokinetics
IRON • readily absorbed by the proximal jejunum
IRON • only modest amounts are stored in the body
• essential metallic component of heme • decrease in dietary intake within 1-6 months is followed by
• distribution of iron in the body megaloblastic anemia
o mostly contained in hemoglobin Folic acid deficiency
o bound to Transferrin, a transport protein • deficiency usually presents as megaloblastic anemia
o bound to Ferritin, a storage protein • deficiency of folic acid during pregnancy increases the risk of
o children and pregnant women have increased iron requirements neural tube defects in the fetus
Types of Vitamin deficient Anemias VITAMIN B12
• microcytic hypochromic anemia caused by iron deficiency is the • deficiency of either vitamin B12 or folic acid usually manifests as
most common type of anemia megaloblastic anemia
o Laboratory picture: ↓ Iron, ↓ Ferritin, ↑ TIBC
• vitamin B12 deficiency (NOT folic acid deficiency) causes
• megaloblastic anemias are caused by a deficiency of vitamin B12 neurologic defects
or folic acid o Ataxic gait, impaired position and vibratory sense, spasticity
o pernicious anemia is the most common type
• absorbed in the distal ileum in the presence of intrinsic factor
§ caused by a defect in the synthesis of intrinsic factor or by surgical
• stored in the liver in large amounts (5-year supply)
removal of that part of the stomach that secretes intrinsic factor
• 2 available forms: cyanocobalamin and hydroxocobalamin
HEMATOPOIETIC GROWTH FACTORS (IRON) • linked to folic acid metabolism and synthesis of
oral: FERROUS SULFATE, Ferrous gluconate, deoxythymidylate (dTMP), a precursor required for DNA
Ferrous fumarate, Ferrous carbonate
synthesis
parenteral: IRON DEXTRAN, Iron sucrose,
Sodium ferric gluconate complex
All are Preg Cat A
Required for the biosynthesis of heme and heme-containing
MOA
proteins, including hemoglobin and myoglobin
Iron deficiency anemia, Iron supplementation
Uses The best way to give iron is through oral preparation added
with ascorbic acid for better absorption.
Black stools (may obscure acute GI loss)
Acute overdose: necrotizing gastroenteritis, abdominal
SE pain, bloody diarrhea, shock, lethargy, dyspnea
Chronic iron overload: hemochromatosis, organ failure
(heart, liver, pancreas etc.), death
Iron content of some oral Iron preparations (% w/w)
Fe carbonate / Carbonyl Iron 100%
Fe fumarate 33% Vitamin B12 Deficiency
Fe sulfate, dried 30% • administration of folic acid to patients with vitamin B12
Fe sulfate, hydrated 20% deficiency helps refill the tetrahydrofolate pool and partially or
Ferric ammonium sulfate 18% fully corrects the anemia
Fe gluconate 12%
• exogenous folic acid does not correct the neurologic defects of PLATELET GROWTH FACTORS
vitamin B12 deficiency
THROMBOPOIETIN
• Tetrahydrofolate (THF) functions to transport single carbon
groups, for the synthesis of DNA and other biological molecules • glycoprotein made primarily in the liver that stimulates the
formation of megakaryocytes
• Vitamin B12 is linked to the Folate cycle
o needed for methionine synthase enzyme (involved in
MEGAKARYOCYTE GROWTH FACTOR
remethylation of homocysteine)
OPRELVEKIN (IL-11), Thrombopoietin,
Eltrombopag, Romiplastim
HEMATOPOIETIC GROWTH FACTOR (FOLATE AND VITAMIN B12)
Recombinant form of an endogenous cytokine; activates
VITAMIN B9 VITAMIN B12 MOA
IL-11 receptors.
FOLIC ACID, Folacin
CYANOCOBALAMIN, Secondary prevention of thrombocytopenia in patients
Drugs (Pteroylglutamic acid), Uses
Hydroxocobalamin, undergoing cytotoxic chemotherapy for non-myeloid cancers
Folinic acid (Leucovorin),
Methylcobalamin Fatigue, Headache, Dizziness, Anemia, Fluid
L-methylfolate SE
accumulation in the lungs, Transient atrial arrhythmias
Cofactor required for
Notes given SC OD
essential enzymatic
Precursor of an essential
reactions that form
donor of methyl groups SUPPLEMENT: OTHER DRUGS FOR HEMATOLOGIC DISORDERS
tetrahydrofolate, convert
MOA used for synthesis of amino Small-molecule thrombopoietin (TPO)-
homocysteine to
acids, purines, and receptor agonist that interacts with human
methionine, and
deoxynucleotide. TPO receptor -> initiates signaling cascades that
metabolize
induce proliferation & differentiation of mega-
methylmalonyl-CoA
karyocytes from bone marrow progenitor cells
Megaloblastic anemia,
Vitamin B12 deficiency, ELTROMBOPAG
Prevention of neural tube Use: Indicated for treatment of
Megaloblastic anemia
Uses defects (spina bifida), thrombocytopenia in adults and pediatric
(pernicious anemia,
Prevention of coronary patients ≥6 yr with chronic immune
gastric resection)
artery disease (idiopathic) thrombocytopenia (ITP) with
SE No significant toxicity No significant toxicity insufficient response to corticosteroids,
• Folic acid is not toxic in • Parenteral form is immunoglobulins, or splenectomy
overdose but large required for pernicious
amounts can partially anemia and other DRUGS USED IN COAGULATION DISORDERS
compensate for Vit B12 malabsorption
deficiency syndrome
• May put people with • Hydroxocobalamin has
Notes unrecognized B12 a longer t½ than
deficiency at risk of cyanocobalamin
neurologic consequences • Has a storage of up to
of Vit B12 deficiency 5yrs in the liver
(which are not
compensated by folic
acid)
ERYTHRYOPOIESIS-STIMULATING AGENTS
ERYTHROPOIETIN
• produced in the kidney (reduced EPO synthesis in renal failure)
• main stimulus: Hypoxia-inducible factor 1
• stimulates the differentiation and maturation of erythroid
progenitor cells within the bone marrow
• Erythropoiesis-stimulating agents: routinely used for anemia
associated with renal failure Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
In studying drugs for coagulation, it is very essential that you know the whole
EPOETIN ALFA, Darbepoetin Alfa, mechanism of hemostasis. At this point, get your own blank sheet of paper,
Methoxy Polyethylene Glycol – Epoetin Beta and try to create a schematic diagram of the whole hemostasis. Then as you
All are Preg Cat C go through this section, fill it out with the different drugs.
Agonist of erythropoietin receptors expressed by red cell It’s also important to know the difference between ANTIPLATELETS and
MOA ANTICOAGULANTS. Antiplatelets act on the platelets and the substances it
progenitors
Anemia especially associated with chronic renal secretes. AntiCOAGULANTs act on the COAGulation cascade.
ThromboLYTICS, lyses clots, meaning may clot na, pero siya sisira ng clot.
failure, HIV infection, cancer, and prematurity, for
Uses While yung first two, prevents the formation.
prevention of the need for transfusion in patients
Kung meron ANTIclotting drugs, meron din that facilitate clotting, which you
undergoing certain types of elective surgery. will see later
SE Hypertension, Thrombosis, Pure red cell aplasia Dr. Rodriguez
• Hemoglobin levels should be maintained <12 g/dL

• Performance-enhancing drug in athletes (prohibited
use)
Notes
• Darbepoetin is once a week administration, while
Methoxy Polyethylene Glycol- Epoetin Beta is 1-2x per
month administration
MYELOID GROWTH FACTORS

MYELOID GROWTH FACTORS
FILGRASTIM (G-CSF),
Sargramostim (GM-CSF)
Pegfilgrastim, Plerixafor, Lenograstim
Binds receptors on myeloid progenitors and stimulates
MOA cell maturation and proliferation. Accelerates neutrophil
recovery and reduces incidence of infection.
Neutropenia associated with chemotherapy,
myelodysplasia, and aplastic anemia
Uses
Mobilization of peripheral blood cells in preparation for Figure 37-1. Hall JE. Guyton and Hall Textbook of Medical Physiology. 13th ed. 2016
hematopoietic stem cell transplantation

SE Bone pain (arthralgia), Fever, Edema, Splenic rupture
Mechanisms of hemostasis: GPIIB/IIIA INHIBITOR
1. Vasoconstriction
Abciximab, Eptifibatide, Tirofiban
2. Platelet plug formation
Inhibits platelet aggregation by interfering with GPIIb/IIIa
3. Formation of clot via blood coagulation MOA
binding to fibrinogen and other ligands
4. Fibrous Organization
Used during PCI to prevent thrombosis,
1st step: Vasoconstriction: Uses Adjunct to thrombolysis,
• Local autacoid factors from traumatized tissues and platelets Acute Coronary Syndromes (unstable angina, NSTEMI)
o Thromboxane A2 (TXA2): platelet activator and powerful SE Bleeding, Thrombocytopenia
vasoconstrictor Notes Prevents vessel restenosis, reinfarction and death
o Endothelin: a potent endothelium derived vasoconstrictor GPIIB-IIIa mnemonic: May 2 to 3 pack Abs yung mga taga FIBA (basketball)
• Local myogenic spasm Dr. Rodriguez
• Nervous reflexes
ADP INHIBITOR
2nd step: Platelet plug formation (primary hemostasis) CLOPIDOGREL, TiCLOPidine, PrasuGREL, TicaGRELor [
• Exposed subendothelial collagen is highly thrombogenic Irreversibly inhibits binding of ADP to platelet
• Platelet adhesion MOA
receptors, reducing platelet aggregation
o mediated by vWF (essential for binding subendothelial Prevention and treatment of arterial thrombosis
collagen to platelets) by GpIb receptor in the platelet surface (stroke,TIA, unstable angina), Prevention of restenosis
• Platelet release reaction Uses after PCI, Acute coronary syndromes
o Adenosine diphosphate (ADP): platelet aggregation As part of the ACS regimen, a loading dose of 300mg Clopidogrel can
o Thromboxane A2 (TXA2): platelet activator and powerful reduce platelet activity by 80% within 5hrs of administration.
vasoconstrictor Bleeding, Nausea, Dyspepsia, Hematologic
o Serotonin: platelet aggregation and vasoconstriction SE (neutropenia, leukopenia)
• Platelet aggregation → platelet plug Ticlopidine Thrombotic thrombocytopenic purpura
3rd step: Formation of clot via coagulation • GI & Hematologic SE are more common with ticlopidine
• Additive effects with aspirin
• 2 coagulation pathways
Notes • TICAGRELOR specifically inhibits ADP subtype P2Y. IN
o intrinsic pathway: PTT Factor V, VIII, IX,X,XI, XII, prothrombin,
contrast to another antiplatelet drug, it has a binding site
Fibrinogen
different from ADP, making it an allosteric antagonist
o extrinsic pathway: PT V,VII, X, prothrombin, fibrinogen
ADP Inhibitors: Read ADP as “A Dip” – A dip in the pool with Cupid
• net result of coagulation pathways: prothrombin activator (rate (sounds like Clopid). Just remember CLOPIDoGREL here, the rest either
limiting factor causing blood coagulation) have GREL or CLOPID in their name
Dr. Rodriguez
PDE INHIBITOR
Inhibits phosphodiesterase III and increases cAMP in

MOA platelets and blood vessels. Inhibits platelet aggregation
and causes vasodilation.
Prevention of thromboembolic complications of cardiac
valve replacement, Secondary prevention of ischemic
Uses stroke (with aspirin)
Cilostazol used only in refractory intermittent
claudication in patients with PAD.
SE Headache (because it is a vasodilator), Palpitations
• Dipyridamole, by itself, has little or no benefit
Additional MOA: inhibit uptake of adenosine by endothelial
Notes cells and RBC → increasing adenosine levels → inhibition of
platelet aggregation; Cilostazol is contraindicated in heart
failure
4th step: fibrous Organization PDE inh. Mnemonic: “PeDE MoMOLE tayo sa SILOng, mga 3 times” 3 for PDE III
• Fibrin mesh stabilize your platelet plug Dr. Rodriguez
ANTIPLATELETS ASPIRIN TOXICITY

• Arterial thrombosis is the most common cause of acute • Toxic dose = 150 mg/kg Lethal dose = 500 mg/kg
myocardial infarction (MI), ischemic stroke, and limb gangrene • Clinical presentation: HAGMA, dehydration, hyperthermia,
• Predominance of platelets in arterial thrombi collapse, coma
Appreciate on the subheadings below. These are the different substances o Acid Base Disorder: Respiratory alkalosis with HAGMA
secreted by platelets and the important receptors. The antiplatelet drugs § increased respiratory drive leads to hyperventilation and
will involve these mainly. respiratory alkalosis
Dr. Rodriguez
§ uncoupling of oxidative phosphorylation leads to increased
COX INHIBITOR anaerobic metabolism via lactic acidosis and high-anion gap
ASPIRIN (Acetylsalicylic acid, ASA) metabolic acidosis
Salsalate, Sodium salicylate
• TREATMENT
MOA Nonselective, irreversible COX 1&2 inhibitor. o no specific antidote
Prevention of arterial thrombosis (MI, TIA, CVD), o supportive management
Uses Inflammatory disorders (rheumatic fever, o activated charcoal / gastric lavage
Kawasaki disease, juvenile rheumatoid arthritis)
o alkalinize the urine with bicarbonate
Gastrointestinal toxicity, Tinnitus, Hypersensitivity,
SE Hyperventilation, HAGMA, Increased bleeding time,
Nephrotoxicity (AKI and Interstitial Nephritis) ANTICOAGULANTS
• Associated with Reye syndrome in children • Mainly for the prevention and treatment of venous thrombosis
Notes • Do not use as NSAID for gout (pulmonary embolism, deep vein thrombosis)
• SAMTER TRIAD: Asthma, ASA Sensitivity, Nasal Polyps • Drugs which inhibit the formation of fibrin clots
In the COX/LOX pathway, pag nainhibit si COX walang PG and • 2 major types of anticoagulants:
Thromboxane formation. Pag walang thromboxane A2 (a potent o Indirect thrombin inhibitors: heparin, enoxaparin (LMWH),
stimulator of platelet aggregation, edi walang aggregation na
coumarin derivatives (warfarin),
magaganap
Dr. Rodriguez o Direct thrombin inhibitors: Lepirudin
COMPARISON OF HEPARIN AND WARFARIN • Bivalirudin also inhibits platelet activation
PROPERTY HEPARINS WARFARIN *IDARUCIZUMAB is a monoclonal antibody used for
Large acidic reversal of Dabigatran toxicity (needs dose adjustment
Structure Small lipid-soluble molecule for renally impaired patients)
polysaccharide
Route Parenteral Oral
Site of Action Blood Liver INDIRECT THROMBIN INHIBITORS
Onset Rapid (minutes) Slow (days) Heparin
Activates Impairs post-translational Activates antithrombin III
MOA Antithrombin modification of Factors II, VII, IX, MOA (inactivates thrombin or Factor IIa, Factor IXa & Factor Xa
III and X (Vitamin K-dependent) by forming stable complexes with them)
Monitoring PTT PT Deep venous thrombosis, Pulmonary embolism, Myocardial
Antidote Protamine Vitamin K, FFP infarction, Unstable angina, Adjuvant to percutaneous
Mostly acute, Chronic, over weeks to coronary intervention (PCI) and thrombolytics,
Use
over days months Uses Atrial fibrillation
Pregnancy Yes No DOC for anticoagulation during pregnancy, given with
thrombolytics for revascularization procedures, given with
MNEMONIC: PT/PTT GPIIb-IIIa inhibitors for angioplasty and stent placement
What laboratory tests will you request to assess the extrinsic and Heparin-induced thrombocytopenia,
intrinsic coagulation pathways? SE
Osteoporosis with chronic use
PiTT = PTT for intrinsic pathway • Administered IV or SC
PeT = PT for extrinsic pathway • Monitor with aPTT
HEPARIN-INDUCED THROMBOCYTOPENIA Notes • Antidote is Protamine Sulfate
SULODEXIDE: A Heparinoid consisting of 80% Heparin and
• HIT happens in 15% of patients 20% dermatan sulfate
• Pathogenesis involves opsonization of the heparin-platelet
complex. In immunology, large molecules are immunogenic. ENOXAPARIN, Dalteparin, Tinzaparin, Danaparoid,
Large molecules like heparin are immunogenic, leading to its Nadroparin, FONDAPARINUX
own phagocytosis and a decrease number of platelet. Binds and potentiates effect of antithrombin III on
• The key here is to replace heparin with a Low molecular weight MOA
factor Xa (more selective). Less effect on thrombin.
heparin just like Fondaparinux or a Direct Thrombin Uses Same with Heparin
Inhibitor like Lepirudin. SE Less risk of thrombocytopenia
• Does NOT require aPTT monitoring
WARFARIN
• Advantage over regular heparin is higher bioavailability
• inhibits Vitamin K epoxide reductase (which is responsible for and t½
carboxylation reactions to activate the clotting factors II, VII, IX, Notes
• Protamine sulfate is only partially effective in reversing
X, Protein C and S) effects
• Fondaparinux is given SC OD and has less bleeding
ORAL DIRECT FACTOR XA INHIBITOR

rivaroXaBAN [C], ApiXaBAN, BetriXaban, EdoXaban
HEPARIN-WARFARIN OVERLAP MOA Inhibit Factor Xa in the final common pathway
• In patients requiring anticoagulation, why is an overlap between heparin Prevention of Venous thromboembolism,
Uses
and warfarin usually done? Prevention of stroke in patients with Atrial Fibrillation
• Heparin rapidly inhibits the already activated factors, while SE Dizziness, Diarrhea, Edema, Epistaxis
Warfarin inhibits the activation process of the clotting • Have rapid onset of action and shorter half-lives than
factors X, IX, VII and also inhibits Protein C and S (effect on warfarin
Protein C and S is faster). Protein C and S are anti-clotting. Notes • Do not require monitoring. No antidotes
o The initial inhibition of Protein C and S ultimately results in a • Used esp. after hip or knee surgery
• Dose adjustment needed in renally impaired patients
temporary proclotting state.
• Warfarin-Skin Necrosis: due to
initial pro-clotting effect of warfarin ORAL ANTICOAGULANT
o Blood clots block the blood vessels WARFARIN [X], DICUMAROL, ANISINDIONE
and cause necrosis, where an area Inhibits vitamin K epoxide reductase
of skin is destroyed MOA (responsible for γ-carboxylation of the vitamin K-dependent
• Heparin-Warfarin bridging is done to prevent this: You must clotting factors: II, VII, IX, X, Protein C & S)
start first with Heparin to address the activated factors and Chronic anticoagulation (DVT, atrial fibrillation, valve
Uses
replacement) EXCEPT in pregnancy
gradually introduce warfarin.
Warfarin-induced skin necrosis (for patients with protein
WARFARIN AND DRUG INTERACTIONS SE C & S deficiencies),
• Cytochrome P450-inducers increase clearance and reduce the Teratogen (bone defects, hemorrhage)
• Monitor effects with PT
anticoagulant effect of a given dose
• Antidote is VITAMIN K (slow) or FFP (fast)
• Cytochrome P450-inhibitors reduce clearance and increase the Notes • Narrow therapeutic window
anticoagulant effect of a given dose • Active ingredient in most rat poisons
Since anticoagulants prevent coagulation, all of the next drugs might • Highly protein-bound
have BLEEDING as a side effect. The other notable SE will be indicated per
drug card.
Dr. Rodriguez For the anticoagulants focus on the effects on clotting factors II (Thrombin)
and clotting Factor Xa. It’s easier to memorize first, those the directly inhibit
DIRECT THROMBIN INHIBITORS
THROMBIN. They have RUDIN and GATRO/A in their names. They are
LEPIRUDIN, BIVALIRUDIN, known to be used for the indication: _________.
Desirudin, ARGATROBAN, DABIGATRAN Next, memorize those that directly inhibits Factor Xa. Take a look at their
Binds to thrombin's active site and name it has Xa in the middle.
MOA
inhibits its enzymatic action And then, try to check those that indirectly inhibits thrombin (II) which has
Anticoagulation in patients with HEPARIN as the prototype. Usage of heparin should be monitored closely by
Uses heparin-induced thrombocytopenia (HIT), what laboratory test: _______. In comparison, this test is not required for the
Percutaneous coronary angioplasty (with aspirin) monitoring of Low Molecular Weight Heparins – drugs that end with -
PARIN. In pregnancy which can be used for anticoagulation? ___________.
SE Effect-prolonging antibodies, Anaphylactic reactions
In all these drugs please note that Warfarin and its family are the only ones
• Monitor effect with aPTT given ORALLY, and in the clinics to help you remember, they are used
• No reversal agents for?____________________. Kaya minsan you’ll see patients they are on warfarin
Notes
• Used with caution for patients with renal insufficiency if they need to be on anticoagulant for a long time.
• Dabigatran is PO while all the rest are parenteral Dr. Rodriguez
CHEMICAL ANTAGONISTS (ANTIDOTE) ADH AGONIST
PROTAMINE SULFATE
DESMOPRESSIN [B], Vasopressin [C], Terlipressin
Chemical antagonist of heparin. Reverses excessive
MOA MOA ADH/vasopressin V2 receptor agonist
anticlotting activity of unfractionated heparin.
Uses Heparin overdosage Hemophilia A, von Willebrand’s disease, Central diabetes
Uses
SE Hypotension, Bradycardia, Flushing, Hypersensitivity, Dyspnea insipidus
Notes Partially reverses effects of LMWHs SE Headaches, Flushing, Nausea, Hyponatremia, Seizures
Increases the factor VIII activity of patients with mild
FIBRINOLYTIC DRUGS Notes
hemophilia A or von Willebrand disease
• mainly for the treatment of acute myocardial infarction, ischemic
stroke and massive pulmonary embolism SECTION SYNTHESIS
STREPTOKINASE, ALTEPLASE, DESCRIPTION DRUGS
Anistreplase, Reteplase, Tenecteplase, Urokinase Antiplatelets
Tissue plasminogen activator analog. Converts COX inhibitor
MOA plasminogen to plasmin, which degrades the fibrin and GPIIB/IIIA inhibitors
fibrinogen à thrombolysis ADP Inhibitor
Uses Acute myocardial infarction, Ischemic stroke, Pulmonary embolism
PDE Inhibitors
SE Bleeding, Cerebral hemorrhage, Reperfusion arrhythmias
• Loss of effectiveness (on 2nd use) and allergic reactions may Anticoagulants
be observed with streptokinase Direct thrombin inhibitors
Notes
• Tx must be within 6 hrs, better if within 3hrs Indirect thrombin inhibitors
• Antidote is AMINOCAPROIC ACID Factor XA inhibitors
Mnemonic:
Oral anticoagulants
Te Please! Kainis ka! Sinira mo araw ko!!! (WITH FEELINGS!!!)
TePlease – Teplase; Kainis – Kinase, Sinira – Sinira/Lysis of clot Antagonist for heparin
Dr. Rodriguez, Im Fibrinolytic drugs
CONTRAINDICATIONS TO THROMBOLYSIS Tissue plasminogen inhibitors
• history of cerebrovascular hemorrhage at any time Proclotting drugs
• non-hemorrhagic stroke or other cerebrovascular event within tPA inhibitor
the past year
Vitamin K derivatives
• marked hypertension (>180/110 mmHg) at any time during the
acute presentation ADH antagonist
• suspicion of aortic dissection NSAIDS, ACETAMINOPHEN, DMARDS
• active internal bleeding (excluding menses)
AND DRUGS USED IN GOUT
PRO-CLOTTING DRUGS (PROTHROMBOTICS)
INFLAMMATION
• complex response to cell injury that primarily occurs in vascularized
connective tissue and often involves the immune response
• mediators of inflammation function to eliminate the cause of cell
injury and clear away debris, in preparation for tissue repair
• causes pain and tissue damage
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
OTHER DRUGS USED FOR COAGULATION
SUPPLEMENT: General Classification of NSAIDs
DISORDERS
• SALICYLATES
• Antihemophilic factor
o Aspirin
• Anti-inhibitor coagulant complex
• NONSELECTIVE NSAIDs
• Anti-thrombin III
• Factor VIIa, VIII, IX complex
o Ibuprofen, Indomethacin, Ketorolac, Piroxicam
• Somatostatin: Tx of intestinal and pancreatic fistulae, excessive • COX-2 SELECTIVE
secretion from endocrine tumors of the GIT, acute severe GI o Celecoxib, Etoricoxib, Parecoxib
hemorrhage, endoscopic retrograde cholangiopancreatography Kumustaaaaa? You’re more than halfway. Hinga. And congrats for reaching
this part!
ANTIPLASMIN DRUG: AMINOCAPROIC ACID Now as a guide the next few sections will follow this outline. J
Dr. Rodriguez
TRANEXAMIC ACID
Common NSAID Toxicities
Competitively inhibits plasminogen activation
MOA • CNS: headaches, tinnitus, dizziness
by inhibiting tPA
Prevention and treatment of acute bleeding episodes in • CVS: hypertension, edema, heart failure
Uses patients with high risk of bleeding (hemophilia, intracranial • GIT: abdominal pain, dysplasia, nausea, vomiting, ulcers, bleeding
aneurysms, menstrual, obstetric, thrombolytics, postoperative) • HEMATOLOGIC: thrombocytopenia, neutropenia, aplastic anemia
Thrombosis, Hypotension, • HEPATIC: abnormal liver function tests, liver failure
SE
Myopathy, Diarrhea • PULMONARY: asthma
Notes Contraindication: Disseminated intravascular coagulation (DIC) • RASHES: all types, pruritus
• RENAL: renal insufficiency, renal failure, hyperkalemia, proteinuria
VITAMIN K & DERIVATIVES For the side effects pinaka importante to remember diyan ay. GI toxicity,
VITAMIN K1 (PHYTONADIONE), nephrotoxicity and Hypersensitivity. Remember without COX diba walang
VITAMIN K2 (MENAQUINONE) production ng Prostaglandin and Thromboxanes. Now sa stomach, ang
Increases supply of reduced vitamin K, which is required for nagsisilbing gastric protectant mo ay mga Prostaglandins. Without it prone
MOA synthesis of functional vitamin K-dependent clotting and ka to acid attack. Prostaglandin is also important in dilating the afferent
anticlotting factors arteriole (meaning mas madami papasok na blood to the glomerulus dapat.
Vitamin K deficiency, However dahil inhibited PG then magvvasoconstrict = less blood being
Uses Antidote to warfarin, filtered. Lastly yung hypersensitivity an idiosyncratic reaction.
Prevention of hemorrhagic diatheses in newborns NOTE: To simplify the tables and di kayo info overload if these 3 are part of the
SE, I’ll indicate them as letters G N H, GI tox, nephrotox, hypersensitivity
Severe infusion reaction when given too fast
SE respectively.
(dyspnea, chest and back pain) Dr. Rodriguez
ASPIRIN: DOSAGE RANGES Remember also that PG is essential in keeping the ductus arteriosus open. So
• low range (<300 mg/d) since all NSAIDS affect PG synthesis; pag walang PG, magsasara ang DA.
Dr. Rodriguez
o effective in reducing platelet aggregation
o follows first-order elimination kinetics INTRAVENOUS
• intermediate doses (300–2400 mg/d) Ketorolac, Dexketoprofen
o antipyretic and analgesic effects Post-surgical analgesic control (moderate to severe,
• high doses (2400–4000 mg/d) short-term), mainly used for analgesia not for anti-
o anti-inflammatory effects inflammatory effect
o follows zero-order elimination kinetics Uses
An effective replacement for morphine in post-surgical
patient reducing opioid requirement by 25-50%. It has
PARACETAMOL: OVERDOSE no anti-inflammatory effect.
Mechanism of Paracetamol Overdose SE G/N/H
• Oxidation to a cytotoxic intermediate called N-acetyl-p- • Use generally restricted to 72 hours only (due to GI and
benzoquinoneimine (NAPQI) by phase I cytochrome P450 renal damage)
enzymes (CYP2E1) Notes
• Ketorolac has significant analgesic effect but not anti-
• occurs if substrates for phase II conjugation reactions (acetate inflammatory effect
and glucuronide) are lacking
• centrilobular region (zone III) is preferentially involved because FOR PDA CLOSURE
it is the area of greatest concentration of CYP2E1 Indomethacin
• antidote is N-acetylcysteine (NAC), a sulfhydryl donor Anti-inflammatory (gout, arthritis, ankylosing
Uses
Stages of Paracetamol Overdose spondylitis), Closure of patent ductus arteriosus
G/N Pancreatitis, Serious hematologic reactions (aplastic
SE
STAGE TIME PERIOD MANIFESTATIONS anemia, thrombocytopenia), BM suppression
• Inhibits COX1 > COX2
Nausea, vomiting, diaphoresis, Notes • Indomethacin has greater anti-inflammatory effect
I 0.5 to 24 hours
pallor, lethargy, malaise compared to other NSAIDs
Elevated liver enzymes, oliguria,
II 24-72 hours azotemia, increased PT, COX-2 SELECTIVE NSAIDS
hyperbilirubinemia CELECOXIB, Etoricoxib,
Jaundice, hepatic encephalopathy, Rofecoxib, Valdecoxib, Parecoxib [X],
III 72 to 96 hours bleeding diathesis, acute tubular
MOA Selective COX-2 inhibitor.
necrosis, HAGMA, coma, death
IV 4 days to 2 weeks Recovery Uses Analgesia, Antipyretic, Anti-inflammatory
G (reduced risk), N, H
• DOSAGE SE
Myocardial infarction; Stroke (rofecoxib and valdecoxib only)
o toxic dose: 150mg/kg (21 Paracetamol 500 mg tabs)
• Coxibs are 10-20x COX2 > COX1
o lethal dose: 15g (30 Paracetamol 500 mg tabs)
• 50% less GI SE compared to Non-selective NSAIDs
• TREATMENT
Notes • Rofecoxib and Valdecoxib withdrawn from the market
o antidote is N-acetylcysteine
due to increased incidence of thrombosis
o supportive management • MELOXICAM: PREFERENTIAL COX2 selective inhibitor
o gastric decontamination with activated charcoal
Note: Parecoxib is pregnancy category X
Dr. Rodriguez
SALICYLATES
ASPIRIN (Acetylsalicylic acid, ASA), Salsalate, PARACETAMOL
Sodium salicylate, Choline salicylate, Magnesium salicylate Paracetamol (Acetaminophen), Phenacetin
Nonselective, IRREVERSIBLE COX 1&2 inhibitor. Selectively inhibits COX-3. Weak COX-1 and COX-2
MOA Reduces platelet production of thromboxane A2, a MOA
inhibitor. Inhibits prostaglandin synthesis.
potent stimulator of platelet aggregation. Uses Analgesia (mild), Antipyretic
Prevention of arterial thrombosis (MI, TIA, CVD), Hepatotoxicity, Renal papillary necrosis and Interstitial
Uses Inflammatory disorders (rheumatic fever, Kawasaki
SE nephritis (phenacetin only), Methemoglobinemia,
disease, juvenile rheumatoid arthritis) Hemolytic anemia
G/N/H
SE • Increased hepatotoxicity with alcohol use
Tinnitus, Hyperventilation, HAGMA
• Preferred antipyretic in children (does NOT cause Reye’s
• Associated with Reye’s syndrome in children
Notes syndrome)
• Prevents uric acid excretion (don’t use in gout)
Notes • Antidote is N-acetylcysteine
• Low doses undergo first order kinetics while high • t½ is only 2-3h
doses undergo zero order reaction
NON-SELECTIVE NSAIDS DISEASE-MODIFYING ANTI-RHEUMATIC
MECHANISM OF ACTION: DRUGS (DMARDS)
• Reversible COX 1 and 2 Inhibition. Disease-Modifying Anti-Rheumatic Drugs (DMARDs)
Non-selective sila kasi both COX 1 and 2 are inhibited. Later on may COX 2 • heterogeneous group of agents with anti-inflammatory actions
selective tayo. Recall nga sino yung COX na gingamit for normal cellular processes? used in several connective tissue diseases
Dr. Rodriguez
• cause slowing or even reversal of joint damage
ORAL • may take 6 weeks to 6 months for their benefits to become apparent
(see next page for the list of DMARDs and immune modulators)
IBUPROFEN, Diclofenac, Diflunisal, Etodolac, Fenoprofen,
Flurbiprofen, KETOPROFEN, Nabumetone, Naproxen, Oxaprozin,
PIROXICAM, Sulindac, Tolmetin, MEFENAMIC ACID, Bromfenac,
CANCER CHEMOTHERAPEUTIC DRUGS
Meclofenamate, Suprofen, Aceclofenac Methotrexate [X]
Analgesia (musculoskeletal, headache, dysmenorrhea), Inhibits AICAR (5-Aminoimidazole-4-Carboxamide
Uses Ribonucleotide) transformylase and thymidylate
Antipyretic, Anti-inflammatory MOA
Gastrointestinal bleeding (less than aspirin), synthetase, with secondary effects on
SE polymorphonuclear chemotaxis
N (AKI and Interstitial Nephritis), H
• Misoprostol prevents NSAID-induced gastritis Rheumatoid arthritis, SLE, JRA,
• NSAIDs (in general) may cause premature closure of Psoriatic arthritis, Ankylosing spondylitis, Polymyositis,
Notes Uses
Ductus Arteriosus Dermatomyositis, Wegener's granulomatosis, Giant cell
• Ibuprofen and Indomethacin can be used to close PDA arteritis, Vasculitis
In general, basta pag tinanong kayo what are the main uses of your NSAIDS, Nausea, Mucosal ulcers, Hepatotoxicity,
SE
and sagot ay Analgesic, Antipyretic, Anti-inflammatory. Except si Hypersensitivity, Pseudolymphomatous reaction
PARACETAMOL – Analgesic and antipyretic lang. Wala yan anti- • DMARD of first choice to treat rheumatoid arthritis
Notes
inflammatory effect – you’ • Rescue agent is Leucovorin (folinic acid)
Cyclophosphamide [D] OTHER DMARDS:
Forms phosphoramide mustard, which cross-links DNA to -see chapter on Endocrine
MOA GLUCOCORTICOIDS
prevent cell replication. Suppresses T-cell and B-cell function Pharmacology-
Rheumatoid arthritis, SLE, vasculitis, Wegener's Gold compounds MOA is not well
Uses
granulomatosis, Severe rheumatic diseases GOLD COMPOUNDS: understood. Auranofin has a low
Bone marrow suppression, Hemorrhagic cystitis, GOLD SODIUM incidence of serious toxicity but the
SE Hepatotoxicity, Alopecia, SIADH, Cardiac dysfunction, THIOMALATE overall frequency of SE (rash, diarrhea)
Pulmonary toxicity (Auranofin), is higher with Auranofin than any other
Notes Rescue agent is MESNA AUROTHIOGLUCOSE DMARD. Its utility therefore is limited by
low efficacy and poor tolerability
ANTI-MALARIALS Reduces number of T lymphocytes,
inhibits macrophage function, decreases
CINCHONA ALKALOIDS: CHLOROQUINE, HYDROXYCHLOROQUINE PENICILLAMINE
IL-1, decreases rheumatoid factor, and
Suppression of T-lymphocyte responses to mitogens, prevents collagen from cross-linking
decreased leukocyte chemotaxis, Stabilization of Janus Kinase inhibitor (JAK); used for
MOA TOFACITINIB
lysosomal enzymes, Inhibition of DNA and RNA rheumatoid arthritis
synthesis, Trapping of free radicals
Rheumatoid arthritis, SLE,
Uses IMMUNE MODULATORS
Sjögren syndrome, Malaria
Ocular toxicity, Dyspepsia, Nausea, Vomiting, Abdominal CD80 INHIBITOR: CO-STIMULATION MODULATOR
SE
pain, Rashes, Nightmares
Abetacept
Notes Cinchonism: Headache Tinnitus, Vertigo
Inhibits the activation of T Cells by binding to CD80
MOA
TNF-ALPHA INHIBITOR and CD86 on the APC
For moderate to severe Rheumatoid Arthritis
INFLIXIMAB, ADALIMUMAB, ETANERCEPT,
CERTOLIZUMAB, GOLIMUMAB
Uses (monotherapy or in combination with other
MOA Binds to TNF-a and prevents it from activating TNF-a receptor DMARDs)
Crohn’s disease, Rheumatoid arthritis, Increased risk of infection (esp. URTI),
Uses SE
Other rheumatic diseases Hypersensitivity reaction, Infusion-related reaction
Bacterial infections (URTIs), Reactivation of latent Concomitant use with TNF-a blocker is not
tuberculosis, Lymphoma, Demyelination, Reactivation of Notes recommended due to increased incidence of serious
SE infection.
hepatitis B, Autoantibody formation (ANA, anti-dsDNA),
Infusion reactions, hepatoxicity, hematotoxicity, cardiotoxicity
• Synergistic effects with methotrexate NON-BIOLOGIC DMARD
• Crosses placenta
Notes Leflunomide [X]
• This group of drugs has insufficient studies proving
Its active metabolite inhibits Dihydroorotate
their safety among pregnant Px
dehydrogenase → decreased synthesis of ribonucleotide
MOA and arrest of stimulated cells in the G1 phase of cell
OTHER DMARDS growth. Inhibits T cell proliferation and production of
Azathioprine [D] autoantibodies by B cells.
Forms 6-Thioguanine, suppressing inosinic acid Uses Rheumatoid Arthritis
MOA synthesis, B-cell and T-cell function, immunoglobulin Diarrhea, Elevation of liver enzymes, Mild alopecia,
production, and interleukin-2 secretion SE Weight Gain, Increased blood pressure,
Rheumatoid arthritis, Psoriatic arthritis, Leukopenia, Thrombocytopenia
Uses
Reactive arthritis, Polymyositis, SLE, Behçet disease • Converted to its active metabolite in the intestines
Bone marrow suppression, Increased risk of infections, (A77-1726)
SE Increased incidence of lymphoma, Fever, Rash, Notes
• Considered as effective as Methotrexate in
Hepatotoxicity, Allergic reactions Rheumatoid Arthritis
Cannot give Allopurinol with azathioprine (allopurinol
Notes reduces xanthine oxide catabolism of purine analogs à
MONOCLONAL ANTIBODIES
increasing 6-thioguanine nucleotides à severe leukopenia)
CD20 Inhibitor: Rituximab
Cyclosporine Depletes B cells by cell-mediated and complement-
Inhibits interleukin-1 and interleukin-2 receptor dependent cytotoxicity and stimulation of cell apoptosis
MOA production and secondarily inhibits macrophage–T-cell by binding to CD20 antigen on the surface of B
MOA
interaction and T-cell responsiveness lymphocytes → reduced inflammation by decreasing the
Rheumatoid arthritis, SLE, Polymyositis, presentation of antigens to T lymphocytes and inhibits
Uses Dermatomyositis, Wegener's granulomatosis, secretion of cytokine
Juvenile rheumatoid arthritis, Tissue transplantation Moderate to Severe Rheumatoid Arthritis
Nephrotoxicity, Hypertension, Hyperkalemia, Uses (with Methotrexate) in patients with an inadequate
SE
Hepatotoxicity, Gingival hyperplasia, Hirsutism response to TNF-a.
SE Rash, Increased risk of infection, Cardiovascular events
Mycophenolate Mofetil [D]
Notes Monoclonal antibody
Active product (mycophenolic acid) inhibits inosine
monophosphate dehydrogenase (important enzyme in Tocilizumab
MOA
the guanine nucleotide synthesis) and inhibits T-cell
Binds to IL-6 → decreased T cell activation and
lymphocyte proliferation MOA
inflammatory process
SLE nephritis, Vasculitis,
Moderate to Severe Rheumatoid Arthritis in patients
Uses Wegener’s granulomatosis, Rheumatoid arthritis Uses
with an inadequate response to TNF-a.
Least Toxic for SLE nephritis
URTI, Headache, Hypertension, Elevated liver enzymes,
Gastrointestinal disturbances, Headache, Hypertension,
SE SE Neutropenia, Thrombocytopenia, Tuberculosis, Fungal
Reversible myelosuppression (neutropenia)
Viral and other Opportunistic infections
Sulfasalazine [B, D if used for a prolonged time or near term] Screening for Tuberculosis should be done prior to
Notes
Active metabolite (sulfapyridine) inhibits the release of beginning Tocilizumab
MOA
inflammatory cytokines OTHER IMMUNOMODULATORS
Rheumatoid arthritis, Inflammatory bowel disease, JRA, A monoclonal antibody against IL-17; used for
Uses SECUKINUMAB
Ankylosing spondylitis psoriasis and ankylosing spondylitis
Nausea, Vomiting, Headache, Rash, Hemolytic anemia, A monoclonal antibody against IL-2; used to
Methemoglobinemia, Neutropenia, Thrombocytopenia, BASILIXIMAB
SE prevent rejection during organ transplantation
Pulmonary toxicity, Autoantibody formation (anti-
A monoclonal antibody against IL-12 and IL-
dsDNA), Reversible infertility in men USTEKINUMAB
23; used for Crohn’s disease and psoriasis
SECTION SYNTHESIS URICOSURIC AGENTS

PROBENECID, Sulfinpyrazone
In this section, it is easier if you keep in mind that inflammation is the
underlying cause in these diseases and is also associated with a gradual Compete with uric acid for reabsorption in the proximal
MOA
destruction of the different joint structures. Generally, in your mind, divide tubules. Increase uric acid excretion.
the drugs to those that inhibit inflammation (NSAIDS) and those that Uses Gout
prevent further damage or prevent reversal of joint damage (DMARDS) Gastrointestinal irritation, Rashes, Nephrotic syndrome
SE (probenecid only), Aplastic anemia,
NSAIDS have 3 main effects: Anti-inflammatory, Antipyretic, Analgesic.
Sulfa Allergy
However, Paracetamol does not have anti-inflammatory effect hence is not
considered an NSAID. Since NSAIDs inhibit COX enzyme it inhibits the • May precipitate acute gout during early phase of drug
formation of _____________ which is an inflammatory mediator. Take note action (prevent by co-administering with colchicine or
that Prostaglandins are important in the secretion of protective factors in indomethacin)
the stomach, hence NSAIDs are notorious for what AE? _________________. In • Inhibit secretion of weak acids (e.g., penicillin, methotrexate)
the clinic always check if the patient has a possible kidney problem because • May be given together with antimicrobial agents
Notes
NSAIDS are nephrotoxic. Among the NSAIDS, there’s only one that (particularly Penicillins) to prolong therapeutic effect by
irreversibly inhibits COX: ______________. While there are those that selectively inhibiting renal tubular excretion of antibiotics
inhibits COX, can you give 1 example? _____________ (they end in?: _________). • A required minimum 30 ml/min GFR is important before
One is also known for closing PDA: _________ (Can you recall what drug keeps starting Probenecid. Other uricosuric agents are
DA open?_________) Fenofibrate and Losartan.
DMARDS on the other hand alters the course of the disease. One important XANTHINE OXIDASE INHIBITORS
condition is Gout, which is due to the deposition of Uric Acid in different joints, ALLOPURINOL [C] FEBUXOSTAT [C]
causing pain. Uric acid comes from the degradation of ____________ which can Active metabolite Nonpurine reversible that is
be inhibited by what drugs: __________________________, by the inhibition of what (alloxanthine) that an inhibitor of xanthine
enzyme? _________. You also need to know that these two drugs are used in a MOA irreversibly inhibits oxidase (more selective than
condition known as Tumor Lysis Syndrome. In this condition, tumor cells lyse. Xanthine Oxidase and lowers allopurinol). Lowers
Remember that cells contain DNA housed in the nucleus. DNAs are made up of production of uric acid production of uric acid.
purine and pyrimidine. And URIc acid comes from pURIne degradation. 1st line treatment for Chronic gout, Tumor lysis
Hence, rapid lysis of cells causes increase in uric acid levels. Uses chronic gout, Tumor lysis syndrome, Allopurinol
Aside from preventing the formation of uric acid, you can also increase its syndrome intolerance
excretion by giving __________________. Gastrointestinal upset, Rash, Liver function abnormalities,
Acute gout pain can be treated initially with what NSAID? _____________. If Peripheral neuritis, Vasculitis, Headache, Gastrointestinal
Indomethacin is not available Colchicine is also used for Acute gout. On the SE
Bone marrow dysfunction, upset, rash, liver dysfunction
other hand, for Chronic gout what is the primary treatment? _______________. Aplastic anemia, Cataracts (Febuxostat)
There are several DMARDS used for Rheumatoid Arthritis and other • Inhibits metabolism of • Withheld for 1–2 weeks
Rheumatic diseases. Although it’s important to take note of the SEs, most of mercaptopurine and after an acute episode of
their side effects overlap so don’t take too much time knowing everything. azathioprine gouty arthritis (co-
But it is essential that you know the MOAs. Try to divide them in terms of • Withheld for 1–2 weeks administered with
similarity so it’s easier. Let’s try. Name the drug that acts on the following: Notes after an acute episode of colchicine or
1. IL1 and IL2 : _________________:: IL6: ____________________ gouty arthritis (co- indomethacin to avoid an
2. CD80/CD86: __________________::CD 20 :_____________________ administered with acute attack)
Then know the characteristic mechanism for each colchicine or indomethacin • Febuxostat is more
1. AICAR Tranformylase to avoid an acute attack) effective than Allopurinol
2. TNF-alpha
3. Forms 6-Thioguanine
4. Cross-links DNA
5. Inh. Inosine Monophosphate
6. Inh. Dihydroorarotate dehydrogenase
Dr. Rodriguez
SUMMARY OF DMARDs
https://qrs.ly/ncdvedq
DRUGS FOR THE TREATMENT OF GOUT Figure 36-7. Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018.
GOUT
• may be associated with increased serum concentrations of uric acid
• acute attacks involve joint inflammation initiated by GOUT TREATMENT
precipitation of uric acid crystals https://qrs.ly/njdvedu
TREATMENT STRATEGIES FOR GOUT
• The management of gout has 3 strategies:
1. reducing inflammation during acute attacks ENDOCRINE PHARMACOLOGY
2. accelerating renal excretion of uric acid with uricosuric drugs Just a few more topics left guys! Kapit J For this section, let’s start conditioning
3. reducing the conversion of purines to uric acid by xanthine oxidase your mind by running through the sections. First we’ll be tackling the
NSAIDS IN GOUT hypothalamic and pituitary hormones. Then we go to the thyroid followed by
corticosteroids. Then we proceed to Gonadal hormones, the pancrease
• In addition to inhibiting prostaglandin synthase, indomethacin (diabetes) and ending with bone andmineral homeostasis (osteoporosis etc)
and other NSAIDs also inhibit urate crystal phagocytosis Dr. Rodriguez
• Indomethacin is commonly used in the initial treatment of gout HYPOTHALAMIC AND PITUITARY HORMONES
as the replacement for colchicine
• Aspirin is not used due to its renal retention of uric acid at low doses
MICROTUBULE ASSEMBLY INHIBITOR
Colchicine
Inhibits microtubule assembly and LTB4 production leading
MOA
to decreased macrophage migration and phagocytosis
Uses Gout, Familial Mediterranean fever
Diarrhea, Nausea, Vomiting, Abdominal pain, Hepatic
necrosis, Acute renal failure, Disseminated intravascular
SE
coagulation, Seizures, Hair loss, Bone marrow depression
(aplastic anemia), Peripheral neuritis, Myopathy
• Diarrhea: adverse effect which signals toxicity from colchicine
Notes
Not to be given to patients with eGFR of <30
ANTERIOR PITUITARY HORMONES Fetal distress, Placental abruption, Uterine rupture,
Anterior Target Organ SE Fluid retention (water intoxication), Hyponatremia,
Hypothalamic Target
Pituitary hormone(s) or Heart failure, Seizures, Hypotension
Hormone Organ
Hormone mediators (s) • Contraindications to oxytocin include fetal distress,
Growth hormone- Liver, prematurity, abnormal presentation, CPD and
releasing muscle, Insulin-like
Growth Hormone
hormone (GHRH) bone, growth factor-1
predispositions for uterine rupture
(GH, Somatotropin)
(+) Somatostatin kidney, and (IGF-1)
Notes ATOSIBAN is an oxytocin receptor blocker (not yet FDA
(-) others approved since there is concern about increased rates of infant death)
Thyroid- Thyrotropin-
stimulating releasing Thyroxine, CARBETOCIN is an agonist of peripheral Oxytocin receptors
Thyroid
hormone Hormone (TRH) Triiodothyronine
(TSH) (+)
Corticotropin-
Glucocorticoids,
DRUGS RELATED TO ADH
Adrenocorticotropin releasing Adrenal ADH ANTAGONIST
(ACTH) hormone (CRH) Cortex
Mineralocorticoids ADH AGONIST
, Androgens DESMOPRESSIN CONIVAPTAN,
(+)
Follicle-stimulating
Gonadotropin- Estrogen,
Vasopressin/ADH TOLVAPTAN, LIXIVAPTAN
Hormone (FSH) Desmopressin relatively
releasing Gonads Progesterone,
Luteinizing
Hormone (LH)
Hormone (GnRH Testosterone selective for V2
receptors. Vasopressin V2
Prolactin (PrL) Dopamine (-) Breast -
receptor agonist which
• All the anterior pituitary hormones are under the control of a Antagonist at V1a, V2
causes insertion of water
hypothalamic hormone receptors. Increases renal
channels in the collecting
• All mediate their ultimate effects by regulating the production by MOA excretion of water in
duct leading to more water
conditions associated with
peripheral tissues of other hormones EXCEPT prolactin reabsorption → decrease
increased vasopressin
• Four anterior pituitary hormones (TSH, LH, FSH, and ACTH) and the excretion of water; Act
their hypothalamic regulators are subject to feedback regulation on extra-renal V2 receptors
by the hormones whose production they control to increase Factor VIII and
• Hormones secreted by the Posterior Pituitary are: Vasopressin VWF factor
& Oxytocin. Take note that both are potent vasoconstrictors. Central diabetes insipidus,
SIADH, Hyponatremia in
Hemophilia A, von
hospitalized patients,
ON GONADOTROPINS: OVULATION INDUCTION Willebrand’s disease,
offset fluid retention in
Uses Esophageal variceal
• FUNCTIONS acute heart failure and
bleeding, Primary nocturnal
o in women, FSH directs follicle development, whereas FSH and SIADH which causes
enuresis (pediatric Px),
LH collaborate in regulating ovarian steroidogenesis hyponatremia (dilutional)
colon diverticula
o in men, FSH regulates spermatogenesis, whereas LH GI disturbance, Headaches,
stimulates androgen production Flushing, Nausea, Infusion site reactions,
SE
• CLINICAL UTILITY Hyponatremia, Seizures, Hyperkalemia
o to stimulate spermatogenesis in infertile men Allergic reactions
o to induce ovulation in women with refractory anovulation • May be given intranasally, • Central pontine myelinolysis
Ovulation Induction Protocol PO or IV may occur with rapid
• endogenous gonadotropin production is inhibited by • Also contracts vascular correction of hyponatremia
administration of a GnRH agonist or antagonist smooth muscles via V1 • Tolvaptan is more
• follicle development is driven by daily injections of a preparation Notes receptor leading to selective for V2 receptors
with FSH activity (menotropins, FSH, FSH analog) vasoconstriction (Used as • Lixivaptan and
• final stage of oocyte maturation is induced with an injection of treatment for esophageal Tolvaptan are selectively
varices or colon active against the V2
LH or human chorionic gonadotropin (hCG)
diverticula) receptor
Complications of Ovulation Induction
• multiple pregnancies
SUPPLEMENT: Diabetes Insipidus
• ovarian hyperstimulation syndrome
• CLINICAL FEATURES
o syndrome of ovarian enlargement, ascites, hypovolemia and o syndrome of polyuria, polydipsia, and hypernatremia
possibly shock o excessive urination due to an inability of the kidney to resorb water
properly from the urine
DRUGS RELATED TO PROLACTIN • TYPES
o central diabetes insipidus is associated with deficient secretion of ADH
BROMOCRIPTINE, PERGOLIDE, CABERGOLINE, QUINAGOLIDE o nephrogenic diabetes insipidus is associated with end-organ
*All are Preg Cat B resistance to the effects of ADH
DOPAMINE AGONIST, hence inhibiting prolactin
release from the pituitary gland.
MOA DRUGS RELATED TO GROWTH HORMONES
Also slightly inhibits GH release.
Dopaminergic effects on CNS motor control and behavior GH AGONISTS
Hyperprolactinemia, Pituitary adenoma (prolactin-
Uses RECOMBINANT GROWTH HORMONE
secreting), Acromegaly, Parkinson’s disease
GI disturbance, Nausea, Headache, Light-headedness, SOMATROPIN
Orthostatic Hypotension, Fatigue, Behavioral Changes, Increases release of IGF-1 in the liver and cartilage.
Erythromelalgia, Raynaud’s phenomenon (vasospasm), MOA Stimulates skeletal muscle growth, amino acid transport,
SE Pulmonary infiltrates (in high doses) protein synthesis and cell proliferation.
Erythromelalgia is a rare disorder characterized by Growth hormone deficiency, Genetic diseases associated
burning pain and warmth and redness of the with short stature (Turner, Noonan, Prader-Willi), failure to
extremities Uses thrive due to chronic renal failure or SGA, AIDS wasting,
Given PO or vaginally (for Hyperprolactinemia) improve GI function in patients who underwent intestinal
Notes Slightly inhibits GH release if given in high doses resection that led to malabsorption syndrome
CI in patients with history of psychotic illness Peripheral edema, Myalgia, Arthralgia, Intracranial
SE hypertension, pseudotumor cerebri, slipped capital
femoral epiphysis, progression of scoliosis, hyperglycemia
DRUGS RELATED TO OXYTOCIN • Performance-enhancing drug (increases muscle mass)
Oxytocin [X], Demoxytocin Notes that is banned by athletics committees
Activates oxytocin receptors. Stimulates uterine • Given SC
MOA contraction and labor. Stimulates mammary glands,
lactation and milk let-down.
Labor induction, Labor augmentation, Control of
Uses
postpartum hemorrhage
RECOMBINANT IGF-1 Ovarian Suppression, Controlled ovarian
MECASERMIN hyperstimulation, Endometriosis, Myoma uteri,
Uses
Same as somatropin. But no release of IGF-1 because it’s Central Precocious puberty,
MOA Advanced Prostate cancer
IGF that you gave already
Uses For children unresponsive to GH therapy Hot flushes, Sweats, Headache, Light-headedness,
SE Injection site reactions, Nausea, Osteoporosis,
SE Hypoglycemia, increased LFT, intracranial HTN
Gynecomastia, Reduced libido, Decreased hematocrit
Remedy to hypoglycemia: give patient some snacks prior
Notes • Symptoms of hypogonadism with continuous
to dose
treatment
Note yung difference sa SE in terms of the level of blood sugar. Yung isa
• Temporary exacerbation of precocious puberty or
hyperglycemia, recom IGF-1 is hypoglycemia.
Dr. Rodriguez prostate cancer, Apoplexy and Blindness during the
GH ANTAGONIST first few weeks of therapy (remedy: co-administer
Notes Flutamide, an androgen receptor antagonist)
GH RECEPTOR ANTAGONIST • May be given Intranasally, depot formulation also
PEGVISOMANT available
MOA Block GH receptor • Gonadorelin is a synthetic human GnRH
Uses Acromegaly • Leuprolide has a long agonist activity; its other name
Diarrhea, nausea, flu-like syndrome, elevated LFTs, is leuprorelin/leuprorelin
SE
hypersensitivity reaction
Notes Onset of action is expected within 2wks of use GNRH ANTAGONIST
SOMATOSTATIN ANALOG GANIRELIX, CETRORELIX, ABARELIX, DEGARELIX
OCTREOTIDE, LANREOTIDE Blocks GnRH receptors.
Suppresses the release of growth hormones, glucagon, MOA
MOA Reduces endogenous production of LH and FSH.
insulin, gastrin, IGF-1, serotonin and gastrointestinal peptides Prevents premature LH surge during Controlled ovarian
Acromegaly, Pituitary adenoma (GH-secreting), Uses
Uses hyperstimulation, Advanced Prostate cancer
Carcinoid, Gastrinoma, Glucagonoma, Variceal bleeding Nausea, Headache, Hypersensitivity (Abarelix), Hot
Gastrointestinal disturbances, Gallstones, SE flushes, Gynecomastia, decreased libido, Decreased
SE
Arrhythmias/cardiac conduction abnormality hematocrit, Osteoporosis
• Can alter requirements for antidiabetic agents • Does NOT cause a tumor flare-up when used for treatment of
• Regular release: given BID-QID SC advanced prostate cancer
Notes
• If slow release: every 4wks IM • Less likely to cause ovarian hyperstimulation
• Are long-acting synthetic analogs of somatostatin syndrome
When you hear “Somatostatin” always think that it will suppress the release Notes • Degarelix is used for prostate CA while Ganirelix prevent
of hormones. Ginagawa ko to remember, STATIN is related to STATIC = LH surge in controlled ovulation
meaning parang walang movement – or no action – no release Directly inhibits the receptors and so causes antagonistic
Dr. Rodriguez
(decrease in hormones) effect right away. Thus, there is no
flare-up
DRUGS RELATED TO GONADOTROPINS VERY IMPORTANT. Kindly notice the use of each for controlled ovarian
All gonadotropin related drugs are Pregnancy Category X hyperstimulation. Notice how they differ each in their use for controlled
Dr. Rodriguez ovarian hyperstimulation. LH gagamitin mo para ipaovulate na yung
FSH ANALOGS patient. The Antagonists prevents premature surge of LH. Remember in this
procedure you have to mimic the regular menstrual cycle. May tamang
FOLLITROPIN ALFA, MENOTROPINS (hMG),
timing kung kelan dapat irelease si LH.
UROFOLLITROPIN, FOLLITROPIN BETA Dr. Rodriguez
MOA Activates FSH receptors. Mimics effects of endogenous FSH.
Controlled ovarian hyperstimulation, Infertility due to The effect of GnRH agonists will depend on the dosing that you give
Uses
hypogonadotropic hypogonadism in men to the patient.
Headache, depression, edema, ovarian hyperstimulation
syndrome (ovarian enlargement, ascites, hypovolemia,
SE
shock), multiple pregnancies in women, gynecomastia in
men
Follitropin alfa and beta are recombinant FSH forms
Notes while Urofollitropin is a purified preparation from urine
GNRH ANALOGUES 1 GNRH ANALOGUES 2
of postmenopausal women
https://qrs.ly/p4dvedw https://qrs.ly/imdvedv
Notice in the name, they have FOLLI in their name = from FOLLICLE Dr. Pereyra-Borlongan
stimulating hormone
Dr. Rodriguez THYROID AND ANTITHYROID DRUGS
LH ANALOGS
CHORIOGONADOTROPIN ALFA,
HUMAN CHORIONIC GONADOTROPIN (hCG),
MENOTROPINS (hMG), LUTROPIN ALFA
Activates LH receptors.
MOA
Mimics effects of endogenous LH.
Initiation of ovulation during controlled ovarian
hyperstimulation (ovulation induction), ovarian follicle
Uses
development in women with Hypogonadotropic
hypogonadism, male Hypogonadotropic Hypogonadism Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2018
SE Same with FSH analogs above
• Menotropins are mixtures of FSH and LH from Synthesis and Transport of Thyroid Hormones
postmenopausal women • TRANSPORT
Notes
• Choriogonadotropin alfa is a recombinant hCG while o iodide ion is converted to iodine by thyroid peroxidase (TPO)
Lutropin is a recombinant LH • IODINE ORGANIFICATION
GNRH AGONIST o tyrosine residues in thyroglobulin are iodinated to form
LEUPROLIDE, GONADORELIN, GOSERELIN, monoiodotyrosine (MIT) or diiodotyrosine (DIT)
HISTRELIN, NAFARELIN, TRIPTORELIN • COUPLING
Agonist of GnRH receptors. o 2 molecules of DIT combine to form T4, while 1 molecule each
Intermittent administration: Inc. LH and FSH secretion of MIT and DIT combine to form T3
Prolonged Continuous administration: Reduced LH • PROTEOLYSIS
MOA
and FSH secretion (due to downregulation of GnRH o T4 and T3 are released from the thyroid and transported in the
receptors in the pituitary cells that normally release LH blood by thyroxine-binding globulin (TBG)
and FSH)
THIONAMIDES
Propylthiouracil [D]
Thyroid Maculopapular pruritic rash, Gastrointestinal distress,
gland Fulminant hepatitis, Agranulocytosis, Urticaria,
Transport Peroxidase Organification
Thyroglobulin SE Vasculitis, Lupus-like syndrome, Lymphadenopathy,
I— I— I° MIT-DIT-T3-T4 Hypoprothrombinemia, Exfoliative dermatitis,
- Iodides Polyserositis, Arthralgia, Hypothyroidism
- DOC: Pregnant Hyperthyroid Patients
- Iodides,
Proteolysis
thioamides Preferable during the first trimester of pregnancy because

SCN —, ClO4 —
it is more strongly protein-bound and, therefore, crosses
the placenta less readily
Peripheral
T4, T3 • Shorter DOA (6-8h)
Blood Notes
Tissues • Faster onset of action: Reaches effect within hrs
T4, T3 Radiocontrast media,
Due to a black box warning about severe hepatitis,
- β-blockers,
corticosteroids, propylthiouracil should be reserved for use during the first
amiodarone trimester of pregnancy, in thyroid storm, and in those
T3 experiencing adverse reactions to methimazole (other than
Adapted from Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018. agranulocytosis or hepatitis)
Key Features of Thyrotoxicosis and Hypothyroidism
THYROTOXICOSIS HYPOTHYROIDISM Methimazole [D], Carbimazole
Warm, moist skin Pale, cool, puffy skin Same as above (don’t forget AGRANULOCYTOSIS)
SE
Sweating, heat intolerance Sensation of being cold Altered sense of taste or smell
Tachycardia, increased Bradycardia, decreased stroke • Drug of choice for nonpregnant hyperthyroid Px
stroke volume, cardiac volume, cardiac output, and because of longer DOA (24h) and increased potency
output, and pulse pressure pulse pressure • Methimazole and Carbimazole are teratogens (causes
Pleural effusions, Aplasia Cutis Congenita) in the 1st trimester
Dyspnea hypoventilation, • Given as once daily dosing
Notes • THIAMAZOLE is the other name of Methimazole
and CO2 retention
Increased appetite Reduced appetite • Slow onset of action (3-4 weeks for full effect)
Nervousness, hyperkinesia, Lethargy, general slowing of Because the thioamides do not inhibit the release of
tremor mental processes preformed thyroid hormone, their onset of activity is
Weakness, increased deep Stiffness, decreased deep usually slow, often requiring 3–4 wk for full effect.
tendon reflexes tendon reflexes
Menstrual irregularity, Infertility, decreased libido,
IODIDES
decreased fertility impotence, oligospermia
Weight loss Weight gain Radioactive Iodine [X] (I131)
Exophthalmos Emits beta rays causing destruction of thyroid
parenchyma
DRUGS FOR HYPERTHYROIDISM MOA Administered orally in solution as sodium 131I, it is rapidly
absorbed, concentrated by the thyroid, and incorporated
Graves Disease into storage follicles
• autoimmune disorder where B lymphocytes produce an Hypothyroidism (permanent), sore throat, sialadenitis
antibody that activates the TSH receptor (TSIs), causing SE
Associated with radiation exposure: papillary thyroid CA
thyrotoxicosis • Preferred treatment for most patients
• these B lymphocytes are not susceptible to negative feedback • Permanent cure of thyrotoxicosis without surgery
• expected thyroid profile: high T3/T4, low TSH and no effect on other tissues
STEPS BLOCKED P M KI BB • Advantages include easy administration, effectiveness,
low expense and absence of pain
Thyroid peroxidase
• Contraindicated in pregnant women or nursing
Organification Notes mothers
Peripheral conversion of T4 to T3
Proteolysis (hormone release) * Since it crosses the placenta to destroy the fetal thyroid
For this part frens, let’s summarize all MOA in this table, so that in the drug gland and is excreted in breast milk
cards below, hindi na sila uulit ulitin J *for propranolol only • Patients should be euthyroid or on BB before RAI
For the MOA of each, ofcourse para sila sa Hyperthyroidism and/or thyroid Onset of action is 6-12 weeks, Maximum effect seen in 3-
storm. Same as before, yung mga must knows nalang ilalagay natin ulit 6 months.
para di magulo.
Dr. Rodriguez IODINE
OTHER ANTI-THYROID POTASSIUM IODIDE [D], LUGOL’S SOLUTION /
Anion Inhibitors: perchlorate (ClO4–), pertechnetate (TcO4–), Potassium Iodide Saturated Solution (KISS)
thiocyanate (SCN–) Additional use: Reduce size and vascularity of thyroid
• block uptake of iodide by the gland through competitive inhibition of MOA
gland prior to surgery.
the iodide transport mechanism Preparation for surgical thyroidectomy to reduce the
• The major clinical use for potassium perchlorate is to block thyroidal Uses size and vascularity of the thyroid gland, Radiation
reuptake of I– in patients with iodide-induced hyperthyroidism (e.g. prophylaxis.
amiodarone-induced hyperthyroidism). However, potassium
Iodism, Acneiform rash, Swollen salivary glands, Mucous
perchlorate is rarely used clinically because it is associated with
aplastic anemia membrane ulcerations, Conjunctivitis, Rhinorrhea, Drug
SE
fever, Metallic taste, Bleeding disorders, Anaphylactoid
Most of the time in the clinics, you’ll encounter PTU and methimazole being
reactions
used for the treatment of hyperthyroidism. Kindly take time to understand
these two drugs. • Should not be used alone (escape in 2–8 weeks)
Dr. Rodriguez • Prevents radiation-induced thyroid damage
CLINICAL PEARLS • Prenatal exposure causes fetal goiter
• PTU is preferred in the first trimester and should be replaced • Onset is faster compared to Thioamides (2-7 days) but
by Methimazole (MMI) after this trimester. effect is transient (thyroid gland escapes iodide block
Notes
• Choanal and esophageal atresia of fetus in MMI-treated and after several weeks of treatment)
maternal hepatotoxicity in PTU-treated pregnancies are of utmost • Acts through inhibition of thyroglobulin proteolysis.
concern. Improvement in thyrotoxic symptoms occurs rapidly—
• Maintaining free thyroxine concentration in the upper one-third of within 2–7 days—hence the value of iodide therapy in
each trimester-specific reference interval denotes success of therapy. thyroid storm.
• MMI is the mainstay of the treatment of postpartum
hyperthyroidism, in particular during lactation.
BETA BLOCKER AMIODARONE-INDUCED THYROID DISEASE

PROPRANOLOL, ESMOLOL, METOPROLOL, ATENOLOL • hypothyroidism through its ability to block the peripheral
Blocks beta-receptors (control HR and other cardiac conversion of T4 to T3
abnormalities of severe thyrotoxicosis). o TREATMENT: levothyroxine
MOA Slows pacemaker activity; • hyperthyroidism either through an iodine-induced mechanism in
Inhibits peripheral conversion of T4 into T 3 (Only persons with an underlying thyroid disease or through an
Propranolol) inflammatory mechanism that causes leakage of thyroid hormone
Hyperthyroidism esp Thyroid Storm, Adjunct to control o TREATMENT: thioamides or corticosteroids
Uses tachycardia, HTN and Atrial Fibrillation, Post-MI OTHER ANTI-THYROID
prophylaxis against sudden death Anion Inhibitors: perchlorate (ClO4–), pertechnetate (TcO4–),
Bronchospasm, Cardiac depression, AV block, thiocyanate (SCN–)
SE
Hypotension, Bradycardia • block uptake of iodide by the gland through competitive inhibition of
• Esmolol may be used to treat thyrotoxicosis-related the iodide transport mechanism
arrhythmias • The major clinical use for potassium perchlorate is to block thyroidal
• Onset is within hours but DOA is also short (4-6 hrs) reuptake of I– in patients with iodide-induced hyperthyroidism (e.g.
• Use Beta blockers without intrinsic amiodarone-induced hyperthyroidism). However, potassium
sympathomimetic activity (e.g. metoprolol, perchlorate is rarely used clinically because it is associated with
propranolol, atenolol) aplastic anemia
Notes
• Beta blockers cause clinical improvement of
hyperthyroid symptoms but do not typically alter DRUGS FOR HYPOTHYROIDISM
thyroid hormone levels.
Myxedema Coma
• Propranolol at doses greater than 160 mg/d may also
reduce T3 levels approximately 20% by inhibiting the • CLINICAL PRESENTATION
peripheral conversion of T4 to T3. o medical emergency representing the end state of untreated
hypothyroidism
SECTION SYNTHESIS o progressive weakness, stupor, hypothermia, hypoventilation,
Drugs for hypothyroidism are easier to memorize since you just replace the hypoglycemia, hyponatremia, water intoxication, shock and death
low/absent with Levothyroxine (T4). For the drugs for hyperthyroidism, it’s • TREATMENT
easier to recall them if you try to draw a diagram of the synthesis of thyroid § intravenous loading dose of levothyroxine (300–400 mcg),
hormones and add to that diagram the different drugs which act on the followed by 50–100 mcg daily
different stages. Among the drugs for hyperthyroidism, the most common § intravenous hydrocortisone is indicated if the patient has
you’ll hear is PTU and Methimazole. If the patient is pregnant your choice associated adrenal or pituitary insufficiency
among the two is __________________. If not, your choice would be
__________________.In practice, when you use thionamides, please monitor for
the development of sore throat, oral ulcers, fever as these can be signs of DRUGS FOR HYPOTHYROIDISM
Agranulocytosis DO NOT FORGET. On the other hand, if your patient Thyroid hormones:
doesn’t want surgery, but needs the removal of the thyroid tissues, you can LEVOTHYROXINE (T4) [A],
give RAI. LIOTHYRONINE (T3) [A], LIOTRIX [A]
Meanwhile, the sympathetic effects associated with hyperthyroidism can be Activation of nuclear receptors results in gene
controlled by using ______________, which also has the capacity to prevent
MOA
expression with RNA formation and protein synthesis
conversion of T4 to T3. Uses Hypothyroidism, Myxedema coma
Dr. Rodriguez
Dry skin, Sweating, Tachycardia, Nervousness, Tremor,
SE
SUPPLEMENT: Agranulocytosis Weight loss, Weakness, Heat intolerance
AGRANULOCYTOSIS • T4 dose must be lowered in patients with
o acute severe neutropenia: granulocyte count < 500 cells/mm3 cardiovascular disease or longstanding
o often heralded by sore throat or high fever hypothyroidism (increased cardiosensitivity)
o increased susceptibility to infections • LIOTRIX is a 4:1 ratio of T4:T3
Notes
o increased risk in older patients and in those receiving high-dose • Thyrotropin (a recombinant human TSH) is also
methimazole therapy (> 40 mg/d) available
• CLINICAL PRESENTATION Maximum effect is seen after 6-8 weeks of therapy
o acute severe neutropenia Liothyronine has a faster onset but shorter half-life
o often heralded by sore throat or high fever
o increased susceptibility to infections SUPPLEMENT: Thyroid hormones
• TREATMENT
MOA of T4 and T3
o discontinue PTU or methimazole
• T4 is converted to T3 in target cells
o administer recombinant G-CSF to accelerate recovery
o treat with prophylactic broad-spectrum antibiotics • T3 is about 10 times more potent than T4
GCSF: FILGRASTIN • thyroid hormones bind to intracellular receptors that control the
GMCSF: SARGRAMOSTIM expression of genes responsible for many metabolic processes
Dr. Pereyra-Borlongan MNEMONIC: 4 B’s of thyroid hormone: Brain maturation, Bone
growth, Beta-adrenergic effects, and increase in Basal metabolic rate
THYROID STORM
• CLINICAL PRESENTATION
o sudden acute exacerbation of all of the symptoms of CORTICOSTEROIDS AND ANTAGONISTS
thyrotoxicosis, presenting as a life-threatening syndrome
• Treatment of Thyroid Storm
o PTU blocks thyroid hormone synthesis
o iodides (SSKI) retards release of thyroid hormones
§ always administer PTU before iodides (SSKI)
o propranolol controls severe cardiovascular manifestations
o hydrocortisone protects against shock and also blocks
peripheral conversion of T4 to T3
WOLF-CHAIKOFF VS JOD-BASEDOW
• Wolf-Chaikoff effect: ingestion of iodine causes hypothyroidism
• Jod-Basedow phenomenon: ingestion of iodine causes
hyperthyroidism Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2018
KEY LEARNING POINTS

Which drugs inhibit peripheral What drugs can cause drug- GLUCOCORTICOID ACTIVITY
conversion of T4 to T3? induced hyperthyroidism? https://qrs.ly/5xdvedz
Propylthiouracil CAM
Propranolol Clofibrate, Amiodarone,
Hydrocortisone Methadone
MAJOR GROUP OF CORTICOSTEROIDS INTERMEDIATE TO LONG ACTING
• GLUCOCORTICOIDS These drugs are considered medium to high potency.
o important effects on intermediary metabolism, catabolism, Dr. Rodriguez
immune responses, and inflammation

• MINERALOCORTICOIDS Prednisone, Prednisolone, Methylprednisolone, Meprednisone,
o regulate sodium and potassium reabsorption in the collecting Dexamethasone, Betamethasone, Triamcinolone
tubules of the kidney MOA Suppresses inflammation and immune response
Wide variety of inflammatory, allergic, autoimmune
(collagen and rheumatic disease etc.) and neoplastic
diseases (hematopoietic cancers), Prevention of organ
Uses transplant rejection, Asthma, lung maturation in
preterm labor (betamethasone and dexamethasone),
chemotherapy-induced vomiting, hypercalcemia,
mountain sickness
Adrenal suppression, Growth inhibition, Muscle wasting,
Osteoporosis (especially among elderly women), Salt
retention, Glucose intolerance, Behavioral changes
SE (psychosis)
Behavioral changes secondary to steroid use is termed
“Steroid Rage”
• Betamethasone and Dexamethasone hastens fetal
lung maturation
Notes • Prednisolone is the active metabolite of prednisone
• This group has a long t½, reduced salt-retaining effect
Outline of major pathways in adrenocortical hormone biosynthesis. The names
and better penetration of lipid barriers
of major adrenal secretory products are in shaded boxes. The enzymes and
cofactors for the reactions progressing down each column are shown on the left
and across columns at the top of the figure. When a particular enzyme is GLUCOCORTICOID SYNTHESIS INHIBITOR
deficient, hormone production is blocked at points indicated by the shaded bars
• DESMOLASE – CONVERTS CHOLESTEROL TO PREGNENOLONE DESMOLASE INHIBITOR
• 21B hydroxylase deficiency: salt-wasting Amino-glutethimide [D]
• 11B hydroxylase: salt-wasting Inhibits Desmolase, blocking conversion of cholesterol
• 17a hydroxylase deficiency: non-salt wasting MOA to pregnenolone. Reduces synthesis of all hormonally
active steroids.
SOME COMMONLY USED NATURAL AND SYNTHETIC Uses Breast cancer, Cushing syndrome
CORTICOSTEROIDS FOR GENERAL USE:
Equiv.
SE Skin rash, Hepatotoxicity, Hypothyroidism
Activity1
Oral Dosage • Abused by body builders to lower circulating levels of
Dose Forms
Agent (mg) Notes cortisol in the body and prevent muscle loss
Anti- Salt-
inflammatory
Topical
Retaining • Also inhibits synthesis of all hormonally active steroids
Short- to medium-acting glucocorticoids
Hydrocortisone
(cortisol)
1 1 1 20 OIT CYP450 INHIBITOR
Cortisone 0.8 0 0.8 25 O Ketoconazole
Prednisone 4 0 0.3 5 O
Inhibits cholesterol side-chain cleavage, cytochrome
Prednisolone 5 4 0.3 5 OI
Methyl- 5 5 0.25 4 OI
MOA P450 enzymes and other enzymes necessary for
prednisolone synthesis of all steroids
Meprednisone2 5 - 0 4 OI Adrenal carcinoma, Hirsutism, Breast cancer, Prostate
Uses
Intermediate-acting glucocorticoids cancer, Cushing’s syndrome, Fungal infections
Triamcinolone 5 53 0 4 OIT Hepatotoxicity, Many drug interactions, Androgenic
Paramethasone2 10 - 0 2 OI SE
effect
Fluprednisolone2 15 7 0 1.5 O
Long-acting glucocorticoids • Potent inhibitor of CYP450 enzymes
Notes
Betamethasone 25-40 10 0 0.6 OIT • Itraconazole is an alternative to Ketoconazole
Dexamethasone 30 10 0 0.75 OIT
Mineralocorticoids
Fludrocortisone 10 0 250 2 Oral 11-B-HYDROXYLASE INHIBITOR
Desoxycorticoster Metyrapone
0 0 20 - IP
one acetate 2
Selective inhibitor of steroid 11-hydroxylation,
1 Potency relative to hydrocortisone, 2 Outside United States, 3 Triamcinolone MOA
interfering with cortisol and corticosterone synthesis
acetonide: Up to 100. O=Oral, I=Injectable, T=topical P=Pellets
Katzung BG. Basic and Clinical Pharmacology 14th ed. 2018. Diagnostic testing for adrenal function,
Uses
Cushing’s syndrome
GLUCOCORTICOIDS SE Dizziness, Gastrointestinal disturbances
SHORT-ACTING Notes
• Drug of choice for pregnant patients with Cushing’s
Low potency Hydrocortisone (cortisol) syndrome
Medium potency Fluticasone, Mometasone
High-potency Desoximetasone, Clobetasol GLUCOCORTICOID ANTAGONIST
Mifepristone (RU486) [X]
Activates glucocorticoid receptors, leading to altered Competitive inhibitor at the GC receptor as well as
MOA gene transcription. Suppresses inflammation. Replaces MOA
progesterone receptor
cortisol when deficient.
Uses Cushing Syndrome
Acute adrenal insufficiency associated with life-threatening
Abdominal pain and cramping, uterine cramping, nausea,
shock, chronic adrenal insufficiency (Addison's disease), SE
Uses headache, vomiting, diarrhea, dizziness, vaginal bleeding
congenital adrenal hyperplasia, Insect bites, Contact
dermatitis, Status asthmaticus, Thyroid storm Also used as an approved abortifacient for medical
Notes
None common when used topically or at physiologic abortion (usually together with misoprostol)
SE
replacement doses
• Hydrocortisone (cortisol) is the prototype CUSHING’S SYNDROME
glucocorticoid. • Syndrome caused by any condition that produces elevated
• Betamethasone is the glucocorticoid with the highest glucocorticoid levels
Notes
anti-inflammatory potency. • Causes of Cushing’s syndrome (CS)
• Fludrocortisone is the mineralocorticoid with the o iatrogenic Cushing’s syndrome due to exogenous steroid
highest salt-retaining potency intake is the most common cause
o adrenal CS due to cortisol-secreting adrenal adenoma
o pituitary CS (Cushing’s disease) due to ACTH-secreting
pituitary adenoma
o ectopic CS due to paraneoplastic ACTH production (usually
from lung tumors)
MNEMONICS FOR SIDE EFFECTS OF CORTICOSTEROIDS:
CUSHINGOID: Cataract, Ulcers, Striae, Hypertension, Hirsutism,
Immunosuppression, Infection, Necrosis of the femoral head, Glucose
elevation, Osteoporosis, Obesity, Impaired wound healing, and Diabetes
ESTROGENS AND PROGESTINS

ESTROGENS
• Major ovarian estrogen in women is estradiol
• MOA: involves entry into cells, binding to cytosolic receptors,
and translocation of the receptor-hormone complex into the
nucleus, where it modulates gene expression
• mixtures of conjugated estrogens from biologic sources
(Premarin) are used for hormone replacement therapy (HRT)
• synthetic estrogens with high bioavailability (ethinyl estradiol,
mestranol) are used as hormonal contraceptives
MINERALOCORTICOID MINERALOCOTICOID MECHANISM OF ACTION

AGONIST ANTAGONIST • Activates estrogen receptors; leads to changes in rates of
Drug transcription of estrogen-regulated genes
FLUDROCORTISONE [C],
SPIRONOLACTONE
DEOXYCORTICOSTERONE
Strong agonist of SIDE EFFECTS
mineralocorticoid receptors and • Breakthrough bleeding, Nausea, Breast tenderness
moderate activation of Blocks Aldosterone • Migraine, Thromboembolism (DVTs),
MOA
glucocorticoid receptors. receptors • Gallbladder disease
Increases Na reabsorption, • Hypertriglyceridemia, Hypertension,
K and H excretion • Premature closure of the epiphysis in young females,
Chronic adrenal insufficiency • Increased risk of breast and endometrial cancer (remedy: add
(Addison’s disease), Congenital progesterone to the preparation)
adrenal hyperplasia, Adrenal For Heart failure,
replacement therapy post- For hypokalemia due
ESTROGEN
Uses adrenalectomy to other diuretics,
Ethinyl Estradiol [X], Mestranol [X], Estradiol Cypionate,
for post-MI,
Adrenalectomy should be done Premarin, Estriol
hyperaldosteronism
for px with adrenal tumor such Primary hypogonadism, Postmenopausal hormonal
as pheochromocytoma Uses replacement therapy, Osteoporosis, Contraception,
Salt and fluid retention, Intractable dysmenorrhea
Hypokalemia, Congestive heart Hyperkalemia, anti- “PREMARIN is from PREgnant MARe’s urine”
SE failure, Muscle wasting, androgenic effect • Ethinyl Estradiol has low bioavailability
Osteoporosis, Glucose (e.g. gynecomastia) PO/TD/IM/Intravaginal
Notes
intolerance, Behavioral changes • Estradiol cypionate is IM with longer t½
• Additive hypokalemia with • Also, with weak • Premarin is a mixture of conjugated estrogen used in HRT
loop diuretics and thiazides antagonist effect at • Effects of Estrogen: growth of genital structures and
• Deoxycorticosterone is the the androgen
precursor of aldosterone receptor SYNTHETIC ESTROGEN
Notes • Fludrocortisone also has Diethylstilbestrol (DES) [X]
significant glucocorticoid activity Atrophic vaginitis, Hormone replacement therapy,
• Aldosterone is implicated in Uses Prevention of adverse pregnancy outcomes, Metastatic
myocardial and vascular fibrosis prostate cancer
and baroreceptor dysfunction Associated with Infertility, Ectopic pregnancy
Notes Clear cell vaginal adenocarcinoma in daughters of
mothers who took DES
GONADAL HORMONES AND INHIBITORS
PROGESTINS
Norgestrel [X], Norethindrone, Ethynodiol, Megestrol, Desogestrel,
Norelgestromin, Norgestimate, Etonogestrel, Progesterone,
Levonorgestrel, Dydrogesterone, Ulipristal, Tibolone, Norethisterone,
Dienogest
Activates progesterone receptors; Changes rates of
MOA
transcription of progesterone-regulated genes
Hormone replacement therapy (given together with
Estrogen, to prevent estrogen-induced endometrial
Uses cancer), contraception, assisted reproduction (for
maintenance of pregnancy), anovulation induction
(given in high doses to suppress FSH and LH)
Hypertension, Decreased HDL, Weight gain, Reversible • BIPHASIC or TRIPHASIC
SE decrease in bone mineral density, Delayed resumption of o combination preparations in which the progestin or estrogen
ovulation after use dosage, or both, changes during the month
• Prevents estrogen-induced endometrial cancer when o more closely mimics hormonal changes in menstrual cycle
used in combination • PROGESTIN-ONLY PREPARATIONS
• Megestrol is used as an appetite stimulant o recommended for breastfeeding moms since they do not affect
• Medroxyprogesterone has a better oral bioavailability lactation
• L-Norgestrel and Norethindrone has more androgenic effect
• Effects of progesterone: induces secretory changes in Postcoital Contraceptives/ Emergency Contraception
Notes the endometrium, stabilize the endometrium, affect • prevent pregnancy if administered within 72 h after
carbohydrate metabolism and stimulate deposition of unprotected intercourse
fat, high doses suppress FSH and LH secretion • progestin (L-Norgestrel) alone, estrogen alone, combination of
TIBOLONE is a synthetic steroid with weak estrogenic, estrogen and progestin
progestogenic and androgenic activity, and hence is an o progestin-only preparation causes fewer side effects than the
agonist of the estrogen, progesterone and androgen
estrogen-containing preparations
receptor. It is primarily used in menopausal hormone
therapy, postmenopausal osteoporosis and endometriosis.
COMBINED ORAL CONTRACEPTIVE
Oral Contraceptives: Contraindications and Disease Risk ESTRADIOL + NORETHINDRONE [X]
Contraindications ETHINYL ESTRADIOL + DESOGESTREL/NORGESTREL
ETHINYL ESTRADIOL + DROSPIRENONE
Absolute
ETHINYL ESTRADIOL + NORGESTIMATE
• Women age >35 years who smoke > 15 cigarettes per day ETHINYL ESTRADIOL + NORETHISTERONE
• Known ischemic heart disease or multiple risk factors for Combined oral contraceptive, activates estrogen and
cardiovascular disease (older age, smoking, diabetes, and progesterone receptors, inhibits ovulation, effects on
hypertension) MOA cervical mucus gland, uterine tubes and endometrium
• Past thromboembolic event, stroke or known thrombogenic mutations lead to decreased fertility, inhibit ovulation when given
• Complicated valvular heart disease before the LH surge
• Complicated solid organ transplantation Contraception, Hypogonadism, Acne, Hirsutism,
• Hypertension (systolic >160 mmHg or diastolic >100 mmHg) Uses
Dysmenorrhea, Endometriosis
• Systemic lupus erythematous (positive or unknown Breakthrough bleeding, Nausea, Breast tenderness, Skin
antiphospholipid antibodies pigmentation, Thromboembolism (DVTs), Breast cancer
• Cirrhosis, hepatic adenoma or hepatoma (earlier onset), headache, skin pigmentation, depression,
• Pregnancy and early postpartum (<21 days) SE weight gain and hirsutism for older OCPs
• undiagnosed abnormal uterine bleeding OCPs: increase HYPERCOAGUABILITY
Relative Breakthrough bleeding – bleeding in between dosages of OCPs
• Hypertension (adequately controlled or systolic 140-159 or • Lifetime risk of breast cancer is NOT changed
diastolic 90-99) Notes
• Combined OCPs may be used for androgen-induced hirsutism
• Women receiving anticonvulsant drug therapy
• Women following bariatric surgery (malabsorptive procedure) PROGESTIN-ONLY CONTRACEPTIVE
Disease Risks
MEDROXY-PROGESTERONE ACETATE [D]
Increased
Activates progesterone receptors. Prevents conception
• Coronary heart disease- increased in smokers >35; no relation to
MOA by altering cervical mucus and creating a hostile
progestin type
endometrium
• Hypertension-relative risk 1.8 (current users) and 1.2 (previous
Uses Contraception, Hormone replacement therapy
users)
• Venous thrombosis relative risk ~4; may be higher with third- Breakthrough bleeding, Hair loss, Dysmenorrhea,
SE
generation progestin, drospirenone, and patch; compounded by obesity Delayed return of fertility, Osteoporosis
(tenfold increased risk compared with nonobese, no OCP); markedly Notes • Intramuscular depot preparation (Depo-Provera)
increased with factor V Leiden or prothrombin gene mutations
• Stroke—slight increase; unclear relation to migraine headache POSTCOITAL CONTRACEPTIVE
• Cerebral vein thrombosis-relative risk ~13-15; synergistic with LEVONORGESTREL,
prothrombin gene mutation ETHINYL ESTRADIOL + LEVONORGESTREL
• Cervical cancer—relative risk 2—4 Activates estrogen and/or progesterone receptors.
MOA
• Breast cancer—may increase risk, particularly in carriers of Thickens cervical mucus. Inhibits ovulation.
BRCA1 and possibly BRCA2 Uses Emergency contraception
Decreased Severe nausea, vomiting, Breast tenderness, Irregular
Ovarian cancer—50% reduction in risk SE Bleeding, Headache, Dizziness (fewer SE compared to
Endometrial cancer—40% reduction in risk estrogen alone and combination contraceptives)
CONTRACEPTIVES *Do not protect against STIs Must be taken within 72 hours of unprotected sexual
Notes
intercourse (not effective once implantation has occurred)
CONTRACEPTIVES
HORMONAL CONTRACEPTIVES
SELECTIVE ESTROGEN
• contain either a combination of an estrogen and a progestin or a RECEPTOR MODULATORS (SERMS)
progestin alone • mixed estrogen agonists that have estrogen agonist effects in some
• available in a variety of preparations tissues and act as partial agonists or antagonists in other tissues
o oral pills TAMOXIFEN [D], TOREMIFENE [D]
o long-acting injections (good for 3 months) Estrogen antagonist actions in breast tissue and CNS.
MOA
o implants (good for 3 years) Estrogen agonist effects in uterus, liver and bone.
o transdermal patches Hormone-responsive breast cancer, prophylaxis of
o vaginal rings Uses breast CA esp. in those with high risk
o intrauterine devices (IUDs) Given for breast cancer patients who are ER+ PR+
MOA of Combination Hormonal Contraceptives Hot flushes, Thromboembolism (DVTs), Endometrial
SE
• inhibition of ovulation (the primary action) hyperplasia, Endometrial cancer
• effects on the cervical mucus glands, uterine tubes, and • Prevents osteoporosis in post-menopausal women
and decreases risk of atherosclerosis at the risk of
endometrium that decrease the likelihood of fertilization and
causing endometrial cancer
implantation Notes
Types of Oral Contraceptives FLUVESTRANT is a FULL ESTROGEN RECEPTOR ANTAGONIST
• MONOPHASIC (No agonist effect) for hormone receptor positive metastatic
breast cancer resistance to Tamoxifen
o combination estrogen-progestin tablets that are taken in
constant dosage throughout the menstrual cycle
RALOXIFENE [X] GNRH ANTAGONISTS
Estrogen antagonist actions in breast tissue, uterus and Ganirelix [X], Cetrorelix, Abarelix, Degarelix
MOA CNS. Estrogen agonist effects in liver and bone.
Agonist of GnRH receptors. Increased LH and FSH
Increases bone mineral density.
secretion with INTERMITTENT administration. Reduced
Osteoporosis, Breast cancer prevention
LH and FSH secretion with PROLONGED CONTINUOUS
Uses MOA
Preferred in patient with history of breast cancer in the administration (due to downregulation of GnRH
management of hot flushes. receptors in the pituitary cells that normally release LH and
SE Hot flushes, Thromboembolism (DVTs) FSH)
• Reduces incidence of breast cancer in women who are Ovarian Suppression, Controlled ovarian
Notes at very high risk Uses hyperstimulation, Endometriosis, Myoma uteri, Central
• No estrogenic effects on endometrial tissue Precocious puberty, Advanced Prostate cancer
Note the difference in the MOA of Tamoxifen and Raloxifene (location). Also Hot flushes, Sweats, Headache, Light-headedness,
appreciate the difference in usage of tamoxifen as an agonist and SE Injection site reactions, Nausea, Osteoporosis,
antagonist Gynecomastia, Reduced libido, Decreased hematocrit
Dr. Rodriguez
• Symptoms of hypogonadism with continuous
treatment
CLOMIPHENE [X]
Temporary exacerbation of precocious puberty or
Partial agonist of estrogen receptors in pituitary. Notes
prostate cancer, Apoplexy and Blindness during the first
MOA Reduces negative feedback by estradiol. Increases FSH
few weeks of therapy (remedy: co-administer
and LH output.
Flutamide, an androgen receptor antagonist)
Induction of ovulation for women who want to get
pregnant
Uses Acts as antagonist to estrogen receptors in the pituitary GLUCOCORTICOID AND PROGESTERONE
→ inhibit negative feedback mechanism by estrogen → RECEPTOR ANTAGONIST
leads to pituitary stimulation causing ↑ LH and FSH MIFEPRISTONE (RU-486) [X]
Hot flushes, Eye symptoms (afterimages), Headache, Pharmacologic antagonist of glucocorticoid and
SE Constipation, Reversible hair loss, Ovarian enlargement, MOA
progesterone receptors
Multiple pregnancies (10%) Uses Medical abortion, Cushing's syndrome
Increased risk of low-grade ovarian cancer with long- Vaginal bleeding, abdominal pain, GI upset (vomiting,
Notes SE
term use diarrhea), uterine cramping, nausea, headache, dizziness
• Combination with misoprostol results in abortion of 95%
MISCELLANEOUS ESTROGEN ANTAGONISTS of early pregnancies
Notes Complication: failure to induce complete abortion àsepsis
AROMATASE INHIBITOR d/t unusual organisms
ANASTROZOLE [X], LETROZOLE, EXEMESTANE (Clostridium sordelli)
Reduces estrogen synthesis by inhibiting aromatase
MOA Aromatase is the enzyme which converts Testosterone to ANDROGENS
Estrogen(Estradiol) TESTOSTERONE
Uses Breast cancer, Precocious puberty • synthesized from progesterone and dehydroepiandrosterone
Hot flushes, Musculoskeletal disorders, Osteoporosis, (DHEA)
SE
Joint pains • partly bound to sex hormone-binding globulin (SHBG)
• Effective against breast cancers that have become resistant o increased by estrogen, thyroid hormone and cirrhosis
Notes to tamoxifen
o decreased by androgen, growth hormone and obesity
Exemestane is an IRREVERSIBLE inhibitor
o converted in several organs (e.g. prostate) to
dihydrotestosterone (DHT), which is the active hormone in
OVARIAN INHIBITOR (ANTI-ANDROGEN) those tissues
DANAZOL [X]
Weak cytochrome P450 inhibitor and partial agonist of CLINICAL USE OF TESTOSTERONE
MOA
progestin and androgen receptors • Replacement therapy in hypogonadism
Endometriosis, Fibrocystic disease, Hemophilia, • Stimulate RBC production in certain anemias
Uses
Angioneurotic edema • Promote weight gain in patients with wasting syndromes (e.g.
Acne, Hirsutism, Weight gain, Menstrual disturbances, AIDS patients)
SE
Hepatic dysfunction • performance enhancement in athletes
• Contraindicated during pregnancy and breast-feeding o exploited illicitly to increase muscle bulk and strength
Notes
May also act on Glucocorticoid receptors
• Effects of androgen: secondary sexual characteristics, fertility
and libido, male pattern baldness, increases muscle mass,
GNRH AGONISTS increased RBC production, decreased urea nitrogen excretion,
LEUPROLIDE, GONADORELIN [B], maintains normal bone density
GOSERELIN, HISTRELIN, NAFARELIN, TRIPTORELIN
All are Preg Cat X except Gonadorelin ANDROGEN RECEPTOR ANTAGONIST
Agonist of GnRH receptors. Increased LH and FSH
secretion with INTERMITTENT administration. Reduced Flutamide [D], Bicalutamide, Nilutamide
LH and FSH secretion with PROLONGED CONTINUOUS MOA Competitive antagonist at androgen receptor
MOA
administration (due to downregulation of GnRH Uses Prostate cancer, Surgical castration (Nilutamide)
receptors in the pituitary cells that normally release LH and SE Gynecomastia, Hot flushes, Impotence, Hepatoxicity
FSH) • Less hepatotoxicity with bicalutamide and nilutamide
Ovarian Suppression, Controlled ovarian • GnRH analogs (leuprolide) must be co-administered
Uses hyperstimulation, Endometriosis, Myoma uteri, Central Notes
with flutamide to prevent acute flare-up of prostate
Precocious puberty, Advanced Prostate cancer cancer
Hot flushes, Sweats, Headache, Light-headedness,
SE Injection site reactions, Nausea, Osteoporosis,
CYPROTERONE [X], CYPROTERONE ACETATE
Gynecomastia, Reduced libido, Decreased hematocrit
Antagonist at androgen receptor. Marked progestational
• Symptoms of hypogonadism with continuous
MOA effect that suppresses the feedback enhancement of LH
treatment
and FSH.
Temporary exacerbation of precocious puberty or
Notes Hirsutism, Component of combined oral contraceptives,
prostate cancer, Apoplexy and Blindness during the first Uses
few weeks of therapy (remedy: co-administer Decreases sexual drive in men
Flutamide, an androgen receptor antagonist) Hepatotoxicity, Adrenal suppression, Depression,
SE
Gynecomastia, Galactorrhea, Thromboembolism
Notes Orphan drug status
ANDROGEN SYNTHESIS INHIBITOR INSULIN [B]

5-ALPHA-REDUCATSE INHIBITORS • Rapid: LISPRO, ASPART, GLULISINE
• Short: REGULAR (Humulin R)
FINASTERIDE [X], DUTASTERIDE
• Intermediate: NPH, LENTE (Humulin N)
Inhibits 5a-reductase enzyme that converts Drug
• Long: ULTRALENTE, GLARGINE, DETEMIR,
testosterone to dihydrotestosterone
INSULIN DEGLUDEC
MOA Dihydrotestosterone is the most potent form of • Premixed Insulin: Humulin 70 NPH/30 Regular
testosterone, essential in the development of male Activates insulin receptors → Reduces circulating glucose
secondary sexual characteristics. by increasing glucose uptake; Promote glucose transport
Benign prostatic hyperplasia (BPH), Male-pattern MOA
and oxidation, glycogen lipid and protein synthesis and
baldness, Hirsutism regulates gene expression
Uses
Giving 5-alpha reductase aids in the management of Type 1 and Type 2 Diabetes mellitus, Diabetic
Uses
smooth muscle hypertrophy in the prostate. emergencies (DKA, HHS – rapid acting), Hyperkalemia
SE Impotence (rare), Gynecomastia, Depression Hypoglycemia, Insulin allergy, Immune insulin resistance,
• Controversial use in prevention of prostate cancer Lipodystrophy at injection site, Weight Gain, Increased
Notes SE
Dutasteride is newer with longer t½ cancer risk (linked to insulin resistance and
hyperinsulinemia in Px with prediabetes and T2DM)
• Beta-blockers may mask signs of hypoglycemia
PANCREATIC HORMONES • All insulin preparations contain zinc
ANTIDIABETIC DRUGS AND GLUCAGON • Parenteral (IV or SC)
• Effects of insulin: increased glycogen and protein
synthesis, decreased protein catabolism, increased TG
storage
• Rapid acting insulins are injected a few mins prior to
meals and they are the preferred insulin for continuous
Notes
SC infusion devices
• Short-acting insulins are injected more than an hour
before a meal
• Intermediate acting insulins are often combined with
regular and rapid acting insulins
• Long acting insulins are called "peakless" insulins
• *The ratio of zinc and other substances to insulin
Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2018 influences the rate of release and duration of action
Okay beshies, favorite topic to and mga high yield rin in practice, so know this Rapid acting insulin has “amino acids” in their name. Lis (lysine) Pro (Proline).
by heart. J Just to guide you through, start by creating a mental picture of Etc. Because to make them rapid acting, binaliktad yung positions ng mga
what’s ahead. We’ll first discuss about insulin, then followed by the non- amino acid na ito para maging rapid acting.
insulin anti-DM drugs. We will follow the chart above. Glargine sounds like LARGE! Tunog Long yung effect
Dr. Rodriguez DeteMIR ends with MIR for Myristic Acid. A fatty acid added to the structure
to make it long acting
Dr. Rodriguez, Im
DIABETES MELLITUS Insulin Types and Activity
• chronic disorder of carbohydrate, fat, and protein metabolism Peak Duration
due to a relative or absolute deficiency in insulin secretory Rapid Acting 0.25 to 0.5 3 to 4
response Lispro, Aspart, Glulisine
Types of Diabetes Mellitus Short Acting 0.5 to 3 5 to 7
• TYPE 1 DIABETES Regular
o usually has its onset during childhood Intermediate Acting 8 to 12 18 to 24
NPH, Lente
o results from autoimmune destruction of pancreatic b cells
Long Acting 8 to 16 18 to 28
• TYPE 2 DIABETES
Ultralente
o progressive disorder characterized by increasing insulin
Ultra-Long Acting No peak >24
resistance and diminishing insulin secretory capacity
Glargine, Detemir, Lantus
o frequently associated with obesity and is much more common
than type 1 diabetes • 0.25 TO 0.50 OF AN HOUR: 15-30mins
o usually has its onset in adulthood • When mixing intermediate with rapid acting insulin, NPH preferred
Type 1 DM: no C-peptide. Type 2: have C-peptide over Lente because Lente retards the onset of action of regular insulin
Duration of Action of Different Types of Insulin
INSULIN
• synthesized as prohormone proinsulin
• cleavage of proinsulin and cross-linking result in formation of
insulin and a residual C-peptide
• C-peptide is used to:
o differentiate type 1 and type 2 DM
o diagnose MEN
o rule out factitious hypoglycemia
o assess insulin resistance in patients with PCOS
• neither proinsulin nor C-peptide appears to have any
physiologic actions
MOA of Insulin
• binds to a tyrosine kinase receptor, which phosphorylates itself Figure 41-1. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
and a variety of intracellular proteins when activated by the

hormone STRATEGIES FOR INSULIN THERAPY
• activation of phoshphatidylinositol-3 kinase pathway and MAP • BASAL BOLUS
kinase pathway o most physiologic strategy because it copies the body’s
• translocation of glucose transporters (especially GLUT 4) to normal production of insulin as closely as possible
the cell membrane o long-acting insulin (BASAL) + short-acting insulin with every
o increase in glucose uptake meal (BOLUS)
o increased glycogen synthase activity • SLIDING INSULIN SCALE
o increased glycogen formation o fixed amounts of long-acting insulin to be given routinely
Insulin is also capable of inducing entry of K+ (potassium) into cells o amount of short-acting insulin varied depending on pre-
Dr. Pereyra-Borlongan prandial CBG
Routes of Insulin Administration: subcutaneous and IV For the secretagogues look at the ending they all end in -IDE. So if nalito ka na
OTHER ROUTES REASON WHY NOT USED? sa buhay mo, hahaha pag Nakita mo DM drug tapos may IDE highly likely
Does not result in a reproducible and sufficient that it’s under SECRETAGOGUES. BUT THERE ARE EXCEPTIONS. Let’s
Transdermal discuss later. Park muna sa brain cells niyo. Goal ng secretagogues based sa
transfer of insulin across the skin
Oral Lack of a specific peptide carrier system in the gut name is to secrete. Later yung susunod, mga SENSITIZERS, which increases
Bioavailability was low and metabolic effect lasted sensitivity of cells to insulin.
Intranasal For the indication of these di ko nauulit ulitin, it’s for DM Type 2.
too short to be of clinical usefulness
Intramuscular Overall metabolic response not comparable to SC MOA of all is: CLOSES ATP SENSITIVE POTASSIUM CHANNEL. Tignan niyo
Most promising; comparable to SC and IV but is picture sa taas. Pag blocked yun, di makakalabas si potassium, mas
Inhalation magiging positive yung inside ng cell. If mas positive sa loob, diba
still presently in Phase III trials (Exubera)
nagdedepolarize ang cell = pag ganun nangyari, nasesecrete yung laman
na insulin ni beta cell.
ON INSULIN: HONEYMOON PERIOD For SE: Don’t forget HYPOGLYCEMIA
• period in type 1 DM when exogenous insulin requirements Dr. Rodriguez
decrease due to an increase in the endogenous production of

insulin 1ST GENERATION SULFONYLUREAS
• initiation of insulin therapy causes activation of residual Chlorpropamide, Tolbutamide, Tolazamide
pancreatic beta cells Hypoglycemia, Weight gain, Disulfiram reaction,
• transient phase followed by total lack of endogenous insulin Hyperemic flush after alcohol ingestion, Dilutional
SE
production hyponatremia, Hematologic toxicity,
Hypersensitivity reaction, rash
INSULIN AND HYPOGLYCEMIA • Tolbutamide and chlorpropamide are highly protein
Hypoglycemia bound drugs → Drugs that compete for protein binding
• NEUROGLYCOPENIC SYMPTOMS may enhance hypoglycemic effects
o result of central nervous system (CNS) glucose deprivation Notes • Requires islet cell function
o EXAMPLES: • Lower Potency, Greater Toxicity
High propensity to cause hypoglycemia especially
§ behavioral changes, confusion, fatigue, seizure and loss of
among elderly patients that’s why it is seldom used
consciousness
• NEUROGENIC (OR AUTONOMIC) SYMPTOMS
o result of CNS-mediated sympathoadrenal discharge 2ND GENERATION SULFONYLUREAS
o EXAMPLES: Glipizide, Glimepiride, Glyburide/Glibenclamide, Gliclazide
§ adrenergic symptoms: palpitations, tremor, anxiety Hypoglycemia (less), Weight gain, Photosensitivity,
§ cholinergic symptoms: sweating, hunger, paresthesia SE Hematologic toxicity,
• At Risk for Insulin-related Hypoglycemia: Advanced renal Cholestatic jaundice (Glibenclamide)
disease, elderly, children <7 y/o • Contraindicated in patients with hepatic impairment
and renal insufficiency
Notes
• Requires islet cell function
NONINSULIN ANTIDIABETIC AGENTS May come in combination with Metformin
MEGLITINIDES
Meglitinide, Repaglinide, Nateglinide, Mitiglinide
Hypoglycemia (least), Headache,
Upper respiratory tract infections
SE
Has the lowest risk of developing hypoglycemia since they
have short duration of action
• Used in diabetics with sulfa allergies
• Nateglinide has the least incidence of hypoglycemia
and may be used in CKD patients
Notes
• Requires islet cell function
• Very short DOA (4-8hrs only)
• May come in combination with Metformin
INSULIN SENSITIZERS
Figure 41-3. Katzung and Trevor’s Pharmacology Examination and Board Review. 11 ed. 2015
BIGUANIDE
th
MOA OF BIGUANIDES
NON-INSULIN
ANTI-DIABETIC AGENTS • reduces postprandial and fasting glucose levels
https://qrs.ly/99dvee1 • activates AMP-stimulated protein kinase leading to inhibition
hepatic and renal gluconeogenesis
• other effects:
INSULIN SECRETAGOGUES o stimulates glucose uptake and glycolysis in peripheral tissues
MOA OF INSULIN SECRETAGOGUES o slows glucose absorption from the gastrointestinal tract
• stimulate the release of endogenous insulin by promoting closure of o reduces plasma glucagon levels
potassium channels in the pancreatic B-cell membrane o reduce the risk of diabetes in high-risk patients
• depolarizes the cell and triggers insulin release Metformin
• not effective in patients who lack functional pancreatic B cells FIRST LINE: T2DM, also DM Prevention
Uses
PCOS, DOC for OBESE Diabetic
Most common: GI disturbance,
Worse SE: lactic acidosis
SE
(especially in renally and hepatically impaired patients,
hence contraindicated), Vit B12 malabsorption, weight loss
• May also cause slowing of glucose absorption from GIT
and decreased plasma glucagon
• Causes a decrease in endogenous insulin production by
Notes
increasing insulin sensitivity of tissues "Insulin Sparing
Effect" therefore does not have weight gain as a SE
Does NOT cause hypoglycemia
Metformin and its cousin Thiazolidinediones bypass the insulin receptor.
Both of these medications act via gene expression to sensitize tissue
receptor to insulin
THIAZOLIDINEDIONE DPP-4 INHIBITORS

MOA OF THIAZOLIDINEDIONES Sitagliptin, Saxagliptin, Linagliptin,
Vildagliptin, Teneligliptin
• increase target tissue sensitivity to insulin by activating the
Headache, Nasopharyngitis, Upper respiratory tract
peroxisome proliferator-activated receptor-gamma nuclear SE
infections, hypersensitivity reactions, pancreatitis
receptor (PPAR-g receptor) • Administered orally as monotherapy or in
• increase glucose uptake in muscle and adipose tissue combination with metformin
• inhibit hepatic gluconeogenesis and have effects on lipid Notes Incretins are substances in the body that augments
metabolism and the distribution of body fat
glucose-stimulated insulin release. Some can suppress
• reduce both fasting and postprandial hyperglycemia. glucagon release while some would have anorectic effect
• reduce the risk of diabetes in high-risk patients
SGLT-2 INHIBITOR
Pioglitazone, Rosiglitazone, Troglitazone
Fluid retention, Anemia, Weight gain, Congestive heart Empagliflozin, Dapagliflozin, Canagliflozin
failure, Bone Fractures especially in women, Macular NA-GLUCOSE CO-TRANSPORTER 2 (SGLT 2) INHIBITOR
SE edema, Dyslipidemia (↑ HDL & LDL, ↓ TG), MOA → inhibits reabsorption of glucose in the kidneys back to the
Rosiglitazone Cardiovascular events (MI) blood → excretion of glucose out in the urine.
Troglitazone Hepatotoxicity URINARY TRACT INFECTION, Dizziness,
• CI: Pregnancy, chronic liver disease and congestive SE strong smell of urine, edema, weakness, nausea,
heart failure vomiting, decrease in the amount of urine
• Pioglitazone reduces mortality and macrovascular • Do NOT use among renally impaired patients
events (myocardial infarction and stroke) Notes • Increased incidence of UTI since you have higher sugar in
• Rosiglitazone binds to PPAR-gamma ONLY your urine
Notes
• PPAR regulates transcription of genes encoding • Used by many to lose weight
proteins involved in carbohydrate and lipid SUPPLEMENT:
metabolism BILE ACID SEQUESTRANT
• May increase risk for developing Bladder Cancer Drug COLESEVELAM [B]
• Increased risk by 63% for bladder CA – Pioglitazone MOA Binds bile acids. Lowers glucose through unknown mechanism
Uses Type 2 diabetes mellitus
ALPHA-GLUCOSIDASE INHIBITOR constipation, dyspepsia, myalgia, asthenia
Acarbose, Miglitol, Voglibose SE Lack of bile acids will cause malabsorption of fat-
soluble vitamins and steatorrhea.
Inhibits intestinal a-glucosidases → reduce conversion
MOA of starch and disaccharides to monosaccharides →
reduce post prandial hyperglycemia SECTION SYNTHESIS
Gastrointestinal disturbance (flatulence, diarrhea, Identify the drug class of the following drugs:
SE abdominal pain), Hypoglycemia (when taken with 1. Glipizide
sulfonylureas), Increased liver enzymes 2. Metformin
• Relatively minor glucose-lowering benefit 3. Drugs ending in -GLITAZONE
• Treat hypoglycemia with oral glucose (dextrose) NOT 4. Drugs ending in -GLINIDE
sucrose, because absorption is impaired 5. Drugs ending in -BOSE
Notes 6. Drugs ending in -GLIFOZIN
• Taken immediately before a meal
• Contraindicated in patients with renal and hepatic 7. Drugs ending in -GLIPTINS
impairment and intestinal disorders Look at the names of secretagogues. They all end in -IDE. So if they ask you
about DM drugs and it ends in -IDE, the MOA will be related to increasing
Kaya may flatulence kasi di na didigest yung mga carbs mo sa GI tract. Eh
the insulin secretion. With the exception of GLP-1 Angonist. Second
favorite yan ng mga bacteria sa tiyan mo. As a result busog sila, so nagbburp
generation SURs all start in “G” Meglitinides end in GLINIDE – “Glinide ni
sila ng maraming gas (Flatulence) haha J - mga gas forming bacteria
Dr. Rodriguez Meg yung floor”
Amylin analogs have AMYLIN in their name e.g.. prAMLINtide
AMYLIN ANALOG - GlitazONEs are ThiazolidinediONES (One true PPAR [pair])
- BOSE are Alpha-Glucosidase inhibitors – related to glucose
PRAMLINTIDE
- GLP1 inhibitors mnemonic: GLP (Read as GULP): Diba sa 7/11 may Gulp na
Activates amylin receptors. Reduce post-meal glucose drink? Imagine mo may person na bumibili ng GULP, pangalan ay LIRA.
MOA excursions Suppresses glucagon release. Delays gastric Nagexena si LIRA sa 7/11 dahil mali ang order niya”
emptying. Stimulates CNS to reduce appetite (anorectic effect). Dr. Rodriguez, Im
Uses Also used for TYPE 1 DM DRUGS FOR OBESITY

Hypoglycemia, Gastrointestinal disturbances, nausea,
SE SUPPLEMENT:
anorexia, headache
• Administered as an injectable preparation (SC) together An appetite suppressant which is an
PHENTERMINE
Notes with insulin to control post-prandial glucose amphetamine derivative. Side effects will be
[X]
similar with amphetamine
• Short t1/2 of 48mins
ORLISTAT (Xenical)
INCRETIN MODULATORS MOA
Inhibits gastrointestinal and pancreatic lipases. Reduces
MOA OF GLP-1 AGONIST AND DPP4 INHIBITOR absorption of fats.
• Activates GLP-1 receptors → reduction of post-meal glucose Uses Obesity, Type 2 diabetes
excursions. Weight loss, Flatulence, Steatorrhea, Fecal incontinence,
SE Malabsorption of fat-soluble vitamins (A, D, E, K),
• Inhibits dipeptidyl peptidase-4 (DPP-4) that degrades GLP-1 Hepatotoxicity
and other incretins → raises circulating GLP-1 levels. • Rebound weight gain upon discontinuation
o Reduces post-meal glucose excursions. Notes Contraindicated in pregnancy, reduced hepatobiliary
• Ultimately for both: Augments glucose-stimulated insulin release function and malabsorption states
from pancreatic B cells. Retards gastric emptying. Inhibits glucagon
secretion. Produces satiety SIBUTRAMINE
GLP-1 AGONIST Inhibits norepinephrine and serotonin reuptake in the
MOA
CNS. Reduces appetite (anorectic effect).
Exenatide, Liraglutide,
Lixisenatide, Semaglutide, Dulaglutide Uses Obesity
Hypoglycemia, Acute pancreatitis, Nausea, Vomiting, Dry mouth, Gastrointestinal disturbance, Tachycardia,
SE SE Hypertension, Cardiovascular events (myocardial
Headache, Anorexia, Mild Weight Loss
infarction, arrhythmias), Stroke
• Administered as an injectable preparation
• Withdrawn due to increased risk of cardiovascular events
(SC - Long-acting injectables )
Notes and strokes
• Used in combination with metformin or a sulfonylurea Notes
Familiar with Reductil? This has been banned since this
• Liraglutide has possible thyroid carcinoma risk drug is a relative of Methamphetamine
RIMONABANT Active Vitamin D
Organ PTH
Selectively blocks cannabinoid-1 (CB-1) receptors. Metabolites
MOA Calcium and
Reduces appetite (anorectic effect). Direct effect is increased
Uses Obesity, Smoking cessation, Drug addiction phosphate
calcium and phosphate
resorption increased
SE Suicidality, Depression, Nausea resorption;
by continuous high
Withdrawn because of increased risk of suicides, depression Bone indirect effect is promoting
Notes concentrations. Low
and other serious psychiatric problems mineralization by increasing
intermittent doses
the availability of calcium
increase bone
and phosphate
GLUCAGON formation
GLUCAGON (Secreted by A cells of pancreas) Net Serum calcium
MOA Activates glucagon receptors
effect on increased, Serum calcium and
serum serum phosphate phosphate both increased
Severe hypoglycemia, Diagnosis of endocrine disorders,
levels decreased
Beta-blocker overdose, Radiology of the bowels
Uses Glucagon can increase heart rate and force of contraction Drug SERM: RALOXIFENE [X]
Increases hepatic glycogenolysis and gluconeogenesis Interacts selectively with estrogen receptors leading
Relaxes smooth muscle
MOA to inhibition of bone resorption w/o stimulating breast or
SE Nausea, Vomiting, Hypotension endometrial hyperplasia
Glucagon-secreting tumors (glucagonomas) present with Uses Osteoporosis
Notes decreased amino acids in blood, anemia, diarrhea, weight SE Increased risk of VTE
loss and necrolytic migratory erythema
PARATHYROID HORMONE
DRUGS THAT AFFECT BONE • acts on membrane G-protein-coupled receptors to increase
cAMP in bone and renal tubular cells
AND MINERAL HOMEOSTASIS
• inhibits calcium excretion, promotes phosphate excretion and
stimulates the production of active vitamin D metabolites
• promotes bone turnover by increasing the activity of both
osteoblasts and osteoclasts
o osteoclast activation is not a direct effect and instead results
from PTH stimulation of osteoblast formation of RANK ligand
(RANKL)
• at high doses, net effect of elevated PTH is increased bone
resorption, hypercalcemia, and hyperphosphatemia
• low intermittent doses of PTH produce a net increase in bone
formation
• Stimulus: decreased free ionized calcium stimulates PTH release
MNEMONICS: Parathyroid Hormone
What are the signs and symptoms of excess PTH?
Painful bones
Renal stones
Abdominal groans
Psychiatric overtones
CALCITONIN
• Peptide hormone secreted by parafollicular C cells in the thyroid gland
• decreases serum calcium and phosphate by inhibiting bone
resorption and inhibiting renal excretion of these minerals
• bone formation is not impaired initially, but ultimately it is reduced
• MNEMONIC: Calcitonin means CALCium INside the bone
RECOMBINANT PARATHYROID HORMONE

Teriparatide
Acts through PTH receptors to produce a net increase in
MOA
bone formation, stimulates bone turnover
Uses Osteoporosis
Hypercalcemia, Hypercalciuria, arthralgia, rhinitis, nausea,
SE
weakness, dizziness, pharyngitis, dyspepsia, rash
• Must be administered in low intermittent doses to
Notes stimulate bone formation
• Used IV for osteoporosis
VITAMIN D
Drugs under this section will be divided mainly under hormonal regulators, • MOA: Regulates gene transcription via the vitamin D receptor.
and the non-hormonal regulators. Stimulates intestinal calcium absorption, bone resorption, renal
Dr. Rodriguez
calcium and phosphate reabsorption. Decrease PTH, promote
Innate Immunity
HORMONAL REGULATORS • USES:
Active Vitamin D o Vitamin D deficiency (rickets, Osteomalacia, intestinal
Organ PTH
Metabolites osteodystrophy, CKD, chronic liver disease,
Indirectly increases hypoparathyroidism, nephrotic syndrome)
calcium and o Osteoporosis, psoriasis, Renal Failure, malabsorption
Increased calcium and
Intestine phosphate absorption • SE: Hypercalcemia, Hyperphosphatemia, Hypercalciuria
phosphate absorption
by increasing
Vitamin D metabolites INACTIVE
Increased resorption of ERGOCALCIFEROL, CHOLECALCIFEROL
Decreased calcium
calcium and phosphate but • Commonly added to dairy products and other food
excretion,
Kidney usually net increase in products
increased phosphate Notes
urinary calcium due to • Given topically for psoriasis; given with calcium
excretion
effects in GI tract and bone supplements for osteoporosis
ACTIVE CINACALCET
CALCITRIOL, DOXERCALCIFEROL, PARICALCITOL, CALCIPOTRIENE Cinacalcet
• The active form Calcitriol is preferred in patients with MOA Activated calcium-sensing receptor → Inhibits PTH secretion
CKD, chronic liver disease and hypoparathyroidism
Uses HyperPTH
• Doxercalciferol is a prodrug that is converted in the
liver to 1,25-dihydroxyvitaminD SE Nausea
Notes • Paricalcitol, Calcipotriene are analogs of calcitriol and are “Sinakal siya! Patay!, Cinacal siya, PTHay”
Dr. Rodriguez
used topically for psoriasis and are being investigated for
malignancies and inflammatory disorders
• Doxercalciferol, Paricalcitol and Calcipotriene cause ANTIBIOTIC AGENTS
less hypercalcemia and hypercalciuria OVERVIEW
CALCITONIN
Calcitonin, Salcatonin
Acts through calcitonin receptors to inhibit bone resorption
MOA
MNEMONIC: Calcitonin means CALCium INside the bone
Paget's disease of bone, Hypercalcemia, Osteoporosis,
Uses INTRODUCTION TO ANTIBACTERIALS:
Tumor marker for thyroid cancer
SE Rhinitis, Nausea, Vomiting, Facial flushing, Tingling ANTIBACTERIAL AGENTS 1 AN OVERVIEW
https://qrs.ly/78dvee2 https://qrs.ly/ncdvee5
• Administered as a nasal spray
Notes Used for osteoporosis but is less effective than
bisphosphonates and teriparatide
NON-HORMONAL REGULATORS
BISPHOSPHONATES
Alendronate, Etidronate, Ibandronate, Pamidronate, Risedronate,
Tiludronate, Zoledronic Acid (Prototype)
Suppresses the activity of osteoclasts in part via
inhibition of Farnesyl Pyrophosphate synthesis.
MOA
Inhibits bone resorption and secondarily, bone formation
by acting on the basic hydroxyapatite crystal structure
Paget's disease of bone, Hypercalcemia especially in
Uses
malignancies, Osteoporosis, Bone metastases
Adynamic bone, Esophagitis, Osteonecrosis of the jaw,
SE
Renal impairment, GI irritation
• Take drugs with large quantities of water and avoid
situations that permit esophageal reflux
• Remedy for GI irritation and prevent reflux: take lots of
Notes water and keep patient in an upright position for 30mins
after intake of drug
• Contraindicated in those with renal impairment, esophageal
motility disorders and peptic ulcers
Notice that the names contain DRONATES.
Dr. Rodriguez
CALCIUM
Calcium, Phosphate, Strontium
Multiple physiologic actions through regulation of
multiple enzymatic pathways. Strontium suppresses
MOA
bone resorption and increase bone formation, Ca and
PO4 are required for bone mineralization
Adapted from TheMediSchool.com
Uses Osteoporosis, Osteomalacia, Deficiencies in Ca and PO4
SE Ectopic calcification TYPES OF ANTIBIOTIC AGENTS
• BACTERICIDAL
Calcium Content of different Calcium supplements: o can eradicate an infection in the absence of host defense mechanisms
Ca carbonate 40% o kills bacteria
Tricalcium phosphate 39%
• BACTERIOSTATIC
Ca chloride 27%
Ca acetate 25%
o inhibits microbial growth but requires host defense
Ca citrate 21% mechanisms to eradicate the infection
Ca lactate 13% o does not kill bacteria
Ca gluconate 9% To generalize, those that inhibit cell wall synthesis and nucleic acid synthesis
Ca gluceptate 8% are CIDAL! Kasi imagine parang binalatan mo yung buong bacteria at
CA glubionate 6.5% tinanggalan mo ng control center (DNA) paano pa siya mabubuhay?
While those that inhibit protein synthesis are STATIC except for
PHOSPHATE BINDING RESINS AMINOGLYCOSIDE which is CIDAL. Mnemonic for the protein synthesis
Sevelamer inhibitors: Buy AT 30 CELL (sell) at 50
AT (Aminoglycosides and Tetracyclines): Inhibit 30S subunit needed for
MOA Binds to dietary phosphate and prevents its absorption translation (remember Translation is protein synthesis). But keep in mind
HyperPTH in CKD, HypoPTH, that Aminoglycosides are CIDAL even if they are protein synthesis inh.
Uses
Vitamin D intoxication CELL (Chloramphenicol, Erythromycin/and other macrolides, Lincosamides
SE Hypotension, hypertension, GI disturbance and Linezolid inhibit 50S subunit.
Dr. Rodriguez
• Can significantly reduce uric acid levels
Notes
• Contraindicated in hypoPO4 and bowel obstruction
MINIMUM INHIBITORY CONCENTRATION
ANTI-RANKL MONOCLONAL ANTIBODY • lowest concentration of antimicrobial drug capable of inhibiting
Denosumab growth of an organism in a defined growth medium
Binds to RANKL and prevents it from stimulating osteoclast
MOA
differentiation and function → inhibits bone resorption
Uses Osteoporosis
SE Increased risk of infection
BACTERIAL CELL WALL SYNTHESIS INHIBITORS EXTENDED SPECTRUM PENICILLINS

(AMINO-PENICILLINS)
Ampicillin, Amoxicillin
Infections due to enterococci, Listeria monocytogenes,
MOA Escherichia coli, Proteus mirabilis, Haemophilus
influenzae and Moraxella catarrhalis (HELPSE)
SE Pseudomembranous colitis and Rash (ampicillin)
• Inactivated by beta-lactamase (penicillinase)
• Enhanced effect when used with beta-lactamase
Okay para hindi overwhelmed, summary ng lahat ng cell wall synthesis Notes
inhibitors (clavulanic acid, sulbactam)
inhibitors ay ang mga sumusunod: Penicillins, Cephalosporins,
Carbapenems, Monobactams, Betalactamase inhibitors, plus yung iba pang • Synergistic effect with aminoglycosides
inhibitors
Dr. Rodriguez
ANTI-PSEUDOMONAL PENICILLINS
PENICILLINS Piperacillin, Ticarcillin, Carbenicillin
Greater activity against G(-) infections. Infections due to
MOA OF BETA-LACTAM ANTIBIOTICS MOA
Pseudomonas, Enterobacter and Klebsiella
• binds to penicillin-binding proteins (PBPs) located in the • Inactivated by beta-lactamase (penicillinase)
bacterial cytoplasmic membrane • Enhanced effect when used with beta-lactamase
• inhibits the transpeptidation reaction that cross-links the Notes
inhibitors (clavulanic acid, tazobactam)
linear peptidoglycan chain constituents of the cell wall • Synergistic with aminoglycosides against Pseudomonas
• activates autolytic enzymes that cause lesions in the bacterial Note: Sino yung nag-iisa sa kanilang hindi affected ng penicillinase/beta-
cell wall lactamase?
• Capable of entering the blood brain barrier Dr. Rodriguez
Keywords mo diyan yung PBP and inhibition of transpeptidation. MNEMONICS: Ampicillin/Amoxicillin

Dr. Rodriguez
PENICILLIN RESISTANCE Describe the antimicrobial coverage of extended spectrum
Penicillins (HELPSE):
• Enzymatic hydrolysis of beta-lactam ring by formation of beta- Amoxicillin HELPS kill Enterococci
lactamases (penicillinases) Haemophilus influenzae Proteus mirabilis
o EXAMPLE: Staphylococcus aureus Escherichia coli Salmonella sp.
o Beta-Lactamase Inhibitors (Clavulanic Acid, Sulbactam, Listeria monocytogenes Enterococci
Tazobactam) prevent inactivation MNEMONIC: Antipseudomonal Penicillins
• structural change in target PBPs TCP: Takes Care of Pseudomonas
o EXAMPLES: MRSA, Pneumococci, Enterococci Ticarcillin Carbenicillin Piperacillin
• changes in the porin structures in outer cell wall impeding access PSEUDOMONAS is actually a mnemonic AHA. What are the diseases
of Penicillins to PBPs associated with Pseudomonas? Pneumonia, Sepsis, Ecthyma
o EXAMPLE: Pseudomonas aeruginosa gangrenosum, UTI, DM, Otitis externa, Mucopolysaccharidoses –
SIDE EFFECTS Cystic Fibrosis, Osteomyelitis, Nosocomial infection (HAP and VAP)
Skin infection (in burns and hot tub folliculitis)
• Hypersensitivity, cross allergenicity with other penicillins Dr. Calderon Jr.
• GI Upset
• For the other side effects specific for each drug, we will place MEMORY AID:
them under the drug cards PENICILLINS AND
Let’s go through this section per section.. Natural penicillins are called natural CEPHALOSPORINS
kasi sila yung nadiscover ni Fleming noong unang panahon. Take a look at https://qrs.ly/tydveea
the notes. They are destroyed by beta-lactamase which are secreted by
bacteria, thereby causing resistance. Pause for a while and try to search for
the structure of penicillins. Do you see the square shape in the structure? CEPHALOSPORINS
That’s your beta lactam ring, destroyed by your beta-lactamases. Now, **Bactericidal; mostly IV; all have renal excretion
scientists before wanted to make pencillin resistant to beta-lactamase, kaya EXCEPT Cefoperazone and Ceftriaxone **
nagdagdags sila ng isoxazolyl structure. Try to looking at pictures of
isoxazolyl penicillins in the net. O diba napakalaki?!?! The reason for this is MNEMONIC: First Generation Cephalosporins
to block the beta-lactam from being degraded by beta-lactamases. Altho Which microbes are covered by the spectrum of activity of first
resistant na siya to inactivation (look at the table), sobrang lumiit yung generation cephalosporins?
spectrum of activity niya to only Staphylococcal species. Hence they were FIRST GENERATION CEPHALOSORINS
called Anti-staphylococcal pens. To remember, use the mnemonic: STAPH PEcK FIRST
your Balak (B-Lac) on MONday. Staph for anti staph. B-lac to remember Proteus mirabilis
they are resistance. MON for Methicillin, Oxacillin, Nafcillin. Escherichia coli
Later on, the spectrum was extended to cover more bacteria, by adding an Klebsiella pneumoniae
amino group. Notice that the name of these penicillins start with AM-. Lastly How do you remember first generation cephalosporins?
they were also able to discover, anti-pseudomonal penicillins. FIRST GENERATION CEPHALOSPORINS
Dr. Rodriguez FADer, help me FAZ my PHarmacology boards!
NATURAL PENICILLINS CeFADroxil CePHalothin CePHradine
CeFAZolin CePHapirin CePHalexin
PENICILLIN G (IV),
PENICILLIN V (oral) MNEMONIC: Second Generation Cephalosporins
DOC for syphilis, for streptococcal, pneumococcal, Which microbes are covered by the spectrum of activity of
MOA
meningococcal, G+ bacilli, spirochete infection second generation cephalosporins?
SE Seizures SECOND GENERATION CEPHALOSORINS
HEN PEcKS
• Inactivated by beta-lactamase (penicillinase)
Haemophilus influenzae Proteus mirabilis
• Probenecid: Renal tubular secretion inhibited Enterobacter aerogenes Escherichia coli
Notes (prolonging the effect of pens) Neisseria spp. Klebsiella pneumoniae
• Benzathine Penicillin & Procaine Penicillin: long- Serratia marcescens
acting IM preparations
How do you remember second generation cephalosporins?
ANTI-STAPHYLOCOCCAL PENICILLINS SECOND GENERATION CEPHALOSPORINS
(ISOXAZOLYL PENS) In a FAMily gathering, you see your
Methicillin, nafcillin, oxacillin, FOXy cousin wearing a FUR coat and drinking TEA.
CeFAMandole, CeFOXitin,
Cloxacillin, dicloxacillin
CeFURoxime, CefoTEtan
MOA Staphylococcal infections
SECOND GENERATION CEPHALOSPORINS
Interstitial nephritis (methicillin),
SE FAC! LORA the PROfessional AZhOLE is still on the FONe.
Neutropenia (nafcillin)
CeFAClor, LORAcarbef, CefPROzil,
• Resistant to inactivation by beta-lactamase CefmetAZOLE, CeFONicid
Notes
(penicillinase) – IMPORTANT!
MNEMONIC: Anti-Pseudomonal Cephalosporins NOVEL CEPHALOSPORINS
ANTI-PSEUDOMONAL CEPHALOSPORINS • A novel Cephalosporin, usually combined with
Ceftazidime Cefepime Cefoperazone Tazobactam, used for the treatment of
You can also use a general mnemonic in classifying the generation of the complicated urinary tract and
cephalosporin: intraabdominal infections; very good activity
1st Generation: Starts with CEPH. Including DRO+ZOL. (CefaDROxil and CEFTOLOZANE
against Gram negative organisms including
CefaZOLin) they start in CEF but are 1st gen Pseudomonas aeruginosa, most extended-
2nd Generation: Starts with CEF. Doesn’t end in -ONE and -IME, plus LORA spectrum-B-lactamase-producing organisms
ceFU!!!! (dapat with feelings na parang inaaway mo si LORA! (LORAcarbef
and some anaerobes
and Cefuroxime)
3rd Generation: Starts with CEF. Ends in -ONE and -IME. Plus Moxi Dinir, • Siderophore Cephalosporin: entry into
Ditoren, Buten. bacterial cells is by binding to iron, which is
4th Generation: Cefipime, Cefipirome actively transported into the bacterial cells.
• Used to treat complicated urinary tract
The higher the generation, the greater the gram (-) coverage. In the exam, they
infections and pneumonias when no other
can ask which drugs can have a coverage, therefore it is important to know
the gram stain of the organism and the possible drugs that can be given. options are available; Indicated for the
Remember that in micro-pharma, a lot of drugs can be given for different CEFIDEROCOL treatment of multi-drug-resistant Gram-
organisms. So be wise in studying. Don’t memorize everything. All these negative bacteria including P. aeruginosa.
drugs are Preg-cat B • Common side effects include diarrhea, infusion
Dr. Rodriguez site reactions, constipation and rash. May also
cause serious and life-threatening allergic
FIRST GENERATION CEPHALOSPORINS reactions, severe diarrhea caused by C. difficile
Cefazolin, Cefadroxil, Cephalexin, and seizures. (Warning for higher mortality)
Cephalothin, Cephapirin, Cephradine
Infections due to GRAM POSITIVE COCCI (Staph and strep) MONOBACTAM
Uses UTI, Skin and soft tissue infection, bone infections Aztreonam
Cefazolin Surgical prophylaxis
Binds to penicillin-binding proteins. Inhibits
Hypersensitivity, Cross-allergenicity (partial with MOA
transpeptidation in bacterial cell walls.
SE Penicillins, complete with cephalosporins),
Infections resistant to beta-lactamases produced by
Injection site reactions, Phlebitis, GI upset
gram-negative rods, including Klebsiella, Pseudomonas
+Aminoglycosides: Nephrotoxicity Uses and Serratia
Notes Minimal activity against G- cocci, enterococci, MRSA and Aztreonam is the silver bullet. It is design for gram negative
most G- rods rods. Pseudomonas is a gram-negative rod.
Para mas madali, diba ang mga (+) cocci ay usually nakikita sa skin, sa genito Gastrointestinal upset, Superinfection, Vertigo,
urinary tract. Kaya look at the uses SE
Dr. Rodriguez
Headache, Hepatotoxicity, Skin rash
• Resistant to beta-lactamase
SECOND GENERATION CEPHALOSPORINS Notes
• No cross-allergenicity with Penicillins
Cefaclor, Cefamandole, Cefmetazole, Cefonicid, Cefuroxime, • No activity against gram-positive bacteria or
Cefprozil, Ceforanide, Cefoxitin, Cefotetan, Loracarbef anaerobes
Uses + Coverage: Haemophilus, Enterobacter and Neisseria
Same above CARBAPENEMS
SE Cefamandole, IMIPENEM-CILASTATIN, ERTAPENEM, MEROPENEM,
Disulfiram reaction
Cefotetan DORIPENEM
• + aminoglycosides: Nephrotoxicity Binds to penicillin-binding proteins. Inhibits
MOA
• Slight less activity against G+ but extended G- activity transpeptidation in bacterial cell walls.
Improved action against pneumococcus Wide coverage against gram-positive and gram-negative
Notes Cefuroxime Uses
and H. influenzae bacteria. For serious infections such as pneumonia and sepsis
Cefotetan Good activity against B. fragilis Hypersensitivity, Cross-allergenicity (partial with
and Cefoxitin (abdominal and pelvic infections) SE Penicillins), GI upset, CNS toxicity (confusion,
encephalopathy, seizures)
THIRD GENERATION CEPHALOSPORINS • Cilastatin inhibits renal metabolism (Hydrolysis) of
Cefoperazone, Cefotaxime, Ceftazidime, Ceftizoxime, imipenem by Dihydropeptidase (thus given together)
Ceftriaxone, Cefixime, Cefpodoxime Proxetil, Cefdinir, Cefditoren • Reserved for serious life-threatening infections
Pivoxil, Ceftibuten, Moxalactam Notes • Low susceptibility to B-lactamases
Decreased gram-positive coverage. Increased gram- • Active against Pseudomonas and Acinetobacter EXCEPT
negative activity (Pseudomonas, Bacteroides), against Ertapenem
Uses • Partial cross-allergenicity with Penicillins
Providencia, Serratia, Neisseria, Haemophilus;
Ceftriaxone and Cefixime DOC for gonorrhea
CARBAPENEM RESISTANCE
Same with first gen but no Phlebitis.
SE • Production of carbapenemases (carbapenem-hydrolyzing enzymes)
Cefoperazone Disulfiram reaction
• + aminoglycosides: Synergistic effect
is the most important mechanism of carbapenem resistance
• Slight less activity against G+ but extended G- activity • Other methods of resistance: Porins, efflux pumps, mutations in
Cefoperazone and penicillin-binding proteins
All have renal excretion except • One method of circumventing carbapenem resistance is to add
Ceftriaxone
Cefoperazone and Beta-lactamase inhibitor in combination.
All penetrate BBB except
Notes Cefixime
Has very good CNS penetration Ceftriaxone BETA-LACATAMASE INHIBITORS
Has very good action on • Inhibits inactivation of Penicillins by bacterial beta-lactamase
Ceftazidime
pseudomonas (penicillinase)
Most active against Penicillin Ceftriaxone and Clavulanic acid, Sulbactam, Tazobactam
resistant S. pneumoniae Cefotaxime Inhibits inactivation of Penicillins by bacterial beta-
MOA
lactamase (penicillinase)
FOURTH GENERATION CEPHALOSPORINS Infections against beta-lactamase producing
Cefepime, Ceftaroline (5th in other references), Cefpirome Uses
gonococci, streptococci, E. coli and H. influenzae
Wide coverage against gram(+) and gram (-) bacteria SE Hypersensitivity, Cholestatic jaundice
Uses
Ceftaroline MRSA • Usual combinations include: Amoxicillin-Clavulanate,
SE Same with first gen Ampicillin-Sulbactam, Piperacillin-Tazobactam
• More resistant to beta-lactamase produced by • Most active against plasmid encoded beta lactamases
Notes
Notes Enterobacter, Haemophilus, Neisseria and Pneumococcus (Gonococci, Streptococci, E coli and H. Influenzae)
• Resistant to beta-lactamase. Broad G(-) activity • Not good inhibitor of inducible chromosomal beta
lactamases (Enterobacter, Pseudomonas, Serratia)
NOVEL CARBAPENEMASE INHIBITORS POLYMYXIN B,
Drugs DAPTOMYCIN [B]
Diazobicyclooctanes Share five-membered Polymyxin E
(DBOs) diazabicyclooctane ring Cationic detergents.
Used to treat complicated urinary tract Binds to cell membrane Attach to and disrupt
AVIBACTAM infections, complicated Intra-abdominal MOA causing depolarization and bacterial cell membrane,
(Ceftazidime/ Infections (cIAI)and hospital-acquired rapid cell death bind and inactivate
Avibactam) bacterial pneumonia, ventilator- endotoxin. Bactericidal.
associated pneumonia. Gram-negative bacteria.
Broadly active against a wide variety of Infections caused by G (+) For salvage therapy of
Gram-negative pathogens, Uses bacteria including sepsis Acinetobacter,
RELEBACTAM including Enterobacterales, P. aeruginosa and endocarditis Enterobacteriaceae and
(Imipenem/ and the anaerobic Bacteroides spp. More Pseudomonas aeruginosa
Relebactam) importantly, it has demonstrated excellent Myopathy
Eosinophilia, fever,
activity against key multidrug-resistant Monitor Creatine
Nephrotoxicity,
pathogens. SE Phosphokinase weekly to
Neurotoxicity, Rash,
Boronic acid check for severity of
Derived from boronic acid myopathy
Urticaria
derivatives
• Active against E. coli, K. pneumoniae • More rapidly bactericidal • Proteus and Neisseria are
and E. cloacae complex. Used for than Vancomycin resistant
treatment of infections (urinary tract Notes • Inactivated by pulmonary • For Topical use only (to
VABORBACTAM infection, hospital-acquired surfactants so cannot be limit toxicity)
(Meropenem/ • pneumonia / ventilator-associated used against pneumonia • *Both are Preg Cat C
Vaborbactam) pneumonia, complicated intra- QUICK REVIEW:
abdominal infections or bloodstream 1. Penicillins resistant to beta-lactamase
infection) caused by carbapenem- 2. All penicillins are Static/Cidals?
3. Generation of Cefixime?
resistant Enterobacterales (CRE).
4. DOC for gonorrhea
5. Penicillin that causes interstitial nephritis
OTHER CELL WALL INHIBITORS Answers (1) Methicillin, Oxacillin Nafcillin (Remember Staph your BLAC on
Monday) (2) Cidal – remember all that disrupt the wall are cidal) (3) 3rd gen
GLYCOPEPTIDES (4) Ceftriaxone (5) Methicillin
Vancomycin, Teicoplanin, Dalbavancin, Telavancin Dr. Rodriguez
SUPPLEMENT: OTHER DRUGS ACTING ON CELLWALL
Inhibits cell wall synthesis by binding to the D-Ala-D-
Ala terminus of nascent peptidoglycan → inhibit Inactivates the enzyme UDP-N-
acetylglucosamine-3-enolpyruvyltransferase
MOA transglycosylation →
which is important in peptidoglycan synthesis
prevent elongation and cross-linking of peptidoglycan
(very early stage of bacterial cell wall synthesis)
chain
FOSFOMYCIN → prevents formation of N-acetylmuramic acid
Serious infections caused by drug-resistant gram- (a peptidoglycan precursor molecule); for
positive organisms (MRSA), sepsis, endocarditis & uncomplicated UTI; safe for pregnant patients;
Uses meningitis, Pseudomembranous colitis renal excretion; resistance emerges rapidly;
Teicoplanin and Telavancin are not absorbed in the GIT synergistic with Beta lactam and quinolones
à used for bacterial enterocolitis,
Red Man syndrome, Nephrotoxicity, SUPPLEMENT: MNEMONICS – Drugs of Last Resort
SE Which antibiotics are considered drugs of last resort?
Ototoxicity, Chills, Fever, Phlebitis
I AM your Last Shot at Victory
• Reserved for serious life-threatening infections
Imipenem Linezolid
• Treat red man syndrome by slowing the rate of infusion Amikacin Streptogramins
• Use oral formulation for Pseudomembranous colitis Meropenem Vancomycin
• Narrow spectrum
Notes • VRSA and VRE are due to D-Ala-D-Lactate formation BACTERIAL PROTEIN SYNTHESIS INHIBITORS
• Decrease dose for renally impaired patients
• Dalbavancin has very long t½ (6-11 days) which
permits once-weekly dosing and is more active than
Vancomycin
PEPTIDE ANTIBIOTICS
Bacitracin
Interferes with a late stage in cell wall synthesis in
MOA
gram-positive organisms Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2018
Uses Infections due to gram-positive bacteria

SE Nephrotoxicity Reiterate lang natin dito. Those that inhibit protein synthesis are STATIC
except for AMINOGLYCOSIDE which is CIDAL. Mnemonic for the protein
Reserved for topical use only due to marked synthesis inhibitors: Buy AT 30 CELL (sell) at 50
Notes
nephrotoxicity AT (Aminoglycosides and Tetracyclines): Inhibit 30S subunit needed for
translation (remember Translation is protein synthesis). But keep in mind
CYCLOSERINE that Aminoglycosides are CIDAL even if they are protein synthesis inh.
CELL (Chloramphenicol, Erythromycin/and other macrolides, Lincosamides
Cycloserine and Linezolid inhibit 50S subunit.
Blocks incorporation of D-Ala into the pentapeptide We won’t be placing these repeatedly sa mga drug cards para easier J
MOA
side chain of the peptidoglycan Dr. Rodriguez
Uses Drug-resistant tuberculosis (2nd line drug) MNEMONIC: Protein Synthesis Inhibitors
“AT CELLS”
SE Neurotoxicity (tremors, seizures, psychosis)
Aminoglycosides
Notes Only used as a second-line agent in TB Tetracyclines
Chloramphenicol (HNBS)*
Must knows: Erythromycin (Macrolides)
• Vancomycin – D-Ala-D-Ala (Dala Dala niya yung Vanco!). Redman Lincosamides (Clindamycin)
syndrome Linezolid
• Baci(+)racin – For gram (+), (+)oxic, (+)opical use Streptogramins
Dr. Rodriguez
All bacterial protein synthesis inhibitors are bacteriostatic except
Aminoglycosides, Streptogramins, and Chloramphenicol to the
following bugs: Hemophilus, Neisseria, Bacteroides and Streptococcus
pneumoniae.
Dr. Uy
Bacterial protein synthesis inhibitors are STATIC or CIDAL? ____________. • All macrolides inhibit CYP450 EXCEPT
They are considered as bacteriostatic except for what drug again? ____________. Azithromycin
Important to remember Buy AT 30 and CELL at 50. In addition add to your • Resistance is due to development of efflux pumps and
knowledge 23S for Linezolid. production of methylase enzyme
Must knows for Protein Synthesis Inhibitors: Cross-resistance among macrolides: complete or partial
1. Drugs for MRSA and VRSA: _________________________________ resistance with drugs acting on the 50S
2. DOC for Community acquired pneumonia: ____________________ Notes Azithromycin has a good pharmacokinetic profile. It is
3. Gray baby syndrome: ____________________ neither an inhibitor or inducer of general substrate.
4. Tooth discoloration: ____________________ Azithromycin has a tremendous 4-day half-life and has
5. Aplastic anemia: ____________________ a high volume of distribution. It is greater in tissue
6. QT prolongation: ____________________
macrophage than the plasma level.
7. Pseudomembranous colitis: ____________________
Dr. Rodriguez Azithromycin Highest Vd and slowest elimination
TETRACYCLINES Telithromycin Used for macrolide-resistance
Tetracycline, Doxycycline, Minocycline,
Tigecycline, Demeclocycline, Lymecycline LINCOSAMIDES
(All are Preg Cat D) Clindamycin, Lincomycin
Infections caused by M. pneumoniae, Chlamydia, Skin and soft tissue infection, Anaerobic infections,
Rickettsia and Vibrio, Peptic ulcer disease, Lyme disease, Backup drug against gram-positive cocci, Endocarditis
Uses Malaria prophylaxis, Amebiasis Uses
prophylaxis (penicillin-allergy), PCP pneumonia,
Demeclocycline SIADH Toxoplasmosis
Doxycycline CAP and Bronchitis Pseudomembranous colitis (C. difficile overgrowth)
GI disturbance, Teratogen (tooth enamel dysplasia/ SE Gastrointestinal disturbance, Skin rash, Neutropenia,
discoloration) Hepatic dysfunction,
SE
Hepatotoxicity, Nephrotoxicity, Photosensitivity, • Cross-resistance between clindamycin and macrolides
reversible Vestibulotoxicity (especially Minocycline) is common
• Do not drink with milk (decreased absorption with • Resistance is due to methylation of binding sites and
divalent cations like calcium) – minimal for Doxycycline Notes
enzymatic inactivation
• High Vd, cross the placenta, enterohepatic recycling • G (-) aerobes are resistant because of poor penetration
• Resistance is due to development of efflux pumps for through the outer membrane
active extrusion of tetracyclines and the formation of MNEMONIC: Clindamycin VS Metronidazole
ribosomal protection proteins that interfere with
• CLINDAMYCIN for anaerobic infections ABOVE the diaphragm.
Notes tetracycline binding (but not present with Tigecycline
• METRONIDAZOLE for anaerobic infections BELOW the diaphragm.
EXCEPT in Proteus and Pseudomonas)
• Broadest spectrum and has the longest
t½ (30-36hrs) OXAZOLIDINONE
Tigecycline • Given IV only and is unaffected by Linezolid, Tedizolid
common tetracycline resistance
MOA Binds to the 23S ribosomal RNA of 50S subunit.
mechanisms.
Infections caused by drug-resistant gram-positive cocci
MNEMONIC: Tetracycline
Uses such as Staphylococci and Enterococcus (MRSA, VRSA,
T = TeTracyclines
VRE), Listeria, Corynebacteria
Block aTTachment of T-RNA to acceptor site
Teeth-racycline = tooth enamel dysplasia / discoloration
Bone marrow suppression, Thrombocytopenia,
Neutropenia, Serotonin syndrome (when given together
SE
with serotonergic drugs such as SSRIs), Neuropathy,
CHLORAMPHENICOL Optic neuritis
Chloramphenicol Resistance is due to decreased affinity of drug to binding
Notes
Additional: Inhibits transpeptidation (catalyzed by site
MOA From the parent compound name, meron sila lahat ZOLID
peptidyl transferase) Dr. Rodriguez
Meningitis (S. pneumoniae, H. influenzae, N. meningitidis),
Uses
Backup for Salmonella, Rickettsia and Bacteroides
Gastrointestinal disturbance,Aplastic anemia STREPTOGRAMIN
SE
(idiosyncratic), Gray baby syndrome, dose-related anemia Quinupristin-Dalfopristin
• Inhibits hepatic drug-metabolizing enzymes causing MOA Binds 50S subunit. Bactericidal.
many drug interactions Infections caused by drug-resistant gram-positive cocci
• Resistance is due to the formation of Uses
such as Staphylococci and E. faecium (MRSA, VRSA, VRE)
acetyltransferase that inactivates drug Injection site reactions, severe Arthralgia-myalgia
Notes SE
May be used as topical agent syndrome
Chloramphenicol is a bacteriostatic antibiotic but is Inhibits CYP450 enzymes, causing multiple drug
bactericidal to the ff: Hemophilus influenza, Neisseria, Notes
interactions
Bacteroides and Streptococcus pneumoniae.
CHLORAMPHENICOL: GRAY BABY SYNDROME
AMINOGLYCOSIDES
• premature neonates are deficient in hepatic
Gentamicin, Tobramycin
glucuronosyltransferase
o Glucuronidation is the way to metabolize chloramphenicol Aerobic gram-negative bacteria (E. coli, Enterobacter,
Klebsiella, Proteus, Providencia, Pseudomonas, Serratia),
o Immature livers very sensitive to doses of chloramphenicol
Uses Endocarditis (caused by staphylococci, streptococci and
• Gray Baby Syndrome: enterococci),
characterized by decreased red
Ocular infections
blood cells, cyanosis and Both are the MOST VESTIBULOTOXIC, NEPHROTOXIC
cardiovascular collapse Notes
Synergistic with: Beta-lactams and vancomycin
• Characteristic ashen gray skin
Amikacin
MACROLIDES Multi Drug-Resistant Tuberculosis (2nd line drug)
ERYTHROMYCIN, AZITHROMYCIN, CLARITHROMYCIN, Uses
Aerobic gram-negative bacteria (same above)
TELITHROMYCIN, ROXITHROMYCIN Synergistic with: Beta-lactams
Community-acquired pneumonia, Pertussis, Diphtheria, Notes LEAST RESISTANCE but
Uses
Chlamydial infections NARROWEST therapeutic window
Gastrointestinal upset, QT prolongation,
Cholestatic hepatitis, Hepatotoxicity,
SE
Drug interactions, rare fulminant hepatic failure
(Telithromycin)
Streptomycin • require oxygen for uptake
Tuberculosis, Tularemia, Bubonic plague, Brucellosis, o ineffective against anaerobes
Uses
Enterococcal endocarditis • bind to the 30S ribosomal subunit and interfere with protein
Additional: Teratogen (congenital deafness), Injection synthesis:
SE
site reactions o block formation of the initiation complex
Synergistic with: Beta-lactams o cause misreading of the code on the mRNA template
• Administered IM o inhibit translocation
Notes • Has widespread resistance
• If given together with Pens can be used for enterococcal RESISTANCE TO AMINOGLYCOSIDES
endocarditis, TB plague and tularemia • plasmid-mediated formation of inactivating enzymes (group
transferases)
Neomycin, Kanamycin, Paromomycin o AMIKACIN is often resistant to many enzymes that inactivate
Skin infections, Bowel preparation for elective surgery other aminoglycosides
Uses (to decrease aerobic flora), Hepatic encephalopathy, • resistance to STREPTOMYCIN develops due to changes in the
Visceral leishmaniasis (paromomycin) ribosomal binding site
NEOMYCIN: Topical and oral use only
Calcium Gluconate & Neostigmine: Reversal of NM MNEMONIC: Aminoglycosides
Notes AminOglycosides require O2 for transport.
block
KANAMYCIN: MOST OTOTOXIC They won’t work under anaerobic conditions.
Spectinomycin MNEMONICS – Aminoglycosides

Mean GNATS canNOT kill anaerobes.
Drug-resistant gonorrhea, Gonorrhea in penicillin-
Uses Gentamicin Nephrotoxicity
allergic patients
Neomycin Ototoxicity
SE Additional: Anemia
Amikacin Teratogen
• No cross-resistance with other drugs used in Tobramycin
Notes gonorrhea Streptomycin
• Given IM
TOXICITIES OF AMINOGLYCOSIDES
• OTOTOXICITY
Summary of Side Effects
o MOST OTOTOXIC: kanamycin, amikacin
SIDE EFFECT GT A S NKP Sp
o MOST VESTIBULOTOXIC: tobramycin, gentamicin
Nephrotoxicity R R R R R
o cumulative ototoxicity when used with loop diuretics
Ototoxicity I I I I I • NEPHROTOXICITY
Neuromuscular blockade o acute tubular necrosis
Hypersensitivity o MOST NEPHROTOXIC: tobramycin, gentamicin
Don’t forget to learn about the additional SEs mentioned per drug card above. § Toxicities of Aminoglycosides
R= Reversible, I=Irreversible • NEUROMUSCULAR BLOCKADE
Dr. Rodriguez
o curare-like effect (nondepolarizing NMJ block) reversible with
calcium and neostigmine
Modes of Antibacterial Action
• SKIN REACTIONS
• CONCENTRATION-DEPENDENT KILLING ACTION
commonly from Neomycin and Streptomycin
o as the plasma level is increased above the MIC, an increasing
proportion of bacteria are killed and at a more rapid rate
SUPPLEMENT: OTHER PROTEIN SYNTHESIS INHIBITOR
o EXAMPLE: aminoglycosides
Inhibits translocation process during protein
• TIME-DEPENDENT KILLING ACTION
FUSIDIC ACID or synthesis; an antibiotic isolated from the
o efficacy is directly related to time above MIC Na FUSIDATE fermentation broth of Fusidium coccineum;
o efficacy independent of concentration once the MIC has been (Group: Fusidane) used as topical antimicrobial against most
reached common skin pathogens including S. aureus
o EXAMPLES: Penicillins, cephalosporins
• POST-ANTIBIOTIC EFFECT
o seen in aminoglycosides & quinolones NUCLEIC ACID SYNTHESIS INHIBITORS
o killing action continues when their plasma levels have declined
below measurable levels
o greater efficacy when administered as single large dose
o toxicity depends on a critical plasma concentration and on the
time such a level is exceeded
§ shorter with single large dose than multiple small doses
§ basis for once-daily aminoglycoside dosing protocols
Aminoglycosides are easy to identify. They end in -MICIN or MYCIN. NEVER

EVER forget the toxicities that are related to their use. It’s always asked in
exams.
Take the Letter I from Aminoglycoside and pahigain niyo. Mukha na siyang (-) Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2018
negative sign. Because they are used for Gram Negative bacteria.
Dr. Rodriguez
PHARMACOKINETICS OF AMINOGLYCOSIDES ANTIMETABOLITE DRUGS
• not absorbed after oral administration SULFONAMIDES
o must be given IM or intravenously for systemic effect • weakly acidic compounds that have a common chemical nucleus
• limited tissue penetration due to its water solubility resembling p-aminobenzoic acid (PABA)
o do not readily cross the blood-brain barrier • solubility may be decreased in acidic urine
• glomerular filtration is the major mode of excretion o combination of 3 separate sulfonamides (triple sulfa) to reduce
o plasma levels greatly affected by changes in renal function the likelihood that any one drug will precipitate
• Amikacin has the narrowest therapeutic window among Classification of Sulfonamides
aminoglycosides Intermediate
• GROUP PREGNANCY CATEGORY: D Short Acting Long Acting
Acting
Sulfacytine Sulfadiazine Sulfadoxine
MOA OF AMINOGLYCOSIDES Sulfisoxazole Sulfamethoxazole * Pyrimethamine
• bactericidal inhibitors of protein synthesis Sulfamethizole Sulfapyridine
• aminoglycoside transport can be enhanced by cell wall synthesis * Trimethoprim
inhibitors (synergistic effect)
TRIMETHOPRIM TOXICITY OF SULFONAMIDES
• structurally similar to folic acid • HYPERSENSITIVITY
• weak base that is trapped in acidic environments o spectrum: EM, SJS/TEN, PAN, exfoliative dermatitis
reaches high concentrations in prostatic and vaginal fluids o most common drug triggers
o cross-allergenicity should be assumed
• GASTROINTESTINAL DISTRESS
o nausea, vomiting, diarrhea and mild hepatic dysfunction
• HEMATOTOXICITY
o granulocytopenia, thrombocytopenia, aplastic anemia
o cause acute hemolysis in G6PD deficient patients
• NEPHROTOXICITY
o crystalluria, hematuria
• DRUG INTERACTIONS
o displace protein binding affecting levels of warfarin and
methotrexate
o displace bilirubin binding sites leading to kernicterus
SUPPLEMENT: Kernicterus
• caused by increased levels of unconjugated bilirubin
Figure 46-1. Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015 • due to immaturity of fetal blood brain barrier
• histopathology
MOA OF ANTIFOLATES o bilirubin deposits in subcortical nuclei and basal ganglia
• SULFONAMIDES • clinical presentation
o bacteriostatic inhibitors of folic acid synthesis o hypo/hypertonia, lethargy, high-pitched cry, opisthotonos
o competitive inhibitors of dihydropteroate synthase 1. Sulfadrugs are contraindicated in patients with what biochemical
o selective toxicity of sulfonamides results from the inability of disorder?___________
mammalian cells to synthesize folic acid 2. Drug combination used for PCP pneumonia? ___________
o must use preformed folic acid that is present in the diet 3. DOC for toxoplasmosis? ______________
• TRIMETHOPRIM (intermediate acting) Answers: (1) G6PD deficiency, (2) Co-trimoxazole (3) Sulfadiazine-
o selective inhibitor of bacterial dihydrofolate reductase pyrimethamine
Dr. Rodriguez
o bacterial dihydrofolate reductase is 4–5x more sensitive to
inhibition by trimethoprim QUINOLONES
• TRIMETHOPRIM PLUS SULFAMETHOXAZOLE MOA OF QUINOLONES
o when the 2 drugs are used in combination, antimicrobial
• interfere with bacterial DNA synthesis by inhibiting:
synergy results from the sequential blockade of folate
o Topoisomerase II (DNA Gyrase) in gram-negative organisms
synthesis
§ prevents relaxation of supercoiled DNA
o drug combination is bactericidal
o Topoisomerase IV in gram-positive organisms
S for S = Synthase for Sulfonamide; § interferes with the separation of replicated chromosomal
Don’t forget: when used alone they are bacteriostatic. What used together they DNA during cell division
act bactericidal.
• usually bactericidal against susceptible organisms
• exhibit post antibiotic effect
RESISTANCE TO ANTIFOLATES
• should not be taken with other preparations containing cations
• plasmid-mediated and results from: (should be taken 2 hours before or 4 hours after any product
o decreased intracellular accumulation of the drugs containing cations)
o increased production of PABA by bacteria
• may damage growing cartilage and cause arthropathy
• decrease in the sensitivity of dihydropteroate synthase to
CLASSIFICATION AND ANTIMICROBIAL SPECTRUM
Co-Trimoxazole • 1ST GENERATION
Sequential blockade of dihydropteroate synthase o Nalidixic acid, Cinoxacin, Rosoxacin, Oxolinic acid
MOA (Sulfamethoxazole) and dihydrofolate reductase o Urinary tract infections
(Trimethoprim). Bactericidal. • 2ND GENERATION
Urinary tract, respiratory, ear and sinus infections o Ciprofloxacin, Ofloxacin, Norfloxacin, Lomefloxacin, Enoxacin
(Haemophilus, Moraxella, Aeromonas), P. jiroveci o gram negatives, gonococci, gram positive cocci and Mycoplasma
Uses
pneumonia, Toxoplasmosis, Nocardiosis, Cholera • 3RD GENERATION
(backup), Typhoid fever, Shigellosis o Levofloxacin, Gemifloxacin, Moxifloxacin, Sparfloxacin,
• Displaces protein binding of other drugs/bilirubin Grepafloxacin, Gatifloxacin, Pazufloxacin, Tosufloxacin, Balofloxacin
• Low solubility in acidic urine causing formation of o less gram negative and more gram positive activity,
stones streptococci and enterococci
Notes • Trimethoprim (also Pentamidine, an antiprotozoal) inhibit • 4TH GENERATION
distal tubular Na reabsorption through the amiloride-
o Trovafloxacin, Alatrofloxacin, Prulifloxacin, Clinafloxacin
sensitive ENaC channel leading to urinary loss of Na
o broad spectrum, including anaerobes
and Cl
*WITH INCREASING GENERATION, INCREASING GRAM POSITIVE
ACTIVITY (unlike cephalosporins where increasing generation leads to
Silver Sulfadiazine, Mafenide Acetate increasing gram negative activity)
MOA Inhibit dihydropteroate synthase. Bacteriostatic OTHER GENERALIZATION
Uses Burn infections • General SE/Note for ALL Quinolones:
Notes Displaces protein binding of other drugs/bilirubin o Avoid use in young children and pregnant women
o Enhance toxicity of methylxanthines (theophylline)
OTHER SULFONAMIDES AND ANTIFOLATE DRUGS o Oral absorption is impaired by cations
SULFISOXAZOLE only for lower UTI • General properties of quinolones: good oral bioavailability, high Vd,
SULFADIAZINE- t½ 3-8hrs, absorption is impeded by antacids, elimination is via
DOC for Toxoplasmosis kidneys by tubular secretion (may compete with probenecid for
PYRIMETHAMINE
SULFADOXINE- excretion) EXCEPT for MOXIFLOXACIN
2nd line agent for Malaria
PYRIMETHAMINE SIDE EFFECTS
used for lower UTI, may be safely given to
TRIMETHOPRIM • Gastrointestinal distress,
patients with sulfonamide allergy
• CNS effects (dizziness, headache)
co-administered with Leucovorin to limit
PYRIMETHAMINE bone marrow toxicity • Tendonitis and Tendon rupture
• QTc prolongation (Third and Fourth Gen)
SECOND GENERATION NITROFURAN

Ciprofloxacin, Ofloxacin, Norfloxacin, Nitrofurantoin [B, X at term]
Lomefloxacin, Enoxacin Forms multiple reactive intermediates when acted upon
Urinary tract infections and GIT infections MOA by bacterial nitrofuran reductase →
(Gram-negative rods [Shigella, Salmonella, ETEC & disrupt protein, RNA and DNA synthesis. Bactericidal.
Campylobacter], gonococci, gram positive cocci), Uncomplicated Urinary tract infections (EXCEPT
Uses
Uses Atypical pneumonia, Tuberculosis (2nd line drug), Proteus and Pseudomonas)
Infection of soft tissue, bones and joints; Intraabdominal Anorexia, Nausea, Vomiting, Skin rashes,
MDR organisms (such as Pseudomonas and SE Pulmonary infiltrates, Phototoxicity, Neuropathies,
Enterobacter) Hemolysis in patients with G6PD deficiency
Most active agent against Gram Proteus and Pseudomonas are resistant
Ciprofloxacin Notes
Negative organisms esp. Pseudomonas Contraindicated in Renal insufficiency
Notes
Does not achieve adequate plasma
Norfloxacin
levels for use in systemic infections TOPICAL ANTI-INFECTIVE. PSEUDOMONIC ACID
Mupirocin
THIRD GENERATION Inhibits Staphylococcal isoleucyl tRNA synthetase.
MOA
Levofloxacin, Sparfloxacin, Moxifloxacin, Gemifloxacin, Pazufloxacin, Bactericidal.
Tosufloxacin, Balofloxacin Gram positive cocci including methicillin-susceptible
Uses
Lung infections caused gram-positive cocci, and MRSA, for minor skin infections such as Impetigo
Uses Atypical pneumonia (Chlamydia, Mycoplasma), Epistaxis, Stinging or burning sensation on the skin, mild
Tuberculosis (2nd line drug) SE
skin rash, headache
Grepafloxacin Withdrawn (Severe cardiotoxicity) Only used topically (available as intranasal ointment)
Gatifloxacin Withdrawn (Diabetes mellitus) Notes Do not used over large, infected areas such as decubitus
Not for patients with UTI. Hepatic ulcers or open surgical wounds (may lead to resistance)
Moxifloxacin
clearance → lower urinary levels
Ofloxacin C. trachomatis
ANTIMYCOBACTERIAL DRUGS
Newest members of this family and are
considered to have the broadest
Moxifloxacin
spectrum of activity with increased
Gemifloxacin
activity against anaerobes ang atypical
agents.
CAP caused by Chlamydia, Mycoplasma
and Legionella “THE ATYPICALS”
Notes Levofloxacin
superior activity against G(+) bacteria
including S. pneumoniae ;
Gemifloxacin Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2018
Levofloxacin Prolong QT
Moxifloxacin
High resistance especially for C. jejuni, gonococci, G+ cocci
like MRSA, Pseudomonas and Serratia ANTIMYCOBACTERIAL AGENTS
Used as alternatives to Ceftriaxone and Cefixime in https://qrs.ly/y9dveei
gonorrhea
• FQ elimination is via kidneys by tubular secretion (may
compete with probenecid for excretion) EXCEPT DRUG THERAPY FOR MYCOBACTERIAL INFECTIONS
Moxifloxacin • chemotherapy is complicated by numerous factors
o limited information about mechanisms of drug action
FOURTH GENERATION o development of resistance
Trovafloxacin, Alatrofloxacin, Prulifloxacin, Clinafloxacin o intracellular location of mycobacteria
Broad spectrum activity (gram-negatives, gram- o chronic nature of mycobacterial disease
Uses o patient compliance
positives), Enhanced activity against anaerobes
Same as others • chemotherapy always involves the use of drug combinations to
SE delay the emergence of resistance and to enhance efficacy
Trovafloxacin: Hepatotoxicity
Notes Widest spectrum of activity among fluoroquinolones
MNEMONIC: Hepatotoxicity of Anti-TB Drugs
RESISTANCE TO FLUOROQUINOLONES Which anti-TB drugs are hepatotoxic?
ISO a Red PYRe! (I saw a red fire!)
• decreased intracellular accumulation of the drug via the Isoniazid < Rifampin < Pyrazinamide
production of efflux pumps SUPPLEMENT: Alternative Antimycobacterial Drugs
• changes in porin structure • AMIKACIN
• changes in the sensitivity of the target enzymes via point o streptomycin-resistant or multidrug-resistant mycobacterial strains
mutations in the antibiotic binding regions • CIPROFLOXACIN, OFLOXACIN
o active against strains of M. tuberculosis resistant to first-line agents
• ETHIONAMIDE
MISCELLANEOUS ANTIBACTERIALS o no cross-resistance with INH
NITROIMIDAZOLE (ANTIPROTOZOAL) o SE: severe gastrointestinal irritation and neurotoxicity
Metronidazole, Tinidazole, Secnidazole • P-AMINOSALICYLIC ACID (PAS)
o rarely used because primary resistance is common
Reactive reduction by ferredoxin forming free radicals
MOA o SE: gastrointestinal irritation, peptic ulcers, hypersensitivity
that disrupt electron transport chain. Bactericidal.
reactions, effects on kidney, liver, and thyroid function
Anaerobic or mixed intra-abdominal infections, Vaginitis • CAPREOMYCIN
Uses (Trichomonas, Gardnerella), Pseudomembranous colitis, o SE: ototoxicity, renal dysfunction
Brain abscess, Protozoal infections • CYCLOSERINE
Gastrointestinal irritation, Metallic taste, Headache, o SE: peripheral neuropathy, CNS dysfunction
SE Dark urine, Leukopenia, Dizziness, Ataxia, Neuropathy, • BEDAQUILINE
Seizures, Disulfiram reaction o Inhibits ATP synthase in mycobacteria, has in vitro activity against
DOC for amoebiasis, giardiasis & both replicating and nonreplicating bacilli, and has bactericidal and
Notes
Pseudomembranous colitis sterilizing activity
o Taken in combination with at least three other active medications,
may be used for 24 weeks of treatment in adults with laboratory-
confirmed pulmonary tuberculosis if the isolate is resistant to both
isoniazid and rifampin
o SE: nausea, arthralgia, headache, hepatotoxicity QT prolongation
DRUGS FOR TUBERCULOSIS • Perform baseline ophthalmologic examination before

starting antimycobacterial therapy
USES
Notes • Dose adjustment if needed in renal patients
• First line agents: Isoniazid, Rifampicin, Pyrazinamide, • Always used in combination with other drugs for TB
Ethambutol • Take with meals
o All can be used for ACTIVE TB. Isoniazid and Rifampicin can
be used for LATENT TB.
AMINOGLYCOSIDE
• Second line agents:
o Amikacin, Aminosalicyclic acid, Bedaquiline, Capreomycin, Streptomycin
Clofazimine, Cycloserine, Ethionamide, Levovloxacin, Linezolid, Inhibit protein synthesis by binding to S12 ribosomal
MOA
Moxifloxacin, Rifabutin, Rifapentine, Streptomycin, Levofloxacin subunit. Bactericidal.
Tuberculosis (for Drug-resistant strains), Tularemia,
Uses
NICOTINIC ACID DERIVATIVE Bubonic plague, Brucellosis
Isoniazid Hypersensitivity, Nephrotoxicity (reversible),
Ototoxicity (vestibulotoxic, irreversible),
MOA Inhibits mycolic acid synthesis. Bactericidal. SE
Neuromuscular blockade
Hepatitis, Neurotoxicity (seizures, neuritis, insomnia), Teratogen (congenital deafness), Injection site reactions
SE Acute hemolysis in G6PD deficiency, Drug-induced • Synergistic effect with beta-lactam antibiotics
lupus, Drug interactions Notes
Administered IM
• Prevent neurotoxicity by co-administering
Pyridoxine (Vitamin B6) For TB drugs it is very important to know the MOA of each. Let’s Try (1)
• Liver metabolism by acetylation (Filipinos are fast Inhibits mycolic acid (2) Inh. Arabinosyl transferase (3) Inhibits DNA-
acetylators) dependent RNA polymerase
Notes
• Potent CYP450 inhibitor All the drugs are used for active TB but two are important for latent TB:
• Less Active against other Mycobacteria ___________________ - these drugs are also the first line drugs. It’s very
• Structural congener of pyridoxine important to assess also our patients for the common AEs for TB drugs.
• Best taken 1 hour before or 2 hours after meals Identify the drug that may have caused these (1) Doc parang may
tumutusok tusok po na kuryente sa kamay at paa ko – What do you give?
RIFAMYCINS (2) Doc kulay dugo po yung ihi ko. (3) Doc di ko madistinguish yung red and
green sa Christmas tree namin.
Rifampicin (Rifampin), Rifabutin, Rifapentine, Rifaximin Dr. Rodriguez
Inhibits DNA-dependent RNA polymerase → inhibits
MOA
RNA production. Bactericidal. DRUGS USED IN LEPROSY
Additional: Atypical Mycobacterial Infections,
Leprosy, Prophylaxis for meningococcal and Dapsone, Acedapsone (Sulfones)
Uses MOA Inhibition of folic acid synthesis. Bacteriostatic.
staphylococcal carrier states,
Drug-resistant infections (MRSA, PRSP) Uses Leprosy, PCP pneumonia (backup)
Red-orange Body Fluids, Light chain proteinuria, Gastrointestinal irritation, Fever, Skin rashes,
Skin rash, Thrombocytopenia, Nephritis, Hepatotoxicity, SE Methemoglobinemia,
Flulike Syndrome, Anemia, Cholestasis Acute hemolysis in patients with G6PD deficiency
SE The Rs of Rifampicin • Most active drug against M. leprae
RNA polymerase inhibitor • Usually in combination with rifampicin and clofazimine
Notes
Red-orange body fluids • Acedapsone is a repository form of dapsone which has
Rapid development of resistance drug action that can last for several months
Revs up cytochrome P450 (inducer)
• Potent CYP450 inducer Clofazimine
• Rapid development of resistance if used alone MOA Binds to guanine bases in bacterial DNA. Bactericidal.
• Delays the emergence of resistance to dapsone
Uses Leprosy (sulfone-resistance)
• RIFAXIMIN is a Rifampin derivative that is not
absorbed in the GIT, and so is used for the prevention Gastrointestinal irritation, Skin discoloration (ranging
SE
of hepatic encephalopathy, for treatment of traveler’s from orange to red brown to nearly black)
Notes
diarrhea, (off-label use: for IBS and
Pseudomembranous colitis) ANTIFUNGAL AGENTS
• Rifabutin is equally effective as anti-mycobacterial
agent with less drug interaction and it is the preferred
anti-TB for AIDS patients
• Best taken 1 hour before or 2 hours after meals
PYRAZINE DERIVATIVES
Pyrazinamide
Unknown. Converted to active pyrazinoic acid under acidic
MOA conditions of macrophage lysosomes. Bacteriostatic but can
be bactericidal on actively dividing mycobacteria.
Hepatotoxicity, Non-gouty polyarthralgia, Asymptomatic SUPERFICIAL MYCOSES
SE hyperuricemia, Myalgia, GIT irritation, Rash, Porphyria, SYSTEMIC DRUGS
Photosensitivity
MICROTUBULE INHIBITORS
• Also known as “sterilizing agent” used during the
first 2 months of therapy Griseofulvin
• Most hepatotoxic anti-TB drug Interferes with microtubule function. Inhibits
Notes MOA synthesis and polymerization of nucleic acids.
• Require metabolic conversion via pyrazinamidases in MTb
• Decrease dose in hepatic and renal patients Fungistatic.
• Take with meals Uses Dermatophytosis
Headache, Mental confusion, Gastrointestinal irritation,
BUTANOL DERIVATIVE SE Photosensitivity, Hepatotoxicity, Disulfiram reaction,
Ethambutol Drug interactions
Inhibits arabinosyl transferases involved in the • from Penicillium griseofulvum
MOA synthesis of arabinogalactan in mycobacterial cell wall. • Accumulates in keratin
Bacteriostatic. Notes • Potent CYP450 Inducer
Uses Others: atypical mycobacterial infections • Contraindicated in porphyria
Absorption is increased by intake of fatty meal
Visual disturbances (decreased visual acuity, red-green
SE color blindness, retrobulbar neuritis, retinal damage),
Headache, Confusion, Hyperuricemia, Peripheral neuritis
ALLYLAMINE AZOLES
Terbinafine, Butenafine, Naftifine • MOA: Inhibit fungal P450-dependent enzymes blocking
Interfere with ergosterol synthesis by inhibiting fungal ergosterol synthesis. Fungistatic.
MOA
squalene oxidase. Fungicidal. • SE: Gastrointestinal disturbances (vomiting, diarrhea), Rash and
Uses Dermatophytosis, Onychomycosis Hepatotoxicity
Gastrointestinal upset, Rash, Headache, Taste Narrow spectrum
SE
disturbances, Hepatotoxicity
Ketoconazole
• Accumulates in keratin
Uses Chronic mucocutaneous candidiasis, Dermatophytosis
Notes • Given PO and topical
• More effective than griseofulvin in onychomycosis Rarely used due to drug interactions and narrow spectrum
• Potent CYP450 inhibitor (Affect Phase I metabolism)
TOPICAL DRUGS • Limited to topical use because of systemic toxicity
Notes
• Interferes with Steroid hormone synthesis
POLYENE • Resistance is due to changes in the sensitivity of target
Nystatin, Natamycin enzyme
Binds to ergosterol in fungal cell membranes, forming
MOA Broad spectrum, Good CNS Penetration
artificial pores. Fungicidal.
Uses Candidiasis (Oropharyngeal, Esophageal, Vaginal) Fluconazole [D], Voriconazole, Posaconazole
Cryptococcal meningitis (treatment and prophylaxis)
SE Nephrotoxicity (severe)
Uses Candidiasis (esophageal, oropharyngeal, vulvovaginitis),
• Minimal mucocutaneous absorption Coccidioidomycosis
Notes
• Available as a swish and swallow preparation • Alternative to Amphotericin B in the treatment of
C. neoformans
AZOLES
• As effective as Amphotericin B in candidemia
Clotrimazole, Miconazole, Ketoconazole, Butoconazole, Econazole, Notes • Posaconazole has the BROADEST spectrum triazole
Sulconazole, Oxiconazole, Terconazole, Tioconazole (the only azole with activity against Rhizopus sp.
Inhibit fungal P450-dependent enzymes blocking (mucormycosis)
MOA
ergosterol synthesis. Fungistatic. • Potent CYP450 inhibitor
Mucocutaneous candidiasis, Dermatophytosis,
Uses Broad spectrum, Poor CNS Penetration
Seborrheic dermatitis, Pityriasis versicolor
SE Nonsignificant when administered topically Itraconazole
Notes Limited to topical use because of systemic toxicity Blastomycosis, Sporotrichosis, Dermatophytosis,
Uses Chromoblastomycosis, Alternative for infections due to
Aspergillus, Coccidioides, Cryptococcus and Histoplasma, Candida
• Much more selective for fungal cells than Ketoconazole but
Notes with poor entry intro CNS
• May also be used for subcutaneous chromoblastomycosis
ECHINOCANDIN
Caspofungin, Anidulafungin, Micafungin
MOA Inhibits b-glucan synthase decreasing fungal cell wall synthesis
Disseminated and mucocutaneous candidiasis, Salvage
Uses
therapy for invasive aspergillosis
Headache, Gastrointestinal distress, Rash, Fever,
SE
Flushing (histamine release), Elevated liver enzymes
• All are given IV
Notes • Micafungin can increase levels of cyclosporine and
tacrolimus
For antifungal drugs you need to know first if the condition is superficial or
systemic in nature.
Very high yield to memorize the mechanism of actions of these drugs.:
1. Inhibits microtubule function ___________________
SYSTEMIC MYCOSES 2. Binds to ergosterol creating artificial pores. ___________________
POLYENE a. Follow up question: One is for superficial mycoses, the
other is for systemic mycosis. Which drug is used for
Amphotericin B
which?
Binds to ergosterol in fungal cell membranes, forming b. Which has the widest antifungal spectrum?
MOA
artificial pores. Fungicidal. 3. Converted to 5-FU and inhibits thymidylate synthase.
Systemic fungal infections (Aspergillus, Blastomyces, 4. Causes inhibition of ergosterol synthesis by inhibition of P450
Uses
Candida albicans, Cryptococcus, Histoplasma, Mucor) dependent enzymes
Infusion reactions (chills, fever, muscle spasms, a. Can they be given for superficial? How about for
SE hypotension), Nephrotoxicity (Renal Tubular Acidosis with systemic infections?
magnesium and potassium wasting) b. Among the azole, what can you give in cryptococcal
• Control infusion reactions by slowing rate of infusion and meningitis (remember it needs to cross BBB!)?
premedication with antihistamines c. Which has a narrow spectrum of activity?
• +Aminoglycosides: Nephrotoxic 5. Inhibits beta-glucan synthase
Notes • LIPID FORMULATIONS: Ambisome, Amphotec, Abelcet Dr. Rodriguez
• Highly lipid soluble, poorly absorbed in the GIT ANTIVIRAL CHEMOTHERAPY AND
• High Vd except in the CNS with a t½ of 2 weeks
• Has the WIDEST antifungal spectrum PROPHYLAXIS
PYRIMIDINE ANTIMETABOLITE
Flucytosine
Accumulated in fungal cells by the action of permease and
MOA converted by cytosine deaminase to 5-FU, which inhibits
thimidylate synthase. Fungistatic.
Cryptococcosis, Systemic candidal infections,
Uses
Chromoblastomycosis
SE Myelosuppression, Alopecia, Hepatotoxicity
• Selective toxicity occurs because mammalian cells have
low levels of permease and deaminase
Notes
• Decrease dose in renal patients
• Amphotericin B and Triazoles: Synergistic effect
DRUGS FOR HIV

HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
• initiation of treatment with 3 or more anti-retroviral drugs, if
possible, before symptoms appear
• usually 2 NRTIs plus 1 protease inhibitor
• combination of different drug classes to achieve synergism and
combat resistance
MNEMONIC: NNRTIs (Non-Nucleoside RT inhibitors)

“Never Ever Deliver Nucleosides”
Nevirapine Efavirenz / Etravirine Delavirdine
NUCLEOSIDE REVERSE
TRANSCRIPTASE INHIBITORS (NRTIS)
Zidovudine [C], Abacavir, Didanosine, Emtricitabine, Lamivudine,
Stavudine, Tenofovir, Zalcitabine
Inhibit HIV reverse transcriptase after
MOA
phosphorylation by cellular enzymes
DRUGS FOR HERPESVIRUS HIV infection, Prevention of maternal-fetal HIV
Uses
transmission
Acyclovir [B], Valacyclovir, Penciclovir, Famciclovir, Docosanol,
Trifluridine • Lactic Acidosis with hepatic steatosis
Activated by viral thymidine kinase (TK) to forms • Zidovudine: Bone marrow suppression
MOA • Abacavir: Hypersensitivity
that inhibit viral DNA polymerase
SE • Didanosine: Pancreatitis
Uses Infections due to HSV-1, HSV-2, VZV
• Stavudine, Zalcitabine: Peripheral neuropathy
Nausea, Diarrhea, Headache, Delirium, Tremor, Seizures,
SE Abacavir, Emtricitabine, Lamivudine and Tenofovir are
Hypotension, Nephrotoxicity (crystalluria)
• No activity against strains of HSV with absent safe for pregnant
Thymidine Kinase activity
• DOCOSANOL inhibits fusion between the HSV NON-NUCLEOSIDE
envelope and plasma membranes REVERSE TRANSCRIPTASE INHIBITORS (NNRTIS)
• VALOMACICLOVIR is an investigational agent which
Delavirdine [C], Efavirenz, Etravirine, Nevirapine, Rilpivirine
Notes acts as an inhibitor of viral DNA polymerase for
shingles and EBV Inhibit HIV reverse transcriptase.
MOA
• Dose adjustment in renal patients No phosphorylation required.
• Valacyclovir is a prodrug that is converted to Acyclovir • Delavirdine, Nevirapine: Rash, Increased AST/ALT
and reached plasma levels 3-5x (longer t½) more than • Efavirenz: Teratogenicity
acyclovir SE • Etravirine: Increased cholesterol, triglycerides
NO bone marrow suppression in NNRTs because these are
not incorporated in the DNA.
Ganciclovir, Valganciclovir
Notice that they have -VIR- in the middle of the drug name. COMPARE THE
Inhibits viral DNA polymerase, causing chain PHOSPHORYLATION STEP FOR THE PREVIOUS DRUG CLASS
MOA
termination. Dr. Rodriguez
Uses Infections due to CMV, HSV-1, HSV-2, VZV

SE
Leukopenia, Thrombocytopenia, Mucositis, PROTEASE INHIBITORS
Hepatotoxicity, Seizures, Neutropenia Indinavir [C], Amprenavir, Atazanavir, Darunavir, Indinavir,
• No activity against strains of HSV with absent Lopinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir,
thymidine kinase activity Fosamprenavir, Boceprevir, Telaprivir
Notes • Given as IV or intraocular implant (for CMV retinitis) MOA Inhibit viral protein processing
• Valganciclovir is a prodrug of ganciclovir with
• Hyperlipidemia, Fat redistribution, Hyperglycemia,
increased oral bioavailability
Insulin resistance
• Atazanavir, Fosamprenavir, Lopinavir, Nelfinavir,
Cidofovir SE Saquinavir: GI distress and diarrhea
Inhibits viral DNA polymerase, causing chain • Atazanavir: Peripheral neuropathy;
MOA
termination. • Amprenavir: Rash;
CMV retinitis, Mucocutaneous HSV infections, • Indinavir: Hyperbilirubinemia and nephrolithiasis
Uses Acyclovir-resistance, Ganciclovir-resistance, Drug names end in NAVIR
Genital warts, Molluscum contagiosum Dr. Rodriguez
SE Nephrotoxicity
• Active against strains of HSV with absent thymidine ENTRY INHIBITORS
Notes kinase activity FUSION INHIBITORS
• Dose adjustment in renal patients
Enfuvirtide
Binds to gp41 subunit of viral envelope glycoprotein,
Foscarnet [C] (Pyrophosphate Analogue) MOA
preventing fusion of viral and cellular membranes
Inhibits viral RNA polymerase, DNA polymerase, and Injection site reactions, Hypersensitivity, Increased
MOA HIV reverse transcriptase. Binds to pyrophosphate SE
incidence of bacterial pneumonia
binding site. Notes No cross-resistance with other anti-HIV drugs
CMV retinitis,
Uses Acyclovir-resistance,
HSV infection in patients with AIDS
CCR5 RECEPTOR ANTAGONIST
Nephrotoxicity, Electrolyte abnormalities Maraviroc
SE (hypocalcemia), Genitourinary ulceration, CNS effects Blocks viral attachment via transmembrane chemokine
MOA
(headache, hallucinations, seizures) receptor CCR5
• Active against strains of HSV with absent thymidine Cough, Diarrhea, Muscle and joint pain, Increased
SE
kinase activity hepatic transaminases
Notes Minimal cross-resistance with other anti-HIV drugs
• Does not require phosphorylation for antiviral activity Notes
Dose adjustment in renal patients
INTEGRASE INHIBITORS ANTIPROTOZOAL DRUGS

Raltegravir, Dolutegravir
Integrase inhibitor (an enzyme essential for replication of
Notes HIV) leading to inhibition of strand transfer; DI: avoid
using rifampicin concomitantly (lowered blood levels)
DRUGS FOR INFLUENZA

UNCOATING NEURAMINIDASE
INHIBITOR INHIBITOR
Drugs
Amantadine [C], Oseltamivir [C], Zanamivir,
Rimantadine Peramivir
Inhibit early step Inhibits Neuraminidase.
replication and prevent Decreases release of progeny
MOA
uncoating by binding to virus.
M2 proton channels
Influenza A and B, Shortens Katzung and Trevor’s Pharmacology Examination and Board Review. 12th ed. 2018
Uses Influenza A only
duration of symptoms
• GI irritation, Dizziness, • Oseltamivir: ANTIMALARIAL DRUGS
Cerebellar dysfunction Gastrointestinal effects; CATEGORIES
SE
(ataxia, dysarthria), • Zanamivir: Bronchospasm
• TISSUE SCHIZONTICIDES
Livedo reticularis in asthmatics
o kill schizonts in the liver
Amantadine is also used OSELTAMIVIR: Presently the
o EXAMPLE: primaquine, atovaquone
Notes in treating drugs of choice for influenza
Parkinsonism (including H1N1) • BLOOD SCHIZONTICIDES
o kill these parasitic forms only in the erythrocyte
DRUGS FOR HBV AND HCV o EXAMPLES: chloroquine, quinine mefloquine, atovaquone,
pyrimethamine, doxycycline, halofantrine, artemisinin
Interferon-a [X]
• GAMETOCIDES
Degrades viral RNA via activation of host cell RNAse
MOA o kills gametocides in human blood
(ribonuclease)
o EXAMPLES: primaquine
HBV infection, HCV infection, Kaposi sarcoma,
Uses
Genital warts • SPORONTICIDES
Alopecia, Myalgia, Depression, o prevent sporogony and multiplication in the mosquito
SE o EXAMPLES: proguanil, pyrimethamine
Flu-like syndrome, Thyroid dysfunction, Hearing loss
Contraindications include autoimmune disease, history
Notes TREATMENT OF MALARIA
of cardiac arrhythmias and pregnancy
CLINICAL
Ribavirin [X] DRUG OF CHOICE / ALTERNATIVE
SETTING
Inhibits guanosine triphosphate formation. Prevents Chloroquine-
MOA capping of viral mRNA. sensitive P. Chloroquine
Blocks RNA-dependent RNA polymerases. falciparum
Uses HCV infection, RSV infection P. vivax and
Chloroquine then Primaquine
Hemolytic anemia, Conjunctival and bronchial irritation, P. ovale
SE
Teratogen Uncomplicated Artemether + Lumefantrine (CoArtem) /
Early IV administration of ribavirin decreases mortality Chloroquine- Malarone or Mefloquine or Quinine Sulfate +
in viral hemorrhagic fevers resistant Clindamycin or other Artemisinin-based
Notes P. falciparum combination regimen
OTHER DRUGS FOR RSV: Pavilizumab (monoclonal
antibody against RSV antigen) Severe or Artesunate then Doxycycline or Clindamycin
Complicated or CoArtem ; Quinidine gluconate /
LAMIVUDINE [C], Adefovir Dipivoxil, Entecavir, Telbivudine, P. falciparum Artemether or Quinine dihydrochloride
Tenofovir, Clevudine
MOA Inhibits HBV DNA polymerase Chloroquine, Hydroxychloroquine, Amodiaquine, Piperaquine
Uses Hepatitis B infection, HIV infection (lamivudine) Prevents polymerization of heme into hemozoin.
MOA
Adefovir: Lactic acidosis, Blood schizonticide.
SE Renal and hepatic toxicity Malaria (non-falciparum, chloroquine-sensitive),
Entecavir: Headache, Dizziness, Fatigue, Nausea Uses Chemoprophylaxis (chloroquine-sensitive areas),
Co-infection between HBV and HIV may increase the risk Rheumatoid arthritis, Amebic liver abscess
Notes
of pancreatitis with lamivudine use SE Retinal damage, Auditory impairment
SUPPLEMENT: MISCELLANEOUS ANTIVIRALS: Notes May precipitate porphyria
an immune response modifier effective for
IMIQUIMOD
external genital and perianal warts Quinine [C], Quinidine Gluconate
Licensed for the treatment of cell-mediated
Complexes with DNA to prevent strand separation.
INOSINE immune deficiencies associated with viral
ACEDOBEN infections; used for genital warts, herpes virus
MOA Blocks DNA replication and transcription. Blood
DIMEPRANOL infection, subacute sclerosing panencephalitis schizonticide.
and other conditions Malaria (chloroquine-resistance),
Uses
Severe falciparum malaria (quinidine)
Application: Give the best drug for the following presentations: SE Blackwater fever, Cinchonism
1. Painful and pruritic small fluid filled lesions all over the skin. • Quinine is commonly used with doxycycline or
Lesions appear as the classic “dew drop on a rose petal” Notes clindamycin to limit toxicities
2. Loss of vision in a patient with AIDS DOC for malaria in pregnant patients
Answers: (1) Acyclovir (2) Ganciclovir – think of CMV retinitis
QUICK RECOGNITION EXERCISE: Mefloquine [B]
1. Has -VIR- in the middle of the name MOA Unknown. Blood schizonticide
2. Ends in -NAVIR Chemoprophylaxis (chloroquine-resistant areas),
3. Ends in -GRAVIR Uses Alternative to quinine in acute attacks of falciparum
4. Has “FU” in its name
malaria
5. Ends in TADINE
6. Has -MIVIR in the name SE Seizures, Cardiac conduction defects
Answers (1) NNRTI (2) Protease Inhibitor (3) Gravir has GRA in inteGRAse.
(4) FU for FUsion (5) TADINE sounds like TADA!!! Imagine someone uncoating
and saying “TADA!!!!” (6) MIvir - NeuraMInidase
Dr. Rodriguez
Primaquine DRUGS FOR AMEBIASIS
Forms electron-transferring redox compounds that act DISEASE FORM DRUG(s) OF CHOICE
MOA
as cellular oxidants. Tissue schizonticide. Gametocide.
Asymptomatic
Malaria (radical cure of P. vivax, P. ovale), Terminal Luminal agent (diloxanide furoate,
Uses intestinal
prophylaxis (vivax, ovale), PCP pneumonia iodoquinol, paromomycin)
colonization
SE Methemoglobinemia Amebic colitis Metronidazole or Tinidazole plus Luminal
• Should be used with a blood schizonticide (dysentery) agent*
Notes • Eradicates hypnozoites in the liver, preventing • Metronidazole or Tinidazole
malarial relapse followed by Luminal agent*
Amebic liver • Percutaneous or surgical drainage if:
Atovaquone – Proguanil [C]
abscess o Abscess is 5 cm or greater diameter
Atovaquone disrupts mitochondrial electron transport. o if they are in the left lobe
MOA Blood and tissue schizonticide. o no clinical response to medical therapy
Proguanil inhibits folate synthesis. Sporonticide.
Treatment and chemoprophylaxis (chloroquine- LUMINAL AMEBICIDES
Uses
resistant P. falciparum) – all stages
Diloxanide Furoate
SE Increased liver enzymes
MOA Unknown.
SIDE EFFECTS C Q M P AP Asymptomatic cyst carriers of E. histolytica
Uses
Gastrointestinal irritation (drug of choice)
Rashes, Pruritus SE Flatulence, Nausea, Abdominal cramps
Headaches Iodoquinol
Neurologic (neuropathies) MOA Unknown.
QT Prolongation Mild-to-severe intestinal amebiasis
Uses
G6PD Hemolysis *Used in combination with Metronidazole
Psychiatric disorder (psychosis) Gastrointestinal distress, Thyroid enlargement, Skin
SE reactions due to iodine toxicity, Neurotoxicity
Ask yourself the question first, is the organism SENSITIVE or RESISTANT to (peripheral neuropathy, visual dysfunction)
chloroquine. Shempre if sensitive siya best drug is Chloroquine both for treatment
and prophylaxis. If it’s resistant ask “Am I treating?” or “Is this for prophylaxis. Paromomycin
Give QUININE, or ATOVAQUONE-PROGUANIL or LUMEFANTRINE for
treatment. Give Mefloquine or ATOVAQUONE-PROGUANIL for prophylaxis. If
Inhibits protein synthesis. Binds to 16S ribosomal
MOA
the malaria species has an extraerythrocytic form (meaning hindi lang siya subunit. Luminal amebicide.
nagtago sa RBCs – i.e. Vivax and Ovale), give PRIMAQUINE Asymptomatic cyst carriers (backup), Intestinal
Uses
Dr. Rodriguez amebiasis, Cryptosporidiosis
Sulfadoxine-Pyrimethamine [C] SE Headaches, Dizziness, Rashes, Arthralgia
Sequential blockade of folic acid synthesis.
MOA Blood schizonticide. TISSUE AMEBICIDES
Sporonticide (pyrimethamine). Metronidazole [B],
Uses Malaria (chlorine-resistant P. falciparum) Tinidazole [C], Secnidazole
Skin rashes, GI distress, Hemolysis, Kidney damage, Reactive reduction by ferredoxin forming free radicals
SE Drug interactions, MOA
that disrupt electron transport chain. Tissue amebicide.
Folic acid deficiency (pyrimethamine) Severe intestinal and extraintestinal amebiasis
• Competition for plasma protein binding sites with (drug of choice), Trichomoniasis, Giardiasis,
Notes other drugs Uses
Bacterial vaginosis, Anaerobic infections
• Pyrimethamine is a long-acting folate antagonist (B. fragilis, C. difficile), Peptic ulcer disease
Gastrointestinal irritation,
Doxycycline [D] SE Metallic taste, Headache, Dark urine, Leukopenia,
Impairs progeny of malarial apicoplast genes, resulting Dizziness, Ataxia, Neuropathy, Seizures, Disulfiram reaction
MOA
in abnormal cell division. Blood schizonticide.
Uses Chemoprophylaxis (Multidrug-resistant) Nitazoxanide
GI disturbance, Teratogen (tooth enamel MOA Same with metronidazole
SE dysplasia/discoloration), Hepatotoxicity, Metronidazole-resistant amebiasis, Giardiasis,
Nephrotoxicity, Photosensitivity, Vestibulotoxicity Uses
Cryptosporidiosis (drug of choice)
Notes Do NOT drink with milk (decreased absorption) SE GI distress
Halofantrine [C], Lumefantrine Emetine, Dehydroemetine

Unknown. Inhibit proteins synthesis. Blocks ribosomal movement
MOA MOA
Blood Schizonticide. along messenger RNA.
Malaria (chloroquine-resistance), Backup drug for severe intestinal and extraintestinal
Uses
Severe falciparum malaria (quinidine) Uses amebiasis * Reserved only for situations when
Abdominal pain, Diarrhea, Vomiting, Cough, Rash, metronidazole can’t be used
SE Headache, Pruritus, Elevated liver enzymes, GI distress, Muscle weakness, Cardiovascular dysfunction
Cardiotoxicity (prolongs PR and QT interval), Teratogen SE
(arrhythmias and congestive heart failure)
• Lumefantrine used in combination with artemether
(Co-Artem) DRUGS FOR PNEUMOCYSTOSIS AND
Notes Artemether-Lumefantrine (Co-Artem) is the drug of TOXOPLASMOSIS
choice for uncomplicated falciparum malaria in the
Philippines Sulfadiazine-
Pyrimethamine [C],
Drug Co-Trimoxazole [C]
Artemisinin, Artesunate, Artemether, Dihydroartemisinin Pyrimethamine +
Forms toxic free radicals in malarial food vacuole. Clindamycin
MOA Sequential blockade of Sequential blockade of
Blood schizonticide.
Uses Malaria (uncomplicated falciparum, quinine-resistant) dihydropteroate synthase dihydropteroate synthase
MOA (sulfamethoxazole) and (sulfadiazine) and
SE Nausea, Vomiting, Diarrhea
dihydrofolate reductase dihydrofolate reductase
Artemisinin-based combination therapy is current the (trimethoprim) (pyrimethamine)
first line of malaria treatment recommended by the Prophylaxis and treatment
WHO for children, adults and pregnant women in 2nd or of pneumocystosis Prophylaxis and treatment
Notes 3rd trimester. Due to potential embryotoxicity of Uses (drug of choice), of Toxoplasmosis
artemisinins identified in animal studies, artemisinins Prophylaxis (drug of choice)
are not considered safe for use in 1st trimester of (T. gondii, I. belli)
pregnancy.
Sulfadiazine- Pentamidine
Pyrimethamine [C], Unknown. Probably inhibits glycolysis or interferes with
Drug Co-Trimoxazole [C] MOA
Pyrimethamine + nucleic acid metabolism.
Clindamycin Prophylaxis for pneumocystosis,
GI upset, Uses
Gastric irritation, Glossitis, Kala-azar (visceral leishmaniasis)
Acute hemolysis in G6PD Notes Administered by nasal spray (aerosol)
Neurologic symptoms
deficiency,
(headache, insomnia,
Nephrotoxicity, Suramin
tremors, seizures),
Hypersensitivity (assume Unknown. Probably inhibits glycolysis or interferes with
SE Hematotoxicity MOA
cross-hypersensitivity, nucleic acid metabolism.
(megaloblastic anemia,
SJS/TEN), Uses Onchocerciasis (backup)
thrombocytopenia),
Hematotoxicity,
Pseudomembranous colitis Notes Used in combination with melarsoprol
Drug interactions,
(clindamycin)
Kernicterus Eflornithine
• Recommended at CD4
Notes MOA Suicide inhibitor of ornithine decarboxylase
count < 200
Notes Considerably less toxic than melarsoprol
TREATMENT OF OTHER PROTOZOA
Melarsoprol
ORGANISM DRUG OF CHOICE / ALTERNATIVE
Organic arsenical. Inhibits enzyme sulfhydryl groups in
Clindamycin or Quinine / Atovaquone or MOA
Babesia sp. trypanosomes.
Azithromycin
• Administered intramuscularly
Balantidium Coli Tetracycline / Metronidazole Notes
Usually administered with suramin
Cryptosporidium sp. Paromomycin / Azithromycin
Cyclospora cayetanensis TMP-SMX Nifurtimox
Dientamoeba fragilis Iodoquinol/Tetracycline or Paromomycin MOA Inhibits trypanothione reductase
Metronidazole or Tinidazole / African sleeping sickness (backup), Mucocutaneous
Giardia lamblia Use
Furazolidone or Albendazole leishmaniasis, Drug of choice for leishmania
Isospora belli TMP-SMX/Pyrimethamine or Folinic Acid
Microsporidia Albendazole
Sodium stibogluconate / Meglumine or ANTIVIRALS AND
Leishmania Pentamidine or Amphotericin or ANTIPROTOZOALS
Miltefosine or Paromomycin https://qrs.ly/c3dveem
TMP-SMX / Pentamidine or TMP-
Pneumocystis
Dapsone or Clindamycin + Primaquine
jirovecii ANTIHELMINTHIC DRUGS
or Atovaquone
Pyrimethamine + Clindamycin + Folinic acid or
Toxoplasma gondii Spiramycin / Pyrimethamine +
Sulfadiazine + Folinic acid
Trichomonas
Metronidazole or Tinidazole
vaginalis
Trypanosoma cruzi Nifurtimox or Benznidazole
DRUGS FOR TRYPANOSOMIASIS

First-line Alternative DRUGS AGAINST TREMATODES AND CESTODES
Disease Stage
drugs drugs Drug Praziquantel [B] Niclosamide
Suramin, Increases membrane
Early Pentamidine
Eflornithine permeability to calcium → Uncouples oxidative
West
Melarsoprol, MOA paralysis. Causes muscle phosphorylation or
African CNS paralysis, vacuolization and by activating ATPases
Eflornithine Eflornithine-
involvement death.
Nifurtimox
Early Suramin Pentamidine Drug of choice for Alternative drug for
East trematodes (Schistosoma, cestode infections
CNS
African Melarsoprol - Paragonimus, Clonorchis, (Taenia,
involvement
Uses Opisthorchis, Fasciolopsis, Diphyllobothrium,
USE Heterophyes) Hymenolepsis,
African Sleeping Sickness P S E M N Sb and cestodes (Taenia, Dipylidium, Fasciolopsis,
Hemolymphatic stages Diphyllobothrium, Hymenolepsis) Heterophyes)
Drug of choice Headache, Dizziness, Nausea,
Malaise, drowsiness, GI upset, Gastrointestinal distress,
Drug of choice (Advanced) SE
arthralgia, myalgia, pruritus, Headache, Rash, Fever
Chagas (DOC) skin rash,
Leishmaniasis (DOC) • Contraindicated in ocular • Kills scolices and cestode
cysticercosis (may cause segments but has no
SIDE EFFECTS P S E M N Sb irreparable eye damage) effect on ova
Anemia • Used with corticosteroids in • Avoid ethanol
Notes
GI Disturbance treating neurocysticercosis consumption for 48h
• May be used as an adjunct to upon drug
Seizures Albendazole in Hydatid administration
Neuropathies disease
Rashes
Fever DRUGS AGAINST NEMATODES
MICROTUBULE INHIBITORS
More specific side effects
Respiratory stimulation followed by depression, Albendazole
Pentamidine Hypotension, Hypoglycemia, Neutropenia, Ascariasis, Hookworm, Pinworm, Hydatid disease
Hepatitis, Pancreatitis (drug of choice), Whipworm infections, Cutaneous &
Uses
Suramin Hemolytic anemia, Agranulocytosis, Visceral Larva migrans, Cysticercosis (larval stages of T.
Thrombocytopenia, Leukopenia CROSSES BBB (the solium), Angiostrongylus cantonensis, Capillaria philippinensis
Eflornitine Reversible leukopenia, Alopecia, Elevation of liver
rest doesn’t) SE
Melarsoprol Reactive encephalopathy, function tests, Bone marrow suppression
Nifurtimox Restlessness, Insomnia
• Improved penetration (>Praziquantel) of the
Notes subarachnoid space in Neurocysticercosis
Sodium Cardiotoxicity (T wave changes, QT prolongation)
Should not be given to patients with Cirrhosis
Stibogluconate Sterile Abscess, Myalgia, Arthralgia
Mebendazole • Baricitinib is a Janus kinase (JAK) inhibitor.
Whipworm infections JAKs are tyrosine protein kinases that play
Uses (drug of choice), Trichinosis, Visceral larval migrans an important role in pro-inflammatory
(backup), Ascariasis, Pinworm signaling pathways.
o We suggest the use of baricitinib in
GI irritation, Agranulocytosis,
SE addition to dexamethasone and
Alopecia, Elevated liver enzymes
remdesivir as treatment for hospitalized
Thiabendazole BARICITINIB
COVID-19 patients who require low-flow
Uses Trichinosis (drug of choice), Strongyloidiasis (backup) oxygen, high-flow oxygen, and non-
GI irritation, Headache, Dizziness, invasive ventilation.
Drowsiness, Leukopenia, Hematuria, Hypersensitivity o There is insufficient evidence to
SE recommend baricitinib as an alternative to
reactions (SJS), Hepatotoxicity (intrahepatic
cholestasis, liver failure) tocilizumab as treatment for hospitalized
COVID-19 patients.
Notes Reactions caused by dying parasites
• Bamlanivimab is a neutralizing human
IgG1κ monoclonal antibody against the
DIETHYLCARBAMAZINE SARS-CoV-2 spike (S) protein.
DEC • Etesevimab aims to neutralize SARS-CoV-2
Filariasis (drug of choice), by specifically binding to the virus' surface
Uses Eye worm disease (drug of choice), spike protein receptor binding domain. This
Onchocerciasis (backup) high affinity binding then prevents SARS-
Headache, Malaise, Weakness, CoV-2 from binding to the ACE2 host cell
surface receptor.
SE Anorexia, Filarial fever (fever, rashes, ocular damage,
o We suggest the use of bamlanivimab and
joint and muscle pain, lymphangitis)
etesevimab combination therapy as
• May cause Mazzotti reaction when used for treatment for mild to moderate, non-
onchocerciasis hospitalized COVID-19 patients with at
Notes
• DOXYCYCLINE has also shown significant activity least 1 risk factor* for progression to
against W. bancrofti BAMLANIVIMAB + severe disease.
ETESEVIMAB (*Risk factors for severe COVID-19: age ≥65
IVERMECTIN years, body-mass index ≥35 kg/m2,
Ivermectin cardiovascular disease (including
hypertension), chronic lung disease (including
Strongyloidiasis (drug of choice), Onchocerciasis,
Uses asthma), chronic metabolic disease (including
Cutaneous larva migrans, Filariasis (back up) diabetes), chronic kidney disease (including
Mazzoti reaction (fever, headache, dizziness, rashes, receipt of dialysis), chronic liver disease, and
SE pruritus,tachycardia, hypotension, pain in joints, muscles immunocompromised conditions.)
and lymph glands), corneal opacities o This combination regimen is also used for
• Contraindicated in pregnancy and children < 5y/o post-exposure prophylaxis of COVID-19 in
Notes Avoid concomitant use of Ivermectin with other drugs that unvaccinated or immunocompromised
enhance GABA activity(Barbiturates, BZDs etc.) adults and pediatric individuals, including
neonates, who are at high risk of
PYRANTEL PAMOATE progression to severe COVID-19, including
hospitalization or death.
Pyrantel Pamoate
• Casirivimab is a recombinant human IgG1
Ascaris, Hookworm and Pinworm infections (drug of monoclonal antibody targeting the receptor
Uses
choice), Trichostrongylus sp. binding domain of the spike protein of SARS-
SE GI distress, Headache, Weakness CoV-2; a protein playing an important role in
Notes Contraindicated in patients with hepatic dysfunction viral attachment, fusion, and entry into the cell.
A general rule to help you in the treatment of helminths, know first if it’s a • Imdevimab is a recombinant human IgG1
nematode or a flatworm (Trematode/Cestode). If it’s a nematode it’s usually monoclonal antibody targeting the receptor
safe to answer ALBENDAZOLE. Except for the following Mebendazole for binding domain of the spike protein of SARS-
Whipworm (WHIP ME!!!), and Thiabendazole for Trichinella ( T.T – parang CoV-2; a protein playing an important role in
umiiyak na emoticon. Kasi di mo na siya mahanap o makita. Remember viral attachment, fusion, and entry into the
Trichinella nagtatago yan sa muscles ng pigs). Filariasis (Elephantiasis) – target cell by binding to the ACE2 receptor.
“ELEPHANT DEC <censored haha>” Ivermectin = Strong rIVER!. Pyrantel • Together, they neutralizes the spike protein
Pamoate (PAMaypay ni NICO) – stimulates nicotinic receptors. of SARS-CoV-2
Dr. Rodriguez o We suggest the use of casirivimab-
imdevimab as treatment for symptomatic,
COVID DRUGS non-hospitalized patients with at least 1
TREATMENT FOR COVID-19 (FROM THE PHILIPPINE risk factor* for severe COVID-19.
COVID-19 LIVING RECOMMENDATIONS) o We recommend against casirivimab-
imdevimab as treatment for hospitalized
• Remdesivir is a nucleoside analog nucleotide COVID-19 patients.
analogue that competes with ATP for o There is insufficient evidence to recommend
incorporation into newly synthesized viral RNA. CASIRIVIMAB + casirivimab-imdevimab as treatment for
o We suggest the addition of remdesivir to IMDEVIMAB asymptomatic COVID-19 patients.
dexamethasone in patients with COVID-19 (*Risk factors: age >50 years, obesity,
REMDESIVIR
infection who have O2 saturation < 94% cardiovascular disease (including
and/or requiring oxygen supplementation. hypertension), chronic lung disease (including
o We suggest against the use of remdesivir asthma), chronic metabolic disease (including
in patients with COVID-19 infection who diabetes), chronic kidney disease (including
are already on invasive mechanical ventilation. receipt of dialysis), chronic liver disease, and
• Tocilizumab is a recombinant humanized immunocompromised conditions.)
monoclonal antibody IL-6 receptor inhibitor o We suggest the subcutaneous use of
(Interleukin 6 (IL-6) is a pro-inflammatory casirivimab + imdevimab as day 4 post-
cytokine produced by cells such as T-cells exposure prophylaxis for COVID-19 close
and B-cells) contacts*, ages 12 years and above
o We recommend the addition of tocilizumab to weighing at least 40 kilograms, who are at
systemic steroids in patients showing rapid risk for severe disease or
TOCILIZUMAB respiratory deterioration and/or requiring hospitalization**.
high doses of oxygen (high-flow nasal cannula, ( **This includes the following people: elderly;
noninvasive or invasive mechanical BMI >25; those with chronic diseases such as
ventilation) and with elevated biomarkers of hypertension, diabetes, and chronic kidney
inflammation (CRP). disease; those who are not expected to mount
o We recommend against the use of an adequate immune response to the vaccine
tocilizumab among patients with COVID- due to immunosuppressive therapy or those in
19 infection who do not require oxygen an immunocompromised state.)
• Molnupiravir is an orally bioavailable o We recommend the use of carbon dioxide
isopropylester cytidine analog used to treat (CO2) monitors in enclosed spaces to
CO2 MONITORS
COVID-19. Molnupiravir is hydrolyzed in guide actions to improve ventilation and
vivo to N4-hydroxycytidine, which is reduce transmission of SARS-CoV-2.
phosphorylated in tissue to the active 5’- o We recommend continuing maintenance
triphosphate form, and incorporated into RAAS INHIBITORS RAAS blockers for hypertension among
the genome of new virions, resulting in the patients with COVID-19 infection.
accumulation of inactivating mutations, COVID-19 VACCINE RECOMMENDATION:
known as viral error catastrophe
• We recommend the use of the following vaccines to prevent
MOLNUPIRAVIR o We suggest the use of molnupiravir within
5 days of symptom onset among non- symptomatic SARS-CoV-2 infection in adults:
hospitalized adult patients (18 years old o 1. BNT162b2 (Pfizer/BioNTech) (given as 0.3ml (30ug)
and older) with mild to moderate COVID- intramuscular injections, in 2 doses, 21 days apart)
19 infection with at least one risk factor* o 2. mRNA-1273 (Moderna) (given as 0.5ml (100ug)
for progression. intramuscular injections, in 2 doses, 28 days apart)
(*Risk factors for progression include: age >60 o 3. ChAdOx1 (AstraZeneca) (given as 0.5 ml (5 x 106 vp)
years, active cancer, chronic kidney disease, intramuscular injections, in 2 doses, at least 12 weeks apart)
chronic obstructive pulmonary disease, obesity,
o 4. Gam-COVID-Vac (Gamaleya) (given as rAd-26 0.5ml
serious heart conditions or diabetes mellitus)
o We recommend the use of dexamethasone
intramuscular injection, then rAd-5S 0.5 ml intramuscular
for up to 10 days among patients with injection 21 days after)
severe and critical COVID-19. o 5. COV2.S (Janssen/Johnson&Johnson) (given as 0.5ml single
o We recommend the use of 6 mg to 12 mg dose intramuscular injection)
per day of dexamethasone among patients • We recommend the use of CoronaVac (Sinovac) (given as 0.5ml
INTRAVENOUS with severe and critical COVID-19. (600SU) intramuscular injection, in 2 doses, at 28 days apart) to
CORTICOSTEROIDS o We recommend against the use of prevent symptomatic SARS-CoV-2 infection among healthy
corticosteroids among mild and moderate
adults.
(non-oxygen requiring) COVID-19 patients.
o We suggest that steroid therapy be • We recommend the use of BNT162b2 (Pfizer/BioNTech),
initiated as soon as diagnosed or mRNA-1273 (Moderna), ChAdOx1 (Astrazeneca), Gam-COVID-
categorized as severe or critical COVID-19. Vac (Gamaleya) and Ad26.COV2.S (Janssen/ Johnson&Johnson)
o We recommend the use of prophylactic vaccines to prevent symptomatic SARS-CoV-2 infection in older
over therapeutic dose anticoagulation adults (>64 year old)
among hospitalized patients with • We recommend the use of BNT162b2 (Pfizer/BioNTech),
moderate, severe or critical COVID-19
mRNA-1273 (Moderna), ChAdOx1 (Astrazeneca), Gam-COVID-
disease unless there are any
contraindications.
Vac (Gamaleya), CoronaVac (Sinovac) and Ad26.COV2.S
ANTICOAGULATION (Janssen/ Johnson&Johnson) vaccines in pregnant and
o We recommend the use of standard dose
prophylactic anticoagulation over lactating women after consultation with a physician.
intermediate dose prophylactic • We recommend the use of BNT162b2 (Pfizer/BioNTech),
anticoagulation among hospitalized mRNA-1273 (Moderna), ChAdOx1 (Astrazeneca), Gam-COVID-
patients with COVID-19 disease unless Vac (Gamaleya) and Ad26.COV2.S (Janssen/ Johnson&Johnson)
there are any contraindications. vaccines to prevent SARS-CoV-2 infection in adults who have
o We recommend against the routine use of stable medical comorbidities and are at risk for severe
antibiotics in patients with severe and
critical COVID-19 infection, unless with
infection.
EMPIRICAL • We recommend the use of BNT162b2 (Pfizer/BioNTech),
suspicion of secondary bacterial co-infection.
ANTIMICROBIAL mRNA-1273 (Moderna), ChAdOx1 (Astrazeneca), Gam-COVID-
For patients on empiric antibiotics, they
THERAPY
should be assessed daily for the need for Vac (Gamaleya),CoronaVac (Sinovac) and Ad26.COV2.S
discontinuation, continuation or escalation (Janssen/ Johnson&Johnson) vaccines to prevent SARS-CoV-2
based on clinical and laboratory parameters. infection in immunocompromised patients (i.e., diagnosed
o We suggest the use of conservative fluid with HIV, hepatitis B and C, those with cancer undergoing
management rather than liberal fluid chemotherapy, transplant patients receiving immune-
management strategy in mechanically
FLUID
ventilated adult COVID-19 patients with
suppression) after medical clearance from a physician.
MANAGEMENT
acute respiratory distress syndrome who
are adequately resuscitated*. (Low quality CANCER CHEMOTHERAPY
of evidence; Conditional recommendation)
o We suggest self-proning position in non-
intubated patients with severe and critical
SELF-PRONING COVID-19
SIDE-LYING o There is insufficient evidence to
POSITION recommend the use of side lying in non-
intubated patients with severe to critical
COVID-19
o We suggest the use of high flow nasal
cannula for patients with severe to critical
HIGH FLOW NASAL
COVID-19 who do not respond to
CANNULA
conventional oxygen therapy (low flow
nasal cannula/face mask)
o We suggest the use of ECMO for Adapted from Katzung and Trevor’s Pharmacology Examination and Board Review. 11th ed. 2015
EXTRACORPOREAL judiciously selected COVID-19 patients LOG-KILL HYPOTHESIS

BRANE with severe Acute Respiratory Distress
OXYGENATION Syndrome (ARDS) based on the • anticancer drugs kill a fixed proportion of a tumor cell
(ECMO) Extracorporeal Life Support Organization population, not a fixed number of tumor cells
(ELSO) criteria • Drug combinations are done to achieve: 1) Synergism and 2)
o We suggest light over deep sedation in prevention of drug resistance.
COVID-19 patients who are mechanically • We target both cancer cells that are highly dividing (use of cell-
SEDATION AND
ventilated and who are anxious or agitated. cycle specific) and cancer cells with low growth fraction (use of cell
NEUROMUSCULAR
o We suggest against routine use of NMB in
BLOCKADE cycle non-specific drugs) at the same time.
mechanically ventilated COVID-19 ARDS
patients. ANTICANCER DRUGS: ACTING ON THE CELL CYCLE
o We suggest the use of either high flow
nasal cannula or non-invasive positive Classification of Drugs: Based on Cell Cycle
NON-INVASIVE pressure ventilation in COVID-19 patients • CELL CYCLE NONSPECIFIC DRUGS (CCNS)
VENTILATION with hypoxemic respiratory failure, in the o act on tumor stem cells when they are traversing the cell cycle
absence of any indication for emergent and when they are in the resting phase
invasive mechanical ventilation.
• CELL CYCLE SPECIFIC DRUGS (CCS) RESCUE THERAPY
o act selectively on tumor stem cells when they are traversing • alleviation of toxic effects by giving rescue drugs
the cell cycle, and not when they are in the G0 phase o Methotrexate: Leucovorin
o Cyclophosphamide: MESNA
o Doxorubicin: Dexrazoxane
o Cisplatin: Amifostine
For Cancer Chemotherapy we’ll be giving some pre-test for you to answer. It’s
okay if some you can’t answer yet. But later, return to this section to
complete the test. Answers are all in the table to help you note the important
concepts.
Alkylating agents:
1. Rescue therapy for cyclophosphamide
2. Associated with pulmonary fibrosis
3. Platinum compounds are included in alkylating agents (T/F)
4. 5-fluorouracil is an example of an alkylating agent (T/F)
Antimetabolites:
1. These drugs mimic _________________
2. Because they insert in the DNA they are known to cause what SE?
3. What is a DMARD that is also used for Cancer Chemotherapy?
4. Rescue therapy for methothrexate
5. Drug used for Acute leukemias in blast crisis
CANCER TREATMENT MODALITIES
Natural Products:
• PRIMARY INDUCTION CHEMOTHERAPY 1. Inhibits microtubule assembly
o drug therapy is administered as the primary treatment 2. In contrast to number 1, these drugs inhibit Mitotic spindles
• NEOADJUVANT CHEMOTHERAPY 3. Inhibits topoisomerase I
o use of chemotherapy in patients with localized cancer before 4. Inhibits topoisomerase II
performing local therapy (surgery) 5. Vinca alkaloid known to cause neuropathy; how about
myelosuppression?
o goal is to render the local therapy more effective
Antibiotics used for Cancer Chemo
• ADJUVANT CHEMOTHERAPY 1. Drugs ending in -RUBICIN are classified as ______________
o chemotherapy done after local treatment procedures such as 2. Associated with dilated cardiomyopathy
surgery or radiation 3. Rescue therapy for Anthracycline toxicity
o reduce the risk of local and systemic recurrence and to 4. Produces free radicals which causes DNA strand breaks
improve disease-free and overall survival Miscellaneous drugs for cancer:
1. Treatment for CML
CHEMOTHERAPY AND TOXICITIES 2. Treament for HER2 positive breast cancer
3. Inhibits VEGF preventing the angiogenesis in tumors
4. CD20 inhibitor
5. Drugs ending in -TINIBs are known as _______________
Face is puffy
6. Known therapy for acute PROMYELOCYTIC leukemia
from decadron C for Cispla4n/Carbopla4n: Dr. Rodriguez
Nephrotoxic, acous4c nerve damage
ALKYLATING AGENTS
• Alkylating agents are inserted in the DNA of the cancer cells.
They will cause chain termination because the cancer cell will
D V for Vincris4ne:
Peripheral neuropathy lack 3’OH. As a general concept, in terms of side effect they will
cause bone marrow suppression (pancytopenia)
D for Doxorubicin: cardiotoxic Cyclophosphamide, Ifosfamide, Chlorambucil, Mechlorethamine
B for Bleomycin: pulmonary fibrosis All are Preg Cat D
Forms DNA cross-links, resulting in inhibition of DNA
MOA
C for Cispla4n/Carbopla4n: synthesis and function. Cell cycle non-specific.
Nephrotoxic, acous4c nerve damage Non-Hodgkin's lymphoma,
Breast cancer, Ovarian cancer, Neuroblastoma,
CY for Cyclophosphamide:
Uses Chronic lymphocytic leukemia,
56 56
hemorrhagic cys44s
Wilms Tumor, Rhabdomyosarcoma
M for MTX, 5 for 5-FU, 6 for 6-MP: CLL is most common leukemia in adults, with Smudge cells
myelosuppression Bone marrow suppression, Hemorrhagic cystitis,
SE Hepatotoxicity, Alopecia, SIADH, Cardiac dysfunction,
M M V for Vincris4ne: Pulmonary toxicity
Peripheral neuropathy • Rescue therapy is MESNA
Notes
Cystitis can be prevented with adequate hydration
Cisplatin, Carboplatin, Oxaliplatin

MOA Same as above
CHEMOTOX MAN Testicular cancer, Ovarian cancer, Bladder cancer, Lung
cancer, Advanced colon cancer and pancreatic cancer
https://qrs.ly/crdveeo
(oxaliplatin), breast cancer, H&N cancer, Gastroesophageal
cancer
Uses
Oxaliplatin is part of your FOLFOX and FOLFIRI regimen
used in the treatment of solid tumors that are resistant to
MNEMONIC Drugs causing Pulmonary Fibrosis Cisplatin and Carboplatin in the basis of mismatch repair
“BBBAN Me” defect
Bleomycin Amiodarone Nausea, Vomiting, Nephrotoxicity, Neurotoxicity (peripheral
Busulfan Nitrofurantoin SE
neuritis, acoustic nerve damage)
Bromocriptine Methotrexate • Rescue therapy is AMIFOSTINE
• Decrease nephrotoxicity by administering Mannitol with
SUPPLEMENT: HAND-FOOT SYNDROME forced hydration
Notes
• “Palmar-Plantar erythrodysesthesia” • Carboplatin has a wider spectrum of coverage in solid
• a side effect of some cancer treatments tumors and has less renal and GIT side effects and is widely
• redness, swelling and pain on the palms and soles, sometimes even used in transplant regimen..
with blistering
• may also occur elsewhere in the skin such as the knees and elbows
Procarbazine [D] CAMPTOTHECIN
Forms hydrogen peroxide, which generates free radicals Topotecan, Irinotecan
MOA
that cause DNA strand scission. Cell cycle non-specific.
Inhibits topoisomerase I.
Hodgkin's lymphoma, MOA
Cell cycle specific.
Uses Non-Hodgkin's lymphoma,
Topotecan: Advanced ovarian cancer (2nd line), Small cell
Brain tumors
Uses lung cancer
Bone marrow suppression, Pulmonary toxicity, Hemolysis,
Irinotecan: Metastatic colorectal cancer
Neurotoxicity,
SE SE Bone marrow suppression, Diarrhea, Nausea and vomiting
Disulfiram-like reaction, Leukemogenic,
Hypersensitivity reaction
• Forms hydrogen peroxide, which generates free radicals TAXANES
Notes Paclitaxel, Docetaxel, Cabazitaxel
• Procarbazine has the highest carcinogenic potential
amongst alkylating agent. Interferes with mitotic spindle.
MOA Prevents microtubule disassembly into tubulin monomers.
Dacarbazine [C] Advanced breast and ovarian cancers, lung cancer,
Forms hydrogen peroxide, which generates free radicals Uses gastroesophageal cancer, gastric cancer, prostate cancer,
MOA
that cause DNA strand scission. Cell cycle non-specific. bladder cancer, head and neck cancer
Hodgkin's lymphoma, • Paclitaxel: Neutropenia, Thrombocytopenia, Peripheral
Uses
Non-Hodgkin's lymphoma, Melanoma, Soft Tissue Sarcoma neuropathy, Hypersensitivity, arrhythmias,
Alopecia, Skin Rash, Gastrointestinal distress, SE myelosuppression
Bone marrow suppression, Phototoxicity, Flu-like • Docetaxel: Neurotoxicity, Bone marrow suppression, fluid
SE
Syndrome, CNS Toxicity (ataxia, lethargy, confusion, retention, hypersensitivity
neuropathy)
Forms hydrogen peroxide, which generates free radicals ANTIMETABOLITES
Notes
• Antimetabolites mimic your purine and pyrimidines. They are
Busulfan [D]
inserted in the DNA and because they are not real purine and
pyrimidines, once inserted in the DNA of cancer cells they will
Forms DNA cross-links, resulting in inhibition of DNA
MOA cause chain termination and eventual cessation of cancer cell
synthesis and function. Cell cycle non-specific.
Uses Chronic myelogenous leukemia growth. Because they are inserted in the DNA, as a side effect,
Pulmonary fibrosis, they will cause bone marrow suppression.
SE Adrenal insufficiency,
Skin pigmentation METHOTREXATE
Specific to CFU-GM line. Used as a myelosuppressive agent MTX
Notes
prior to bone marrow transplant. Inhibits Dihydrofolate reductase. Decreases synthesis of
MOA thymidylate, amino acids, purine nucleotides. Cell cycle
Carmustine, Lomustine, Bendamustine specific.
(Nitrosoureas) Choriocarcinoma, Acute leukemias, Non-Hodgkin's
MOA Same as previous lymphoma, Primary CNS lymphoma, Breast cancer, Head
Uses
Brain tumors, Melanoma, and neck cancer, Bladder cancer, Rheumatoid arthritis,
Skin cancer, Lymphoma, CLL Psoriasis, Ectopic pregnancy
Uses Nitrosoureas are special alkylating agent because they are Bone marrow suppression, Pulmonary infiltrates and
designed for brain tumors. These medications are highly
SE
fibrosis, Mucositis, Crystalluria, diarrhea
lipophilic and can cross the blood brain barrier. Rescue therapy is LEUCOVORIN (folinic acid)
CNS toxicity (dizziness, ataxia), Nausea and vomiting, Notes We need Folic acid for erythrocyte maturation and DNA
SE
Bone marrow suppression, Skin flushing synthesis
Highly lipophilic, allowing ease of passage through BBB into
Notes
the CNS PURINE
6-Mercaptopurine, 6-Thioguanine, Azathioprine
All are Preg Cat D
NATURAL PRODUCT ANTICANCER DRUGS Inhibits de novo purine nucleotide synthesis. Activated
VINCA ALKALOIDS MOA by HGPRT. Cell cycle specific. Fludarabine and
Vincristine Cladribine inhibit ribonucleotide reductase
Prevents microtubule assembly. Causes cell arrest at
Acute leukemias (AML, ALL), Chronic myelogenous
Uses
metaphase. leukemia, Lymphomas
MOA Cell cycle specific. Bone marrow suppression, Immunosuppression,
SE
Acts primarily in M phase of cancer cell cycle Hepatotoxicity (cholestasis, jaundice, necrosis)
Acute leukemias, Lymphomas, Wilms tumor, Notes 6-MP metabolism inhibited by allopurinol and febuxostat
Uses
Neuroblastoma, Rhabdomyosarcoma
• Areflexia, Peripheral neuritis, Paralytic ileus, Pemetrexed [D]
Nausea/Vomiting, Myelosuppression, SIADH Inhibits Thymidylate Synthase, Dihydrofolate Reductase
SE MOA
Vincristine will not likely cause bone marrow suppression and purine nucleotide synthesis
rather it will cause neuropathy Mesothelioma,
Uses
non-small cell lung cancer
Vinblastine, Vinorelbine Bone marrow suppression, skin rash, mucositis,
SE
MOA Same as previous diarrhea, fatigue, Hand-Foot Syndrome
Inhibits Thymidylate Synthase, Dihydrofolate Reductase
Lymphomas, Neuroblastoma, Testicular carcinoma, Kaposi's Notes
Uses and purine nucleotide synthesis
sarcoma, germ cell tumor, breast cancer
• Bone marrow suppression, Alopecia, Gastrointestinal
distress, mucositis, SIADH, constipation, vascular events
PYRIMIDINE
SE 5-Fluorouracil [D]
vinBLASTine BLASTS the Bone marrow (vinblastine causes
myelosuppression) Inhibits thymidylate synthase → Inhibition of DNA
MOA Synthesis and Function. Causes thymineless death of
PODOPHYLLOTOXIN cells. Cell cycle specific.
Bladder cancer, Breast cancer, Colorectal cancer, Anal
Etoposide, Teniposide cancer, Head and neck cancer,
Inhibits DNA topoisomerase II Uses
Liver cancer, Ovarian cancer,
MOA (DNA Gyrase). Inhibits mitochondrial electron transport. Skin cancer (basal cell cancer, actinic keratoses)
Bone marrow suppression, Gastrointestinal irritation,
Lung cancer, Prostate cancer, Testicular cancer, Non- SE
Uses Alopecia, mucositis, neurotoxicity
Hodgkin’s lymphoma, Gastric cancer
Bone marrow suppression, GI irritation, Alopecia
TEGAFUR is a chemotherapeutic prodrug of 5FU. It is a
SE Notes
component of the combination drug Tegafur-Uracil
Cytarabine [D] Flutamide, Bicalutamide, Nilutamide
Inhibits DNA synthesis and repair. Inhibits Class Androgen antagonist
MOA ribonucleotide reductase with reduced formation of MOA Competitive antagonist at androgen receptor
dNTPs. Cell-cycle specific. Prostate cancer,
Uses Acute leukemias (AML, ALL), CML in blast crisis Uses
Surgical castration (nilutamide)
Gastrointestinal irritation, SE Gynecomastia, Hot flushes, Impotence, Hepatoxicity
SE Bone marrow suppression, Neurotoxicity (cerebellar • Less hepatotoxicity with bicalutamide and nilutamide
dysfunction, peripheral neuritis) Notes GnRH analogs (leuprolide) must be co-administered with
Notes Most specific for the S phase of the cell cycle flutamide to prevent acute flare-up of prostate cancer
Gemcitabine, Capecitabine Leuprolide [D], Gonadorelin [B], Nafarelin [X]

All are Preg Cat D
Class GnRH analog
MOA Same with Cytarabine
Increased LH and FSH secretion with intermittent
Pancreatic cancer, MOA administration. Reduced LH and FSH secretion with
Non-small cell lung cancer, Bladder cancer, prolonged continuous administration.
Non-Hodgkin's lymphoma, Controlled ovarian hyperstimulation, Endometriosis,
Uses Uses
Breast cancer, soft tissue sarcoma
Myoma uteri, Precocious puberty, Prostate cancer
Capecitabine: HCC, Gastroesophageal cancer, colorectal
Hot flushes, Sweats, Headache, Osteoporosis,
cancer
SE Gynecomastia, Reduced libido, Decreased hematocrit,
Bone marrow suppression, Neutropenia, Pulmonary
SE Apoplexy, Blindness
toxicity, Hand-Foot Syndrome (Capecitabine)
Must be co-administered with flutamide to prevent
Notes
tumor flare-up on initiation of treatment
ANTITUMOR ANTIBIOTICS
Doxorubicin, Daunorubicin, Idarubicin, Epirubicin, Mitoxantrone Anastrozole [X] ,Letrozole [D]
MOA Anthracycline Class Estrogen synthesis inhibitor
Intercalates between base pairs. Inhibits topoisomerase MOA Reduces estrogen synthesis by inhibiting aromatase
Uses II. Generates free radicals → single and double-stranded Uses Breast cancer, Precocious puberty
DNA breaks. Cell cycle non-specific. Nausea, Diarrhea, Hot flushes, Bone and back pain,
Hodgkin and Non-Hodgkin lymphoma, Breast cancer, SE
Dyspnea, Peripheral edema
soft tissue sarcoma, Endometrial cancer, small cell and Effective against breast cancers that have become
SE non-small cell Lung cancer, Ovarian cancer, Acute Notes
resistant to tamoxifen
leukemias – AML, ALL (especially Daunorubicin,
Idarubicin for AML), Wilms tumor, Neuroblastoma
Notes Rescue Therapy: DEXRAZOXANE MISCELLANEOUS ANTICANCER DRUGS
Imatinib, Dasatinib, Nilotinib, Crizotinib, Afatinib, Nintedanib,
Bleomycin, Mitomycin Regorafenib
Inhibits tyrosine kinase activity of the protein product of
MOA Antitumor antibiotic
BCR-ABL oncogene in CML.
Generates free radicals, which cause DNA strand breaks. MOA
Inhibits c-kit tyrosine kinase in GIST.
Intercalates with DNA. Tyrosine Kinase Inhibitors
Uses
Cell cycle specific. Chronic Myelogenous leukemia, Gastrointestinal stromal
Most specific for the G2 phase of the cell cycle Uses
tumor (GIST)
Hodgkin and Non-Hodgkin lymphoma, Testicular cancer, Diarrhea, Myalgia, Fluid retention, Congestive heart
Head and neck cancer, Skin cancer, germ cell cancer SE
SE failure, Drug interactions
Mitomycin: Superficial bladder, cancer, Gastric cancer, • Interactions with other drugs that depend on or affect
Breast cancer
the cytochrome P450 system
Notes
• Nintedanib is also used for Idiopathic Pulmonary
Actinomycin D (Dactinomycin) Fibrosis
MOA Antitumor antibiotic
Binds to double-stranded DNA. Trastuzumab [B], Pertuzumab [D], Lapatinib [D]
Uses Inhibits DNA-dependent RNA synthesis. Acts against breast cancer cells that overexpress the
Cell cycle non-specific. MOA
HER-2/neu receptor for epidermal growth factor
Melanoma, Wilms tumor, Rhabdomyosarcoma, Uses Metastatic breast cancer
SE Choriocarcinoma, Kaposi’s sarcoma,
Nausea and vomiting, Chills, Fever, Headache,
Gestational trophoblastic neoplasia SE
Cardiotoxicity (congestive heart failure)
HORMONAL ANTICANCER DRUGS Bevacizumab [C], Sorafenib, Sunitinib, Pazopanib, Lenvatinib

Prednisone [D] Inhibits binding of VEGF to VEGFR leading to inhibition
Class Glucocorticoid of VEGF signaling. Inhibits tumor vascular permeability
MOA but enhances tumor blood flow and drug delivery.
Suppresses inflammation and immune response. May
MOA
trigger apoptosis and work on nondividing cancer cells. BV: BeVacizumab for blood vessel. It inhibits angiogenesis!
Uses Chronic lymphocytic leukemia, Hodgkin’s lymphomas Metastatic colorectal cancer, Breast cancer, Non-small
Uses
Adrenal suppression, Growth inhibition, Muscle wasting, cell lung cancer, Renal cancer
SE Osteoporosis, Salt retention, Glucose intolerance, Hypertension, Infusion reactions, Arterial thrombosis,
Behavioral changes SE Impaired wound healing, Gastrointestinal perforation,
Notes Glucocorticoid Proteinuria
Lenvatinib acts a multiple kinase inhibitor against
Notes
Tamoxifen, Toremifene VEGFR1 to 3 kinases and is used for thyroid cancer
Class Selective Estrogen Receptor Modulator
Rituximab [C]
Estrogen antagonist actions in breast tissue and CNS.
MOA Binds to a surface protein in NHL cells. Induces
Estrogen agonist effects in uterus, liver and bone.
complement-mediated lysis, direct cytotoxicity, and
Uses Hormone-sensitive breast cancer MOA
induction of apoptosis
Hot flushes, Thromboembolism (DVTs), Endometrial CD20 inhibitor
SE
hyperplasia, Endometrial cancer
Uses Non-Hodgkin lymphoma (low-grade)
Prevents osteoporosis and decreases risk of
Notes SE Hypersensitivity reactions, Bone marrow suppression
atherosclerosis at the risk of causing endometrial cancer
Cetuximab, Panitumumab, Nimotuzumab Sodium bicarbonate: belching, metabolic alkalosis, fluid
Binds to EGFR and inhibits downstream EGFR signaling, retention
MOA SE
enhances response to chemotherapy and radiotherapy Calcium carbonate: hypercalcemia, renal insufficiency,
Colorectal cancer, head and neck cancer (together with metabolic alkalosis (milk-alkali syndrome)
Uses • Caution in giving to Px with Renal Insufficiency
radiotherapy), non-small cell lung cancer
Infusion reaction, skin rash, hypomagnesemia, fatigue, • Impairs absorption of tetracyclines, fluoroquinolones,
SE itraconazole and iron → should not be given within 2 hours
interstitial lung disease
with these drugs
Erlotinib, Gefitinib Notes • When used regularly in large doses needed to
significantly raise the stomach pH, antacids decrease
Inhibits EGFR tyrosine kinase → inhibition of EGFR
MOA recurrence rate of peptic ulcers
signaling
Aluminum and Magnesium are always given together to
Uses Non-small cell lung cancer, pancreatic cancer
cancel out each other's adverse effect
Diarrhea, hypertension, skin rash, anorexia, interstitial
SE H2-RECEPTOR ANTAGONIST
lung disease
Cimetidine [B], Ranitidine [B], Famotidine, Nizatidine
Interferon-Alpha [B] MOA Competitive pharmacologic block of H2 receptors
Endogenous glycoproteins with antineoplastic, Peptic ulcer disease, Zollinger-Ellison syndrome,
MOA Uses
immunosuppressive, and antiviral actions Gastroesophageal reflux, Dyspepsia
Hairy cell leukemia, Chronic myelogenous leukemia, T- Gynecomastia (cimetidine only), Diarrhea, Headache,
Uses Fatigue, Myalgias, Constipation, Nosocomial pneumonia,
cell lymphomas SE
Alopecia, Myalgia, Depression, Flu-like syndrome, Mental status changes, Bradycardia, Hypotension, Blood
SE Thyroid dysfunction, Hearing loss, Bone marrow dyscrasias
suppression, Neurologic dysfunction • Cimetidine is a potent inhibitor of CYP450
Contraindications include autoimmune disease, history • Highly-effective in suppressing Nocturnal acid secretion
Notes
of cardiac arrhythmias and pregnancy Notes but only modest effect on meal-stimulated secretion
• Ranitidine: Adjust doses for Renally impaired patients
Asparaginase [C] May be used for pregnant patients
Hydrolyzes circulating L-asparaginase → rapid
MOA
inhibition of protein synthesis PROTON PUMP INHIBITORS
Uses Acute lymphoblastic leukemia Omeprazole [C], Lansoprazole [B], Rabeprazole [C],
Nausea, Fever, Hypersensitivity reactions, Acute Pantoprazole [B], Esomeprazole [C]
SE Pancreatitis, Increased risk of bleeding, mental Irreversible blockade of H+/K+ ATPase in active gastric
depression, nephrotoxicity MOA parietal cells. Long-lasting reduction of meal-stimulated
and nocturnal acid secretion.
All-Trans Retinoic Acid [X] Peptic ulcer disease (DOC), Zollinger-Ellison syndrome,
Allows DNA transcription and differentiation of Gastroesophageal reflux, Dyspepsia, SJS
MOA immature leukemic promyelocytes into mature Uses PPIs are given for bleeding PUD, for 3 important reasons 1).
granulocytes (differentiation therapy). To maintain the stability of the clot 2). To maintain an
Uses Acute promyelocytic leukemia intragastric pH of 6 and 3) to reduce mortality.
Retinoic acid syndrome (dyspnea, fever, weight gain, Diarrhea, Headache, Abdominal pain, Malabsorption (Vit
SE B12, Ca, Fe, Zn), Infections (respiratory, enteric),
peripheral edema) SE
• Only vitamin that can cure cancer Hypergastrinemia, Atrophic gastritis, Fractures of the
Notes hip and spine
Treat retinoic acid syndrome with dexamethasone
• PPIs should be taken before meals, ideally 30mins to 1
hour before breakfast
GASTROINTESTINAL • May interfere with absorption of drugs where gastric
pH is an important determinant of their bioavailability
PHARMACOLOGY (e.g. Ketoconazole, Ampicillin, Ferrous salts, Digoxin)
• Use with caution in Hepatically-impaired (Omep, Esomep,
Notes Panto) and Renally-impaired (Omep, Panto) patients
• PPIs are possibly associated with Clostridium difficile-
associated diarrhea
• Daily long-term use (more than 3yrs) may lead to
malabsorption or deficiency of Vit B12
Amongst the PPI, pantoprazole has the least drug-drug
interaction.
MUCOSAL PROTECTIVE AGENTS

Sucralfate
Binds to injured tissue and forms a protective covering
over ulcer beds. Accelerates healing of peptic ulcers and
reduces recurrence rate.
DRUGS FOR PEPTIC ULCER DISEASE MOA
Coats the ulcer bed to protect it from the stomach acid →
PEPTIC ULCER DISEASE healing. Needs frequent dosing since it will be washed
away when you drink or eat.
• chronic most often solitary lesions that occur in any portion of
the gastrointestinal tract exposed to the aggressive action of Uses Peptic ulcer disease
acid-peptic juices SE None
• at least 98% occur either in the first portion of the duodenum or • Highly insoluble, requiring frequent dosing
Notes
in the stomach • Caution in chronic renal impairment
ANTACIDS Misoprostol [X]
Magnesium-Aluminum Hydroxide [C], Calcium Carbonate, Sodium Activates EP receptors. Causes increased HCO3 and
Bicarbonate mucus secretion in stomach. Uterine contraction.
Neutralize stomach acid by reacting with protons in the MOA
MOA Activates PGE1 receptor which decreases acid secretion
lumen of the gut
and increases mucus secretion in the stomach
Peptic ulcer disease
Peptic ulcer disease,
Uses MAGnesium hydroxide causes diarrhea: MAGtatae ka! Uses Prevention of NSAID-induced gastric mucosal injury,
ALUMinum hydroxide causes constipation: Ayaw Abortifacient
LUMabas!
Abdominal pain, Diarrhea, Uterine cramping,
SE
Miscarriage
Bismuth Salicylate [C] OSMOTIC LAXATIVE
Forms a protective coating on ulcerated tissue. Lactulose [B], Magnesium Oxide, Sorbitol, Magnesium Citrate, Sodium
Stimulates mucosal protective mechanisms, direct Phosphate,
antimicrobial effects and sequestration of enterotoxins. Polyethylene Glycol
MOA
This drug has dual activity: mucosal protective agent Soluble but nonabsorbable compounds that result in
and bactericidal effect on H. pylori from its heavy metal MOA increased stool liquidity due to an obligate increase in
component (Bismuth) fecal fluid
Uses Peptic ulcer disease, Dyspepsia, Infectious diarrhea Constipation, Hepatic encephalopathy (lactulose),
Black stools, Darkening of tongue, Encephalopathy Uses Preparation for endoscopy
SE (polyethylene glycol)
(ataxia, headaches, confusion, seizures)
Notes Reduces stool frequency and liquidity in infectious diarrhea • Diarrhea, Flatus, Abdominal cramps,
• Electrolyte abnormalities
REGIMENS RECOMMENDED FOR H. PYLORI ERADICATION SE
(hyperphosphatemia, hypocalcemia, hypernatremia,
Drug Dose hypokalemia, hypermagnesemia)
Triple Therapy
1. Bismuth subsalicylate plus 2 tablets qid STIMULANT LAXATIVE
Metronidazole plus 250 mg qid Bisacodyl [B], Aloe, Senna, Cascara, Castor Oil
Tetracycline 500 mg qid Unknown. Directly stimulate enteric nervous system
2. Ranitidine bismuth citrate plus 400 mg bid MOA
and colonic electrolyte and fluid secretion.
Tetracycline plus 500 mg bid
Uses Constipation
Clarithromycin or metronidazole 500 mg bid
3. Omeprazole (lansoprazole) plus 20 mg bid (30 mg bid) • Diarrhea,
Clarithromycin plus 250 or 500 mg bid SE • Melanosis coli (anthraquinone-containing laxatives
Metronidazole or 500 mg bid like Senna)
Amoxicillin 1 gr bid
Quadruple Therapy ANTIDIARRHEAL AGENTS
Omeprazole (lansoprazole) 20 mg (30mg) daily
Opioid: Diphenoxylate [C], Loperamide,
Bismuth subsalicylate 2 tablets qid
Drugs Non-Opiod: Kaolin + Pectin,
Metronidazole 250 mg qid
Colloidal Bismuth, Difenoxin
Tetracycline 500 mg qid
Activates opioid receptors in enteric nervous system.
MOA
Slows motility with negligible CNS effects.
DRUGS THAT PROMOTE UPPER GI MOTILITY Uses Diarrhea (nonspecific, noninfectious)
PROKINETIC AGENTS SE Drowsiness, Nausea, Paralytic ileus
Drugs Metoclopramide [B], Domperidone [C], Erythromycin [B] • Do not use in children less than 4 years of age
Metoclopramide and domperidone block D2 receptors. Notes (increased chance of causing paralytic ileus)
Erythromycin stimulates motilin receptors. Increases • Reverse ileus by administering Bethanechol
gastric emptying and intestinal motility.
MOA
Correlation to Surgery: Erythromycin is used in bowel
preparation prior surgery because it binds to the motilin
ANTIEMETICS
receptor. Diarrhea is a common side effect of macrolides. Ondansetron [B], Granisetron, Dolasetron,
Drugs
Antiemetic for post-operative / chemotherapy vomiting, Palonosetron, Alosetron, Tropisetron
Uses Block chemoreceptor trigger zone and enteric nervous
Diabetic Gastroparesis (drug of choice)
SE Parkinsonism, Extrapyramidal effects, Hyperprolactinemia system 5-HT3 receptors.
MOA
Notes Domperidone does not cross the BBB (less toxic) 5HT3 receptors are found in the CTZ (Chemoreceptor
trigger zone) on the floor of the 4th ventricle of the brain
Uses Vomiting (post-chemotherapy, postoperative)
LAXATIVES Headache, Dizziness, Constipation, QRS and QT
SE
• Substance that increases the probability of a bowel movement prolongation (dolasetron only)
by several mechanisms: The process of vomiting has an interplay of factors. Activating D2 receptor
o irritant or stimulant action on the bowel wall in the area postrema triggers vomiting, substance P binding neurokinin
o bulk-forming action on the stool → reflex contraction of the bowel can cause pain-induced vomiting, we may give Aprepitant in this case.
Stimulation of the cholinergic receptor in the auditory canal can cause
o softening action on hard or impacted stool motion sickness, we can give an anticholinergic Scopolamine and the
o lubricating action that eases passage of stool through the rectum famous 5HT3 receptor antagonist in the area postrema Ondansetron for
SUPPLEMENT: Melanosis Coli post-operative and chemotherapy-induced vomiting. Many drugs can
• benign disorder of colonic pigmentation cross the area postrema because it is devoid of the blood brain barrier.
Dr. Calderon Jr.
• due to accumulation of brown lipofuscin pigments in macrophages
• usually result from intake of anthraquinone-containing laxatives (e.g. Senna) DRUGS FOR INFLAMMATORY BOWEL
DISEASE
BULK-FORMING LAXATIVE THERAPY FOR INFLAMMATORY BOWEL DISEASE
Psyllium [B], Methylcellulose, Polycarbophil, Maltodextrin
Indigestible, hydrophilic colloids that absorb water,
MOA forming a bulky, emollient gel that distends the colon
and promotes peristalsis
Uses Constipation
SE • Diarrhea
STOOL SOFTENER
Docusate [C], Glycerine Suppository, Mineral Oil
Soften stool material, permitting water and lipids to
MOA
penetrate
Constipation
Usually given to patients after MI so
Uses
that they don’t have to do Valsalva
when defecating
Diarrhea, Aspiration (lipid pneumonitis)
SE
Malabsorption of fat-soluble vitamins (A, D, E, K)
IMMUNOMODULATOR: Hepatoprotectant; MOA is not yet well
Mesalamine (5-Asa) [C], Balsalazide, Olsalazine, understood but there are some proposals:
Drugs as antioxidant, scavenger and regulator of
Sulfasalazine, Mesalazine
Unknown. Probably inhibits production of eicosanoid intracellular content of glutathione
MOA as cell membrane stabilizers and permeability
inflammatory mediators.
regulators that prevent hepatotoxic agents from
Inflammatory bowel disease (mild to moderate)
entering hepatocytes as promoters of ribosomal
Uses Used only for mild CONTROLLED cases. Flareups should RNA synthesis, stimulating liver regeneration and
be given immunosuppressants such as corticosteroids, TNF SILYMARIN as inhibitor of the transformation of stellate
antagonists, Cyclosporine etc. hepatocytes into myofibroblasts, the process
Gastrointestinal upset, Headaches, Arthralgias, Myalgias, responsible for the deposition of collagen fibers
SE Bone marrow suppression, Malaise, Hypersensitivity leading to cirrhosis. Anti-inflammatory and anti-
reactions (severe) carcinogenic properties have also been
documented; is able to neutralize the
• TNF ANTAGONIST: hepatotoxicity of several agents, including
o ADALIMUMAB, CERTOLIZUMAB, INFLIXIMAB Amanita phalloides, ethanol, paracetamol and
• CORTICOSTEROIDS: carbon tetrachloride in animal models
o BUDESONIDE, HYDROCORTISONE, METHYLPREDNISOLONE ROWACHOLÒ Increases biliary secretion, relieves spasms of the
– menthol, bile ducts, enhances metabolic liver function and
THERAPY FOR GALLSTONES menthone, reduces biliary stasis; can also inhibit HMG-CoA
Ursodiol (Ursodeoxycholic Acid) alpha and beta reductase enzyme leading to reduced cholesterol
Drug
(Bile Acid) pinene, borneol, production (maintaining the bile above the
Decreases the cholesterol content of bile by reducing camphene, cineol saturation level, assisting dissolution of
cholesterol secretion; appears to stabilize hepatocyte and gallstones and preventing precipitation of further
MOA canalicular membranes possibly through a reduction in the olive oil stones)
concentration of other endogenous bile acids or through
inhibition of immune-mediated hepatocyte destruction. ANORECTAL PREPARATIONS
Dissolution of small cholesterol gallstones in Px with Potent venotropic drug used in the treatment of venous
symptomatic gallbladder disease who refuse surgery or insufficiency; increases venous tone, improves lymph
are poor surgical candidates, for prevention of gallstones DAFLONÒ drainage and protects microcirculation; the flavonoids
Uses
in obese Px undergoing rapid weight loss therapy, (Diosmin + contained in Daflon has been demonstrated to restrain
reduces liver function abnormalities and improve liver Hesperidin) lysosome enzymes and interfere with enzymes involved in
histology in early-stage primary biliary cirrhosis the flow of arachidonic acid which causes inflammation. It
• None. Diarrhea is rare also demonstrated an antioxidant activity.
Policresulen arrests bleeding by coagulating blood
SE • Chenodeoxycholate (predecessor) has been associated
protein and inducing the muscle fiber of small blood
with hepatotoxicity
vessels to contract. The coagulating properties and
FAKTUÒ
acidic pH brings about the antimicrobial action
(Policresulen
THERAPY FOR KIDNEY STONES +
against E.coli, Staphylococci sp., Streptococci sp.,
Pseudomonas aeruginosa, Proteus vulgaris, Candida
Drug Potassium Citrate Cinchocaine)
and other bacteria. Thus, the wound is protected
Metabolized to bicarbonate, which alkalinizes urine & against infection; Cinchocaine has local anesthetic
MOA
raises urinary citrate action which relieved pain and itching
Hypocitraturic calcium oxalate nephrolithiasis, Renal
Uses tubular acidosis with calcium stones, Uric acid lithiasis,
Urine alkalinization TOXICOLOGY
Abdominal discomfort, vomiting, diarrhea, loose bowel
• branch of pharmacology that encompasses the deleterious
movements, nausea. Potentially Fatal: Hyperkalemia.
SE effects of chemicals on biologic systems
Precaution giving to those with impaired K excretion AIR POLLUTANTS
(e.g. severe myocardial damage or heart failure) Agents
CARBON MONOXIDE SULFUR DIOXIDE
• odorless, colorless gas that • colorless,
competes avidly with oxygen irritating gas
MISCELLANEOUS GI DRUGS for hemoglobin from combustion
An amino acid derivative of quinolinone that is used • affinity of CO for hemoglobin is of fossil fuels
for mucosal protection, healing of gastroduodenal more than 200-fold greater • forms sulfurous
REBAMIPIDE ulcers, and treatment of gastritis; Works by than that of oxygen acid on contact
enhancing mucosal defense scavenging free radicals Features
• threshold limit values of CO: with mucous
and temporarily activating genes encoding for COX-2 for an 8-h workday is 25 parts membranes
A prokinetic benzamide derivative unlike per million (ppm)
metoclopramide or domperidone; inhibit • in heavy traffic, the
ITOPRIDE dopamine and acetylcholine esterase enzyme concentration of CO may
and have gastrokinetic effect; for functional exceed 100 ppm
dyspepsia and gastroparesis; take before meals
• headache, confusion, • conjunctival and
Changes surface tension of gas bubbles and causes decreased visual acuity, bronchial
SIMETHICONE collapse of foam bubbles, thus allowing easier cherry red skin, tachycardia, irritation
passage of gas and preventing gas pockets in GIT syncope, coma, seizures, death (bronchospasm)
A gastroprokinetic agent that acts as a selective • collapse and syncope occur • heavy exposure
5HT4 agonist. Its major active metabolite, known when ~ 40% of hemoglobin may lead to
as M1, additionally acts 5HT3 antagonist, which has been converted to delayed
MOSAPRIDE accelerates gastric emptying throughout the Effects
carboxyhemoglobin pulmonary
whole GIT; used for the treatment of gastritis, edema
• prolonged hypoxia can result
GERD, functional dyspepsia and IBS; taken 1-
in irreversible damage to the • chronic low-level
2hrs before meals
brain and the myocardium exposure may
Increases the availability of endogenous opioids aggravate
(enkephalins) by inhibiting membrane-bound cardiopulmonary
enkephalinase. Unlike other opioid medications disease
used to treat diarrhea which reduce intestinal
RACECADOTRIL • removal of the source of CO • removal from
motility, Racecadotril has an antisecretory
and 100% oxygen exposure to SO2
effect – it reduces the secretion of water and
Treatment • Hyperbaric oxygen accelerates • relief of
electrolyte into the intestine; reduces both the
the clearance of CO irritation and
frequency and duration of acute diarrhea
inflammation
A probiotic; has been found to produce
antimicrobial substances that are active against
BACILLUS
gram positive bacteria including Staphylococcus
CLAUSII
aureus, Enterococcus faecium and Clostridium
difficile
AIR POLLUTANTS ANTIDOTES
Agents
NITROGEN OXIDES OZONE ANTIDOTE POISON
• brownish irritant gas • bluish irritant gas Acetylcysteine Acetaminophen
formed in fires and produced in air and Atropine Cholinesterase inhibitors
Features silage on farms water purification
Bicarbonate Quinidine, TCAs
devices and in electrical
fields Calcium Fluoride, CCBs
• deep lung irritation • irritation /dryness of the Deferoxamine Iron
and pulmonary edema mucous membranes Digoxin antibodies (Digibind) Digoxin
• irritation of the eyes, • pulmonary function Caffeine, Theophylline,
Esmolol
nose and throat impaired at higher sympathomimetics
Effects concentrations Ethanol Methanol, Ethylene glycol
• chronic exposure leads Flumazenil Benzodiazepines, Zolpidem
to bronchitis, Fomepizole Methanol, Ethylene glycol
bronchiolitis, pulmonary Glucagon Beta-adrenoceptor blockers
fibrosis and emphysema
Glucose Hypoglycemics
• no specific treatment • no specific treatment is
Hydroxocobalamin Cyanide
is available available
Treatment
Naloxone Opioids analgesics
• measures to reduce • measures to reduce
inflammation and inflammation and Oxygen Carbon monoxide
pulmonary edema pulmonary edema Physostigmine Muscarinic receptor blockers
Pralidoxime Organophosphates
SOLVENTS Protamine sulfate Heparin
Agents ALIPHATIC AROMATIC Vitamin K, FFP Warfarin
HYDROCARBONS HYDROCARBONS CHELATORS
• Agents: halogenated • Agents: benzene, Chelator As Hg Pb Cu Fe
solvents such as carbon toluene, xylene Dimercaprol A A C
Features
tetrachloride, chloroform
and trichloroethylene Succimer
• CNS depression (nausea, • CNS depression with Penicillamine
vertigo, locomotor ataxia and coma EDTA C
disturbances, headache, • long-term exposure Deferoxamine
coma) to benzene is
• chronic exposure leads to associated with
• A = Acute C= Chronic
Effects hepatotoxicity and hematotoxicity • Chelating will form water soluble complexes
nephrotoxicity (thrombocytopenia, Dimercaprol
• long-term exposure to aplastic anemia, Transient hypertension, Tachycardia, Headache, Nausea and
tetrachloroethylene or to pancytopenia) and SE vomiting, Paresthesia, Fever, Injection site reactions (pain,
trichloroethane has caused hematologic cancers hematomas), Thrombocytopenia, Increased prothrombin time
peripheral neuropathy (leukemia) Co-administered with EDTA in severe chronic lead
Notes
• removal from exposure • removal from poisoning
and CNS supportive exposure and CNS
Treatment
measures supportive Succimer
measures
Gastrointestinal distress,
HEAVY METALS AND CHELATORS SE CNS effects,
Skin rash, Elevation of liver enzymes
Administered at blood lead concentrations greater than 45
Notes
mcg/dL
Penicillamine
Nephrotoxicity with proteinuria, Pancytopenia,
SE Autoimmune dysfunction (drug-induced lupus, hemolytic
anemia)
Edetate Calcium Disodium (EDTA)

Hypocalcemia, Nephrotoxicity
SE (renal tubular necrosis),
ECG changes
• Co-administered with dimercaprol in severe chronic lead
Chelating Agent / Chelator poisoning
• a molecule with 2 or more electronegative groups that can form stable Notes
To prevent dangerous hypocalcemia, EDTA is given as the
coordinate complexes with multivalent cationic metal atoms calcium disodium salt
• EXAMPLES: dimercaprol, succimer, EDTA, penicillamine,
deferoxamine Deferoxamine, Deferasirox, Deferiprone
Skin reactions (blushing, erythema, urticaria), Neurotoxicity
(e.g., retinal degeneration), Hepatotoxicity, Nephrotoxicity,
SE
Coagulopathies, Hypotension, ARDS, Increased
susceptibility to infections
COMMON POISOING SYNDROMES

LEAD ARSENIC ARSINE MERCURY IRON
Acute Inorganic Chronic Inorganic
Agent Organic Lead Acute Arsenic Chronic Arsenic Acute Inorganic Chronic Inorganic Organic Mercury
Lead Poisoning Lead Poisoning Arsine Gas Iron Poisoning
Poisoning Poisoning Poisoning Mercury Poisoning Mercury Poisoning Poisoning
(Plumbism)
• industrial exposures (usually via the • usually due to • widely used in industrial processes • occupational • mercury-containing materials in dental laboratories • ingestion of ferrous
inhalation of dust) tetraethyl lead or • released during burning of coal hazard formed • manufacturing of wood preservatives, insecticides and batteries sulfate tablets
• children who have ingested large tetramethyl lead • toxicity is entirely due to the trivalent form during the • organic mercury compounds are used as seed dressings and
quantities of chips or flakes of lead- contained in refinement and fungicides
Setting containing paint (PICA) antiknock gasoline processing of • inhalation of • inhalation of • consumption of
additives certain metals used inorganic mercury vapor fish or grains
in semiconductors elemental containing
mercury methylmercury
• acute abdominal • peripheral • hallucinations, • severe • hair loss, bone marrow • headache, dyspnea, • chest pain, • loosening of • Minamata • vomiting,
colic (lead colic) neuropathy headache, gastrointestinal depression and weakness, vomiting, shortness of gums and teeth, disease gastrointestinal
and CNS changes (wrist-drop), irritability, discomfort, anemia, chronic abdominal pain breath, nausea gastrointestinal (cerebral palsy, bleeding, lethargy,
(acute anorexia, anemia, convulsions, coma vomiting, rice- nausea and • massive hemolysis and vomiting, disturbances, and deafness, gray cyanosis
encephalopathy) tremor, weight water stools, gastrointestinal (jaundice, kidney damage, neurologic and blindness, • severe
• high mortality loss, dehydration, disturbances hemoglobinuria) gastroenteritis, behavioral mental gastrointestinal
rate gastrointestinal shock • transverse bands in leading to pigment CNS damage changes retardation) necrosis,
Presentation symptoms • sweet, garlicky nails (Mee’s lines) overload and renal • life-threatening (ERETHISM) pneumonitis,
• in children, odor in breath • skin changes (raindrop failure hemorrhagic jaundice, seizures,
growth and the stools hyperpigmentation, gastroenteritis coma
retardation, milk and roses followed by renal • chronic excessive
neurocognitive complexion, failure intake leads to
deficits, hyperkeratosis) hemosiderosis or
developmental hemochromatosis
delay
• prompt chelation • removal from the • decontamination, • supportive • DIMERCAPROL • Exchange • intensive • may redistribute • uncertain • DEFEROXAMINE is
therapy is source of exposure seizure control therapy to replace therapy transfusion, supportive care mercury to the benefits from the chelating agent
mandatory • chelation therapy water and • *Arsenic is a known vigorous hydration, • prompt chelation CNS chelation of choice
• oral SUCCIMER in electrolytes carcinogen hemodialysis with oral therapy
outpatients • chelation therapy • chelators are of no SUCCIMER or IM
Treatment
• EDTA ± with clinical value DIMERCAPROL
/Notes
DIMERCAPROL in DIMERCAPROL
severe cases
• dietary
modification (high
dietary calcium)
COMMON POISONING SYNDROMES

Agents ANTIMUSCARINIC POISONING CHOLINOMIMETIC (Organophosphate poisoning) OPIOIDS SALICYLATES
delirium, hallucinations, seizures, coma, tachycardia, anxiety, agitation, seizures, coma, bradycardia or lethargy, sedation, coma, bradycardia, confusion, lethargy, coma, seizures, hyperventilation,
hypertension, hyperthermia, mydriasis, decreased tachycardia, pinpoint pupils, salivation, sweating, hypotension, hypoventilation, pinpoint hyperthermia, dehydration, hypokalemia, anion gap
bowel sounds, urinary retention hyperactive bowel, muscle fasciculations, paralysis pupils, cool skin, decreased bowel metabolic acidosis
sounds, flaccid muscles
use hot as a hare mnemonic use DUMBBELSS mnemonic use CHAFS mnemonic
HOT as a hare (hyperthermia) use PCR mnemonic Coma
Clinical Features DRY as a bone Pupillary constriction Hyperventilation
(decreased secretion) Comatose state Acidosis/HAGMA
RED as a beet Respiratory depression Fever
(cutaneous vasodilation) Seizures
BLIND as a bat (cycloplegia)
MAD as a hatter
(CNS toxicity)
• control hyperthermia • support respiration • administer naloxone • correct acidosis and fluid and electrolyte imbalance
Key
• physostigmine may be helpful, but not for tricyclic • treat with atropine and pralidoxime • alkaline diuresis / hemodialysis to aid elimination
Intervention
overdose • decontaminate
Agents SEDATIVE-HYPNOTIC STIMULANTS TRICYCLIC ANTIDEPRESSANTS

disinhibition initially, later lethargy, stupor, coma agitation, anxiety, seizures antimuscarinic effects
nystagmus, decreased muscle tone, hypothermia hypertension, tachycardia, arrhythmias,
small pupils, hypotension, decreased bowel sounds in severe overdose mydriasis, vertical and horizontal nystagmus with PCP. use 3Cs mnemonic
Clinical Features
skin warm and sweaty, hyperthermia, Coma
Precaution giving to those with impaired K excretion (e.g. severe myocardial damage or increased muscle tone, Convulsions
heart failure) possible rhabdomyolysis Cardiotoxicity
• airway and respiratory support • control seizures, hypertension and hyperthermia • control seizures
Key • avoid fluid overload • correct acidosis and cardiotoxicity with sodium bicarbonate
Intervention • consider flumazenil for benzodiazepine overdose • give norepinephrine for hypotension
• control hyperthermia
MANAGEMENT OF THE POISONED PATIENT

SUPPLEMENT: Herbal Medicines
DECONTAMINATION
COMMON SCIENTIFIC INDICATIONS
• removal of any unabsorbed poison from the skin or NAME NAME
gastrointestinal tract Lagundi Vitex negundo Cough, colds, fever, asthma
• strategies for decontamination include: Yerba Buena
Clinopodium Pain, cough, colds, nausea,
o removal of clothing douglasii dizziness, pruritus
o adsorption using activated charcoal Blumea Hypertension, kidney
Sambong
o gastric lavage to remove noncorrosive balsamifera stones
o inducing vomiting (emesis) by administering syrup of ipecac Tsaang gubat Carmona retusa Gastroenteritis
Niyog-
o whole bowel irrigation with a balanced polyethylene-glycol Quisqualis indica Anti-helminthic, headache
niyogan
o cathartics decrease absorption and hasten removal of toxins Akapulko Cassia alata Antifungal
SUPPLEMENT: Utility of Activated Charcoal Ulasimang Peperonia Gout, rheumatic pains, boils,
EFFECTIVE for NOT EFFECTIVE for bato pellucida abscesses
• Amitriptyline • Iron Lowers blood cholesterol
Bawang Alium sativum
• Barbiturate • Lithium levels, antiseptic
• Carbamazepine • Potassium Momordica Lowers blood sugar levels,
Ampalaya
• Digitalis • Alcohols charantia fertility regulation
• Glycosides • Cyanide Guava Psidium guajava Antidiarrheal, antiseptic
• Phencyclidine • Corrosive BOTANICAL
• Propoxyphene • Acids COMMON INTENDED USE
SUPPLEMENT
• Theophylline • Solvents Decrease duration and intensity of cold
Echinacea
• Tricyclic antidepressants symptoms
• Valproic acid Ephedra Treatment of respiratory ailments such as
(Ma Huang) bronchitis and asthma, and a CNS stimulant
ENHANCEMENT OF ELIMINATION For cholesterol lowering and
• adjust urine pH to enhance renal excretion of weak acids and bases Garlic
atherosclerosis
• hemodialysis – patient's blood is pumped through a column with a Treatment for intermittent claudication,
Ginkgo
semipermeable membrane allowing removal of many toxic and cerebral insufficiency and dementia
compounds Improvement of physical and mental
Ginseng
performance
SUPPLEMENT: Utility of Hemodialysis Limitation of hepatic injury and as an
Milk thistle
EFFECTIVE for NOT EFFECTIVE for antidote to Amanita mushroom poisoning
• Carbamazepine • Amphetamines Improvement in symptoms of benign
Saw palmetto
• Ethylene glycol • Antidepressants prostatic hyperplasia
• Lithium • Antipsychotic drugs St. John’s Wort Treatment of mild to moderate depression
• Methanol • Benzodiazepines Improvement of ischemic heart disease and
Coenzyme Q10
• Metformin • Calcium channel blockers for Parkinson disease
• Phenobarbital • Digoxin Reduction of pain associated with
Glucosamine
osteoarthritis
• Salicylate • Metoprolol
Melatonin Decrease jet lag symptoms and as a sleep aid
• Theophylline • Propranolol
• Valproic acid • Opioids
END OF PHARMACOLOGY – MAIN HANDOUT
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valuable than they are? And which of you by worrying can add even one hour to
APPENDIX
his life? Why do you worry about clothing? Think about how the flowers of the
To all my Topnotch babies, Always Remember this: With God NOTHING
filed grow; they do not work or spin. Yet I tell you that not even Solomon in all
IS IMPOSSIBLE (Luke 1:37) J his glory was clothed like one of these! And this is how God clothes the wild
grass, which is here today and tomorrow is tossed into the fire to heat the oven,
“The favors of the Lord are not exhausted, His mercies are not spent, they won’t He clothe you even more, you people or little faith? So then, do not worry
are renewed each morning, so great is His faithfulness” Lamentations saying “What will we eat?” or “What will we wear?” For the uncoverted pursue
3:22-23 these things, and your heavenly Father knows that you need them. But above
all, pursue His kingdom and righteousness, and all these things will be given to
“The one who began a good work among you will bring it to completion you as well. So then do not worry about tomorrow, for tomorrow will worry
by the day of Jesus Christ” Philippians 1:6 about itself. Today has enough trouble of its own.
“There is only one secure foundation: a genuine, deep relationship with Jeremiah 20:11
Jesus Christ, which you will carry through any and all turmoil. No matter “But the Lord is with me to help me like an awe-inspiring warrior. Therefore
what storms are raging all around, you’ll stand firm if you stand on His those who persecute me will fail and will not prevail over me. They will be
love” Charles Stanley thoroughly disgraced because they did not succeed. Their disgrace will never be
forgotten.
2 Tim 4:17
“But the Lord stood by me and strengthened me…” John 6:20
“But He said to them, “It is I. Do not be afraid”
Matt 6:25-34
“Therefore, I tell you, do not worry about your life, what you will eat or drink, Matt 11:28-30
or about your body, what you will wear. Isn’t there more to life than food and “Come to me, all you who are weary and burdened and I will give you rest. Take
more to body than clothing? Look at the bird in the sky: They do not sow, or my yoke on you and learn from me, because I am gentle and humble in heart,
reap, or gather in barns, yet your heavenly Father feeds them. Aren’t you more and you will find rest for your souls. For my yoke is easy to bear, and my load is
not hard to carry.
3 when my aunt was not able to attend to her class. For the record, I came from
Feast Declaration of Abundance: Novena to God’s Love a family of teachers. My grandparents are teachers, my mother is a teacher, my
Today, I receive all of God’s love for me. sister is a teacher and many of my aunts, uncles and cousins are teachers. That
Today, I open myself to the unbounded, limitless, overflowing abundance of could probably explain it. My first tutoring stint was in June year 2000. I went
God’s universe. to my Alma Mater St. Mary's College QC to pay some of my favorite teachers a
Today, I open myself to God’s blessings, healing and miracles. visit. Little did I know that my "teaching career" will start there. My English
Today, I open myself to God’s word so that I become more like Jesus every day. teacher Ms Cecilia Asejo recommended me to one of her student's parents as a
Today I proclaim that I’m God’s Beloved, I’m God’s Servant, I’m God’s Powerful personal tutor in preparation for her Science High School entrance exam. I was
Champion,
in my first year at Quezon City Science High School back then. I accepted the "Job
And because I am blessed, I am blessing the world, In Jesus’ Name. AMEN
Offer" without second thoughts. I knew I needed the job. After my classes at 4-
5pm, I would assist for a while in the English Center as a student assistant.
Keep believing God for it! Praying for all of you J
Checking my batchmates’ quizzes, cleaning the English center or reading my
- Doc Yns Pereyra-Borlongan J <3
crush's English journal (hehe). After that, I would walk to Teacher's Village (just
in front of SM Annex) to go to my "tutee". My salary then was only Php50/hr, of
I know that I will never get the chance to say a valedictory speech, or get to give course with free meryenda, dinner and pabaon from tita Letty and Jessica. After
an opening remark in any kind of school affair, for I was never a “stellar” student around 2-3hours of tutorial, I would then head home, feeling so excited to hand
hahaha. But let me share with you my story, that hopefully, will inspire you a bit that Php150 to mama for her to buy us dinner the next day. While my salary as
J student assistant I use for my everyday expenses at school.
I came from a poor but hardworking family. My papa worked in Saudi as a My parents' friends learned that I was doing tutorials, so they started to hire me
machine operator while my mother used to sell “isaw-isaw” when I was born. I as well, increasing my salary to Php150/hr. During those times, that little money
could say that mama had delicate pregnancies, for I was born premature and meant so much to me. It made me feel relieved knowing that I am helping my
had a prior miscarriage and two of my sisters died. One because of parents in earning money and not add to their financial responsibilities. My
hydrocephalus, and the other one due to sepsis. Because we do not have the brother and sister were also studying already, I knew my parents would get any
funds to provide for my sisters’ hospitalization, mama had to appear on national kind of help they could have grip on. The tutorials continued, having tutorial
television asking for financial aid for my sister. She was so happy when she classes all days of the week. It was tough, I must admit. It took away so much
finally had the needed resources to pay for my sister’s operation. Unfortunately, time from me. I have less time for studying. I have less time for rest. I have less
she died before her scheduled surgery. My mother then donated the funds to time for other things I would like to pursue. I also have to sell food (Samosa,
another child who had hydrocephalus. These stories that my mother told me Karyoka, Siomai etc) to my classmates and teachers everyday to further
were major motivators for me to become a doctor. increase my income. I was the student council president. I was active in the
church choir, I would attend our weekly practices and sing my best for The Lord
Even though both my parents came from poor families themselves, they have during the Holy Mass. I know that it was all God's grace that I was able to do
always believed in one important thing: that good education is the only those things all at the same time.
inheritance they could ever give to us. I’m sure this will sound cliché to you. But I graduated High School and went to UP for college. My clients further increased.
I myself strongly adhere to this belief, and will surely apply this principle when Now, aside from Science High School entrance exam, I also taught UPCAT-ACET-
I too become a parent someday. And since my parents have always aspired for USTET entrance exam, Algebra, Geometry, Trigonometry, Calculus, Basic
good education for me and my siblings, they have decided to enroll us in private Sciences, Physics and Chemistry. I actually never imagined myself teaching
catholic schools. Of course, with the great help of some our relatives abroad, Math and hardcore science subjects, because I think I was not that good at them.
they still persevered in sending us to private schools. That’s why I have always But I had no choice, I needed to continue teaching. So, I prepared well for my
considered myself a “scholar” since elementary. Because somebody else was classes. My salary got bigger, it was now Php250-350/hr. I now have more
financing my education. money to spend for my school needs (Pharma was very expensive, so many Lab
I could say that life was never easy when I was young. At the age of 6 I knew all equipment to buy) and have more money to give to my parents. I even
kinds of household chores: cooking, ironing clothes, sweeping the floor, doing remember giving baon to my siblings and using my savings to pay for their
the laundry etc. I even remember being able to do a perfect “sinaing”, “sinangag” tuition fee. During those times, I keep thanking God that He provided for my
and sunny side up at the age of 6. I’m pretty sure that when it comes to family. We may not be living luxuriously, but God always provided enough, and
“domestication”, I belong to the 99+ percentile of people my age. And for my on time. I also praise Him for keeping my family together, despite the fact that
mother, that’s a great achievement. During that time, especially during summer, mama was already working as an OFW. I was a scholar of the QC SYDP
we had to sell balot/penoy/chicharon, biskwit and ice candy around our (Scholarship Youth Development Program), so I do not need to pay any tuition
neighborhood to help augment our parents’ income. We literally “lako” our fee during college. This, again, was big blessing to our family. God was very good
products door-to-door. Some by coercion, some by virtue of mercy. Then, all the to us.
profit we will get will be used to pay our school expenses, or when times are I still did student assistant duties, now at UPCP library (my salary was
harder, to pay our Meralco bill. I can accurately remember what my notebooks Ph25/hour which was very small hahaha. But I kept doing it, since I get to
were, for they have the same design each and every year (for they were among borrow all needed books from the library since I don’t have my own book. Also,
the cheapest) we did not have any computer at home. So I would do overtime job at the lib to
Assignment ntbk: Lapu-Lapu (because this is ntbk number 1 and he is the very do some typing and printing for free yey! Or I would go on overnight at my
first Filipino hero) bestfriend’s house to type on her computer). Still sold food to my classmates,
Filipino ntbk: Apolinario Mabini (He looks very Filipino to me) but of course with an upgrade! I now sell palabok, pancit and spaghetti which I
AP: Andres Bonifacio (for he was the bravest for me) get from my friendly neighborhood cook. And sitsirya from Divisoria (hahaha).
Science: Jose Rizal (self-explanatory) This cycle continued even until I was in med school.
MAPE: Juan Luna (because he was an artist) I was accepted into the Ateneo School of Medicine and Public health (ASMPH)
Math: the 3 martyrs (for they are more than 1) also as a scholar. Maybe my life story was so interesting to my panel of
Etc etc etc interviewers that I got a full scholarship. Life was still hard, for my sister is now
I even recycle them when there are still much of the paper left. Despite these in college and while my brother is in High school, and both of them are studying
boring ntbk designs, I still feel blessed that I was never forced by mama to get in a private school. But I had so much blessings then! I got a Neo Laptop that was
Jolina, Stefano Mori or Magic Temple ntbks. If you know what I mean J gifted to me by my Tita Sarah (I used until I was in Topnotch hahaha imagine
teaching with a laptop that would turn off when the charger was pulled out of
When I was in grade 4, my papa lost his job. That was certainly one of the the socket hahaha). I always have MRT ticket load and get to go home together
greatest challenge my family had ever experienced. There were many nights with my papa some days of the week (He used to work in Ortigas). I would
that we did not have electricity, we had only 1 nilagang manok (as in without usually walk from ASMPH to Ortigas MRT station to save up on money and to
vegetables, just plain boiled chicken) for Noche Buena of 1998, our ulam was lose some weight (hahaha). I would get free siomai from papa at the MRT
always adobong kangkong and dilis and we had to do extra work as students. station. That’s why I love going home with papa. And until now, even if he was
During weekends, our whole family worked for the printing press company of already gone, I would eat the same siomai when I’m at the Ortigas MRT station.
one of mama’s friends. At school, my sister and I would go around the campus I was still doing tutorial (but now only on weekends and Friday nights since Med
to get tin cans (to be sold to junk shops) and get soft drink bottles to get their School was more demanding) and still sold food (with the addition of cellphone
“deposit” (which was Php2) from the cafeteria. This is why I always bring two load ahahaha) so that I won’t have to ask money from my parents. I even have
bags with me. One for my school stuff and the other for my loot. Every day I my own corner at our clasroom where I leave my “honesty” store (which my
would volunteer to become the cleaner in our class, for I will get all the tin cans batchmates would call as “Cantyña”). I also learned how to bake! I was also
and plastics from our trash can so that I can bring them home. I didn’t have selling cakes and cupcakes to my schoolmates and to consultants at The Medical
complete books then. It was only during the third quarter of the year that I had City. I also ventured into selling pasta (red sauce, white sauce, lasagna, pesto
a complete set of books. Because my teachers decided to give me a copy of the etc). I bring around 30packs of pasts to school which I sold at TMC (believe me,
book out of their own salary. I must say, my elementary teachers were kind to they are always sold out), while I have a staff that sold them at the canteen
me, and had always faith in me. They also collect tin cans and plastics for me. where my sister works (She was already an English teacher back then). I think
That went on for 2yrs. I just study hard. I still manage to be at the top of our I also have “sales” and business skills running in my genes. I also did market
class despite having to “work” and study at the same time. I knew I had to help research interview sessions to earn Php2,000-3,000 per session (I will just
my parents, the turo-turo/karinderya business they put up from papa’s pretend to be rich and part of the class A of the society so I can get the 2k fee
separation pay was doing ok, but the profit is not enough to meet all our needs, hahaha. I always borrow clothes from my fashionable friends of course so I can
considering that I still have a baby brother during that time. Until finally, play the part well). All kinds of “raket” I think I have already done. I even
graduation came. My father found a new (and stable) job and I was admitted to planned on applying some short course TESDA subjects to improve my skills,
a science high school (which means free tuition for me Yayyyy!). hahaha which I never had the time to do.
I believe that getting into a science high school was my gateway for everything, But you know, God had an even brighter and better plan for me. I reviewed for
and believe me, it is during high school that my teaching career started. I started my Pharmacy board exam with the hope that I would top the exam. It was tough,
teaching at the age of 12. Well, probably earlier since I was teaching "drama" juggling studying, tutoring and doing MBA internship at the same time. I wasn't
classes (imagining I was Judy Ann Santos) and ABCs and 1-2-3s to my neighbors. able to attend all the classes and never had the opportunity to take any drills,
I also did substitute teaching for a class of grade2 students when I was in grade
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY MARIA YNA PEREYRYA-BORLONGAN, MD-MBA Appendix
comprehensive exam or the pre-board exam. I was doing everything I can so La Salle’s Brother Gus Boquer once shared Dr. RA’s inspiring story, which
that when I top the boards, the owner of the review center would hire me to be Dr. Willie Ong wrote about in his column in The STAR.
a lecturer. With God's perfect will, I was 0.03 short of getting into the top10. I “I believe doctors are doing God’s work. The way they help the sick and put a
felt devastated. I felt my dream of becoming a lecturer melt away. But I knew smile on a poor patient never fails to amaze me. We have a doctor here in De La
that God did this on purpose. He had the best plan for me in mind. I still felt Salle, Dr. Romeo P. Ariniego, who has pledged to give his life’s earnings to De La
thankful that He made me pass the boards. I sent a message to one of the owners Salle. He has already given P10 million for a new library. And he has already
(who is also my teacher at the review center) to thank Him for teaching us and donated his house and lot to De La Salle Institute, which will take effect after he
in case He needs any assistance in anything, I am just one message away. passes away. How can you not be amazed by doctors like this?”
The poor boy from Vigan had a dream and attained it. And now his dream is
Sometime in August 2010 one of the staff of the review center called me. He said
to be able to let others live their dreams, too.
that my teacher was asking me to make the module 1 exam for the upcoming
review season. When I ended the phone call, I cried. And I cried a lot. I did not
imagine that God would work this way. I was contacted by the review center to
make exams for them, and yes, I was still given a chance to become a lecturer. I
felt so thankful to God, that indeed, he answers our prayers. God is indeed
faithful! He is the one who planted dreams and aspirations in my heart, and I am
certain that each one of them would come true, according to His perfect will.
And so, I started teaching at Manor Review Center. At first, I was only asked to
make exams and discuss the rationale to the students. But later, one of the
owners also asked me to teach his subject because he could not make it to the
assigned dates. I was very nervous. It was my first time to teach a class of 200+
people (except of course for NSTP hehe), and I would be teaching Microbiology
for 3 days. I prayed and prepared well for the lecture, thinking that I was doing
it for God and to live up to my boss' expectation. The lecture ended. I was given
a good feedback. I was congratulated by the owners and my teaching career at
Manor already started. I was given more teaching load, now teaching other
subjects such as Organic Medicinal Chemistry, Dosage Forms, Clinical and
Hospital Pharmacy, Pharmacognosy, and the longest and probably the most
dreaded subject of students: Pharmacology and Toxicology. I feel extremely
blessed having been trusted by my mentors to teach their subjects. And now,
God even gave me the opportunity to reach out to medical students like you
through Topnotch J I will forever be grateful to all those people, whom God
used, to bring me to the state of contentment that I am in now. I am now happily
married, can pay for Grab rides, can drive our car, lives in a decent apartment
with our loving dog Matty, and hopefully, in God’s perfect time, kids of our own
J. I have already sent two of our house helpers to college (and their siblings at
their provinces to school) and they are now working in restaurants around the
metro (both of them took HRM). I also supported one of our loyal “masahista”
in her endeavors of working aborad. She is now in UAE working in a hotel as a
masseur. I am planning to send more students to school, and will definitely
sponsor a medical student in the future. And currently, as a medical resident in
a public hospital, God is also using me to help poor patients not only by giving
them the medical care they need, but also by providing them food, toiletries,
medicines not available in our pharmacy, even their fare back to their provinces
(as far as Visayas and Mindanao). These things, for me, are insignificant to the
amount of blessing God has bestowed upon my life. I am just paying it forward,
to people who needs it most. And as I continue living my life for the Lord, may I
continue glorifying Him with all the talents and treasures He has bestowed upon
me J HAPPY REVIEWING DEARY! J I am always praying for you, Doc! J God
bless you more! J
Doc Yns Pereyra-Borlongan J
HAPPY ARAL PO DOCTORS! J <3 - Matty, Peanut and Summer <3
Giving back
Not one to forget his humble beginnings, Romy has made conscious efforts to
“give back. Aside from his medical practice, Romy, also known as “Dr. RA,” also
dutifully served in the academe, working as a teacher, professor, and even
administrator at the De La Salle Health Sciences Institute for 27 years.
The well-loved Dr. RA has touched the lives of many — co-workers, students
and many young Lasallian scholars. He has also helped the children of his own
staff in pursuit of a medical degree.
For years, his home and his extensive medicine library were open to scholars.
His clinic always reportedly has the longest queue of patients of all ages at the
De La Salle University Medical Center.
Dr. RA was instrumental in the construction of the DLSHSI library. “I know
how important a library is especially for poor students. Throughout my years of
studying, I survived because of the kind librarians who were lenient when it
came to my borrowing of books because they knew I didn’t have the money to
buy my own copies,” said Dr. RA.
De La Salle Health Sciences Institute now has the Romeo P. Ariniego, M.D.
Library, which houses major resources from around the world, and serves as a
converging point for students, faculty and researchers who all share Dr. RA’s
love for learning.
TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN DIGITAL HANDOUT BY MARIA YNA PEREYRYA-BORLONGAN, MD-MBA Appendix

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TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY MAIN HANDOUT BY DR.

YNS PEREYRA-BORLONGAN, MD-MBA

MNEMONIC: Pharmacokinetics vs Pharmacodynamics

QUANTAL DOSE-RESPONSE RELATIONSHIP

o absorption is faster in organs with larger SA (intestinal > A. ABSORPTION

2. Buccal and Sublingual

• Ordered by Increasing ability to retard evaporation: STEADY STATE

1. SIZE OF THE ORGAN

stool, bile, exhaled air)

Ethanol Fetal alcohol syndrome PHASE 1 TRIAL

Skeletal muscle (β2 and less

Smooth muscle Relaxation

companies in creating their own drug formulations. Example si biogesic, lacrimal,

nervous system (β2, ɑ)

A. ACETYLCHOLINE AND ITS BIOSYNTHESIS TYPICAL RESULT OF

Adapted from Katzung BG. Pharmacology Board Exam Review

STEP 1 – TRANSPORT AND SYNTHESIS

o Inhibited by INDIRECT-ACTING CHOLINOMIMETICS DIRECT ACTING CHOLINERGIC AGONISTS

GANGLIONIC BLOCKERS STEP 2 – STORAGE

SE Tachycardia, confusion, urinary retention, increased IOP

ADRENERGIC PHARMACOLOGY B. ADRENERGIC RECEPTORS

(ADRENERGIC AGONISTS) DOPAMINE: DOSE DEPENDENT ACTIONS

ALPHA-2 AGONIST Phenoxybenzamine

blocking effects of TCAs)

SELECTIVE BETA BLOCKERS Beta-2 agonists

EFFECTS NOT RELATED TO BETA BLOCKADE

D1 Receptor Agonist: Fenoldopam

mentioning all these repeatedly. We’ll focus on the other buzzwords

ANGIOTENSIN RECEPTOR BLOCKERS (-SARTANS) ANGINA PECTORIS

SUPPLEMENT: HYPERTENSION IN PREGNANCY

CYANIDE POISONING: NITRATES AS A PART OF THE ANTIDOTE

CHF: THERAPEUTIC STRATEGIES

AMIODARONE, Dronedarone, Vernakalant

CLASS 4 ANTIARRHYTHMICS DIURETICS

NON-DHP CCBs (Verapamil, Diltiazem)

CARBONIC ANHYDRASE INHIBITORS OSMOTIC DIURETIC

Synergistic ototoxicity with AMINOGLYCOSIDES

DRUGS FOR DYSLIPIDEMIA CHOLESTEROL ABSORPTION INHIBITORS

BILE ACID BINDING RESINS Antihyperlipidemic Combinations to watch out for!

DESCRIPTION DRUGS AUTACOIDS

SEROTONERGIC DRUGS HISTAMINE RECEPTORS AND EFFECTS

5-HT2 Receptor ANTAGONIST (UTEROSELECTIVE) H2 RECEPTOR ANTAGONIST

BRONCHODILATORS AND OTHER DRUGS RELIEVERS

SHORT ACTING BETA-2 AGONIST

Strategies of Asthma Therapy MUSCARINIC RECEPTOR ANTAGONIST

CONTROLLERS • biological agents that interfere in different steps of the TH2

Notes and late BA responses) • N-acetylcysteine is also used in the management of

SE sputum & inhibits ciliary activity, reducing clearance of

CENTRALLY ACTING (NON-OPIOID)

SUPPLEMENT: OTHER DRUGS USED FOR COUGH

SHORT ACTING BENZODIAZEPINES

INTERMEDIATE ACTING BENZODIAZEPINES

NEWER HYPNOTICS ALCOHOLS

MNEMONICS: Disulfiram Reaction

ENHANCE NA+ CHANNEL INACTIVATION IMPORTANT OTHER USES

• Wide set eyes

BRANCHED-CHAIN FATTY ACID GABA ANALOGUE

Decreases Ca2+ currents (T-type) in thalamus

GENERAL ANESTHETICS GENERALIZATION

depression (it is a bronchodilator) making it ideal for

o hypercalcemia antagonizes local anesthetic activity AMIDE LOCAL ANESTHETICS

charged form will predominate. This will not be able to cross

SUPPLEMENT: APPLICATIONS – Lethal Injection DEPOLARIZING NEUROMUSCULAR BLOCKERS