Pharma Compilation

DRUGS
— means study of
— body of knowledge

DRUGS PHARMACODYNAMICS
• any substances that bring about a change in biologic function its • study of the mechanism of action
chemical actions • study of biologic activity that a drug has on a living system
• may be synthesized within the body (ex: hormones) or may be • what does the drug do it to the body
chemicals not synthesized in the body (ex: xenobiotics)
• can cause a change in physiologic activities PHARMACOKINETICS
• often associated with addictive, narcotic or mind-altering substances • deals with the magnitude & time course of drug effects
– an unfortunate negative connotation that tends to bias • εxplains the aspects of drug action through absorption,
opinion against any form of chemical therapy distribution, metabolism & excretion
A à absorption
MEDICINE D à distribution
• a chemical preparation which usually but not necessarily contains one M à metabolism
or more drugs, administered with the intention of producing a E à excretion
therapeutic effect
• many substances such as insulin/thyroxine, are endogenous PHARMACOGENOMICS
hormones but are also drugs when they are administered • relationship of the individual’s genetic makeup to his or her
intentionally response to a specific drugs

DRUG ABUSE GENERAL PRINCIPLES OF PHARMACOLOGY
— use of illegal drugs/the misuse of prescription or over-the- Pharmacodynamics: Mechanism of Drug Action
counter drugs for at least a year with negative consequences Pharmacodynamics in Greek:
— ex: potent painkillers
“Pharmakon” à drug
“Dynamics” à action/power
“it covers all the aspects relating to what drug does to the body”
I (drugs with no Ex: Cocaine/Coke/Crack, Heroin,

therapeutic use) Ecstasy/XTC/MDMA
DRUG-RECEPTOR INTERACTION
• drug
• receptor (site of attachment)
II (dangerous • drug-receptor complex
Ex: Methamphetamine (used for people with ADHD)
drugs) • pharmacologic action/effect/response

GENERIC DRUGS DRUG + RECEPTORàDRUG-RECEPTOR COMPLEX =
• a pharmaceutical product, usually intended to be PHARMACOLOGIC ACTION
interchangeable with an innovator product that is RECEPTOR
manufactured without a license from the innovator company & • biologic partners for drug action
marketed after the expiry date of the patent of other exclusive • structures involved in physiologic regulation
rights • ex: cells, enzymes, nucleic acids

ORPHAN DRUGS Classification:
• have been discovered but not financially viable 1. ION-CHANNEL-LINKED RECEPTOR
• considered to be effective a. Voltage- Gated Ion Channels
⇒ Na+, K+, Ca++, H+, Cl-
OVER-THE-COUNTER DRUGS
• available without prescription for self-treatment of a variety of
complaints
• safe when taken or directed there several problems with its use:
1. Mark signs & symptoms of an underlying
disease, making diagnosis difficult
2. Drug interaction & interfere with
drug therapy
3. Overdosing
LABELS OF A DRUG PACKAGE:
a. Storage information
b. Quantity (amount of drugs in a package)
c. Prescription Status
d. Administration b. Ligand-Gated Ion Channels
e. Manufacturer ⇒ Nicotinic receptor
f. Dose/Content (in every tablet)
g. Brand Name (given by the manufacturer) 2. G PROTEIN-LINKED RECEPTOR
h. Generic Name (chemical name of the drug listed in the National — metabotropic receptor
Formulary) — target for non antimicrobial prescription drugs
POISONS — maintenance drugs
• drugs that have almost exclusively harmful effects

TOXINS
• poisons of biologic origin

“PHARMAKON”
— means “poison” in classic Greek
— means “drug” in modern Greek
“LOGIA” 3. ENZYME-LINKED RECEPTOR
KMD| PHARMACOLOGY 2016
— site of attachment for neurotopic peptides growth hormones o have full affinity towards the receptor but intrinsic
— catalytic sites activity is 0 to -1
— cytoplasmic site of the receptor b. ANTAGONISTS
4. INTRACELLULAR RECEPTOR • drug that decrease or oppose the action of another
— sites of attachment within the cells drug/endogenous ligand
• no intrinsic activity
DRUG BINDING FORCES • also known as “BLOCKER”
• drugs interact with receptor by means of chemical forces or bonds • ex: methyldopa = considered as A1 blocker (stops the increase of
• 3 major types: Covalent, Electrostatic & Hydrophobic BP; considered to be as antihypertensive)
a. COVALENT
— very strong & not reversible under biologic conditions BETA BLOCKER à ANTIHYPERTENSIVE “OLOL”
— ex: covalent bon formed between acetyl group of ASA & 1. Nebivolol
cyclooxygenase (enzyme target in platelets) 2. Metoporol
3. Esmolol
ASPIRIN 4. Atenolol
à analgesic 5. Betaxolol
à antipyretic 6. Sotalol
à anticoagulant 7. Propanolol
b. ELECTROSTATIC
— weaker a. CARDIOSELECTIVE
c. HYDROPHOBIC o only targets the B1 receptor
— quite weak & important in interaction of highly lipid-soluble drugs o will not affect the RR of the patient
B - betaxolol
STRUCTURE-ACTIVITY RELATIONSHIP E - esmolol
• structures of a drug molecules are identified in order to determine A - atenolol
their influence on pharmacologic activity M - metoporol
• presence of functional groups b. NONCARDIOSELECTIVE
• ex: Caffeine (1,3,7-trimethylxanthine) ß CNS stimulant; ^HR, o can target both B1 & B2 receptors
^RR, release of EPI *nitrogen causes the adverse effects of o all other OLOLS
coffee
DRUG INTERACTION

— when one drug affect the pharmacological response of a
second drug given at the same time
— 3 major drug interactions:
• DRUG-DRUG INTERACTION à ex: Kremil-S
• DRUG-FOOD INTERACTION
• DRUG-DISEASE INTERACTION
DRUG-DRUG INTERACTION IS DUE TO:
• Pharmacokinetic effects
• Pharmacodynamic effects
DOSE-RESPONSE RELATIONSHIP — Increase drug effects Consequences of Drug
• Threshold concentration — Decrease drug effects Interaction:
• Ceiling Effect — Desired consequences
• Agonists — Adverse/Undesired effects
• Antagonists
DRUG-FOOD INTERACTION
ΟCCUPATION THERAPY: — best absorbed when there is food in the stomach
a. AGONISTS ex: Antibiotics, Anti-fungal antibiotics (requires a fatty meal), Pomelo
• drugs that binds to & activate the receptor, which
directly/indirectly brings about the effect POMELO (Citrus Grandis)
• ex: Alpha, Beta receptors — enzyme induction; potent enzyme inducer
— promotes the production of CYP450 enzyme (helps metabolize
drugs)
— English name: Grapefruit

*all drug interactions are not harmful*

KREMIL-S
— active ingredients: Aluminum Hydroxide (Al(OH)2),
Magnesium Hydroxide (Mg (OH)2)& Simethicone
— adverse effects:
i. FULL AGONIST
—
can cause maximum response to agonist
—
if a drug binds to a receptor and produced a maximal biologic
response that mimics the response to endogenous substance
ii. PARTIAL AGONIST
o have effects greater than or but less that of a full
agonists
o have less effects compare to full agonists
o in the presence of full agonist will act as an
antagonists
iii. INVERSE AGONIST Simethicone
o drug that binds to a receptor & produce an opposite — base + acid = neutralization reaction
effect — cancels out the burping
1. Heat is given off; exothermic
effects of
reaction R – RIFAMPICIN (orange/red color of body fluidsàurine, saliva, sweat,
neutralization
2. Formation of salts tears)
reaction
3. Release of oxygen I – ISONIAZID (peripheral neuritisàtingling sensation of finger tips)
= bubble formation = burp P – PYRAZINAMIDE (liver toxicity)
E – ETHAMBUTOL (optic neuritisàtingling sensation of eyes)
S– STREPTOMYCIN (deaf, nephric toxic)

DRUG ABSORPTION INTERACTION
*Isoniazid: Counterfeit of Vit. B6 (antidote for neurosis/neurotic
1. GI pH (Gastrointestinal)
)* BRAND NAME: Fixcom4 (RIPE; 6mos) & FIXCOM3 (RIE; 2mos)
ex: Cimetidine (increases pH) to Ketaconazole (weak acid drug)
MINIMUM DURATION: 6mos to 1yr

LINEZOLID
— super antibiotic
— administered for not TB patients who takes TB medication
— very toxic

AGE
1. Pediatric Patients
— 0-18yrs old
ex: Chloramphenicol (0-1yrs = Gray baby syndrome)
à antibacterial/antibiotic
à tx for typhoid fever (caused by salmonella typhi)

2. Complexation 2. Geriatric Patients

ROUTES OF ABSORPTION
1. Oral * without alcohol dehydrogenaseàinfinitely drunk or drunk forever*
2. Inhilation

3. Parental (IV, intramuscular, Subcutaneous)
3 PHASES OF ALCOHOL INTOXICATION:
4. Topical
I à drunk (euphoria, slurd speech, respiratory depression, pass out)

II à hangover
DISTRIBUTION
III à recover
— movement of the drug throughout the body
*alcohol dissolves B vitamins*
3 pathways:

DIET
1. First Pass effect – movement of drug to the liverà — affects metabolism
metabolism à eliminated — HOW?
2. Protein Binding – storage/binding of drug to protein ex: WARFARIN
a. Acidic Drugs à binds to albumin; does nothing • blood thinner/anti-coagulant
b. Basic Drugs à binds to α-glycoprotein • overdose = hemorrhage
3. Receptor • not allowed during administration: leafy green vegetables
(contains Vit. Kàcontains clotting factors such as 9,10,7 & 2)
METABOLISM • leafy green vegetables will cancel the effects of warfarin
A. Phase I Metabolic Reaction
• “functionalization reactions” ELIMINATION
• reduction, oxidation, hydrolysis • Major Organs
B. Phase II Metabolic Reaction 1. Liver
• “conjugation reactions” 2. Kidneys – major route
• sulfate conjugation, amino acid conjugation, glutathione • Other Organs
reaction, glucuronic acid conjugation, acetylation, methylation 1. Skin
Factors affecting metabolism: 2. Lacrimal fluid
3. Sweat
4. Expired Air
1. Genetics
5. Saliva
2. Age
3. Sex
4.
5.
Enzyme Induction – promotes metabolism
Enzyme Inhibition – promotes toxicity
ADRENERGIC AGONISTS
6. Diet – affect metabolism
Classification of Adrenergic Receptors:
DRUG: Isoniazid • Alpha 1
— tx for 3rd world disease (tuberculosis) • Alpha 2
— important in genetic factor metabolism • Beta
— metabolized through acetylation & methylation (exaggerated § Beta 1
neuritis) § Beta 2
§ Beta 3 § stimulate Alpha 1 receptors in the
• Dopamine brain
§ D1 § stimulates the blood brain barrier &
§ D2 centrally active adrenergic agonists
§ D3
§ D4 ENDOGENOUS CATECHOLAMINES: Dopamine
§ D5
7. Cardiovascular Effects
Classification of Adrenergic Agonists:
— D1– dilate renal, celiac, hepatic & mesenteric
A. DIRECT ACTING vasculature
— drugs that bind directly to the adrenergic receptor & — Fenoldopam à decrease BP, increase in renal blood
produces effects flow (Drug that decrease BP)
B. INDIRECT ACTING 8. Other Effects
— drugs that increases the amount of Norepinephrine — Nausea & Vomiting
& Epinephrine to stimulate the adrenergic receptors § stimulate medullary chemoreceptor
C. MIXED trigger zone
— can do both (Direct & Indirect acting) — D2 à dopamine binds to lactotrope cells in the
anterior pituitary gland
ENDOGENOUS CATECHOLAMINES (EP, NE & DOPAMINE): § inhibits the release of prolactin (a
NOREPINEPHRINE & EPINEPHRINE have effects on the ff à hormone that stimulates the breast
milk production)
1. Vascular Effects
— when norepinephrine binds to alpha receptors Sir Jace’s explanation: Dopamine also binds to medullary chemoreceptor
à BP, bradycardia, does not affect the heart rate trigger zone (responsible for the stimulation of gag reflex; over stimulation
— causes vasoconstriction = VOMITING)

Sir Jace’s explanation: when norepinephrine binds to an alpha receptors Bromcriptine
this will cause an increase in blood pressure due to vasoconstriction. Does • Dopaminergic agonist
not cause an increase in the heart rate. The NE’s effect is only the on the • treatment for female infertility
blood pressure & not with the heart rate. Contrary, it will cause the slowing • control excessive secretion of growth hormones which are
down of heart rate. associated with adenomas
• stimulate growth hormone release
2. Cardiac Effects
— NE & EP stimulate B1 receptors ALPHA ADRENERGIC RECEPTOR AGONISTS
— increase in HR • Phenylephrine & Methoxamine
— increase rate of force development & subsequent — selective action on Alpha-I adrenergic receptor
relaxation is accentuated — contraction of vascular smooth muscle
— increase BP; bradycardia
Sir Jace’s explanation: both NE & EP will stimulate the B1 receptors (main • Phenylpropanolamine
target is only the heart). Heart will increase the rate of force development & — OTC cold remedy
subsequent relaxation is accentuated. Therefore, there’s an increase in — increase risk for hemorrhagic stroke in women
heart rate. • Midodrine
— synthetic; selective alpha I adrenergic agonist
— vasoconstriction
3. Non-vascular Smooth Muscles — treatment for postural hypotension
— Alpha 1 à causes smooth muscle contraction • Clonidine, Guanabenz, Guanfacine, Methyldopa (Anti-
— Alpha 2 à causes smooth muscle relaxation hypertensive medications)
— enters CNS
Sir Jace’s explanation: Alpha 1 receptors will cause smooth muscle — stimulate selectively alpha 2 adrenergic receptors
contraction. When the smooth muscle contracts it generally stops the exit — centrally acting in the nucleus tractus solitaries of
of the following: urine & feces. For alpha 1 receptors, NE & EP will the brainstem
bind to alpha 1 receptors it will contract the urinary & rectal — moderate decrease in BP
sphincter causing smooth muscle contraction. For beta 2 receptors, — reduce venous return, heart rate, cardiac output
this will affect the lungs causing bronchodilation. • Methyldopa
— vasoconstrictor in local anesthetics
4. Salivary glands • Clonidine
— NE & EPI bind to secretory cells (a & B)
— first used as a nasal decongestant
— Alpha 1 stimulation on myoepithelial cells
— decrease blood pressure
- contract secretory acinar units
— xerostomia ß adverse effect
§ water & electrolyte secretion — *when given to addicts in withdrawal: blocks nausea
— Beta 2 receptors stimulate production of amylase & vomiting, sweating, diarrhea
(an enzyme that breaks down the starch particulary
• Oxymetazoline, Tetrahydrozoline, Xylometazoline
on alpha 1,4 glycosidic bond)
— stimulate alpha 2 adrenergic receptors
5. Metabolic Response
— contraction of smooth muscles in blood vessels
— glycogenolysis
— used as nasal decongestant
— increase in glucagon secretion
• Brimonidine & Apraclonidine
— Beta 3 – lipolysis; increase in free fatty acids
— newer alpha 2 agonists

— decrease intra-ocular pressure in patients with
Sir Jace’s explanation: whenever NE & EPI binds to alpha receptors & causes
glaucoma
glycogenolysis (breakdown of glycogen to its glucose form & undergoes

Kreb’s Cycle causing the conversion of glucose to energy in the form of ATP)
BETA ADRENERGIC RECEPTOR AGONISTS

• cardiac & vascular effects

6. CNS Effects • effects on bronchial smooth muscles
— Ephedrine, Amphetamine • metabolic effects
• nervousness
ISOPROTERENOL • excitability
• Cardiac & Vascular Effects • insomnia
— decreases diastolic BP by Beta 2 receptor-mediated • dizziness
vasodilation • tremors
— increase in systolic BP from increase CO caused by • xerostomia
stimulation of Beta I receptors • sexual dysfunction
— increase in heart rate due to stimulation of Beta I
receptors in the pace maker cells
• Effects on Bronchial Smooth muscle
— relaxes bronchioles, prevents bronchoconstriction
— non selective
— development of tolerance
• Metabolic & Other Effects
— stimulates glycogenolysis & gluconeogenolysis in
the liver
— not as effective as epinephrine
— causes CNS excitation

DOBUTAMINE
• synthetic dopamine
• no effect on dopamine receptors
• Alpha I receptor inhibition
• increase myocardial contractility, CO, heart rate
• inotropic effect by stimulation of beta I receptors
• for short-term treatment of acute myocardial insufficiency
from CHF, MI, surgery

SELECTIVE BETA 2 ADRENERGIC RECEPTOR AGONIST

METAPROTERENOL, TERBUTALINE, ALBUTEROL, LEVALBUTEROL,
PIRBUTEROL, SALMETEROL
• relax bronchial & uterine muscles
• decrease airway resistance
• inhaled drugs

RITODRINE
• uterine relaxant (tocolytic)
• short-term management for labor
• withdrawn from the market

MIXED ACTING ADRENERGIC AGONISTS

EPHEDRINE
• causes the release of NT – Epi & NE
• directly stimulates alpha & beta receptors

AMPHETAMINE, DEXTROAMPHETAMINE, METHAMPHETAMINE
• CNS active, indirect
• causes alertness, relief of fatigue, enhanced athletic
performance, euphoria

GENERAL THERAPEUTIC USES
— local vasoconstriction
— treatment of hypotension & shock
— ‘bronchodilation
— uterine relaxation
— ophthalmic uses
— treat allergic states
— CNS stimulation
— treat hypertension

ADVERSE EFFECTS

Cardiac Disturbances
• MI
• heart attack
• arrhythmias
• ventricular fibrillation
• hypertensive crisis
• rebound hypertension

CNS Reactions
ADRENERGIC ANTAGONISTS

Alpha 1 Adrenergic Receptor Antagonists
• Prazosin
• Terazosin
• Doxazosin

Effects:
— dilates arterioles & veins
• hypotension
— reduce cardiac output
— reduce renin release

THERAPEUTIC USES:
— alleviate signs & symptoms of CHF
• increases survival rate of patients
— treat benign prostatic hyperplasia (BPH)
• doxazosin & terazosin are preferred

Benign Prostatic Hyperplasia à an enlarged prostate gland; noncancerous
increase in the size of prostate.

THERAPEUTIC DOSES
— Prazosin à more than once (2-3x a day)
— Terazosin à once a day
— Doxazosin à once a day

ADVERSE EFFECTS:
— first-dose syncope à best describe by dizziness or fainting
— hypotension
— IFIS (Inoperable Floppy Iris Syndrome)

Sir Jace’s explanation: Syncope is best described by dizziness & fainting
because Prazosin, Terazosin & Doxazosin causes the lowering of BP.

ALFUZOSIN
— prostate-selective
— less likely to cause syncope
— once-a-day dose
— used to treat BPH

Sir Jace’s explanation: Alfuzosin is prostate-selective although this one can
cause the lowering of BP. Alfuzosin is used to treat BPH because its activity
lies mainly with its prostate active agent.

TAMSULOSIN
— treatment for BPH
— less likely to cause orthostatic hypotension & syncope
— Adverse Effects: stuffiness & skin rash

Sir Jace’s explanation: Tamsulosin was developed after Alfuzosin & its now
the drug of choice treating BPH.

NON-SELECTIVE ALPHA ADRENERGIC RECEPTOR

1. IMIDAZOLINES

A. Phentolamine
— antagonists to alpha 1 & 2 receptors
— cholinomimetic
— blocks serotonin
— cause hypotension, reflex tachycardia,
myocardial ischemia & cardiac arrest
— depressant
Uses: control pre-operative BP, management of
phaeochromocytoma, used in clonidine withdrawal, reversal of
soft tissue numbness after administration with local
anesthetics

Sir Jace’s explanation: Phentolamine is an antagonist to both alpha 1 & 2
receptors & at the same time this one will block Serotonin (responsible for
sense of well being). Phentolamine is a depressant & at the same it will
cause hypotension, myocardial ischemia & cardiac arrest. Phentolamine is
injected to patients after surgery to restore sensation. 3. Metabolic Effects
— antagonize beta receptors, hypoglycemia may occur
2. BETA-HALOALKYLAMINES — increase triglyceride concentration

A. PHENOXYBENZAMINE Sir Jace’s explanation: Beta blockers will cause hypoglycemia. When beta
— blocks alpha adrenergic receptors receptors are stimulated includes the effects of glycogenolysis. So that
— inhibits response to histamine, ACh, serotonin means, there’s a breakdown of glycogen to form glucose (WHEN IT IS
— used for pheochromocytoma, relaxes urinary STIMULATED). However, if it is blocked, glycogenolysis is also blocked
sphincter resulting to low blood sugar.
Adverse Effects: NE & EP reuptake, increases cardiac
excitability, contractility rate & cardiac output, orthostatic 4. Ocular Effects
hypotension, hypovolemia — reduce intra-ocular pressure in patients with
glaucoma
Sir Jace’s explanation: Phenoxybenzamine blocks alpha receptors & inhibits — reduce production of aqueous human in the eyes
response to histamine, ACh & serotonin; that means it will not response to
any sort of inflammation, movement & causes depression. Sir Jace’s explanation: Patients with glaucoma (a condition that happens to
your eyes. The optic nerve is stuck between the eye socket resulting to fluid
build up. The fluid build up is due to the increase production of the aqueous
BETA ADRENERGIC RECEPTOR ANTAGONISTS humour. Once the aqueous humour accumulates, it will increase the
à B1, B2, B3 diameter of the eyes & eventually resulting to permanent blindness.

Effects: effects on the CVS, effects on smooth muscles (bronchial & uterine 5. CNS Effects
muscles), gastrointestinal effects, metabolic effects, ocular effects & CNS — treat migraine headache, tremor associated with
effects anxiety
PROPRANOLOL à drug used to treat stage freight &
1. Effects on the CVS white coat syndrome
— decreases the rate & force of myocardial contraction
— blocks beta receptors in Sinoatrial node, THERAPEUTIC USES OF BETA BLOCKERS
Atrioventricular Node, Purkinje system § Hypertension
— no effect on normotensive patients § Ischemic heart disease
— used to treat angina pectoris § Post myocardial infarction
— reduce plasma renin contraction § Congestive heart failure
§ Treat arrhythmias
2 mechanisms in increase BP ADVERSE EFFECTS:
a. Baroreceptors à responsible in increasing BP
b. Renin Angiotensin System (RAS) à found in kidney I. HEART
• withdrawal can result to angina pectoris, myocardial
RENIN êRENIN infarction, sudden death
II. SMOOTH MUSCLES
• reduce adrenergic response to EP
• reduce adrenergic vasodilator response of the
vasculature to EP

Sir Jace’s explanation: Beta blockers will reduce adrenergic response to
ANGIOTENSIN II êANGIOTENSIN II Epinephrine. When a patients has asthma, it should be a Cardioselective
(Potent Vasoconstrictor) = Decrease in BP Beta Blocker so that the effects of beta blocker is exclusively for the heart &
= Increase in BP the BP. If it is Noncardioselective it will affect the bronchial muscles.

Sir Jace’s explanation: If you are going to stimulate B1 receptor there’s an III. METABOLIC EFFECTS
increase in Heart Rate but these are Beta Adrenergic Antagonist it will • hypoglycemia
decrease the heart rate & myocardial contraction & at the same time it will IV. CNS EFFECTS
block your beta receptors in SA node, AV node & Purkinje System (Pace • CNS depression, weakness, fatigue
Maker of heart that are responsible for the Lub-Dub of the heart). Beta • sleep disturbances, insomnia, nightmares
blockers do not have any effects on patients that have normal blood • hallucinations, dizziness, depression of mood
pressure. Used to treat angina pectoris (Chest pain). They are two
mechanisms by which your BP increase: Baroreceptors (responsible in
increasing the BP) but if Baroreceptors are not enough, Renin Angiotensin DRUGS WITH COMBINED EFFECTS:
System (RAS). Renin is found in kidneys which will eventually converted to
a substance called Angiotensin II (potent vasoconstrictor) thus LABETALOL
narrowing the blood vessels which will cause an increase in BP. Beta — administered through IV
blockers will reduce renin concentration in the body that means that lesser — decreases peripheral resistance & BP
the renin present, the lesser the angiotensin, the lesser vasoconstricting — vasodilator
effects therefore resulting to the lowering of BP. — used as long-term treatment of hypertension
CARVEDILOL
2. Effects on Smooth muscles — anti-hypertensive
— prevent sympathetic stimulation of bronchial — decreases morbidity & mortality associated with CHF
smooth muscles (Congestive Heart Failure)
— contraindicated in patients with bronchial — used in treating heart failure
disorders: Asthma & Emphysema

Sir Jace’s explanation: Effects on smooth muscles, first, it has the ability to
prevent sympathetic stimulation of the bronchial muscles. When there’s
sympathetic stimulation of the bronchioles resulting to dilation of the
bronchioles to allow oxygen. Beta blocker will prevent sympathetic
stimulation therefore causing bronchoconstriction.
Mechanism of action:
• Low doses of ACh à activates muscarinic
• High doses of ACh à activates nicotinic

MUSCARINIC RECEPTOR
M3
M1 M2 M4 M5
|
| | | |
SMOOTH
CNS HEART CNS CNS
MUSCLE

NICOTINIC RECEPTOR

N1/Nm N2/Nn
| |
Neuromuscular Autonomic ganglia,
Junction CNS, adrenal medulla

PHARMACOLOGIC EFFECTS:

§ PERIPHERAL MUSCARINIC EFFECTS
• EYE à miosis, decrease intra-ocular pressure
• HEART à decrease in heart rate
• VASCULAR SMOOTH MUSCLE à vasodilation,
decrease in BP
• BRONCHIAL SMOOTH MUSCLE à
bronchoconstriction
• GI SMOOTH MUSCLE à enhance motility & relax
sphincter muscles (urinary & rectal sphincter)
• SECRETORY GLANDS à stimulates the secretion of
saliva, lacrimal & bronchia
• URINARY TRACT à decreases bladder capacity
§ PERIPHERAL NICOTINIC EFFECTS
• N1 à Ganglia (high doses)
• N2 à CNS (low doses)
CHOLINERGIC DRUGS § CNS EFFECTS
• affects central regulation of physiologic functions
• influence cognition & emotion
— agents that mimic the action of endogenous NT à ACh
— also known as cholinomimetic agents or ANTICHOLINESTERASES
parasympathomimetic agents — drugs that stimulate cholinergic transmission by
— receptors: Nicotinic & Muscarinic receptors inhibiting the enzyme acetylcholinesterase
— reversible = edrophonium, neostrigmine, physostigmine
CLASSIFICATION: — irreversible = organophosphates

1. Choline Esters Sir Jace’s explanation: Anticholinesterase are agents that will inhibit or
— synthetic congeners of ACh destroy the presence of an enzyme called acetylcholinesterase.
— Metacholine, Carbachol, Bethanecol
2. Alkaloids & Congeners REVERSIBLE
A. PHYSOSTIGMINE
a. Muscarine (from Amanita Muscarina) • also known as eserine
— rapid onset of action of parasympathetic stimulation • Calabar Bean (Physostigma Venenosum)
b. Pilocarpine (Pilocarpous Jaborandi)
• treatment for glaucoma
c. Cevimeline
B. NEOSTIGMINE
d. Arecoline (Areca Catechu)
• derivative of physostigmine
e. Nicotine (Nicotiana Tabacum)
• treatment for Myasthenia Gravis (an autoimmune

disease)
Sir Jace’s explanation: Alkaloids are secondary metabolites in plants that
Symptoms: looping eyelids
can be used as drugs.
Treatment: neostigmine

Sir Jace’s explanation: When acetylcholinesterase is destroyed, it will still
MECHANISM OF ACTION
allow the production or reproduction of acetylcholinesterase afterwards.
1. Direct Acting
Reversible, these are drugs which will inhibit acetylcholinesterase.
— drug directly binds to nicotinic & muscarinic receptors

2. Indirect-Acting
IRREVERSIBLE
— drug induce the release of cholinergic NT to bind to
A. ORGANOPHOSPHATES
nicotinic & muscarinic receptors
• tetraethyl pyrophosphates

• used as insectides FUNCTIONAL ANTAGONISM
à Organophosphates — also known as “physiologic antagonism”
à Carbamates ex: Epinephrine (tx for anaphylaxis)
• synthesized nerve gas
• responsible of cholinesterase
CHEMICAL ANTAGONISM
— prevents the actions of an agonist by modifying or
THERAPEUTIC USE OF ANTICHOLINESTERASE sequestering the agonist so that it is incapable of binding to &
activating its receptor
ex: Dimercaprol (chelator of Lead)

Lipstick contains Lead (“Cumulative Poisoning”)

Pb binds to specific receptor
Dimercaprol will bind with Lead = complex (neutralized lead)

Heavy Metals: Pb (Lead), Hg (Mercury), Cd (Cadmium) ß used to find
them in batteries
Elements in metallic nature: Iron, Magnesium, Manganese, Silver,
Copper, Gold, Iron, Aluminum

Milk natural chelator of gold

DURATION OF DRUG ACTION
— the effect lasts only as long as the drug occupies the receptor &
dissociation of drug from the receptor automatically
terminates the effect

*Edrophonium is only a diagnostic agent for Myasthenia Gravis. *Teacher’s explanation*
§ it is determined by how long your drug receptor
PHARMACOLOGIC ACTION complex stays in place
• cholinesterase inhibits production of muscarinic effect § how long a drug & a receptor are bound together
• direct-acting cholinergic agonists will determine how long drug effect will last
• cause hypotensive response § if they stay together the pharmacological effect lasts
• anticholinergic poisoning à ataxia, confusion, respiratory longer but if they stay for a very short time the
abnormalities, convulsions, coma & death by respiratory pharmacological effect will be only for a very short
paralysis time
— ex: Paracetamol (taken up every 4hrs ß the duration of action
ADVERSE EFFECTS is only 4hrs)
• inability to accommodate for vision
• severe rhinorrhea, severe headache RECEPTORS & INERT BINDING SITES
• severe SLUD à salivation, lacrimation, urination, defecation (Criteria for a drug & a receptor to bind together)
• fatigue & general weakness — to function as a receptor, an endogenous molecule must:
• muscle twitching, fasciculations, muscle cramps 1. It has to be selective in choosing ligands (drug molecule) to
• over exposed to anticholinesterases à exaggerated bind
parasympathetic effects 2. It must change its function upon binding in such a way that the
function of the biologic system is altered
THERAPEUTIC EFFECTS
• Glaucoma PHARMACOKINETICS (What the body does to the drug)
• Xerostomia
• Reversal of neuromuscular blockage
• myasthenia gravis Absorption
• atropine poisoning Distribution
• paralytic ileus Metabolism
• bladder atony Excretion
• senile dementia (Alzheimer’s disease)

Definition:
1. Permeation – movement of a drug molecule into & within the
COMPETITVE ANTAGONIST biologic environment
2. Prodrug – precursor chemical that is readily absorbed &
— if both the antagonist & the agonist bind to the same site on the distributed the converted to active drug by biologic processes
receptor, they are said to be “competitive” 3. Free Drug – exerts biologic effect
— competitive antagonist will prevent an agonist from binding to 4. Bound Drug – stay in the vascular space & is not metabolized
its receptor & maintain the receptor & maintain the receptor in or eliminated
its inactive conformational state 5. Bioavailability – is the fraction of administered drug that
ex: Beta blocker reaches the systemic circulation
Antihistamine 6. Half Life – period of time required for the concentration of
a. H1 à blockers; anti-allergies drug to decrease by one-half
b. H2 à gastric secretions

Anaphylaxis à H1 à Histamine (antidote for allergies)
treated by: epinephrine DRUG ABSORPTION
— the movement of the drug from its site of administration into
the blood stream or “systemic circulation”

ex: Loperamide

Therapeutic effect *there are no pepsinogen, trypsin present in the mouth*
IV drugs/inj

*tears freezes at 0.52C*

% ACT 3. The drug concentration at the site of absorption
tablet/ § the higher the concentration, the more drug
capsule absorption
4. The are available for drug absorption:
§ mostly small intestines
§ lung also has a large absorbing area

15 min 30 min PHYSIOLOGIC FACTORS:
1. Membrane Physiology
Capsule or Tablet à are designed to take effect 15min after 2. Surface area – ex: Talcum/face powder
IV Drugs/Injections àtakes effect immediately after administration; it 3. Gastric emptying – the longer a drug stays in the stomach the
does not require absorption; requires only a very short time more time to absorb; usually 3-4hrs
4. Motility
FACTORS AFFECTING THE RATE OF DRUG ABSORPTION 5. Permeation
6. Passive Diffusion – the drug movement is from high
1. The ability of the drug to penetrate a biologic membrane concentration to low concentration; no need for carrier proteins
& energy
Biologic membrane of humans à cell membrane (responsible for 7. Facilitated Diffusion – same drug movement but it requires
keeping the organelles in) carrier proteins; no energy
§ nucleus, mitochondria, golgi apparatus, endoplasmic 8. Active Transport – the drug movement is from low
reticulum, smooth & rough ER, proteins & lysosomes) concentration to high concentration; requires carrier proteins &
§ main component à lipid bilayer energy consumption (the energy consumed here is in the form of
ATP)
9. Endocytosis – the cell absorbing a solid material
10. Exocytosis – cell elimination/cell removal

EXAMPLES OF WEAK ACIDS:
1. Acetaminophen/Paracetamol – antipyretic, analgesic
2. Acetazolamide - diuretic
3. Ampicillin – antibacterial/anti-infectives
4. Aspirin – antipyretic, analgesic, anticoagulant
5. Ciprofloxacin - antibacterial
6. Furosemide - diuretic

Lipid Bilayer à doesn’t allow the entry of polar substances 7. Ibuprofen – anti-inflammatory, analgesic
8. Phenobarbital – anti-convulsants (epilepsy, interrogation)
*most drugs are non-polar so that they can have the ability to 9. Phenytoin – anti-convulsants
penetrate the biologic membrane* 10. Salicylic Acid – same with aspirin, anti-inflammatory
11. Warfarin – anti-coagulant
2. Degree of ionization of the drug 12. Methyldopa – Parkinson’s Disease
§ weakly acidic drugs are unionized & more freely 13. Levodopa – Parkinson’s Disease
absorbed at lower pH
§ weakly basic drugs are unionized & more freely EXAMPLES OF WEAK BASES:
absorbed at higher pH 1. Albuterol – asthma/B2 agonist
§ a drug can either be a weak acid or a weak base 2. Allopurinol – gout/anti-gout (deposit of urate crystals to
§ for a drug to be absorbed it has to have a degree of synoviate space)
ionization 3. Amphetamine - ADHD
DRUGS 4. Atropine – anti-cholinergic
5. Chlorpheniramine - decongestant
Intestines Stomach 6. Clonidine – anti-hypertensive
7. Diazepan – topical aesthetic (before) but it has no therapeutic

Weak base Weak acid/ use today
8. Diphenhydramine – narcotic analgesic/ cough syrup (before)

they prefer (dimetap before)
acidic 9. Lidocaine - anesthesia
10. Epinephrine

environment 11. Metoprolol – anti-hypertensive
pH Range 12. Nicotine
13. Pilocarpine – anti-cholinergic
Blood, 14. Scopolamine – anti-vertigo
mouth intestine

AUTONOMIC NERVOUS SYSTEM

Terms:
1 6.5 7 7.4 14 GANGLIA
gastric tears : are group of nerve cell bodies, usually located outside the
acid brand and spinal cord
: it functions as à relay stations between preganglionic and • principally in the paravertebral and prevertebral
second nerve cell, the postganglionic neurons ganglia
: Preganglionic fibers – short, myelinated

: Postganglionic fibers – long, myelinated
NEUROTRANSMITTERS
: Types of activation à synchronized
: are chemical mediators that transmit nerve impulses across
: Types of receptors à alpha, beta, dopamine
junctions such as synapse
: branching of preganglionic fibers à extensive
: chemicals by which neurons communicate
: the substance release by a neuron
: has a specific shape to fit into a receptor site and cause PARASYMPATHETIC NERVOUS SYSTEM
pharmacological response such as nerve impulse : the parasympathetic preganglionic fibers
• leave the CNS through the cranial nerves (especially
SYNAPSE the 3RD, 7TH, 9TH, 10TH )
: the region of communication between neurons • 3RD and 4th are sacral nerve roots
: locus or site of communication between neurons : some preganglionic parasympathetic fibers
• terminate in parasympathetic ganglia located
RECEPTOR outside the organs innervated:
: portion of a sensory neuron that responds to the external a. Ciliary
stimuli b. Pterygopalatine
: drug molecules or hormones c. Submandibular
: site of biophase to which drug molecules can be bound d. Otic
e. Several pelvic ganglia
: majority of parasympathetic preganglionic fibers terminate on
ganglion cells

SYMPATHETIC vs PARASYMPATHETIC
ANATOMY SYMPATHETIC PARASYMPATHETIC
Origins Thoracolumbar Craniosacral nerves
nerves (T1-T12,L1- (CN 10973, S1-S4)
L5)
Length of fibers
Preganglionic Shorter Longer
Postganglionic Longer Shorter
Location of ganglia Near spinal cord Near target organs
Types of activation Synchronized Localized

NEUROTRANSMITTER CHEMISTRY OF THE ANS
— an important traditional classification of the autonomic nerves
is based on the primary transmitter molecules
• acetylcholine or
• norepinephrine
PARASYMPATHETIC NEUROTRANSMITTER
— most parasympathetic postganglionic and a few sympathetic
postganglionic fibers are cholinergic
— a significant number of parasympathetic postganglionic
neurons utilize
• nitric oxide or
• peptides
⇒ as the primary transmitter or
cotransmitters

SOMATIC DIVISION SYMPATHETIC NEUROTANSMITTER
: largely concerned with consciously controlled functions such — most postganglionic sympathetic fibers release
as respiration, posture and movement norepinephrine (also known as noradrenaline)
AUTONOMIC NERVOUS SYSTEM — they are noradrenergic (often called simply adrenergic) fibers
: largely autonomous (independent) in that its activities are not — they work by releasing NE
under direct conscious control — some sympathetic fibers release ACTH
: it is concerned primarily with visceral functions such as — DOPAMINE is a very important transmitter in the CNS and
Cardiac output, Blood flow to various organs and digestion there is evidence that it may be released by some peripheral
: which are necessary for life (Homeostatic functions) sympathetic fibers
: DIVISIONS PARASYMPATHETIC SYMPATHETIC
a. SYPMATHETIC (thoracolumbar) (REST AND DIGEST) (FIGHT OR FLIGHT)
b. PARASYMPATHETIC (craniosacral) HEART 600-100 BPM Tachycardia; éHR;
SYMPATHETIC NERVOUS SYSTEM >100BPM
: the sympathetic preganglionic fibers LUNGS 16-20 RPM éRR > 20RPM
• leave the CNS through the thoracic and lumbar BRONCHIOLES Bronchoconstriction Bronchocdilation
spinal nerves (T10T12, L1-L5) GIT Peristalis êperistalis which
• are short and causes constipation
: terminate in ganglia located EYES Miotic constriction Mydriasis dilation
• in the paravertebral chains that lie on either side of URINARY Relax Contracted
the spinal column SPHINCTER
: location of preganglionic neurons FECAL SPHINCTER Relax Contracted
• T1-T12; L1-3 SWEAT GLANDS No sweat production Diaphoresis
: location of ganglia UTERUS Relax Contracts
PENIS Ejaculation Erection
SALIVARY GLAND Saliva production Dry mouth Sir Jace’s explanation:
Xerostomia • when you take Anti-Histamines it will result to having 0%
LIVER Glycogenesis Glycogenolysis histamine in your body which will cause for you to be drowsy
ARRECTOR PILI Relax Contracts or sleepy
goosebumps
9. Endorphins
ADRENAL No reaction EP/NE will release
MEDULLAR — associated with happiness
— derived from 2 words: endogenous-morphine-
like neurotransmitter
NEUROTRANSMITTER

Neuron:
- chemicals which serves as messengers between the neurons
- located @ the vesicles

• Somatic Nervous System (responsible for posture &
movements)
— Acetylcholine (ACh) à pre-ganglionic
neurotransmitter

Sir Jace’s explanation:
à ACh is a pre-ganglionic neurotransmitter & while it is not yet
activated (Epi & Ne), ACh is the one dominating that particular
nervous system (Sympathetic Nervous System) Synaptic Cleft/Synapse (space between two neurons)

• Autonomic Nervous System
2 subdivisions:
1. Sympathetic Nervous System
— Epinephrine & Norepinephrine
2. Parasympathetic Nervous System
— Acetylcholine (responsible for both sympathetic
& parasympathetic nervous system)

Other neurotransmitters:
1. ACh

— responsible for posture & movement
2. Epinephrine
— emotional response & short-term memory Sir Jace’s explanation:
3. Norepinephrine • Stimulus à Somebody lights a match under your ass, your neuron
— activation of sympathetic nervous system will interpret that as a stimulus in the form of heat. That stimulus
(fight or flight response) will pass through your cell body & axon before it can proceed to the
4. Dopamine axon terminal, what happens? There’s an influx of sodium inside &
influx of potassium (PISO à SIPO/POSI). When there’s an influx
— responsible for motor control (voluntary
of sodium & influx of potassium the stimulus/action potential will
motor control) & behavior pass through your axon terminal & will go through your
— a natural neurotransmitter that when released synaptic cleft/synapse
that binds to the receptors resulting to full • When it reaches the synaptic cleft it will allow another influx of
muscle control & proper behavior calcium, once calcium goes in the vesicles will move to pre-synaptic
Sir Jace’s explanation: cleft & cause the release of neurotransmitter.
• People with low dopamine are associated to have • Since we are talking about setting somebody’s ass on fire, so what
Parkinson’s Disease happens? That person will stand up.
• For that person to stand up, the neurotransmitter ACh should
• If dopamine is low. motor control is also absent so that
transfer from the vesicles into your receptors hereby causing
means, you’re constantly having tremors muscle contraction & eventually muscle movement
• How long does it take for a neurotransmitter to be released? In a
5. Serotonin span of half a millisecond
— responsible for mood & sense of well being • Stimulus à Somebody slaps you in the face. The nerve endings
Sir Jace’s explanation: found on your face interpret that one as pressure. So when pressure
• People with low serotonin are sad is detected it will result to an action potential which will pass
• Prolonged sadness that means low serotonin for long through your cell body and axon before it can completely go to
your axon terminal. Sodium goes inside the myelin sheath into
periods of time (6months) will result to depression
your axon while Potassium goes out (DEPOLARIZATION) & once
that signal goes through, the axon terminal will result to Calcium
6. Gamma-Aminobutyric Acid (GABA) ions going inside your axon terminal & allowing the
— considered to be a inhibitory neurotransmitter neurotransmitter to move to the edge of the axon terminal or
7. Glycine synaptic cleft
— an amino acid & an inhibitory • Afterwards, you will release neurotransmitter that is necessary to
neurotransmitter response to that stimulus that will result movement. So you release
8. Histamine ACh & attached themselves to the receptors resulting to movement
— responsible for consciousness

CHOLINERGIC JUNCTIONS vesicles vesicles they are are susceptible to COMT
— it deals with ACh subject to destruction (Catechol-O-
— helps in activating parasympathetic nervous system à methyltransferase) ß
ADRENERGIC JUNCTIONS ACETYLCHOLINESTE an enzyme that
— it deals with Norepinephrine & Epinephrine RASE (an enzyme that destroys
— helps in activating sympathetic nervous system breaks down ACh into catecholamines (ex: NE,
Acetyl & Choline ß NO EP & Dopamine)
Sir Jace’s explanation: ACTION)
• Norepinephrine & Epinephrine should attach themselves to Cause Carbachol Tyramine
adrenergic junctions to cause a sympathetic response release of - stimulates in releasing - an amino acid found in
• If NE & EP will attach themselves to cholinergic, it has no transmitter ACh to the receptors cheese & wine
effect - precursor for the ff:
1. Norepinephrine
2. Epinephrine
MECHANISM OF ACTIONS FOR PARTICULAR NEUROTRANSMITTERS Activate Cholinomimetic Alkaloids Phenylephrine
THAT BIND WITH ADRENERGIC & CHOLINERGIC JUNCTIONS: postjunctio - alkaloids are - found in Decolgen &
nal secondary Neozep
Site of Action receptor metabolites found in - therapeutic use: nasal
Mechanism Cholinergic Junctions Adrenergic Junctions plants; metabolites decongestants
of Action that will help the - when a drug activates
Interfere Hemicholinium Metyrosine plants for survival & the sympathetic nervous
with - a drug that will cause the - has a similar action to adaptation (ex: system, many things can
synthesis of destruction of ACh; it Hemicholinium but its target Nicotine & Lobeline) happen including
transmitter prevents ACh from being is adrenergic drugs that binds - simply attaches to the increasing of BP
synthesized in the vesicles to other adrenergic junction receptors & mimics the - it has only something to
resulting to êACh or no ACh (NE & EPI) ß prevents NE & cholinergic/ACh do with the BP resulting
at all EPI from being synthesized resulting to to hypertension
resulting to êNE & êEP. parasympathetic
Therefore, you cannot activate response
your sympathetic nervous - When you smoke
system w/o NE & EP cigarettes it will
Causes Methyldopa actually increase your
formation - goes directly to the bowel movement to
of false receptor & acts as 15%
transmitter dopamine Block Atropine Prazosin
- Tx for Parkinson access of - will simply block the - blocks the adrenergic
Disorder because it will transmitter access of transmitter receptor
help with dopamine to to receptor to receptor; standbys
attach to their at the synaptic
adrenergic receptors cleft/synapse
causing muscle control - “anti-cholinergic
w/o any tremors drug”
Prevent Botulinum toxin Guanethidine - it prevents drugs
release of - comes from the - prevents the release of bound to the
transmitter bacteria Clostridium NE & EP cholinergic receptors
Botulinium - only targets the heart from binding to the
- very prevalent in soil this will simple lower receptors
- very poisonous but in the BP Inhibit Phsostigmine Selegiline,
sufficient amounts this - considered as anti- enzymatic - destroys the enzymes Tranylcypromine
can be used for Botox hypertensive breakdown responsible for the - “MAOi” (Monoamine
- lifeblood of cosmetics of breakdown of cholinergic Oxidase Inhibitors)
- injected in cheeks; transmitter drugs - inhibits the enzyme,
paralyzes the cheeks (Acetylcholinesterase) MAOi, responsible for the
- Prevents the release of breakdown of serotonin
ACh (HOW? Botox will - anti-depressants drugs
be found within the
vesicles to prevent the THERE IS SENSE OF BALANCE BETWEEN NEUROTRANSMITTER TO
release of ACh or Botox ANOTHER:
could be found within
the terminal axon or • DOPAMINE & HISTAMINE
Botox can be found — responsible for mental alertness & cognition
within the synaptic — in balance: work memory, clarity, proper
cleft resulting to no motivation
movement — excessive: compulsion (being forced to do
something irresistible), apathy (lack of interest)
Prevent Cocaine • NOREPINEPHRINE, ACETYLCHOLINE & EPINEPHRINE
reuptake of - going back of NE & EP to — responsible for concentration, recall memory &
transmitter the vesicles perseverance
- blocks the reuptake of — excessive: obsession, doubt, hesitation
NE & EP • SEROTONIN & GLUTAMATE
Prevent Vesamicol Reserpine — perception, sensory satisfaction, learning memory,
incorporati - prevents the entry of - blocks the entry of EP, relaxation, pleasure & pain
on of ACh to the vesicles NE & Dopamine from — excessive: paranoia, insensibility (inability to do
transmitter - When ACh is not within entering the vesicles something), anxiety
in storage their corresponding - they stays outside & they

v Excessive Dopamine, Histamine, NE, EPI & ACh = OCD • Macrolides
v Excessive Serotonin & Glutamate = Paranoid • Tetracycline
• Metronidazole
• Clindamycin
ANTIBIOTICS INAPPROPRIATE ANTIBIOTIC USE
• In Dentistry:
INFECTIOUS DISEASES — initiated after surgery
Statistical data: — failure to use prophylactic antibiotics
• 1900 - Diarrhea, Pneumonia, TB, Malaria — used as analgesics
• 1945 - World War II ß started in 1941 — treatment of chronic periodontitis
• AIDS — long-term management of periodontal disease
Bacterial Resistance — antibiotics instead of incision & drainage
— improper situation, dosage & duration
• MRSA (Methycillin Resistance Staphylococcus Aureus)

• VRSA (Vancomycin Resistance Staphylococcus Aureus)
*maximum days/wks of antibiotic medication à 21 days
• Super Bugs (ex: Linezolid)
ex: Amoxicillin 3x/day for 7 days à failed to complete à Next Generation

Amoxicillin
RETRO YEARS (1970’s-1980’s)

à G.R.I.D/AIDS (Gay Related Immunodeficiency Disease)
MECHANISM OF ACTION

• Cell Wall Synthesis Inhibitors

SIGNIFICANT DISCOVERERS
John Snow
— In 1854, John Snow showed the link between cholera (bacteria:
Vibrio Cholera) and drinking water
Anton van Leeuwenhoek
— in 1683, the “animicules” of dental plaque scraped from his
upper gingiva and killed with salt (the rst periodontal
chemotherapy).
— “Father of Microbiology”
Louis Pasteur
— In the 1860s, Louis Pasteur rst used the word germ for living
entities that produced disease,
— in the 1880s, Pasteur developed anthrax and rabies vaccines.
— “pasteurization”
Robert Koch
— founder of modern bacteriology
— known for his role in identifying the specific causative of TB,
cholera & anthrax
Paul Ehrlich
Members:
— In 1891, Paul Ehrlich showed that antibodies were responsible
— Penicillins
for immunity.
à beta lactam ring + thiazolidine ring
— In the early 1900s, Paul Ehrlich used the term magic bullet for
§ Penicillin G
his predicted chemical that would affect only microbial cells
à “Benzylpenicillin”
and have no effect on mammalian cells.
à taken with food or without food
— used fuchsin and mercury (Salvarsan) to treat syphilis.
à salt forms include: Penicillin K &
Alexander Fleming
Penicillin Na
— In 1928 discovered that a mold, Penicillium chrysogenum, lysed
§ Penicillin V
staphylococci; this was later developed to its full potential by
à “Phenoxymethylpenicillin”
the isolation of penicillin from Penicillium notatum by Florey
à it has resistance to hydrolysis by
and colleagues at Oxford in the late 1930s and early 1940s
gastric juice & its ability to produce
— first use of penicillin was in 1941 on an English police
uniform concentrations in blood when
constable with streptococcal and staphylococcal skin
administered orally
abscesses.
§ Methicillin Sodium
— In the United States, penicillin was rst used in 1942 on Anne
à Penicillinase resistant
Miller, who had streptococcal toxemia of pregnancy
à Tx of staphylococcal infections caused
Gerard Domagk
by strains resistant to other penicillins
— 1935 by Gerhard Domagk that sulfanil- amide could be safely
à not to be used in general therapy to
used systemically to treat infectious disease.
avoid possible widespread development
— prontosil
of organisms resistant to it
John Needham
§ Oxacillin Sodium
— “Spontaneous Genesis Theory”
à Penicillinase-resistant
à nonliving things are incapable of producing nonliving
à use is restricted to the tx of infections
substance/thing
caused by Staphylococci sp resistant to
• Selman Waksman
Penicillin G
• QR Bartz § Cloxacillin Sodium
• Benjamin Duggar à the Cl atom ortho to the position of
attachment of the phenyl ring to the
USES OF ANTIBIOTICS isoxazole ring
• Anti infective § Dicloxacillin Sodium
• Anti bacterial à the substitution of chlorine atoms on
• Prophylactic both carbons ortho to the position of
attachment of the phenyl ring to the
— Dentists prescribe 7%-11% of all antibiotics isoxazole ring
— Commonly prescribed by dentists § Nafcillin Sodium
• Beta Lactams à Penicillinase-resistant
à used in infections caused solely by CLAVULANATE POTASSIUM
penicillin G-resistant staphylococci or • antibiotic isolated from Streptomyces clavuligeris
streptococci • Clavulanic acid + amoxicillin (Augmentin)
à also effective against Pneumococci & • intended for the tx of skin, respiratory, ear & UTI caused by β-
group A beta-hemolytic streptococci lactamse-producing bacterial strains
§ Ampicillin
à not resistant to penicillinase SULBACTAM
à used to treat infections caused by gram • synthetic penicillin derivative
(-) bacilli • Sulbactam + ampicillin (Unasyn)
à used for the following infections: • used in the treatment of skin, tissue, intra-abdominal &
ü UTI caused by E.coli, gynecological infections caused by β-lactamase-producing
P.mirabilis strains of: S. aureus, E. coli, Klebsiella, P. mirabilis, B. fragilis
ü Haemophilus influenze
ü w/ probenecid- for N. TAZOBACTAM
gonnorhea • available in fixed-dose, injectable combinations with
§ Bacampicillin Hydrochloride piperacillin (Piptaz)
à prodrug of ampicillin with no • used in the treatment of appendicitis, postpartum endometritis
antibacterial activity & pelvic inflammatory disease
§ Amoxicillin — Carbapenems
à antibacterial spectrum similar to à beta lactam ring
ampicillin à have antibacterial activity similar to penicillins
à resistant to acid, susceptible to alkaline
& β-lactamase hydrolysis THIENAMYCIN
à used in the treatment of UTI • β-lactam antibiotic isolated from Streptomyces cattleya
à less effective than ampicillin in the
• highly active against most aerobic & anaerobic gram (+) & (-)
treatment of bacillary dysentery
bacteria
§ Carbenicillin Disodium, Sterile

à not stable in acids; inactivated by
IMIPENEM
penicillinase
• derived from thienamycin
à must be administered by injection
• with cilastatin – inhibitor of enzyme (prevents inactivation)
(usually IV)
à treatment for: P.aeruginosa, Proteus • tx of bacterial infections of skin & tissues, lower respiratory
sp, Providencia sp tract, bones & joints, GUT, septicemia & endocarditis
§ Ticarcillin Disodium, Sterile
à unstable in acid, thus administered MEROPENEM
parenterally • 2ND-generation carbapenem
à antibacterial spectrum similar to • Tx of infections caused by multiple-resistant bacteria & for
carbenicillin serious infections (bacterial meningitis, septicemia, pneumonia
à 2 advantages: & peritonitis)
ü better pharmacokinetic
properties BIAPENEM
ü greater in vitro potency against • newer 2nd-generation carbapenem
several special of gram (-) • broad-spectrum antibacterial activity (most aerobic gram (-) &
bacilli –P. aeruginosa, (+) bacteria & anaerobes)
Bacteroides fragilis • stable to DHP-1 & resistant to most β-lactamases
§ Mezlocillin Sodium, Sterile — Cephalosporins
à Acylureidopenicillin à beta lactam ring + dihydrothiazine ring
à active against most:
ü Klebsiellasp, P. aeruginosa,
anaerobic bacteria & H.
influenza
à not effective against β-lactamase-
producing bacteria
§ Piperacillin Sodium, Sterile
à most generally useful of the extended-
spectrum acylureidopenicillins
à active against anaerobic bacteria (B.
fragilis & S. faecalis)
à β-lactamse producing strains of these
organisms are resistant to piperacillin
à intravenous or intramuscular routes

BETA LACTAMASE INHIBITORS
• Clavulanic Acid
• Tazobactam
• Sulbactam
à β-lactam ring but no antibacterial activity
à binding bacterial β-lactamase
à always in a fixed-dose combination with a penicillin
à inhibit most of the important bacterial β-lactamases, including those • 1st to 4th generation = increasing activity for gram (-)
produced by staphylococci, gonococci, H. Influenzae, B. Fragilis & some • 4th to 1st generation = increasing activity for gram (+)
Enterobacteriaceae
à Penicillin β-lactamase inhibitor combinations are useful for • Alteration of Cell Membrane
polymicrobial infections where the use of a single commercial agent • Protein Synthesis Inhibitors
(albeit containing 2 drugs) may obviate the need for 2 or more agents • Nucleic Acid Synthesis Inhibitors
• Folic Acid Synthesis Inhibitors
— lowest ABX concentration that inhibits growth for
PRINCIPLES OF ANTIBIOTIC THERAPY B.
18-24hrs
Concentration-Dependent Versus Time-Dependent
Antibiotics
Microbial Resistance: 48hrs C. Postantibiotic Effects
Herxheimer Reaction à symptom felt by the patient after
Antibiotic Resistance Mechanisms: taking an ABX (ex: Fever)
à enzymatic antibiotic activation *Murein Protein Structure – causes the
fever/symptoms if distributed
RESISTANCE IN MAJOR MICROBIAL PATHOGENS: D. Microbial Persistence & Regrowth
1. Streptococcus Pneumoniae
2. Methicillin-resistant Staphylococci III
3. Enterococci
4. Helicobacter Pylori
5. Human Immunodeficiency Virus
II
SPECIFIC ANTIMICROBIAL AGENT RESISTANCE IV
1. Vancomycin
2. Macrolides I
3. Fluoroquinolones
4. Tetracyclines
5. Heavy metal resistance

ANTIBIOTIC RESISTANCE MECHANISMS I (Lag Phase) à determines the incubation period; microorganism are
MECHANISMS ANTIMICROBIAL DRUGS AND still adapting to the environment & starts to replicate
EXAMPLES OF MECHANISMS II (Log Growth) à replicates exponentially
III (Peak Phase) à microorganisms covers the petri dish & it starts to die
Enzymatic antibiotic inactivation B-lactams by B-lactamases
in 2 reasons: Lack of nutrients & Accumulation of waste
Aminoglycosides by
IV (Log Death) à destruction of microorganism
aminoglycoside-modifying

enzymes
E. Dosing & Resistance
Chloramphenicol by
3DAYS à AZITHROMYCIN
acetyltransferases
5DAYS à TETRACYCLINES (Potent ABX)
Streptogramins by
6DAYS
acetyltransferases
7DAYS
Tetracyclines by enzymatic
14DAYS
oxidation
21DAYS
Modification/protection of target B-lactams: altered PBPs 6MONTHS à ANTI-TB MEDICATION
site Fluoroquinolones: altered DNA
gyrase or topoisomerases 2 TYPES OF ABX:
Rifampin: altered RNA polymerase A. Bactericidal à Bacterial Death
Sulfonamides: altered B. Bacteriostatic à Stops the growth for quite some time (ex:
dihdyropteroate Tetracycline)
Trimethoprim: altered
dihydrofolate reductase F. Antibiotic Loading Doses
Macrolide-lincosamide- G. Duration of Antibiotic Dosing
streptogramin B aggregate gene H. Incision & Drainage
(MLSb): methylation of adenine on I. Antibiotic Dosing Variables
23S rRNA
Glycopeptides: change of D-Ala-D- A. AGE – Pediatric, Adult, Geriatric
lactate in cell wall B. LIPID SOLUBILITY
Tetracyclines: ribosomal protection C. PREGNANCY
D. PLASMA PROTEIN BINDING
E. RENAL & HEPATIC FUNCTION
Limiting access of antibiotic B-lactams, fluoroquinolones, most F. SURFACE ARE/WEIGHT
antibiotics: altered outer
membrane porins COMBINATION THERAPY
Most antibiotics: reduced • Cell Wall Synthesis Inhibitors
membrane transport • Beta Lactam
Active antibiotic efflux Tetracyclines: tet genes • Sulfonamides
Fluoroquinolones: Nor A genes
Failure to activate antibiotic Metronidazole: decreased FAILURE OF USE
flavodoxin production • Faulty Dosing
Use of alternative growth Enterococcal auxotrophs • Noncompliance with the prescribed antibiotic regimen
requirements • Poor ABX pharmacokinetics
• Microbial Resistance
Overproduction of target sites Sulfonamides: overproduction of
PABA • Incorrect Diagnosis
Enteric bacilli: overproduction of B-
lactamase COMMON ADVERSE EFFECTS
• ABX Teratology

— Teratogenic
PRINCIPLES OF ANTIBIOTIC DOSING:
— Carcinogenic

• ABX-induced Mania
A. Minimal Inhibitory Concentration
• Long QT interval syndrome
• ABX & Oral Contraceptives
• ABX-induced agranulocytosis — group of fungal diseases in which both the skin & subcutaneous
• ABX-Induced Photosensitivity, Photoallergy & Phototoxicity tissue are involved but no dissemination to the internal organs
• ABX effects on Body flora & Super infections TOPICAL AGENTS FOR DERMATOPHYTES
o Fatty acids
Sebum
ANTIFUNGAL AGENTS
•
• Fatty acids or their salts = antifungal effect

Bacteria à Peptidoglycan a. Propionic Acid
Humans à Phospholipid bilayer; Cholesterol (in humans) § antifungal agent, nonirritating &
Plants à Stigmasterol, Phytosterol nontoxic
b. Zinc Propionate
ANTIFUNGALS § fungicide on adhesive tape
— treatment of fungal infections (mycoses) is more difficult than c. Sodium Caprylate
treating bacterial infections § treat superficial dermatomycoses
— many fungal infections occur in poorly vascularized tissues or caused by C. Albicans &
avascular structures such as superficial layer of the skin, nails Trichophyton, Microsporum &
& hair Epidermophyton spp
— Fungi are eukaryotes; cell membrane are nearly identical d. Zinc Caprylate
— Slightly different in cell membrane: sterol § topical fungicide
Humans: Cholesterol e. Undecylenic Acid
Fungi: Ergosterol § used for athlete’s foot
— Mycoses is divided into 2 groups: f. Triacetin
§ glyceryl triacetate
1. Superficial Mycoses g. Salicylic Acid & Resorcinol
• caused by dermatophytes like SALICYLIC ACID à used externally in ointments
Epidermophyton, Microsporum & & solutions as antifungal & keratolytic
Trichophyton which have their ultimate RESORCINOL à antiseptic & keratolytic
reservoir in the soil h. Benzoic Acid
• includes various forms of tinea or ringworm § Whitfield’s ointment à 6% benzoic
(infections of the hair or hair follicles, flat areas acid (fungistatic) + 3% salicylic acid
of hairless skin & infections of nails) (keratolytic) in a petrolatum base
2. Deep-seated mycoses o Phenols & their Derivatives
• caused by pathogenic saprophytic yeast • topical antifungal properties like hexylresorcinols &
• frequently transmitted from one host to parachlorometaxylenol (Tx of Tinea infections)
another (ex: Athlete’s foot)
• Candida produces a dermatophyte-like disease a. Haloprogin (Halotex)
§ 1% cream for treatment of
*Deep-seated systemic mycoses such as those caused by superficial tinea infections
Blastomyces dermatitidis, Histoplasma capsulatum are difficult b. Clioquinol (Vioform)
to treat & life-threatening § substitute for lodoform
§ for eczema, psoriasis
OPPORTUNISTIC FUNGAL INFECTIONS § 3% ointment/cream as treatment
— a new category of systemic mycoses for Trichomonas vaginalis
— Candida Albicans à member of normal microbial flora of vaginitis
human hosts especially in vagina. Use of contraceptives often § best to be used for treatment of
predisposes a patient to infection by Candida spp. athlete’s foot & jock itch
— Opportunists can grow in immunocompromised patients NUCLEOSIDE ANTIFUNGALS
— Oral candidiasis is common in poorly nourished person, in a. FLUCYTOSINE
patients on immunosuppressive drugs & in persons with AIDS • Treatment for serious systemic infections (Candida
& Cryptococcus sp)
CUTANEOUS INFECTIONS (Dermatophytoses) b. FUNGAL RESISTANCE TO 5-FC
— most common types of human fungal disease • transport system impermeable to 5-FC
— Superficial infections of keratinized epidermis & keratinized • cytosine deaminase
epidermal appendages (hair & nails) • UMP pyrophosphorylate reaction
— Severity of infection depends on: location of lesion & species of
fungus involved ANTIFUNGAL ANTIBIOTICS
— Dermatophytes is responsible for most cases — microbes that has ability to inhibit growth of other microbes
— Tinea Versicolor à caused by Pityosporum orbiculare — 2 classes:
(Malassezia furfur); causes yellow to brown patches or a. Polyenes
continuous scaling over the trunk (legs, face & neck) • 2 groups based on the size of macrolide ring:
— 26- membered-ring polyenes= Natamycin
LOCATIONS OF THE COMMON TYPES OF TINEA — 38-membered-macrocycles =
TYPE LOCATION Amphotericin B & Nystatin

Tinea Manuum Hand
AMPHOTERICIN B (Fungizone)
Tinea Cruris Groin — only polyene useful for treatment of serious
systemic infections
Tinea Sycosis Beard
— from Streptomyces nodosus
Tinea Capitis Scalp — Amphoteric substance with primary amino group
— other polyenes à only for superficial fungal
Tinea Unguium Nails
infections
Tinea Corporis Whole body — causes nephrotoxicity
— A/E: Fever, headache, anorexia, GI distress, malaise,
SUBCUTANEOUS FUNGAL INFECTIONS muscle & joint pain

— topically to treat cutaneous & mucocutaneous • creams, powders, aerosis, gels & solutions for
mycoses caused by C. albicans treatment of ringworm, jock itch & athlete’s foot
— given by slow IV infusion
— for fungal infections of CNS (Cryptococcosis), AZOLE ANTIFUNGAL AGENTS
Amphotericin B is mixed with CSF obtained from — synthetic antifungals
spinal tap. Solution of Amphotericin B is reinjected — effective against most fungi that cause superficial infections of
through the tap skin & mucous membranes including dermatophytes
— MOA: penetrate the fungal cell membrane, acting as — also against yeasts that cause treatment of refractory
false membrane components & bind closely with ringworm infections of the body, hair, nails & feet by systemic
ergosterol causing membrane disruption route caused by dermatophytes
— Parenteral Amphotericin B — SAR: weakly basic imidazole or 1,2,4-triazole ring bonded by
§ treatment of severe, potentially life- nitrogen-carbon linkage to the rest of the structure
threatening infections including
disseminated forms of 2 groups of azoles:
coccidioidomycosis & histoplasmosis • IMIDAZOLES à largest group: clotrimazole,
Amphotericin B for injection econazole, butoconazole, sulconazole, oxiconazole,
§ supplied as sterile lyophilized cake or tioconazole, miconazole, ketoconazole
powder containing 50mg abx with 41mg • TRIAZOLES à new azoles, terconazole, itraconazole,
of Na deoxycholate to be dispersed in fluconazole
10ml h20
§ suspension should be freshly prepared & CLOTRIMAZOLE (Canesten)
used within 24hrs • broad-spectrum antifungal drug used for
treatment of tinea infections &
NYSTATIN (Mycostatin) candidiasis
— Streptomyces noursei • for tinea infections & cutaneous
— aglycone portion = nystatinolide candidiasis
— used only as topical agents • vagina cream & tablets = vulvovaginal
— treatment of local & GI monilial infections candidiasis
caued by Candida sp • causes sever GI disturbances
— Nystatin + Tetracycline = prevent monilial
overgrowth ECONAZOLE NITRATE (Pevaryl)
• for topical treatment of local tinea
AMPHOTERICIN B & NYSTATIN infections & cutaneous candidiasis
— MOA: cause potassium leakage at low,
fungistatic concentration & cell lysis at high, BUTOCONAZOLE NITRATE
fungicidal concentraions • effective against Candida Albicans

• vaginal cream = treatment of vaginal
NATAMYCIN (Natacyn)
candidiasis
— Streptomyces natalensis

— MOA: both potassium ion leakge (fungistatic) &
SULCONAZOLE NITRATE (Exelderm)
cell lysis (fungicidal) at same concentration
• solution & cream in 1% concentration for
— 5% ophthalmic suspension = treatment of
local tinea infections (jock itch, athlete’s
fungal conjunctivitis, blepharitis & keratitis
foot, ringworm)

b. Griseofulvin
OXICONAZOLE NITRATE (Oxistat)
— Penicillium griseofulvum (fungus)
• 1% concentration in cream & lotion for
— treatment of refractory ringworm infections of
tinea pedis, tinea corporis & tinea capitis
the body, hair, nails & feet by systemic route

caused by dermatophytes
TIOCONAZOLE (Trosyd)
— MOA: concentrates at keratin precursor cells
found in nails, skin & hair which are gradually • treatment of vulvovaginal candidiasis
exfoliated & replaced by new tissues • more effective against Torulopsis glabrata
— A/E: rash, urticarial, GI upset, headache, than other azoles
dizziness, insomnia
— take drug with fatty meal to increase MICONAZOLE NITRATE (Monistat, Daktarin,
absorption Micatin)
• treatment of serious systemic fungal
ALLYLAMINES AND RELATED COMPOUNDS infections (candidiasis, cryptococcosis)
— MOA: interfere with fungal ergosterol biosynthesis at an early • treatment of chronic mucocutaneous
stage, namely epoxidation of squalene catalyzed by the enzyme candidiasis
squalene epoxidase. Inhibition of enzyme causes accumulation
of squalene which in turn, damages fungal cell membrane KETOCONAZOLE (Nizoral)
• treatment of systemic fungal infections
1. NAFTIFINE HYDROCHLORIDE (Naftin) • A/E: hepatoxicity
• cream & gel for topical treatment of ringworm, • Ketoconazole + amphotericin B =
athlete’s foot & jock itch antagonize
2. TERBINAFINE HYDROCHLORIDE (Lamisil)
• topical administration of treatment of tinea pedis, TERCONAZOLE (Terazol)
tinea corporis & tinea cruris • control of vulvovaginal moniliasis caused
• more potent than naftifine by candida albicans
3. TOINAFTATE (Tinactin)
• fungicidal against dermatophytes ITRACONAZOLE (Sporanox)
• not an allylamine, inhibits squalene epoxidase & has • alternative to ketoconazole
spectrum of activity similar to allylamines • acidic environment for optimum
solubilization & oral absorption
• treatment of systemic fungal infections
• more effective and better tolerated than
ketoconazole

FLUCONAZOLE (Diflucan)
• treatment of deep organ candidiasis,
esophageal & oropharyngeal candidiasis
• agents of choice for cryptococcal
meningitis & prophylaxis against
cryptococcosis in AIDS patient

ECHINOCANADINS & PNEUMOCANADINS
• act as noncompetitive inhibitors of (1,3)-
B-d, glucan sysnthase

AUREOBASIDINS
— Aureobasidin A: acts as a tight-binding
noncompetitive inhibitor of enzyme

ADVERSE DRUG REACTIONS

• 5% of adults are allergic to one or more medications
• 6-10% of ADRs result from a drug allergy
• 3% of hospital admission are due to ADRs
• 28% of ADRs are preventable
• drugs associated with ADRs: 29% analgesics, 10% sedatives,
9% antibiotics & 7% antipsychotics
§ Propranolol – bronchial asthma
ADRs: 4th leading cause of death § Tetracycline – hypoplasia of the teeth
Study: Drug reactions kill an estimated 100,000 a year
• April 14, 1998 Examples of Bizarre reactions:
§ Hypersensitivity reactions
ADVERSE DRUG REACTIONS (ADRs) § Stevens-Johnson’s Syndrome
— any response to a drug which is noxious & unintended and § Hemolytic anemia
which occurs at doses used in man for prophylaxis, diagnosis
or therapy • TYPE C (CONTINUOUS)
ADVERSE DRUG EXPERIENCE — long term effects are usually related to the dose &
— an undesirable drug effect, whether harmless, resulting from duration of treatment
medications administered in a dosage normally given Examples: Ethambutol (causes neuritis) & NSAIDs (reduces
— it becomes an adverse drug reaction when it is reported & inflammation & blocks pain)
subsequently evaluated to be secondary to the drug usage
• TYPE D (DELAY)
KEY POINTS TO REMEMBER (ADRs) — Teratogenic (formation of monster/deformities)
• are undesirable — Carcinogenic (formation of cancer cells)
• are unintentional Examples: Thalidomide & Vitamin A (not allowed for
• are suspected (not necessarily proven) pregnant women because it will cause birth defects)
• may develop as a consequence of therapy for other procedures
• TYPE E (ENDING OF USE)
*The WHO definition of ADR does not necessarily include: — withdrawal syndromes
à drugs administered or taken in error Examples:
à drugs given by erroneous method § Benzodiazepines – rebound insomnia, agitattion
§ Clonidine – rebound hypertension
FACTORS AFFECTING ADVERSE DRUG REACTIONS: § Corticosteroids – acute adrenal insuffiency
• Patient-related factors § Opioids – narcotic withdrawal
— age
— sex • TYPE F (FAILURE OF EFFICACY)
— genetic influences — Counterfeit medicines
— concurrent diseases (renal, liver, cardiac) — Underdosing of medications
— previous adverse drug reactions — Drug Interactions
— compliance with dosing regimen
— total number of medications WHY REPORT ADRs?
— misc (diet, smoking, environmental exposure) — To prevent drug-induced human suffering
— To avoid financial risks associated with unexpected risks
• Drug-related factors
— dose IMPORTANT:
— duration • The ADR Report form should include the following:
— inherent toxicity of the agent — the brand name of the suspect drug
— pharmacodynamics properties — the manufacturer (if generic)
— pharmacokinetic properties — the lot and batch number
— it should be done in duplicate
SIX CLASSIFICATIONS OF ADR — all reports are confidential
• TYPE A (AUGMENTED)
TEN COMMNANDMENTS TO REDUCE ADRs:
Extension effects: I. Critically review the total condition of the patient. Be
— predictable particularly careful when you prescribe to children,
— dose-related responses elderly, seriously ill, pregnant patients & those with renal,
— prevention: Adjustment of dosage regimen cardiac or lover diseases
Examples: II. Use as few drugs as possible. Balance the seriousness of
§ Benzodiazepines – sedation possible reactions against the beneficial effects of each
§ Furosemide – water & electrolyte imbalance drug that is being considered
§ Heparin, warfarin – spontaneous bleeding III. Know well the drugs that you use. Compare efficacy &
§ Insulin – hypoglycemia safety of each of the available competitive medications
that appear to be worthy of consideration for the patient.
• TYPE B (BIZARRE) IV. Do not change too readily from one drug you know to one
— abnormal effects, unrelated from the drug’s you do not know. If you decide to use a new drug, know
unknown pharmacological actions that drug.
— characteristics: V. Do not hesitate to use textbooks & other references
§ no formal dose-response curve (penicillin providing information on drug reaction & interaction.
hypersensitivity – anaphylaxis) VI. Be especially careful when prescribing drugs known to
§ reaction disappears on discontinuation of exhibit a large variety of reactions/interactions.
the drug VII. Be aware of interactions with certain foods, alcohol &
§ recognizable as an immunological even with household chemicals
reaction VIII. Regularly make an inventory of the drugs.
§ undetectable during conventional testing IX. Review your patient regularly for all the drug used &
§ little or no relation to the usual especially those bought without prescriptions.
pharmacological effects of the drug X. If your patient shows signs & symptoms not clearly
Examples: explained by the course of illness, think of adverse drug
§ INH, Rifampicin, PZA – hepatoxicity reaction.
§ Streptomycin – ototoxicity, nephrotoxicity
§ Captopril – cough DRUG INTERACTIONS
§ Simvastatin – rhabdomyolysis — a reaction that occurs when two drugs are taken
§ Nitrates – headache simultaneously
— Types: Pharmacokinetic & Pharmacodynamic interactions

MARILYN MONROE 3 MAJORS MANIFESTATIONS OF INFLAMMATION:
§ Chloral Hydrate • Rubor (Redness)
§ Pentobarbital (sedative) • Calor (Heat)
JIMI HENDRIX • Tumor (Swelling)
§ Brallobarbital Sedatives, Anticonvulsants • Dolor (Pain)
§ Secobarbital • Loss of function/disturbance of function
§ Hydroxyzine (Anti-allergy)
BRUCE LEE After a person is injured, chemical substances called Mediators of
§ Meprobamate (NSAIDs) inflammation:
§ Aspirin 1. Histamine
ELVIS PRESLY 2. Kinins
§ Methaqualone 3. PG’s (Prostaglandins)
§ Codeine 4. Leukotrienes (LT)
§ Barbiturates
§ Cocaine • Some mediators induce dilation of blood vessels & produce the
KURT COBAINE symptoms of redness & heat
§ Heroin • Also stimulate pain receptors & increase the permeability of
§ Diazepam (sedative-hypnotic) blood vessels (Nociception)
EDDIE GUERRERO • Sometimes the inflammatory response last longer or is more
§ anabolic steroids (stanozolol, HCG) intense then is desirable & drugs are used to suppress the
CHRIS BENOIT symptoms
§ Alprazolam
§ Hydrocodone 1. Antihistamines – blocks the effect of histamine
§ Hydromorphone 2. Aspirin – prevents the synthesis of PG’s; prototype all NSAIDs,
GEORGE BEST analgesic & antipyretic activity
§ Ethanol 3. Cortisone – reduces the release of several mediators of
HEATH LEDGER inflammation
§ Oxycodone - corticosteroids is capable of retaining water
§ Hydrocodone resulting edema
§ Alprazolam side effects: immunocompromizatio of the
§ Diazepam immune system/lowering of the immune
§ Temazepam system & capable of retaining water therefore
§ Doxylamine causing edema
MICHAEL JACKSON
§ Propofol (anesthetic drug) *HISTAMINE à a neurotransmitter that would cause bronchoconstriction
§ Midazolam
§ Lidocaine • IMMUNE RESPONSE occurs when immunologically competent
§ Diazepam
cells are activated in response to foreign organisms or
§ Lorazepam
antigenic substances liberated during the acute or chronic
WHITNEY HOUSTON
inflammatory response
§ Cocaine
• the outcome of the immune response for the host may be
§ Flexeril
beneficial as when it causes invading organisms to be
§ Marijuana
phagocytosed or neutralized
§ Alprazolam
• on the other hand, the outcome may be deleterious if it leads to
§ Diphenhydramine
chronic inflammation without resolution of the underlying
AMY WINEHOUSE
injurious process
§ Ethanol
• Cell damage associated with inflammation acts on cell
PHILIP SEYMOUR HOFFMAN
membrane to cause leukocytes to release lysosomal enzymes:
§ Heroin
arachidonic acid (fatty acids) is the liberated from precursor
§ Cocaine
compounds & various licosanoids are synthesized
§ Benzodiazepine

§ Amphetamine
CORY MONTEITH
§ Heroin
§ Alcohol

*sedative uses: lack of sleep & anxiety issues

NONSTEROIDAL ANTI-INFLAMMATORY
DRUGS

INFLAMMATION/INFLAMMATORY RESPONSE
— occurs when tissues are damaged

AGENTS WHICH CAN CAUSE INJURY:
1. Microorganisms
2. Cold
3. Heat
4. Radiant Energy
5. Chemicals
6. Electricity
— irreversible acetylates & blocks platelet cyclooxygenase, while
most non-COX-seletive NSAIDs are reversible inhibitors

• Selective COX-2 inhibitors do not affect platelet function at
their usual doses
• COX-2 can cause increase CVS thrombotic events
• CELECOXIB has an FDA-initiated “black box” warning
concerning CV risks
• All newer NSAIDs are analgesic, anti-inflammatory & antipyretic
and all (except the COX-2-selective agents & the nonacetylated
salicylates) inhibit platelet aggregation
• NSAIDs are all gastric irritants & can be associated with GI
ulcers & bleeds as well, although newer agents tend to cause less
GI irritation than aspirin
• HEPATOTOXICITY has been observed for all the drugs; Major
issue for NSAIDs
• Several NSAIDs (including aspirin) appear to reduce the induce
of colon cancer when taken chronically

Sir Jace’s explanation: Arachidonic Acid is an essential fatty acid (other two *COX-2 is safe to take when you do not eat food while NONSPECIFIC
fatty acids needed for homeostasiss: Linolenic & Linoleic Acid). Arachidonic NSAIDs are not safe to be taken without food
Acid is the precursor for the production of PG’s. COX2 is responsible for pain
& inflammation while COX-1 is responsible for kidney, GI tract, brain, COMMON ADVERSE DRUG REACTIONS:
nausea, vascular tone & pain. COX-2 is for pain & inflammation while 1. CNS: headache, tinnitus & dizziness
COX-1 is for homeostasis 2. CV: fluid retention, HTN, edema, rarely CHF
3. GI: abdominal pain, dysplasia, N/V & rarely ulcers or bleeding
linolenic & linoleic acid à obtained from coconut oil 4. HEMATOLOGIC: rare thrombocytopenia, neutropenia or
arachidonic acid à obtained from peanuts aplastic anemia
à precursor for production of PGs 5. HEPATIC: abnormal liver function tests & rare liver failure,
Cyclooxygenase à produce PGs 6. PULMONARY: asthma
Lipoxygenase enzyme à yields leukotrienes 7. RASHES: all types, pruritus
8. RENAL: renal insufficiency, renal failure, hyperkalemia &
Treatment of patients with inflammation involve two primary goals: proteinuria
A. The relief of symptoms & the maintenance of function
B. The slowing or arrest of the tissue-damaging process *TINNITUS à ringing of your ears

GLUCOCORTICOIDS • with higher doses, may experience:
— have powerful anti-inflammatory effects & when 1st introduced SALICYLISM: vomiting, tinnitus, decreased hearing, vertigo
were considered to be the ultimate answer to the treatment of salicylic acid à aspirin (rarely used as an anti-inflammatory
inflammatory arthritis medication)

DMARDs (Disease-modifying antirheumatic drugs) *SALICYLISM caused by over dosage & reversible
— agents used to treat rheumatoid arthritis
— they decreases inflammation, usually improve symptoms & MECHANISM OF ACTION
slow the bone damage associated with rheumatoid arthritis 1. Anti-inflammatory effects
1. Late-onset — non-selective inhibitor of both COX isoforms
2. Early-onset (Juvenile Arthritis) — aspirin irreversible inhibits COX & inhibits platelet
aggregation
*first line of drug used for arthritic conditions: ACETAMINOPHEN 2. Analgesic effects
(PARACETAMOL) — aspirin is most effective in reducing mild to
moderate pain
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
— other similar agents used to treat rheumatic disease suppress CLINICAL USES
the signs & symptoms of inflammation • antipyresis, anti-inflammatory effects
— these drugs also exert antipyretic & analgesic effects, but is — decreases the incidence of TIA, unstable angina,
their anti-inflammatory properties that make them most useful coronary artery thrombosis with MI, thrombosis
after coronary artery bypass grafting
1st drug used for arthritic conditions à ACETAMINOPHEN — long-term use at low dosage is associated with lower
incidence of colon cancer
NABUMETONE à a ketone prodrug
• all NSAIDs are weak acids except NABUMETONE NONACETYLATED SALICYLATES
— magnesium choline salicylates, sodium salicylate & salicyl
salicylate
NSAIDs is mediated chiefly through inhibition of biosynthesis of PGs — all nonacetylated salicylates are effective anti-inflammatory
• additional possible mechanisms of action: drugs, although they may be less effective than analgesics than
1. Inhibition of chemotaxis aspirin
2. Down-regulation of interleukin-1 pro
3. Decreases production of free radicals • CELECOXIB
4. Superoxides • ETORICOXIB
5. Interference with calcium-mediated intracellular events — bipyridine derivative
— 2nd generation COX-2 selective inhibitor with the
highest selectively ratio of any coxib for inhibition of
ASPIRIN COX-2
— prototype — extensively metabolized by hepatic P450 enzymes
— elimination half-life of 22 hours

• MELOXICAM • KETOPROFEN
• VALDECOXIB • KETOROLAC
— diaryl-substituted isoxazole, a new highly selective
COX-2 inhibitor • FENOPROFEN
— has no effect on platelet aggregation or bleeding • MECLOFENAMATE & MEFENAMIC ACID
time • PHENYLBUTAZONE
— was withdrawn from the market in early 2005 • TENOXICAM
because of cardiovascular risks & Stevens- • TIAPROFEN
Johnsons syndrome

COXIBS GENERAL ANESTHETICS & LOCAL
— Selectively bind to & block the active site of the COX-2 enzyme ANESTHETICS
much more effectively than that of COX-1
— COX-2 inhibitors have analgesic, antipyretic & anti-
inflammatory effects & have no impact on platelet aggregation ANALGESIA
— a selective COX-2 inhibtor – about 10-20 time more selective — A state of decreased awareness of pain & sometimes with
for COX-2 than for COX-1 amnesia
— associated with fewer endoscopic ulcers than most other GENERAL ANESTHETICS
NSAIDs. Probably because it is a sulfonamide, celecoxib may — A state characterized by unconsciousness, analgesia, amnesia,
cause rashes skeletal muscle relaxation & loss of reflexes
— it does not affect platelet aggregation at usual does
— it interacts occasionally with warfarin as would be expected of STAGE OF ANESTHESIA
a drug metabolized via CYP2C9 1. Analgesia
• analgesia without amnesia
NONSTEROIDAL DRUGS THAT TARGET BOTH COX-1 & COX-2: 2. Excitement
• DICLOFENAC • amnesia, hyperactivity, irregular respiration
— A phenylacetic acid derivative that is relatively 3. Surgical Anesthesia
nonselective as a COX inhibitor • sleep, normal respiration & blood pressure
— GI ulceration may occur less frequently 4. Medullary Depression
— a preparation combining diclofenac & misoprostol • depression of vasomotor & respiratory center (coma
decrease upper GI ulceration but may result in & death)
diarrhea TYPES OF ANESTHESIA
— a 0.1% ophthalmic preparation is recommended for 1. Intravenous Anesthetics
prevention of postoperative ophthalmic a. Barbiturates
inflammation & can be used after intraocular lens - Thiopental (Component for lethal injection & used as
implantation & strabismus surgery truth serum), Methohexital
— a topical agent gel containing 3% diclofenac is b. Benzodiazepines
effective for solar keratosis - Midazolam, Diazepam
— Diclofenac in rectal suppository form can be c. Propofol
considered for preemptive analgesia & d. Ketamine
postoperative nausea e. Opioid
— derived from salicylic acid, it is not metabolized to - Morphine, Fentanyl, Sulfentanil, Alfentanil,
salicylic acid/salicylate Remifentanil
— effective for cancer pain with bone metastases 7 f. Miscellaneous Sedative-hyponotics
for pain control in 3M surgery - Etomidate, Droperidol, Dexmedetomidine

*DICLOFENAC & MISOPROSTOL are used to decrease ulceration 2. Inhaler Anesthetics
*MISOPROSTOL is anti-histamine which will lower the secretion of a. Volatile Liquids
gastric acid (brand name: CYTOTECH) - Halothane, Enflurane, Methoxyflurane, Isoflurane,
Desflurane, Sevoflurane
• DIFLUNISAL
• ETODOLAC b. Gas
— a racemic acetic acid derivative with an - nitrous oxide
intermediate half-life a. Low doses à Laughing gas
— does not undergo chiral inversion in the body b. High doses à Will put you into sleep in a
— the dosage of etodolac is 200-400 mg three to 4x matter of 3 seconds
daily
— provides good postoperative pain relief after Mechanism of action: Depress electrical activity of neurons interaction of
coronary artery bypass oprations anesthetic with lipid cell membrane (Meyer-Overton Principles) with
• FLURBIPROFEN increase fluidity
— is a propionic acid derivative - act on specific receptors (GABA)
— its (S)(-) enantiomer inhibits COX nonselective
— hepatic metabolism is extensive UPTAKE & DISTRIBUTION OF INHALED ANESTHETICS
— its ®(+) & (S)(-) enantiomers are nonmetabolized — Solubility
differently — Pulmonary Ventilation
— it does not undergo chiral conversion — Pulmonary Blood flow
• IBUPROFEN — Arteriovenous Concentration gradient
— simple derivative of phenylpropionic acid
— maximum doses: 2400mg/daily NITROUS OXIDE
— Oral ibuprofen is often prescribed in lower doses — Possess low solubility in blood, reaches high arterial tension
(<2400 mg/d) at which it has analgesic but not anti- rapidly & in rapid equilibrium with the brain & fast onset of
inflammatory efficacy action
— a rapid of anesthetics action is also characteristics of
*maximum dose for paracetamol: 6000mg/day or 6g desflurane & to a lesser extent with sevoflurane
• INDOMETHACIN
ORGANS AFFECTED BY ANESTHESIA
— brain, heart, liver, kidneys & splanchnic bed § recovery is sufficiently rapid with most IV drugs to permit
their use for short ambulatory (outpatient) surgical
procedures
ELIMINATION § most IV anesthetics lack antinociceptive (analgesic) properties
• primary route of elimination: LUNGS § their potency is adequate for short superficial surgical
• primary route of metabolism: LIVER procedures when combined with nitrous oxide or local
anesthetics or both
Rank order for the inhaled anesthetics: § Adjunctive use of potent opioids (ex: fentanyl, sulfentanil or
Methoxyflurane > halothane > enflurane > sevoflurane > isoflurane > remifentanil) contributes to improved CV solubility, enhanced
desflurane > nitrous oxide sedation
GENERAL ANESTHETICS EFFECTS:
I. CNS BARBITURATES
• motor & autonomic systems are inhibited § THIOPENTAL is a barbiturate commonly used for induction of
• respiratory function depressed via CNS anesthesia
• cerebral blood flow increases § THIAMYLAL is structurally almost identical to thiopental &
II. CVS has the same pharmacokinetic & pharmacodynamics profile
• blood pressure may decrease or increase § after an IV injection, thiopental rapidly crosses the BBB (Blood
• adrenal medullary secretion brain barrier) & if given in sufficient dosage, produces loss of
III. SALIVARY & BRONCHIAL SECRETIONS INCREASED consciousness in one circulation time
• inhalation anesthetics irritate mucosal cells § similar effects occur with methohexital
• results in coughing & laryngeal spasms
IV. SKELETAL MUSCLE BENZODIAZEPINES
§ DIAZEPAM, LORAZEPAM & MIDAZOLAM are used for
• depression of reflexes
preanesthetic medication & as adjuvants during surgical
§ via effect on pyramidal systems
procedures performed under local anesthesia
§ by inhibiting activity at
§ as a result of their sedative, anxiolytic & amnestic properties &
neuromuscular junction
their ability to control acute agitation these compounds are
V. LIVER
considered to be the drugs of choice for premedication
§ hepatotoxicity associated with some

anesthetics à halothane, enflurane, chloroform
OPIOID ANALGESICS
§ jaundice & liver necrosis
§ Produce morphine-like effects
VI. EFFECT OF DRUG REDISTRIBUTION
§ types:
§ highly lipid-soluble drugs may be stored in
1. Synthetic
adipose tissue – slows elimination
2. Semi-synthetic
§ redistribution into brain may occur --- residual
3. Natural
confusion & lethargy
§ receptors: Mu, Kappa & Delta
VII. EFFECTS ON THE KIDNEY
§ depending on the concentration, volatile
anesthetics decrease the glomerular filtration
rate & renal blood glow & increase the
filtration fraction
VIII. EFFECTS ON UTERINE SMOOTH MUSCLE
§ Nitrous oxide have little effect on uterine
musculature
§ Halogenated anesthetics are potent uterine
muscle relaxants

GENERAL ANESTHESIA
v Induction of anesthesia (stages 1 & 2)
v Maintenance of anesthesia (stage 3)
BALANCED ANESTHESIA
— pre-operative medication for sedation & analgesia
— neuromuscular blockers during surgery
— combination of inhaled & IV anesthetics generally used

IX. TOXICITY
§ Hepatotoxicity (Halothane)
§ Nephrotoxicity
§ Malignant Hyperthermia
X. CHRONIC TOXICITY
§ MUTAGENICITY
— under normal conditions, inhaled anesthetics
— are neither mutagens nor carcinogens in patients
§ CARCINOGENICITY
— increase in the cancer rate in OR personnel who were exposed
to trace concentrations of anesthetic agents
XI. EFEFCTS ON REPRODUCTIVE ORGANS
— higher incidence of miscarriages, abortions
XII. HEMATOTOXICITY
— prolonged exposure to nitrous oxide decreases methionine
synthase activity & theoretically can cause megaloblastic
anemia (enlargement of RBCs; chocolate brown)
IV ANESTHETICS
§ IV agents are commonly used for induction of general
anesthesia

§ Crosses BBB (blood brain barrier)
§ Converted to Morphine in the body

OXYCODONE & OXYMORPHONE
§ Treatment for moderate to severe pain
§ Twice the analgesic effect to morphine

CODEINE
§ Only 30% analgesic activity compared to morphine
§ used for cough but replaced by dextromethorphan

PENTAZOCINE
§ Agonist on the kappa receptors
§ relieve moderate pain
§ can precipitate a withdrawal syndrome for morphine abuser

NALBUPHINE & BUTORPHANOL
§ Treatment for chronic pain
§ Mimics the symptoms of psychosis
§ Ceiling effect for respiratory depression

TRAMADOL
§ Binds to Mu receptors
§ Lesser respiratory depression to morphine
§ Causes CNS excitation à seizure
§ will test positive for Marijuana

TAPENTADOL
§ binds to mu receptors
*CODEINE à moderate/slow agonist § NE reuptake blocker
§ For the management of moderate to severe pain, both chronic
MORPHINE & acute
§ Actions: § another drug of choice when Tramadol is not
- Analgesia available/substitute for Tramadol
• Raise the pain threshold, alter brain perception
- Euphoria NALOXONE
• disinhibition of dopamine-containing neurons § Reverse coma & respiratory depression in opioid overdose
- Respiratory Depression § Reverse the effects of morphine
- Depression of cough reflex § Competitive Antagonist at the mu, kappa & delta receptors
• Activation of anti-tussive receptors
- Miosis PROPOFOL
- Emesis § 2,6-DIISOPROPYLPHENOL
- Relaxation of GI tract § Has become the most popular IV anesthetics
- Hypotension & bradycardia § used for both induction & maintenance of anesthesia as part of
- Histamine release total IV or balanced anesthesia techniques
- Release of prolactin § agents of choice for ambulatory surgery
- Prolong labor § available in vial dosage forms
§ Therapeutic uses:
- analgesia ETOMIDATE
- Treat diarrhea § A carboxylated imidazole
- Relief of cough § for induction of anesthesia in patients with limited CV reserve
- Treat acute pulmonary edema § its major advantage is that is causes minimal CV & respiratory
MEPERIDINE depression
§ binds to Mu & Kappa receptors
§ Therapeutic uses: Analgesic & not effective for diarrhea &
cough KETAMINE
§ It produces a dissociative anesthetic state characterized by
METHADONE catatonia, amnesia, analgesia with or without loss of
§ Binds to Mu receptors, antagonist of N-methyl-D-aspartate consciousness (hypnosis)
(NMDA) receptor § only IV anesthetic that possesses both analgesic properties &
§ Therapeutic uses: the ability to produce dose-related CV stimulation
- Analgesic in nociception & neurogenic pain § used as tranquilizers for big animals
- Treatment by controlled withdrawal of heroin &
morphine dependency

FENTANYL LOCAL ANESTHETICS
§ Epidural à induce anesthesia & analgesia posroperatively — is the condition that results when sensory transmission from a
§ Transmucosal preparation for patients with cancer who are local area of the body to the CNS is blocked
tolerant to other opioids — can be administered locally by topical application or by injection
in the target area, the anesthetic effect can be restricted to a
SULFENTANIL, ALFENTANIL, REMIFENTANIL localized area
§ Sulfentanil à more potent than fentanyl
§ Alfentanil, Remifentanil à less potent, shorter acting

HEROIN
§ Diacetylmorphine
- nystagmus & muscular twitching
LOCAL ANESTHETICS - tonic-clonic convulsions
§ CVS
- local anesthetics block cardiac sodium channesl & this
depress abnormal cardiac peacemaker activity, excitability &
conduction
ESTERS AMIDES

DOSAGE FORMS

— are the means (or the form) by which drug molecules are
delivered to sites of action within the body
LONG SHORT SURFACE MEDIUM LONG
ACTION ACTION ACTION ACTION ACTION The need for dosage forms:
1. Accurate Dose
2. Protection (coated tablets, sealed ampules)
LIDOCAINE BUPIVACAINE 3. Protection from gastric juice
PROCAINE BENZOCAINE MEPRIVACAINE ROPIVACAINE 4. Masking taste & odour
ARTICAINE LEVOBUPIVACAINE
COCAINE 5. Placement of drugs within the body tissues
(Medium)
6. Sustained release medication
7. Controlled release medication
8. Optimal drug action
— Vasoconstrictor substances such as EP reduce systemic 9. Insertion of drugs into body cavities (rectal, vaginal)
absorption of local anesthetics from the injection site by 10. Use of desired vehicle for insoluble drugs
decreasing blood flow in these areas
— This is important for drugs with intermediate or short They are classified according to:
durations of action such as procaine, lidocaine &
mepivacaine (but not prilocaine)
— When used in spinal anesthesia, EP acts directly on the cord to
both enhance & prolong local anesthetic-induced spinal
anesthesia by acting on a2 adrenoreceptors which inhibit
release of substance P (neurokinin-1) and reduce sensation
neuron firing ROUTE OF ADMINISTRATION PHYSICAL FORM
Oral Solid
METABOLISM & EXCRETION Topical Semisolid
— The local anesthetics are converted in the liver (amide type) or Rectal Liquid
in plasma (ester type) to more water-soluble metabolites Parenteral Gaseous
which are excreted in the urine Vaginal
— Acidification or urine promotes ionization of the tertiary amine Inhaled
base to the more water-soluble charged from leading to more Ophthalmic
rapid elimination Optic
— Ester-type local anesthetics are hydrolyzed very rapidly in the
blood by circulating butyrylchlinesterase
(pseudocholinesterase) to inactive metabolites TYPES OF ORAL DOSAGE FORMS:
MECHANISM OF ACTION
— block voltage-dependent channels & reduce the influx of 1. TABLET
sodium ions, thereby preventing depolarization of the • is a hard, compressed medication in round, oval or
membrane & blocking conduction of the action potential squared shaped
COCAINE • solid dosage form containing unit dose of one or
— the first local anesthetic introduced into medical practice more medication
— Isolated by Niemann in 1860 & introduced into practice by • prepared by mould method or compression method
Koller in 1884 as a topical opthlamic anesthetic
— The only local anesthetic drug available for 30 years The excipients include:
— Einhorn in 1905 synthesized procaine which became the - binders, glidants (flow aids) & lubricants to
dominant local anesthetic for the next 50 years ensure efficient tableting
— first drug used during Napoleonic war - disintegrants to ensure that the tablet breaks
— LIDOCAINE was synthesized in 1943 by Lofgren up in the digestive tract
— COCAINE has intrinsic sympathomimetic action due to its - sweeteners or flavours to mask the taste of
inhibition of NE reuptake into nerve terminal & possesses high bad-tasting active ingredients
surface (topical) activity - pigments make uncoated tablets visually
attractive
The onset of local anesthesia can be accelerated by the addition of sodium A coating may be applied to:
bicarbonate to the local anesthetic solution a. Hide the taste of the tablet’s components
b. Make the tablet smoother & easier to swallow
SYSTEMIC LOCAL ANESTHETIC DRUGS (LA DRUGS) are commonly used c. Make it more resistant to the environment
as adjuvants to the combination of tricyclic antidepressant (Amitripyline) d. Extending its shelf life
& an anticonvulsant (Carbamazepine) in patients who fail to respond to the
combination of antidepressant & anticonvulsant A. BUCCAL & SUBLINGUAL TABLET
• Sublingual & buccal medication are administered
TOXICITY by placing them in the mouth, either under the
§ CNS tongue (sublingual) or between the gum & the cheek
- sleepiness (buccal)
- light-headedness or sedation
• the medications dissolve rapidly & are absorbed
- visual & auditory disturbances
through the mucous membranes of the mouth,
- circumoral & tongue numbness
where they enter into the bloodstream
- metallic taste
- restlessness
• avoid the acid & enzymatic environment of the • the mixed powders may be stored in dry form &
stomach & the drug metabolizing enzymes of the mixture prepared by the pharmacist when required
liver for dispensing, by suspending the powder in the
examples of drugs administered by this route: appropriate vehicle
Vasodilators, steroidal hormones
B. EFFERVESCENT TABLET A. BULK POWDERS
• are uncoated tablets that generally contain acid § are multidose preparations
substances (citric & tartaric acids) & carbonates or consisting of solid, loose, dry
bicarbonates & which react rapidly in the presence particles of varying degrees of
of water by releasing carbon dioxide fineness-contain one or more active
• they are intended to be dissolved or dispersed in ingredients with or without
water before use providing: excipients and if necessary coloring
1. Very rapid tablet dispersion & dissolution matter & flavoring substances
2. Pleasant tasting carbonated drink § usually contain non-potent
medicaments such as antacids since
C. CHEWABLE TABLET the patient measures a dose by
• they are tablets that chewed prior to swallowing volume using a 5ml medicine spoon.
• they are designed for administration to children (ex: The powder is then usually
vitamin products) dispersed in water or in the case of
effervescent powders dissolved
2. CAPSULE before taking
• a medication in a gelatin container 9. LIQUID PREPARATION
• solid dosage form A. ORAL SOLUTION
ADVANTAGE: Mask the unpleasant taste of its • oral solutions are clear liquid preparation for
contents oral use containing one or more active
ingredients dissolved in a suitable vehicle
THE TWO MAIN TYPES OF CAPSULES ARE: B. ORAL EMULSION
a. Hard-shelled capsules • oral emulsions are stabilized oil-in-water
§ are normally used for dry, powdered dispersions, either or both phases of which
ingredients may contain dissolved solids either oil is finely
b. Soft-shelled capsules divided in water or vice versa
§ primarily used for oils & for active C. ORAL SUSPENSION
ingredients that are dissolved or • liquid preparation for oral use containing one
suspended in oil or more active ingredients suspended in a
3. LOZENGE suitable vehicle
• a solid preparation consisting of sugar & gum, the • may show a sediment which is readily
latter giving strength & cohesiveness to the lozenge dispersed on shaking to give a uniform
& facilitating slow release of the medicament suspensions which remains sufficiently stable
• it is used to medicate the mouth & throat for the to enable the correct dose to be delivered
slow administration of indigestion or cough D. SYRUP
remedies • it is a concentrated aqueous solution of a sugar,
4. PASTILLES usually sucrose to which medicaments are
• they are solid medicated preparation designed to added
dissolve slowly in the mouth • flavored syrups are a convenient form of
• they are softer than lozenges & their bases are either masking disagreeable tastes
glycerol & gelatin or acacia & sugar E. ELIXIR
5. DENTAL CONES • it is pleasantly flavored clear liquid oral
• a tablet form intended to be placed in the empty preparation of potent or nauseous drugs
socket following a tooth extraction, for preventing - the vehicle may contain a high proportion of
the local multiplication of pathogenic bacteria ethanol or sucrose together with antimicrobial
associated with tooth extractions preservatives which confers the stability of the
• the cones may contain an antibiotic or antiseptic preparation
6. PILLS F. LINCTUSES
• pills are oral dosage forms which consist of • are viscous, liquid oral preparations that are
spherical masses prepared from one or more usually prescribed for the relief of cough
medicaments incorporated with inert excipients • contain a high proportion of syrup & glycerol
• pills are now rarely used which have a demulcent effect on the
7. GRANULES membranes of the throat
• they are consisting of solid, dry aggregates of • the dose volume is small (5ml) & to prolong
powder particles often supplied in single-dose the demulcent action, they should be taken
sachets undiluted
• they are irregular shape particles which are made to G. ORAL DROPS
improve flow property of powder • are liquid preparations for oral use that are
• some granules are placed on the tongue & intended to be administered in small volumes
swallowed with water other are intended to be with the aid of a suitable measuring device
dissolve in water before taking • they may solutions, suspensions or emulsions
i. GARGLES
Effervescent Granules evolve carbon dioxide when § they are aqueous solutions used in
added to water the prevention or treatment of
throat infections
8. POWDER (ORAL) § usually they are prepared in a
• solid dosage forms à intimate mixtures of dry concentrated solution with
finely divided drug or chemical intended for internal directions for the patient to dilute
or external use with warm water before use
ii. Mouthwashes
§ these are similar to gargles but a re •not for use on open wounds unless the powder
used for oral hygiene & to treat are sterilized
infections of the mouth G. LINIMENTS
• liniments are fluid, semi-solid or occasionally
10. TOPICAL semi-solid preparations intended for
A. OINTMENTS application to the skin
• are semi-solid, greasy preparations for • they may be alcoholic or oily solution or
application to the skin, rectum or nasal mucosa emulsion
• the base is usually anhydrous & immiscible • most are massaged into the skin (ex: counter-
with skin secretions irritant)
• ointments may be used as emollients or to • should not be applied to broken skin
apply suspended or dissolved medicaments to H. LOTIONS
the skin • are fluid preparations (aqueous) for external
B. CREAMS application without friction-either dabbed on
• creams are semi-solid emulsions, that is the skin or applied on a suitable dressing &
mixtures of oil & water covered with a waterproof dressing to reduce
• they are divided into two types: evaporation
i. Oil-in-water (O/W) creams: which I. COLLODION
are composed of small droplets of oil • a solution of nitrocellulose in either acetone,
dispersed in a continuous aqueous sometimes with the addition of alcohols
phase • generic name: Pyroxylin solution
ii. Water-in-oil (W/O) creams: which • highly flammable
are composed of small droplets of • as the solvent evaporates, it dries to a celluloid-
water dispersed in a continuous oily like film
phase • Compound WATER REMOVER consist of
§ are more difficult to handle but acetic acid & salicylic acid in an acetone
many drugs which are incorporated collodion based used in treatment of warts by
into creams are hydrophobic & will keratolysis
be released more readily from a J. PAINTS
water-in-oil cream than an oil-in- • are liquids for application to the skin or
water cream mucous membranes
§ are also more moisturizing as they • skin paints contain volatile solvent that
provide an oily barrier which evaporates quickly to leave a dry resinous film
reduces water loss from the stratum of medicament
corneum, the outermost layer of the • Throat paints are more viscous due to a high
skin
content of glycerol, designed to prolong contact

of the medicament with the affected site
C. GELS (JELLIES)
K. PRESSURIZED DISPENSERS (AEROSOL SPRAYS)
• are semisolid system in which a liquid phase is
• several different types of pharmaceutical
constrained within a 3-D polymeric matrix
product may be packaged pressurized
(consisting of natural or synthetic gum) having
dispensers known as aerosols
a high degree of physical or chemical cross-
• surface sprays produce droplets of 100 um
linking
diameter or greater
• they are used for medicaction, lubrication &
• may be used as surface disinfectants, wound or
some miscellaneous applications like carrier
burn dressing, relive irritation of bites
for spermicidal agents to be used intra
• Spray-on dusting powders are also available
vaginally
from pressurized containers
D. POULTICE
11. RECTAL
• it is soft, viscous, pasty preparation for external
A. SUPPOSITORY
use
• it is a small solid medicated mass, usually cone-
• applied to skin while they are hot
shaped, that is inserted either into the rectum
ex: Kaolin poultice
(rectal suppository), vagina (vaginal
E. PASTES
suppository or pessaries) where it melts at
• are basically ointments into which a high
body temperature
percentage of insoluble solid has been added B. ENEMA
• the extraordinary amount of particulate matter • is the procedure of introducing liquids into the
stiffens the system rectum & colon via the anus
• are less penetrating & less macerating & less
heating than ointment TYPES OF ENEMA:
• make particularly good protective barrier A. Evacuant Enema
when placed on the skin, the solid they contain - used as a bowel stimulant to treat constipation
can absorb & thereby neutralize certain (ex: Soft soap enema & Mgso4 enema)
noxious chemicals before they every reach the - volume may reach up to 2 liters
skin B. Retention Enema
• like ointments, paste forms an unbroken - their volume does not exceed 100ml
relatively water – impermeable film like unlike - may exert:
ointments the film is opaque & therefore can i. Local Effect
be used as an effective sun block accordingly § a barium enema is used as
• two types of paste: a contrast substance in
1. Fatty Pastes (ex: Leaser’s paste) the radiological imaging
2. Non greasy paste (ex: Bassorin paste) of the bowel
F. DUSTING POWDERS ii. Systemic Effect
• these are free flowing very fine powders for § the administration of
external use substances into the
bloodstream. This may be
done in situations where • commonly used to treat asthma & other
it is impossible to deliver respiratory problems
a medication by mouth, B. NEBULIZER or (Atomizer)
such as antiemetics • a device used to administer medication to
§ nutrient enema which people in forms of a liquid mist to the airways
contains carbohydrates, • commonly used in treating asthma & other
vitamins & minerals respiratory diseases
12. VAGINAL • it pumps air or oxygen through a liquid
A. PESSARY medicine to turn it into a vapor, which is the
• are solid medicated preparations designed for inhaled by the patient
insertion into the vagina where they melt or • as a general rule, doctors generally prefer to
dissolve prescribe inhalers for their patients because:
there are three types: 1. These are cheaper
i. MOULD PESSARIES 2. More portable
§ they are cone shaped & prepared in 3. Carry less risk of side effects
a similar way to moulded • Nebulizer are usually reserved only for serious cases
suppositories of respiratory disease, or severe attacks
ii. COMPRESSED PESSARIES 15. OPTHALMIC
§ made in a variety of shapes & are A. EYE DROPS
prepared by compression in a • are saline-containing drops used as a vehicle to
similar manner to oral tablets administer medication in the eye
iii. VAGINAL CAPSULES • may contain steroids, antihistamines or topical
§ are similar to soft gelatin oral anesthetics
capsules differing only in size & B. OPTHALMIC OINTMENT & GEL
shape • are sterile semi-solid preparations intended for
13. PARENTERAL application to the conjunctiva or eyelid margin
• is an infusion method of putting liquid into the 16. OTIC
body usually with a hollow needle & a syringe A. EAR DROPS
which is pierced through the skin to a sufficient • are solutions, suspensions or emulsions of drugs
depth for the material to be forced into the that are instilled into the ear with a dropper
body • it is used to treat or prevent ear infections,
• they are several method of injection, including: especially infections or the outer ear & ear canal
17. NASAL
i. Intravenous injection A. NASAL DROPS & SPRAYS
§ it is a liquid administered into the • drugs in solution may be instilled into the nose from
blood strea, via a vein
a dropper or from a plastic squeeze bottle
§ advantageous when a rapid onset of
• drug may have a local effect (ex: antihistamine,
action is needed
decongestant)
ii. Intramuscular injection
• drug may be absorbed through the nasal mucosa to
§ it is the injection of a substance
exert a systemic effect
directly into a muscle
• use of oily nasal drops should be avoided because of
§ many vaccines are administered
possible damage to the cilia of the nasal mucosa
intramuscularly

§ depending on the chemical

properties of the drug, the
INTERMEDIATE PRODUCTS USED IN COMPOUNDING
medication may be either be

absorbed fairly quickly or more
Extracts
gradually
— are concentrated preparations containing the active principals
§ intramuscular injection are often
of vegetable or animal drugs which have been extracted with
given in the deltoid, vastus lateralis,
suitable solvents & concentrated to form liquid, soft or dry
ventrogluteal & dorsogluteal
extract
muscles
Glycerins
§ injection fibrosis is a complication
— these are solutions of medicaments in glycerol with or without
that may occur if the injections are
the addition of water
delivered with great frequency or
Infusions
with improper technique
— these are dilute solutions containing the readily soluble
iii. Subcutaneous injection
constituents of crude drugs & prepared by diluting 1 part of
§ are given injection a fluid into the
concentrated infusion with 10 parts of water. Concentrated
subcutis, the layer of skin directly
infusions are prepared by bold extraction of crude drugs with
below the dermis & epidermis
25% ethanol
§ are highly effective in administering
Oxymels
vaccines & such medications as
— are preparations in which the vehicle is a mixture of acetic acid
insulin
& honey
14. INHALED
Spirits
A. INHALER
— they are alcoholic or aqueous alcoholic solutions of volatile
• are solutions, suspensions or emulsion of drugs
substances used as flavouring agents
in a mixture of inert propellants held under
Tinctures
pressure in an aerosol dispenser
— these are alcoholic preparations containing the active
• release of a dose of the medicament in the form
principals of vegetable drugs. They are relatively weak
of droplet of 50 um diameter or less from the
compared to extracts
container through a spring-loaded valve
Aromatic Waters
incorporating a metering device. The patient
— these are aqueous solutions, usually saturated of volatile oils or
then inhales the released drug through a
other volatile substances.
mouthpiece
— used as flavoring agents

PRESCRIPTION — the date is important in establishing the medication record of
the patient

— an unusual lapse of time between the date a prescription was
— an order for medication issued by a physician, dentist or other
written & the date it is brought to the pharmacy may be
properly licensed medical practitioner
questioned by a pharmacist
— various states also have licensed other prescriber who have
— also important to a pharmacist in filling prescriptions for
limited scopes of practice
controlled substances
— designate a specific medication & dosage to be administered to
SUPERSCRIPTION
a particular patient at a specified time
— The Rx symbol
— commonly, the prescribed medication also is referred to as
• Latin verb recipe
prescription by the patient
• meaning take thou or you take. Some historians
LICENSED PRECRIBERS: believe this
1. Medical Doctors — originated from the sign of Jupiter
2. Dentists — represented of both prescription & the pharmacy itself
3. Specialized Pharmacists INSCRIPTION
4. Optometrists — Medicated prescribed
5. Specialized Psychologists — this is the body or principal part of the prescription order
6. Veterinarians — it contains:
a. Names
PRESCRIPTION ORDER b. Dosages
— is a part of the professional relationship among the prescriber, c. Quantities of the prescribed ingredients
the pharmacist & the patient — The medications may be prescribe under:
— prescription orders received verbally should be reduced to a. Trademarked or manufacturer’s proprietary name
proper written form immediately or entered directly into a b. Nonproprietary or generic names
prescription computer by the pharmacist
Commonly prescribed drugs by dentsist:
CLASSIFICATIONS OF MEDICATIONS 1. Anti-infectives
— two broad legal classifications of medications: 2. Analgesics
a. Prescription 3. Anti-inflammatrory
b. Without a prescription 4. Anesthetics
1. Non-prescription drugs 5. Narcotic analgesics
2. OTC drugs
ex: Amoxicillin (Himox)
PRESCRIPTION/LEGEND DRUGS 500mg cap
— medications that may be dispensed legally only on prescription
— Legend PARTS OF COMPOUNDING INSCRIPTION
• Must appear on the label of the product as it is 1. Basis – chief active constituent
2. Adjuvant – helps/aids basis in its action
provided to the pharmacist by the manufacturer
3. Corrective – counteracts any undesirable effect/mask taste or
• Occasionally, physicians may issue prescriptions for
odor
nonlegend drugs they desire the patient to receive
4. Vehicle/Diluent – provides desired volume, consistency & form

ELECTRONIC PRESCRIBING
SUBSCRIPTION
• may become the dominate means by which pharmacists
— dispensing direction to Rx
receive prescriptions
— consist of direction to the pharmacist for the preparation of the
• minimize medication errors prescription
• enforce the use of the institution’s drug formulary, numerous — serves merely to designate the:
large hospitals à dosage form
• require physicians to enter orders directly into at computer à number of dosage units
terminal or through a PDA examples:

PATEINT INFORMATION • M ft caps dtd no xxiv
— patient’s full name & address § mix & make capsules. Dispense 24 such
• are necessary on the prescription for identification doses
purposes • Ft sup No xii
• written illegibly should be clarified on acceptance of § make 12 suppositores
the prescription • M ft ung
• incorrect spelling of a patient’s name on a § mix & make an ointment
prescription label might cause • Disp tab No c
§ concern in the patient’s mind as to the § dispense 100 tablets
correctness of the medication SIGNATURA
§ possibly would hamper the desired — directions for patient
professional relationship between the — prescriber indicates the direction for the patient’s use of the
pharmacist & patient medication in the portion of the prescription
• Some prescription blanks used by medical — Abbreviated Signa or Sig means mark thou
specialists, particularly pediatricians, include a SPECIAL LABELING & OTHER INSTRUCTIONS
space of insertion of: — number of authorized refills should be indicated on each
§ Patient’s age prescription by the prescriber
§ Weight — no refills are permitted for Schedule II controlled substances
§ Body surface area PARTS OF A PRESCRIPTION
• This information is placed on the prescription by the 1. Hospital Name
physician when medication dosage is an important 2. Patient information (name, address, age, sex, contact info)
function of age or weight 3. Date of the prescription (determine validity; 6 months from fate
DATE of order)
— Prescriptions are dated at the time they are written & also 4. Rx symbol (Superscription)
when they are received & filled in the pharmacy
5. Medication Prescribed
6. Dispensing Instruction to the pharmacist (Subscription)
7. Direction to the patient (Signa)
8. Special instructions
9. Prescriber Information & Signature (Name, License No.)

PRESCRIPTION DRUG
PRESCRIPTION ERRORS: — drug that requires a prescription because it is considered
1. Erroneous Prescriptions potentially harm if not used under the supervision of a licenses
: Brand name before generic health care practitioner
: Generic in parenthesis — known synonymously as a legend drug because the label of the
: Brand name no parenthesis drug bears the legeng, “Caution: Federal Law Prohibits
2. Violative Prescriptions Dispensing without a prescription” or “Rx only”
: Generic name not written ETHICAL/LEGEND DRUGS
: Generic not legible & brand is legible — Antibiotics: prescription drugs requiring ordinary
: Instruction with “no substitution” prescription
Violation of R.A 6675 — Exempt preparations requiring ordinary prescription with
3. Impossible Prescriptions prescriber’s S2 # (EDD, Rx)
: Generic name is written but not legible — Dangerous drugs requiring yellow prescription in triplicate
: Generic name does not correspond to the brand (DD, Rx) à demerol
name
: Generic name & brand name not legible CONTROLLED/SCHEDULED DRUG
: Drug product prescribed is not registered with PDA — A prescription drug whose use & distribution is tightly
controlled because of its abuse potential or risk
— are classified into schedules
— prescription for controlled substances have additional
requirements by law & these includes the:
a. Potential for abuse
b. Pharmacological effects
c. Risk to public health
d. History, cope, duration & significance of the abuse &
potential for psychic or physiological dependence

A. SCHEDULE I
— drugs have high potential for abuse
— not accepted medical use in the US
— 3 categories of substances: OPIATES, OPIUM
DERIVATIVES & HALLUCINOGENS
— Properly registered persons may use schedule I
substance for research purposes
— Other examples: Heroin, marijuana, peyote,
mescaline, psilobycin, THC, Dihydromorphine, LSD
B. SCHEDULE II
— drugs have high potential for abuse
— not accepted medical use in the US
— it has been determine that the abuse of a drug, or
other substances include in this schedule à
psychological or physical dependence
— categories: OPIATES, OPIUM DERIVATIVES,
DERIVATIVE OF COCA LEAVES & CERTAINE CNS
STIMULANTS & DEPRESSANTS
— Examples: Narcotic substances (Opium, morphine,
codeine, hydromorphone, methadone,
oxycodone+ASA, anileridine, oxymorphone, pantopon,
meperidine, cocaine, Amphetamine,
methamphetamine, phenmetrazine, methylphenidate,
amobarbital, pentobarbital, secobarbital, etorphine TYPES OF INCORRECT PRESCRIPTION
HC, diphenoxylate & phencyclidine 1. Erroneous
C. SCHEDULE III • The brand name precedes the generic name
— drugs have medical use & have a lower potential • The generic name is the one in parenthesis
for abuse than Schedule I & II • The brand name is not parenthesis
— includes compounds containing limited quantities of 2. Impossible
certain narcotic drugs & nonnarcotic drugs such as: • only the generic name is written but is not legible
Derivatives of barbituric acid except Schedule II, • the generic name does not corresponds to the brand
Glutethimide, methprylon, nalorphine, name
benzphetamine, chlorphentermine, clortermine, • both the generic name & the brand name are not
phendimetrazine, paregoric legible
D. SCHEDULE IV 3. Violative
— drugs have low potential for abuse relative to those • The generic name is not written
in schedule III • The generic name is not legible & a brand name that
— Abuse of schedule IV may lead to limited physical is legible is written
dependence or psychological dependence as • The brand name is indicated & instructions added
compared to those included in schedule III
(such as the phrase “NO SUBSTITUTION”) that tend to
— generally the long-acting barbiturates, certain
obstruct, hinder or prevent generic dispensing
hypnotics, minor tranquilizers

— practical purposes: NO REGULATORY DIFFERENCES
BETWEEN SCHED III & IV
— examples: Barbital, Phenobarbital,
Methyphenobarbital, Chloral betaine, Chloral
hydrate, Ethchlorvynol, Ethinamate,
Meprobamate, Paraldehyde, Methohexital,
Fenfluramine, Diethylpropion, Phentermine,
Chlordiazepoxide, Diazepam, Oxazepam,
Clorazepate, Flurazepam, Clonazepam, Prazepam,
Lorazepam, Mebutamate, Propoxyphene,
Pentazocine
E. SCHEDULE V
— drugs have the lowest abuse potential of the
controlled substances
— consist of preparations containing limited quantities
of certain narcotic drugs generally for antitussive &
antidiarrheal purposes
— OTC drugs
— Nonnarcotic substances that may be sold OTC under
the terms of the FD&C may apply to the DEA to have
their product excluded from any schedule
§ Phenobarbital à common substance

LIST OF OTC MEDICINES
• Anti-haemorrhoids
Cough-suppresants
•
• Anti-acne drugs

• NSAIDs
• Antiseptics
• Analgesics
• Decongestants
• Aspirin
• Vasodilators
• Antacids
• Expectorants (Available w/o physician’s Rx)
• Antihistamines (Available w/o physician’s Rx)
• Anti-gas agents
CONTROLLED SUBSTANCE
• all Rx must be written in ink; this practice is compulsory for
Schedule II drugs
• date
• prescriber’s name & address
• patient’s name, age & address
• diagnosis
• no abbreviations
• all doses, number of ampules, tablets, etc should be written in
words (letters) and in figures (numbers)
• prescriber’s signature
• prescription is dispensed once & kept by pharmacist

REFILL
• For schedule II drugs à NO REFILL
• For schedule III & IV drugs à not exceed 5 refills or 6 months
after the issue date
• For schedule V drugs à no restriction


Pharma Compilation

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Pharma Compilation

Uploaded by

Copyright:

Available Formats

DRUGS

KMD| PHARMACOLOGY 2016

KMD| PHARMACOLOGY 2016

KMD| PHARMACOLOGY 2016

KMD| PHARMACOLOGY 2016

KMD| PHARMACOLOGY 2016

KMD| PHARMACOLOGY 2016

You might also like