BASIC PRINCIPLES

MOLECULAR MECHANISM OF ACTION

Pharmacology
Concept: Drug produces an effect because of its mechanism
● study of drugs
of action.

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● 3 areas of focus: (Branches)
○ Effects – MOA (Pharmacodynamic)
Target Protein Mediated - drug targets the protein →
○ Fate and disposition – ADME
alter/modify its effect
(Pharmacokinetic)

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○ Clinical uses (Pharmacotherapeutics) MOA
Target Protein-Mediated Non-Target Protein Mediated
Classes of Drugs (4): A. Structural A. Physical
1. Functional Modifiers a. Tubulins

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● alter/modify the biochemical & physiologic activities b. Microtubule
of the cell B. Regulatory B. Chemical
● Majority of drugs in the market a. Voltage-gated Ion a. Neutralization
channels (VGICs) b. Chelation

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b. Carrier Molecules C. Counterfeit
2. Replenishers
c. Enzymes
● add/supplement endogenous compounds w/c are d. Receptors
considered to be insufficient in the body
● Ex: Hypothyroidism (↓serum Triiodothyronine T3, T4

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Thyroxine) – Tx: Thyroxine
A. TARGET PROTEIN - MEDIATED
○ T3 - 4x more potent than T4 (stronger)
○ T4 - undergoes isomerism A. STRUCTURAL

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■ Levo - preperation of choice ● form cell framework / cytoskeleton
■ Dextro - 4% activity of l-T4 a. Tubulins
● (still non-functional → must aggregate via
3. Diagnostic Agents polymerization → functional–Microtubule)
● For dx purposes b. Microtubule
● Ex: Dobutamine – for Pharmacologic Stress Test ● (functional already) - proteins for cell
○ Stress test - measure of cardiac efficiency w/ division/mitosis, cell movement)

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the use of a trigger–if not pharmacological,
thread mill is used
○ Pharmacologic - use of drug
○ Pharmacologic stress test - use of drug to
measure cardiac efficiency
● Abnormal Mitosis = Cancer
● Abnormal Cell movement = inflammation
Drugs:
➔ Colchicine - 1st line in tx of Acute Gout (do not alter
uric acid level; simply address cell movement)

🤍
○ B1 R Agonist – ➔ Vinca alkaloid (Vincristine) - antiCA
■ – (+) Inotropy, Chronotropy, ➔ Taxanes (Paclitaxel) - antiCA
Dromotropy ➔ Griseofulvin - ⓧ fungal mitosis
● Inotropy - force / strength
● Chronotropy - speed / rate (HR)
● Dromotropy - conduction velocity B. REGULATORY
(related to HR) ● regulate cell activity / functions

4. Chemotherapeutic Agents a. Voltage-gated Ion channels (VGICs)

● Medication that can kill or inhibit growth of foreign ● conduct changes in electric signal (charge)
cells inside the body ● Excitatory vs Inhibitory
○ Foreign cells - normally must be absent Criterion Excitatory Inhibitory
■ Pathogenic bacteria, virus, fungi, cancer Cell charge (+) (-)
cells VGIC Na+, Ca2+ K-, Cl-
● ∴ ANTIbacterial, ANTIviral, ANTIfungal, Opening
ANTIneoplastics State Depolarization Hyperpolarization
● Not all chemotherapeutic agents are limited to Response Stimumulation Depression
Contraction Relaxation
antineoplastics
Dilation

PHARMACODYNAMIC PRINCIPLES Drugs:

➔ Na+ Channel Blockers (Inhibit Depolarization
● Studies the effects of drugs when it is already inside
→ relaxants)
the body
◆ Class I Antiarrhythmics
● “What drug does to the body?
◆ Local anesthetics (-caine) [esters 1,
amides 2)
I. Molecular MOA
◆ Some Anti-convulsants (Carbamazepine,
II. Drug-Receptor Interaction
Phenytoin)
III. Dose-Response Relationship
 ➔ K+ Channel Stimulants (Stimulate
hyperpolarization → relaxants)
◆ Minoxidil - arteriolar vasodilator
◆ Diazoxide - arteriolar vasodilator
➔ K+ Channel Blockers (Inhibit
◆ Selegiline - MAOB-selective [PD]
d. Receptors
● Specific proteins that interacts with ligand (drugs)

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usually in lock & key fashion
hyperpolarization → stimulants) ● Binding of drugs to active site of receptors → signal
◆ Insulin Secretagogues transudcuction mechanism → effect
● Prerequisites of binding:

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b. Carrier Molecules ○ Chemical reactivity
● cell membrane proteins with specific binding sites ○ Electronic distribution
that undergo conformational change ○ Presence of a functional group
○ Topographic mirror-like image of the

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1. Na-K-ATPase Pump receptor
● found in the cardiac muscle–for Ca ion extrusion; ● Signal Transduction Mechanisms:
(intracellular) Sodium goes out, (extracellular) ○ Depolarization / Hyperpolarization
Potassium goes in; Sodium goes back in in

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○ 2° messenger
exchange of Calcium via the Sodium-Calcium ○ Phosphorylation
Exchanger (NCX) ○ Gene-expression
a. Calcium - for contraction IONOTROPIC Receptors /
b. Extrusion - going out of the cell LIGAND-GATED Ion Channels

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Drugs: ● Loc: Cell membrane:
➔ Digoxin - ⓧ NAP → ⃠NCX activation → (+) ● Onset: milisec

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Inotropy for HF
When ligand binds to AS → channel opening
◆ Ca - ↑ → contraction ● Na, Ca - depolarization
◆ Na - ↑ → hypernatremia ● K, Cl - hyperpolarization
◆ K - ↓ → Hypokalemia Ex:
1. GABAA R = Cl- channels →
2. Potassium-Proton Pump Hyperpolarization
● Found in the parietal cells of the stomach Ex:
● For HCl production ➔AGONISTS – Sedative

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● Opening of pump requires activation of receptors Hypnotics
◆ Benzodiazepine - ↑
● Receptors: M1, H2, Gastrin → once activated, allow
Type FREQUENCY of Ca
opening of pump ∴ promotes hyperacidity 1: Channel
○ M1 - Acetylcholine ◆ Barbiturates -
○ H2 - Histamine ↑DURATION of Ca
○ Gastrin - Gastrin Channel
● Allows exchange of:
○ Proton (H) - going out → reacts with Cl in 2. Nicotinic R = Na Chnnels →
Depolarization
the gastric lumen
Ex:
○ Potassium (K) - going in
➔ANTAGONISTS – ⓧN
Drugs: Receptor
➔ Proton Pump Inhibitors - ⓧ PP → ⓧHCl ◆ Curare derivatives
◆ “-prazole” except Aripiprazole (antipsychotic) (-curium, curonium) →
◆ Most effective for hyperacidity skeletal muscle
relaxant
c. Enzymes
● Aka Biological catalyst → hasten biochemical rxn 7-TRANSMEMBRANE / SERPENTINE /
METABOTROPIC / G PROTEIN -
COUPLED (GPCR) Receptor
1. MAO - Monoamine Oxidase
● Loc: Cell membrane
➔ Metabolism of Catecholamines: ● Onset: Sec
◆ NE, EPI, 5-HT: MAOA
◆ DA: MAOB ➔ Most abundant receptor in the body
➔ Disease: ➔ Produces 2° messenger → signals effect
➔ Metabolism is due to enzymes
◆ Major Depression: ↓NE, 5-HT ◆ Adenylyl cyclase
◆ Parkinsonism: ↓DA ● (+) → ↑cAMP via Gs
Drugs: ● (-) → ↓cAMP via Gi
Type ◆ Phospholipase C
➔ MAOIs - ↑ enhance conc of Monoamines 2: ● ↑IP3, DAG → ↑Ca →
◆ Moclobemide - MAOA-selective [MD] Contraction via Gq
◆ Phenylzine - Nonselective MAOI [MD, PD]
➔ 2° Messengers: cAMP, IP3, DAG, Ca
◆ Isocarboxazid - Nonselective MAOI [MD,
PD] Ex:
◆ Tranylcypromine - Nonselective MAOI 1. Sympathetic R: alpha, beta
[MD, PD] a. A1 - Gq
 b. A2 - Gi AC block ↑ ◆ Heparin - acid
c. B1 - Gs AC enhance ↑
d. B2 - Gs AC enhance ↑
Drugs:
A1 Blockers 2. Chelation
● -zosins - ⓧGq → vasodilation

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Drugs:
2. Muscarinic R ➔ Deferoxamine - for Fe
a. M1 - Gq ➔ Penicillamine - for Cu
b. M2 - Gi

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c. M3 - Gq
Drugs: c. Counterfeit Mechanism / Drug Incorporation
M3 Blockers
● “-ipratropium” → ⓧGq → Drugs:
Bronchodilator → COPD and ➔ Analogues of Purines and Pyrimidine bases

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Asthma
/ Antimetabolites

KINASE-LINKED Receptor DRUG RECEPTOR INTERACTION

● Loc: Cell membrane

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● Onset: Minutes ● Drug interaction with receptors
Type
3: Ex: A. FEATURES (Ligand)
1. Insulin Receptor 1. Affinity - ability to bind to R; attraction
2. Growth Factor Receptors GFR

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2. Intrinsic Activity IA - ability to activate the R
a. Epiderminal GFR
b. Platelet-derived GFR

✅ ✅

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B. Classes (Ligand)
GENE TRANSCRIPTION-LINKED / 1. Agonist - affinity, intrinsic activity
NUCLEAR Receptor Depending on IA:
● Loc: Nucleus a. Full agonist = 1 (maximal)
● Onset: Hours b. Partial agonist >0; <1
● Mixed agonist & antagonist effect
MOA: Gene expression
● Transcription: (nucleus) DNA → RNA ● ALONE - agonist
● Translation:cytoplasm)RNA → Protein ○ Ex: Nalbuphine (Partial A) → effective

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Type painkiller
4: Protein created → illicit effect ● COMBINATION w/ FULL - antagonist
Includes hydrophilic ligands ○ Ex: Nalbuphine (Partial A) + Morphine
(Full A) → antagonistic → ↓Analgesia

✅
Ex: c. Inverse Agonist <0
1. Steroidal Hormone Receptor 2. Antagonist - affinity only; no activation (in
2. Thyroid Hormone Receptor equilibrium)
3. Vitamin D & D Derivative R ● 1+1=0
● Cancellation of effect

Types of Antagonism:
B. NON-TARGET PROTEIN MEDIATED 1. MOA
a. Physical Interaction / Colligative Mechanism 2. DOI
● Colligative properties - dependent on the number of 3. SOI
solute particles
● Mannitol (IV) MOA A. Functional / Physiologic
○ Osmotic diuretic = Aquaretic Antagonism
○ Compartments: ● 2 ligands acting on DIFFERENT
■ Where the salt goes the water follows targets / receptors producing
■ Continuous administration of mannitol → ↑ conc opposite effects
in urine thus, water in blood will move to urine ● NE & ACh in the heart:
○ S/E: Hypovolemia (Dehydration), ○ NE on B1 → Tachycardia
Hypernatremia ○ ACh on M2 → Bradycardia

B. Receptor / Pharmacologic
b. Chemical Interaction Antagonism
● Must participate into causing chemical reaction ● 2 ligands acting on SAME targets /
1. Neutralization receptors producing opposite effects
● NE + Propranolol
● Acid-base reaction ○ NE on B1 → Tachycardia
Drugs: ○ Propranolol on B1 → Brady
➔ Antacids for Hyperacidity
◆ Bases + Acid C. Chemical Antagonism
➔ Protamine sulfate for Heparin Toxicity ● Must participate into causing
chemical reaction
◆ Protamine - basic
● Neutralization, Chelation
 DOI Duration of Interaction
A. Reversible - fast DOI
APPLICATION
● Within 24 hrs
● Attachment/force is weak = 1. Efficacy vs Potency
NONCOVALENT ● How to plot potency: Get ½ of efficacy → Get its

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● safer ordered pair
B. Irreversible - short DOI —
NON-Equilibrium Antagonism
● Days to weeks

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● Attachment/force is strong =
COVALENT
● Potentially toxic
SOI Sourmountability of Interaction – ability to
displace antagonist by the agonist

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A. Competitive → Surmountable
● ABLE to displace
● ↑ Dose of agonist
● Reversible → safer

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B. Noncompetitive →
Nonsurmountable
● NOT REALLY able to displace
● Regardless of dose, agonist 2. Agonists
cannot be sourmounted

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● Irreversible → toxic

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DOSE-RESPONSE RELATIONSHIP

A. GRADED DOSE RESPONSE RELATIONSHIP

● Plot:
○ Y axis - Response

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○ X axis - Dose (hyperbolic) / Log Dose
(sigmoidal–more common)
3. Competitive Antagonism

● Parameters: ● A = Agonist only → ↑ effect

○ Efficacy (E)
■ maximum achievable response
■ found on top left of Y axis
○ Potency
■ Dose required to achieve 50% of efficacy
■ Found on X axis
■ Plotted potency near zero = more potent
Note: ↓ amount / dose = ↑ potency
● B = Agonist (same dose) + Competitive Antagonist
→ ↓ effect
● C = Agonist (higher dose) + Competitive antagonist
→ same response but higher dose (rightward shift)
4. Noncompetitive Antagonism

○ Ceiling dose Dc
■ Smallest dose which produces efficacy =
smallest which produces the maximal response
■ Found on X axis
○ Slope
● Nonsurmountable, covalent
■ Degree of changes in response with a change
● A = Agonist only
in the dose of the drug that was administered
● B = Agonist only (same dose) + Noncompetiitve
■ Extent of inclination → assess the safety of
Antagonist → ↓plateau
drug
● C =Agonist (higher dose) + Competitive antagonist
● Steep slope → drastic response; must
→ ↓ response, higher dose (rightward shift)
start at low and slow
● Not steep → dose can easily be
adjusted
 B. QUANTAL DOSE RESPONSE RELATIONSHIP
● Plot: LADME System
○ X axis - Log Dose (sigmoidal) ● Liberation - biopharmacuetic
○ Y axis - Cumulative number of Px ● Absortpion - biopharmaceutic, kinetic
■ Beneficial - lower dose ● Distribution - kinetic

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■ Toxicity - higher dose ● Metabolism - kinetic
● Excretion - kinetic

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● Input Process - Liberation + Absorption
● OUtput Process / Drug Disposition - Distribution
+ Elimination
● Elimination - Metabolism + Excretion

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TRANSPORT MECHANISMS

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● Processes of drug transport across the cell
membrane (barrier)
● Pre-requisite:
○ Drugs in Aqueous solution except in micelles
which is transported via pinocytosis

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● Parameters:

MECHANISMS OF TRANSPORT

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a. Passive Tramsport (Diffusion)
● Major / dominant
● Non-energy requiring
● Movement is ALONG the concentration gradient
(higher to lower solute conc)
● Drug molecules pass through the CM directly
● DOWNHILL mechanism

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● Law: Fick’s Law of Diffusion
𝑑𝑄 𝐷𝑥𝐴𝑥𝐾
𝑑𝑇
= ℎ
(𝐶𝑔𝑖 − 𝐶 𝑝)
○ ED50 - Median Effective Dose
■ Effective dose in 50% of the given population ● Measures the rate of diffusion
■ Computed similarly to potency ○ D, A, K, Cgi, CP directly proportional to
○ TD50 - Media Toxic Dose rate of diffusion
■ Toxic dose in 50% of the given population ○ H inversely proportional to rate
■ Computed similar to potency ● Factors affecting dQ/dT:
○ Therapeutic Index TI ○ Body-related factors:
■ Measure of relative safety 1. A = surface area of the membrane
■ Ratio of TD50/ED50 2. Cgi-Cp = Concentration gradient
■ ↑TI = ↑safer 3. H = membrane thickness (↑H =
○ Margin of Safety ↓diffusion)
○ Drug-related factors:
1. D = diffusion coefficient–property of the
drug in relation to the property of the CM
(relatability of drug to the CM)
● Lipophilicity: ↑Lipophilicity → ↑D →
PHARMACOKINETICS PRINCIPLES
↑dQ/dT
● Fate & disposition (ADME) ○ Degree of dissociation / Ionization
● “What the body does to the drug?” ■ Unionized - nonpolar→ ↑D →
absorbed
■ Ionized - polar - ↓D → excreted
BIOPHARMACUETICS
● Particle size: ↓PS → ↑D → ↑dQ/dT
1. Bio - bioavailability–measure of drug absorption
(fraction of drug that enters the systemic circulation) 2. K = partition coefficient; ratio of the
2. Pharmacutics - process a drug undergoes to make concentation of drug in the oil phase and
drugs available for action / for it to be bioavailable water phase —in two immiscible or slightly
miscible phases
Consideration of Pharmacuetics 𝐶 𝑜𝑖𝑙
𝐾 =
1. Physicochemical 𝐶 𝑤𝑎𝑡𝑒𝑟

2. Dosage Forms ● K > 1 : oily → ↑D → ↑dQ/dT

3. Route of Administration
 LIBERATION
b. Carrier-Mediated Tramsport (Diffusion)
● Aka DRUG RELEASE
● Allows movement of molecules through the aid of
● Process of API release from the dosage form
carrier proteins
● End product: Aqueous solution form

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○ Exception: TRUE SOLUTIONS
■ Syrup
■ Elixir
Features (3)

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● A biopharmaceutic process → highly modifiable
1. Specificity - carriers recognize specific drug
○ S/E of drugs can be overcame by modifying the
molecules
ROA, Dosage form, or physicochemical property
2. Competition / Inhibition / Antagonism limited
carrier

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● INH and Pyridoxine – absorbed via the
same carrier
Biopharmaceutics Classification System
● INH >> Pyridoxine → Vit B6 Malabsorption
Class Solubility Permeability
→ Peripheral neuropathy

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Salitan Partial
3. Saturable – drug that cannot be accomodated must I ↑ ↑
wait II ↓ ↑
a. Display Michaelis-Menten Kinetics / III ↑ ↓
Saturation Kinetics (Zero-order kinetics) IV ↓ ↓

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Ex: High Low

✅ ✅

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Energy Movement Saturable High Class I Class II
Active T
Facilitated D ❎ Uphill
Downhill ✅ Low Class III Class IV

c. Convective Transport
● Allows movement via Water-filled pores
● Only PARACELLULAR transport (beside the CM)
ABSORPTION
● Allowed compound: Ionized sulfonamides

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Features (4):
1. Pore size / Diameter: 7-10Å; too tiny→ only allows
drug moment with MW of 150-400
2. Pore Charges: charge of the pore lining; “opposite
attracts”
● Pore is (+) → allows only (-) Charged drugs
3. Movement is by solvent drag; if H2O moves, drug
follows; if not H2O-soluble, drug will not follow
4. Movement is along the concentration gradient–
non-energy requiring; downhill
● phArmacokinetic: process of drug Entry into the
systemic circulation
● phYsiologic: process of drug Disappearance
FACTORS AFFECTING ABSORPTION
Drug-Related Factors
1. Particle size: ↓PS → ↑Absorption
2. Dose size: ↑Dose → ↑Absorption
3. Chemical Nature of Drugs: Amorphous > Crystalline;
Granules > Tablet

d. Ion-Pair Transport
● “Opposite attracts” Body-Related Factors
● Cation + Anion → neutral complex → Passive 1. Absorption Environment
diffusion ● Organ tasked to absorb the drug
● against electrochemical potential ● PO: Stomach & Small Intestine
● Lipophilic counter ions acts as carriers for ○ ∴Small Intestine - main site of drug
hydrophilic molecules absorption for drugs taken PO
● Absorption-related factors
e. Pinocytosis (cell drinking) ○ Surface area: ↑SA → ↑Absorption
● Endocytosis→ vesicular transport ○ 120-200 m2 SA (microvilli & villi)
● Energy-requiring Stomach Small Intestine
● Transports liquid or small MW drugs through the Thick mucous Vili, Microvilli
vesicle → NO NEED FOR LIBERATION ↓SA ↑SA
(Dissolution)
○ Perfusion (blood flow): ↑Perusion →
Drugs:
↑Absorption
➔ Griseofulvin - ↑ absorption with fatty meals
Stomach Small Intestine
➔ Vit ADEK
↓perfusion ↑perfusion

○ pH of the absorption environment

Stomach Small Intestine
 ↓pH → Acidic ↑pH → Basic ● Appearance: at time Zero, Cp is at

❎
WA: LUNA WA: HIPE peak
WB: HIPE WB: LUNA ● Absorption phase
● RAPID onset of action
● SHORT DOA

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2. Gastric Emptying Time GET ● Elimination phase immediately
● GET - time it takes for the stomach to empty its B. Extravascular - PO
contents → SI
✅
● Appearance: at time Zero, Cp is 0

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○ ↑GET = ↓Rate of Absorption ● Absorption phase
○ ↓GET = ↑Rate of Absorption ● DELAYED onset of action
● Factors affecting GET: ● LONG duration of action
○ ↑GET: ● Hyperbolic

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■ Physical stress applied to stomach →
Gastric ULCER II. Parameters
■ Vigorous physical activity / HEAVY A. Cmax
excercise → muscles are stressed → ● Maximum plasma drug concentration

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blood supply is focused to muscles, few to ● Measures BOTH the rate & extent
stomach ● Most VARIABLE
■ Fatty & proteinaceous meals ● IV: Cmax is at time 0
■ Lying on the LEFT → against pull of B. Tmax
gravity ● The time to reach Cmax

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■ Antimotility drugs (Antidiarrheal) ● Measures the RATE only
■ Atropine (Anticholinergic) ● Ordered pair of Cmax

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○ ↓GET: ● IV: Tmax is 0
■ Too HOT or too COLD C. Area Under the Curve AUC
■ MILD exercise ● Measures the EXTENT only
■ Lying on the RIGHT → favor gravity ● Most IMPORTANT
■ DM patients (polyphagia) → lack ● Space covered below graph curve
INCRETIN hormones which has bloating
and anorexiant effect → satiety effect

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■ Promotility drugs / Prokinetic / Anti-emetic 2. BA Studies
(Metoclopramide, Domperidone)
Absolute Bioavailability Relative Bioavailability
● Compare drug products ● Compare drug products
PHARMACOKINETIC PARAMETERS administered via via SAME ROA & GN
Bioavailability (F) DIFFERENT ROUTES ● Test substance /
● Measure of the rate and extent of pharmacokinetic drug ● SAME GENERIC name Reference standard
𝐴𝑈𝐶𝑝𝑜 𝐴𝑈𝐶 𝐼𝑉 (𝑡𝑒𝑠𝑡)
absorption 𝐹𝑎𝑏𝑐 = 𝐴𝐼𝑈𝐶𝑖𝑣
𝐹𝑅𝑒𝑙 = 𝐴𝑈𝐶 𝐼𝑉 (𝑅𝑒𝑓)
● Deteremines the fraction of drug that enters the Extent EBA and rate RBA of
systemic circulation the bioavailability of a drug
● Expressed as percentage of two or more different
dosage forms given by the
same route of
𝐷𝑟𝑢𝑔 𝑎𝑏𝑠𝑜𝑟𝑏𝑒𝑑 = 𝐷𝑜𝑠𝑒 𝑖𝑛𝑖𝑡𝑖𝑎𝑙 𝑥 𝐹 (𝑑𝑒𝑐𝑖𝑚𝑎𝑙 𝑓𝑜𝑟𝑚) administration
It is necessary when there is
● Change in galenic of the
1. Methods to Calculate BA [EXPERIMENTAL] drug
a. Urine ● Change in the method of
○ Cummulative Urinary Excretion Data manufacture
● Change in the means of
○ Metabolites of drugs are quantified preservation
○ Measures:
■ Ke Criteria for Waiver In Vivo Bioavailability
■ Ka ● IV solution
■ F ● Solution
■ % drug absorbed ● Topical product for local effects
■ Ultimate amt of drug absorbed ● Drugs not intended for PO absorption
■ EBA ● Inhalation product similar to approved one
○ Not all drugs are excreted renally → ● PO (except for EC and CR) dosage form similar to
INACCURATE approved ones (except antiarrhythmics,
b. Blood anticonvulsants, anticoagulants, etc)
○ Plasma Level Curves
I. ROA
A. Intravascular - intracardiac, intravenous,
intraarterial
● Graph: PDC vs Time
🌟
Bioequivalence
Terminologies: PHARMACOKINETIC PARAMETERS
Pharmaceutical SAME ALL 1. Volume of Distribution
Equivalent ➔ API (GN) ● Hypothetical measure of distribution
➔ Salt/ester/complex

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● It is a hypothetical value of body fluid required to
➔ Dose strength
➔ Dosage form dissolve a given amount of drug to a concentration equal
to that of plasma membrane
Ex: Diatabs 2 mg cap ● It is the concentration of drug in the plasma or tissue

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Imodium 2 mg cap depends on the amount of durg systemically absorbed
Pharmaceutical SAME (only 1) and the volume in which the drug is distributed
Alternative ➔ API (GN) ● Applications: estimate the LOADING dose and ACTUAL
DISTRIBUTION of drugs in the body

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Ex: Voltaren 50 mg tab (Diclofenac Na) 𝐷𝑜𝑠𝑒 𝑋0
Cataflam 50 mg tab (Diclofenac K) 𝑉𝐷 = 𝐶𝑜𝑛𝑐 𝐶𝑝
𝑢𝑛𝑖𝑡: 𝐿

Therapeutic ➔ Pharmacuetical Equivalents

Equivalent (API, Salt, DS, DF) ↑VD = ↑Distribution

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➔ Bioequivalents (provided by BE
studies) Assumptions Location
Therapeutic DIFFERENT API (GN) 5L Circulatory System ONLY (4.3%)
Alternative SAME Drug Class 10 - 20 L ECF (15-27%)
25 - 30 L ICF (35-42%)

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Ex: Neobloc 50 mg tab (Metoprolol) 40 L WBF (60%)
Therabloc 50 mg tab (Atenolol) > 100 L Deep tissues (exceeds total BW)

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2. Protein Binding
DISTRIBUTION ● A phenomenon which occurs when a drug combines
with plasma protein or tissue to form a reversible
● Process of drug movement from the central
complex
compartment to different peripheral body compartments

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● Forces of attraction: Van der waals, H bond, ionic bond,
Systemic circulation (central) → organs, tissues (peripheral) hydrophobic bond
● Plasma proteins:
● Purpose: drug delivery to the active site making it ○ Albumin - weak acids; most abundant
effective ○ Alpha-1-acid Glycoprotein - weak bases
○ Globulins - hormones
PHYSIOLOGIC FACTORS
● Whatever happens to the blood, drug follows 2 forms of drugs based on Protein Binding
1. Free drug
● Liberated
1. Cardiac Output ● Available for action → effective
● Volume of blood pumped out by the heart per minute
2. Bound drug
● Normal 2.2 - 3.5L/min/sqm
● Interacted with blood protein → drug changes

↑CO = ↑rate & extent of distribution

Consequences of Bound Drug
● Initially not available for action
2. Regional Blood flow RBF ● DELAYED onset of action
● Portion of CO delivered to specific organs & tisues ● LONGER duration of action (adv)
● Amount of blood flow on the organs ● Interact with other drugs → Drug displacement
↑RBF ↓RBF interaction (disadv)
↑Distribution ↓Distribution
Heart Bones ↑Bound drug = ↓Vd = ↓Distribution
Kidney Adipose tissues
Lungs
Liver
Brain
● Ex: Pneumonia → ↑RBF → Tx: Abx (PO) for 7-14 days
● Ex: Osteomyelitis → ↓RBF → Tx: Abx (IV) for >6 wks

3. Capillary permeability
● Cell membranes vary in their permeability characteristics
depending on the tissue
○ BBB has tight junctions (↓entry)
○ Liver lobule are discontinuous (↑entry)
 1. Liver - major; both synthesizing and excreting
organ by means of biliary excretion (drugs with
HMW)
● Basic anatomical unit: liver lobule
–parenchymal cells in a netrwork of

t
interconnected lymph and blood volume
● Bromosulphthalein - chemical used in the
determination of secretory function of liver

t
2. Kidneys
● Renal dehydropeptidase – targets
Imipenem → inactive (thus Cilastin is
combined to inhibit RDP)

g
3. GIT
● Peripheral l-DOPA Decarboxylase –
targets Levodopa → Dopamine (thus
Carbidopa is added to prevent premature

e
metabolism of Levodopa)
METABOLISM 4. Misc: Placenta
5. Misc: Plasma
● Aka BIOTRANSFORMATION
● Drug → chemical reactions via enzymes → Metabolite

n
● Enzymyatic
FIRST PASS EFFECT
● Major loc: Liver (major metabolizing organ)
● Aka PRESYSTEMIC METABOLISM

ia
● Other loc: Kidneys
● Inactive (drug no longer can exert pharml action) ● Initial metabolism of drugs before reaching the systemic
● HIP → excreted circulation (absorption)
● Nontoxic / less toxic ● Metabolism prior to absorption (small intestine) via the
hepatic arteries & portal vein which goes through the
liver (cont. Enzymes for metabolism) → ↓BA
EXCEPTIONS
● Greater incidence: PO drugs
1. PRODRUGS ● Ex: Catecholamines (no oral prep→ ROA: IV, SQ, IH)

le
● Initially inactive → metabolism → active ○ Endogenous - natural; END EPI, NE, DA

🌟
● Ex: ACEIs (-pril)
○ Not Prodrugs: “Acute ACEIs” CEL
–Captopril, Enalaprilate (IV), Lisinopril
○ Exogenous: Dobutamine, Isoproterenol
● Ex: Lidocaine (for arrhythmia) (IV)
○ 1st line agent in Digoxin-induced VT
○ Oral congener: Mexilitine

PHASES OF METABOLISM
1. PHASE 1 / FUNCTIONALIZATION / ASYNTHETIC
a. Oxidation
● Dominant Phase 1 rxn → majority
● Mechanisms:
○ CYP-mediated: Cytochrome enzyme;
major
2. ACTIVE TO ACTIVE
CYP1A2 Caffeine
● Active → metabolism → active
APAP
● Ex: Diazepam → Oxazepam
Theophylline
CYP2C9 Warfarin
Phenytoin
CYP2C19 Clopidogrel
Propranolol
PPI
3. FORMATION OF TOXIC METABOLITES
CYP2D6 B-blockers
● Active → metabolism → TOXIC Antidepressants
● Ex: Meperidine → Normeperidine (seizure) Some antipsychotics
○ Given for acute pain only Tamoxifen
● Ex: Benzo(a)pyrene → epoxide Codeine
● Ex: Paracetamol → N-acetyl-p-benzoquinone imine) CYP3A4,5,7 Tyrosine kinase inh
Azole antifungal
CCBs
Antivirals

✅ ✅
ORGANS FOR METABOLISM Macrolides
Note: enzymes = metabolism Grapefruit juice
 ○ Non-CYP-mediated:
MAO MAOIs: MPITS
Alcohol ⓧfomepizole
dehydrogenase
Aldehyde ⓧDisulfiram

t
dehydrogenase
Xanthine ⓧfebuxostat, allopurinol

t
b. Reduction
● Nitroreduction (e.g. Chloramphenicol)
● Carbonyl reduction (e.g. Naloxone,
Methadone)
● Azo reduction (e.g. Prontosil)

g
EXCRETION

✅
c. Hydrolysis ● Functional loss of drug from the body
● Ester FG, Amide FG ● Irreversible

e
● Ester Cont: ASA, ACEI, Ester-LA ● Requirement: HIP→E
● Amide Cont: Amide-LA, Procainamide,
B-Lactam Abx MECHANISMS OF EXCRETION
1. Renal (major)

n
● via URINE through the KIDNEYS
● Rqd: HIP, LMWH Drugs
2. PHASE 2 / CONJUGATION / SYNTHETIC
● Processes:

ia
a. Glucuronidation
○ Glomerular filtration - displays first order kinetics
● Dominant, except neonates
(↑GFR → ↑Excretion)
● Enzyme: Glucoronysyl-Acyl-Transferase –
poorly expressed in neonates
○ Active Tubular secretion - ACTIVE process
b. Acetylation ■ Specific, competition, saturated (displays zero
● Enzyme: N-acetyl-transferase order kinetics) ; involved in the peripheral
● Substrates: Hydralazine, INH, Procainamide, capillaries to the lumen of renal tubules;
Sulfonamides ■ Ex: Penicillin + Probenecid

le
c. Sulfation ● Probenecid - inhibits active secretion
● Dominant in neonates of Penicillin
d. Methylation ● Penicillin - reabsorbed
● Enzyme: Cathecol-O-Methyl-Transferase ○ Tubular reabsorption (passive)
e. Glycine Conjugation ■ Transport back into thr plasma
● Substrates: Carboxylic acid, salicylic acid, ■ Ex: Ion trapping—reducing
benzoic acid toxicity
● Present in animals and human ■ Depends on urinary pH
f. Glutamate Conjugation ■ Acidic drug + Basic Urine —>
● Only expressed in humans excretion
g. Glutathione Conjugation / mercapturic Acid /
Mercapturine
● Tripeptide GSH: Glycine G, Glutamate E, 2. Biliary excretion
Cysteine C ● Excretion via bile acids → stools
● Neutralizes free radicals / natural antioxidant ● Requirement: HIP, HMW Drugs (>500)
● Produced by the liver (0.5-1L per day —> emptied into
the duodenum)
ENZYME ALTERATION ● Stroed and released by the gall bladder

➡️⬆️
1. Enzyme Induction ● Magnitude ot bile production depends on type of food.

⬆️
➔ ↑ enzymatic action → ↑metabolism ○ Food rich in proteins bile secretion
2. Enzyme Inhibition ○ Rich in fats —> some bile secretion
➔ ↓enzymatic action → ↓metabolism ○ Rich in CHOs —> hardly any influence

Induction Inhibition Fate of Bile acids:

Common fate: ↑IA = ↓efficacy ↑A = ↑toxicity ● Whatever happens to BA, drug follows
A→IA 1. Excreted (stool) 10%
Prodrugs: IA → A ↑A = ↑efficacy ↑IA = ↓efficacy
2. Reabsorbed (Biliary recycling / enterohepatic
recirculation) 90%

tt
3. Miscellaneous

g
1. Sweat glands: sweat
2. Mammary gland: milk
3. Lungs: expire air (for non-polar volatile drugs)

ne
ia
le
 C. SUBDIVISION OF ANS
ANS Pharmacology 1. Enteric NS
2. Sympathetic NS
3. Parasympathetic NS

t
ANATOMY AND PHYSIOLOGY
1. ANATOMICAL DIFFERENCE OF SYMPA VS
CNS - discontinuous
PARASYMPA

t
A. AUTONOMIC NERVOUS SYSTEM
Criterion Sympathetic Parasympathetic

✅
● Subdivision of the peripheral efferent nervous system
● motor neurons (connect brain → organ) Origin of ➔ T1-T12 ➔ C3, 7, 9, 10
Neurons ➔ L1-L5 ➔ S2-S4

g
○ Pre ganglion - near CNS
■ Ganglion - exclusive to ANS aka ➔ Thoracolumbar ➔ Craniosacral
Length of ➔ Pre: SHORT ➔ Pre: LONG
✅
○ Post ganglion - near effector organ
● impulses / responses to effector organ neurons ➔ Post: LONG ➔ Post: SHORT

e
● Targets Involuntary organs Location of ➔ Spinal cord ➔ Effector organ
○ smooth muscles (uterus, prostate, bronchi, UT) Ganglion
○ exocrine glands (sweat, salivary, lacrimal) Synthesis, ➔ PreG: ACh ➔ PreG: ACh
○ cardiac muscle Storage, ➔ PostG: NE ➔ PostG: ACh
Release

n
(Neurotransmission)
B. SYNAPTIC NEUOTRANSMISSION
● Explains the mechanism of impulse transport across the

ia
Receptors ➔ Ganglion: ➔ Ganglion:
synapse–gap/space betwen the ganglions (Post-synapse) Nicotonic neural Nicotinic neural
➔ Effector: ➔ Effector:
1. Parts of a Synapse Adrenoceptor Cholinoceptor
(𝝰,β) (N, M)
● PRESYNAPSE Sending Cell (left side of the synapse)
○ Originates from the brain
○ Synthesis, storage (vesicle), release (exocytosis) of

le
NT
2. FUNCTIONAL DIFFERENCE OF SYMPA VS
✅
○ Enzymes → metabolism
PARASYMPA
○ Receptors → called AUTORECEPTOR (if
1. General
activated: INHIBITORY)
Sympathetic Parasympathetic
✅
● CLEFT (synapse)
○ Enzymes → metabolism Adrenergic NS Cholinergic NS
● POST SYNAPSEReceiving Cell (right side of the brain Stress – Fight or Flight Basal - Rest & digest

✅
○ Towards the effector organ

✅
○ Receptor → majority (EXCITATORY) 2. Specific Responses: NE vs ACh (Functional/Physologic)
○ Enzymes → metabolism Effector Sympathetic Parasympathetic
Heart Tachycardia Bradycardia
Smooth M Relaxation Contraction
2. Process ↓pressure ↑pressure
Pupil Mydriasis Miosis
Bronchi Bronchodilation Bronchoconstriction
GIT Ileus–loss of Bowel movement
peristalsis Diarrhea
Constipation
Urinary Retention Urination
bladder
(walls)
Sweat glands APOCRINE ECCRINE
(palms, soles) (generalized)
a. Impulse from the brain has reached the sending cell Sweating Sweating
b. Depolarization / excitation of presynaptic CM
c. Ca intrusion / Ca-channel opening → Ca intrusion →
movement of vesicle → fusion of vesicle to membrane
d. Exocytosis → release
e. Binding to post synaptic receptor is the evidence of
synaptic neurotransmission → effect
 Inhibitors (reGus)
● Guanadrel
● Guanethedine
● Bretylium

t
d. Termination
● Occurs in the cleft
● General effect → ↓NE for binding

t
● Mechanisms:
a. Reuptake → Reuptake Inhibitors → ↑NE
● ⊖Sibutamine
● ⊖Atomoxetine

g
● ⊖Cocaine
b. Metabolism
● Enzyme: MAO, COMT
● Product of EPI & NE:

e
○ Vanillyl Mandelic Acid aka
3-Methoxy-4-Hydroxy-mandelic
acid
● Product of DA:

n
SYMPATHETIC DRUGS ○ Homovanillic Acid
● ⊖MAO: Moclobemide, Phenylzine,
1. ENDOGENOUS CATHECOLAMINES
Isocarboxazid, Tranylcypromine, Selegiline

ia
● Epinephrine EPI
● Norepinephrine NE ● ⊖COMT: Tolcapone, Entacapone,
● Dopamine DA c. Passive diffusion

a. Biosynthesis True Love Does Not Exist

a. Formation of L-DOPA 2. ADRENORECEPTORS
● Enzyme: Tyrosine-Hydroxylase (RLE)

le
● Tyrosine (precursor) → L-DOPA
● ⊖ Metyrosine
b. Formation of Dopamine
● Enzyme: L-Dopa-Decarboxylase
● L-DOPA → DA
● Dopamine - first Catecholamine produced
c. Formation of Norepinephrine
● Enzyme: Dopamine-β-Hydroxylase
● Occurs INSIDE THE VESICLE due to chances of
premature metabolism
● DA → NE
d. Formation of Epinephrine
● Enzyme: phenyl-ethanolamine-n-methyl-transferase 𝝰1 : Smooth Muscle – CONTRACTION Gq
PENMT ● Blood vessels – Vasoconstriction → ↑BP
● Occurs in the adrenal medulla → due to enzyme’s ● Bladder Trigone, Sphincter – Closure → Urine
location retention
● Prostatic SM – Contraction → Urine retention
b. Storage of Dopamine ● Radial Muscles (iris) – Contraction → Mydriasis of
● DA enters the vesicles via Vesicular Mono Amine pupil
Transporter (VMAT) ● PIlomotor SM (skin) – Piloerection (goosebumps)
● Due to presence of enzyme in the pre-synapse, DA Pre-Synaptic 𝝰2 – INHIBITORY Gi
is stored in the vesicle ● Autoregulatory – Inhibits further release of NE from
● Purpose: prevent premature metabolism of DA the vesicle → ↓NE binding
● ⊖ Reserpine ● Consequences:
○ Inhibits VMAT → DA not sequestered in vesicle ○ Central (brain): Depression, Sedation
→ DA metabolism → low NE ○ Peripheral (blood vessel): Vasodilation
→ ↓BP
c. Release (Exocytosis) Post-Synaptic 𝝰2 – EYECITATORY Gq
Stimulants: (sTEAMulant) ● Found in the peripheral blood vessel (eyes) →
● Tyramine vasoconstriction
● Ephedrine
● Amphetamine, Angiotensin II
● Methamphetamine

Β1 (Heart) → CARDIAC STIMULATION Gs
● (+) Inotropy, Chronotropy, Dromotropy
B1 (Juxtaglomerular Apparatus) → ↑BP Gs
● (+) Renin → ↑ATII → ↑BP
● Local vasoconstrictor w/ Lidocaine → ↑ LA by
limiting Lidocaine on the site of area, ↓ bleeding
● Dipivefrin - mgt of Glaucoma; prodrug of EPI;
pivalic acid ester of EPI

t
B2 (Smooth Muscle) → RELAXATION/DILATION Gs 2. NE / Noradrenaline / Levarterenol
● Bronchi → Bronchodilation ● 1st line for septic shock (iNfection)
● Uterine M → Tocolysis
● Blood vessel (connected to skeletal muscle) →

t
Vasodilation 3. Dopamine
B2 (Skeletal Muscle) → CONTRACTION Gs ● Alt: Shock states (septic shock, cardiogenic shock)
● → Tremors ● Mgt: Acute heart failure (inotropes) complicated by
● ↑K ion UPTAKE to SM → HYPOkalemia Oliguria and Anuria (↓urine output) D1

g
B3 (Adipcyte) → LIPOLYSIS Gs
● Fat breakdown → FFA → Weight LOSS
Toxic Effects
Gs linked → B receptors all are stimulation except SM ● 𝝰1 overstimulation → vasoconstriction →

e
HYPERtension, digital NECROSIS
● β1 overstimulation → (+) I, C, Dtropy → VTAch
3. ADRENOMIMETICS

n
Classes: MOA Antidote
1. Direct Acting Sympathomimetics – via Adrenoceptor ● Phentolamine
ACTIVATION

ia
2. Indirect Acting Sympathomimetics – ENHANCE THE
CONCENTRATION of NE available for binding
a. Exocytosis Enhancer
b. Reuptake Inhibitors B. ALPHA AGONISTS
3. Mixed Acting Sympathomimetics – combination DA + IA
ALPHA 1 RECEPTOR → CONSTRICTORS
a. Exocytosis Enhancer
Examples:

le
1. PHENYLEPHRINE
Direct Acting Sympathomimetic 2. METHOXAMINE
3. PROPYLHEXEDRINE
● Selectivity:
4. TETRAHYDROZOLINE
○ Nonselective
5. OXYMETAZOLINE
○ Selective
6. NAFAZOLINE
A. NON SELECTIVE – 𝝰, β
Effects / Clinical Uses:
➔ Ex: ENDOGENOUS CATECHOLAMINES
1. Vasoconstriction
➔ Epinephrine, Norepinephrine, Dopamine
a. Local
i. IN –decongestants → tx Nasal congestion
Properties:
● Ex: Oxymetazoline (Drixine®) nasal spray
● High potency @ Adrenoceptor (β > 𝝰) ii. Eye drops → tx Red eyes
● β effect at low dose → 𝝰 effect at higher dose ● Ex: tetrahydrozoline eye drops
● EPI: β1 = β2 >𝝰1 b. Systemic (PO, IV)
● NE: β1 > 𝝰1 i. Tx of nasal congestion (Bioflu, Neozep)
● DA: D1, B1, 𝝰1 ii. Tx of hypotension
○ D1 - renal vasodilation → ↑GFR → ↑diuresis
○ EPI is the only bronchodilator 2. Mydriasis – Phenylephrine eye drops in the conduct of
● Polar → no CNS effect eye examination
● Extensively metabolized by COMT, MAO
● Extremely low BA ∴ no oral prep → short DOA Toxic Effects:
a. Local
Clinical Uses: i. IN → rhinitis medicamentosa (rebound
1. EPI / Adrenaline congestion) if taken for > 3 days
● 1st line cardiac stimulant (β1) b. Systemic
● 1st line for anaphylactic shock (𝝰1) i. Systemic vasoconstricton → ↑BP →
● 1st line for anaphylaxis (IgE) (bronchoconstriction Hypertension
→ β2) ii. Urinary retention (C/I: BPH px)
● 1st line for anaphylactoid (drug-induced–Morphine,
Tubocurarine, Guanethedine) (bronchoconstriction ALPHA 2 RECEPTOR → ANTIGLAUCOMA, ANTIHTN
→ β2) 1. Antiglaucoma: Apraclonidine, Brimonidine
 2. Antihypertensives: Guanabenz, Guanfacine, 6. Modafinil – 1st line for narcolepsy
Clonidine, Methyldopa 7. Methylphenidate – 1st line for ADHD
8. Phenmetrazine – anorexiant
REUPTAKE INHIBITORS
Criterion Methyldopa Clonidine 1. Cocaine – only vasoconstrictor local anesthetic

t
BN Aldomet Catapares 2. Sibutramine – mgt of obesity
MOA Prodrug → Initial: Gq 3. Atomexetine – alt for ADHD
(Unique 𝝰-methyl-NE Vasoconstriction

t
feature) (false/pseudo NT
acting as a 𝝰2 Final: Gi Vasodilation
agonist)
Use HTN in pregnancy Hypertensive crisis Indirect Acting Sympathomimetic
T/E Sedation Withdral syndrome

g
Hepatotoxicity (rebound
(+) Coombs test hypertension) 1. Phenylpropanolamine (PPA)
(+) Hemolytic anemia ● –tx of nasal congestion, hypotension
● T/E: ↑ risk of hemorrhagic stroke in children

e
2. Mephentermine
3. Metaraminol
NON-SELECTIVE BETA 1 AGONISTS
● Isoproterenol / Isoprenaline
○ Synthetic catecholamine

n
○ Alt: shock states, acute HF 4. ADRENOLYTICS
A. ALPHA BLOCKERS

ia
BETA 1 SELECTIVE NON SELECTIVE 𝝰 BLOCKER
● Dobutamine
1. Phenoxybenzamine - irreversible, noncompetitive
○ Pharmacologic Stress Test
● MOA:
○ 1st line for Cardiogenic Shock
○ ⊖ 𝝰 Receptor
○ Mgt for acute HF
○ ⊖ H Receptor
○ ⊖ 5-HT Receptor
● 𝝰 R: Mgt of Pheochromocytoma – tumor in the

le
BETA 2 SELECTIVE adrenal medulla (best tx is surgical
Classes:
removal–complication is managed by
1. Bronchodilators – for BA, COPD
Pheochromocytoma
a. SHORT-ACTING BETA AGONISTS AMPoTa
○ Pre-surgical tx
● Albuterol / Salbutamol
○ Inoperable tumor
● Metaproterenol
● H R: Mgt of Mastocycosis
● Perbuterol
● 5-HT R: Mgt of Carcinoid syndrome (tumor found in
● Terbutaline (only BA via SQ)
the enterochromaffin cell–over secretion of 5HT)
b. LONG-ACTING BETA AGONIST BIFS
● Bambuterol
2. Phentolamine - reversible, competitive
● Indacaterol
● Antidote in the tx of sympathomimetic poisoning
● Formorerol – fast onset
(S/Sx: HTN, digital necrosis, VTach)
● Salmeterol – slow onset
● Mgt of pheochromocytoma
● Tx of Raynaud syndrome (caused by extreme
2. Tocolytics – for preterm labors
climate → digital necrosis)
● Isoxsuprine (Duvadilan®)
● Tx of erectile dysfunction / impotence (as a
● Ritodrine
vasodilator; locally injected)
● Terbutaline

T/E:
ALPHA 1 RECEPTOR BLOCKER “-zosin”
● Tremors
A. VASODILATORS → ANTIHYPERTENSIVES
● Hypokalemia
1. Prazosin
● VTach
2. Doxazosin
3. Terazosin
● T/E: first dose phenomenon: pool of blood is pulled
Indirect Acting Sympathomimetic
by the gravity
RELEASERS → ↑EXOCYTOSIS ○ orthostatic hypotension
○ Syncope
1. Tyramine – D/I with MAOis → hypertensive crisis
● Remedy: take HS
2. Ephedrine – from Ma Huang
3. Amphetamine – alt for ADHD
4. Angiotension II
5. Methamphetamine (Shabu)
B. FOR BENIGN PROSTATIC HYPERPLASIA →
URINATE ONLY ADDITIONAL MOA
● Prostate enlargement → targetted by Finasteride, BETA 1 BLOCKER + INTRINSIC SYMPATHOMIMETIC
Dutasteride (shrink prostate gland) ACTIVITY [ISAng CLAP]
● Significant urine retention → targetted by 𝝰1 ⊖

t
● B1 blockers with agonist action in B2
1. Tamsulosin 1. Carteolol, Celiprolol
2. Alfuzosin 2. Labetalol
● Provide symptomatic relief of urine retention 3. Acebutolol

t
4. Pindolol, Penbutolol
ALPHA 2 RECEPTOR BLOCKER
1. Yohimbine
BETA 1 BLOCKER + MEMBRANE STABILIZER
2. Rauwolscine
ACTIVITY [MiSA PALM]

g
● B1 blocker with local anesthesia
● Risks (eyes): ⓧblinking reflex → abrassion in
B. BETA BLOCKERS
cornea → corneal injury
● MOA: β antagonism → Cardiac depression, Smooth

e
1. Propranolol, pindolol
muscle dilation, Skeletal muscle
2. Acebutolol
● (-) Inotropy, (-) Chronotropy, (-) Dromotropy
3. Labetalol
● Classes: Selectivity & Additional MOA
4. Metoprolol

n
● Clinical Uses:
BETA 1 BLOCKER + ALPHA 1 BLOCKADE
○ Mgt of cardiovascular D/O (VASODILATORY) [BALiC]
■ HTN: 1st line - in px with history of MI

ia
● With vasodilatory effect
■ Angina pectoris 1. Carvedilol
■ Stable HF [BaCaNaMan CHieF] 2. Labetalol
● Bisoprolol
● Carvedilol BETA BLOCKER WITH ↑NO CONC
● Nebivolol - ↑[NO] ● Increase NO concentration → vasodilation
● Metoprolol succinate 1. Nebivolol–most cardioselective BB
■ Arrhythmia – Class II (except Sotalol)

le
○ Mgt of Eye D/O – Glaucoma (↓IOP)
● Timolol
● Betaxolol
○ Tx of Endocrine D/O – Hyperthyroidism
(hypersympathomimetic Sx; prevents conversion or
deiodination of T4 to T3)
● Propranolol
○ Prophylaxis of migraine HA
○ Tx of stage fright
● Carvedilol - alternative; less sedating

● T/E:
○ Bradycardia (HR 60 bpm)
○ Mask hypoglycemic symptoms
○ Bronchoconstriction
○ Hyperlipidemia

SELECTIVITY
NONSELECTIVE BETA BLOCKER
● ⊖β1,β2 → cardiac depression, bronchoconstriction
(risk)
● C/I: COPD & Asthma px
1. Nadolol
2. Sotalol - only Class III β blocker anti-arrhythmic
3. Timolol
4. Propranolol

BETA 1 RECEPTOR BLOCKER / CARDIOSELECTIVE

1. Celiprolol
2. Bisoprolol, betaxolol
3. Esmolol
4. Atenolol, acebutolol
5. Metoprolol
 PARASYMPATHETIC DRUGS 2. CHOLINOCEPTORS
A. Muscarinic Receptor GPCR
Acidity Bradycardia, Basa Contraction
1. ACETYLCHOLINE

t
A. Biosynthesis M1 Gq Parietal cell (+) Proton pump → HCl
a. Active uptake of Choline in the presynapse (stomach) production
● RLE

t
M2 Gi Heart (atria) Bradycardia
● Transporter: Choline transporter – promotes active Exocrine gland WETNESS (sweating,
uptake M3 Gq lacrimation, general
● ⊖Hemicholinium (CT) sweating)
Eyes (ciliary muscle Ciliary muscle - near

g
b. Formation of Acetylcholine CM, circular muscle vision
● Choline + Acetyl CoA from mitochondrion → M3 Gq pupil, Circular muscle - Miosis
Smooth Bronchial muscle Bronchoconstriction
*Choline-Acetyl-Transferase* → Acetylcholine
Muscle GI Tract Bowel movement,

e
diarrhea
B. Storage Urinary bladder Urination
● Vesicle
● Transporter: Vesicle-Associated Transporter VAT →
stores ACh to vesicle to prevent premature metabolism B. Nicotinic Receptor IONOTROPIC

n
● ⊖Vesamicol (VMAT) ● Ion channel– SODIUM (Na) Channel
● (+) Depolarization → Excitatory

ia
C. Release
● (+) 𝝰–latrotoxin Synaptic
NN Ganglion
● (-) Botulinum toxin neurotransmission
Adrenal medulla EPI release
NM Neuromuscular end Contraction
D. Termination
plates (skeletal
● Metabolism
muscle
○ Acetylcholinesterase (hydrolase)

le
○ ACh → AChE → Choline + Acetate
○ Anticholinesterase → ↑ACh
● Passive Diffusion 3. AGONISTS / CHOLINOMIMETICS
Classes (based on MOA):
1. Direct Acting Cholinomimetics (via Cholinoceptor
Summary:
activation)
Sympathetic Parasympathetic
2. Indirect Acting Cholinomimetics (–inhibit ACh
Synthesis Metyrosine Hemicholinium
Storage Reserpine Vesamicol metabolism)
Release Tyramine 𝝰-latrotoxin
Enhancer Ephedrine
Amphetamine DIRECT ACTING CHOLINOMIMETICS
Methamphetamine
CHOLINE ESTERS
Release Guanethidine Botulinum toxin
Inhibitor Guanadrel a. Non-selective
Bretylium ● Active both nicotinic and muscarinic
Termination Cocaine – 1. Acetylcholine
(uptake) Sibutramine 2. Carbachol
Atomoxetine 3. Metacholine - Dx for Pulmonary Challenge Test
Termination Moclobemide Anticholinesterase / b. Muscarinic Selective
(metabolism) Phenylzine Indirect Acting
1. Betanechol (Urecoline®) - Tx of urinary retention
Isocarboxazid Cholinomimetics
Tranylcpromine
Selegiline ALKALOIDS
a. Non-selective
Entacapone ● Arecoline
Tolcapone b. Muscarinic Selective
● Pilocarpine
○ Mgt of Glaucoma
○ Mgt of GI atony
● Muscarine
c. Nicotinic Selective – mgt of smoking cessation
● Nicotine
● Lobeline
● Varenicline
 IRREVERSIBLE
INDIRECT ACTING CHOLINOMIMETICS / ORGANOPHOSPHATE
ANTICHOLINESTERASES
● Not used clinically except ECHOTHIOPHATE
a. Classification:
○ IA for chronic open angle glaucoma
● Reversible - safer

t
● Irreversible - toxic
Agricultural poisons
● CNS Acting Agents - anti Alzheimers
1. Malathion
2. Parathion

t
b. Uses:
● Mgt of Alzheimer’s Disease
Chemical Warfare (Nerve Gas)
○ CNS Acting → ↑ACh
1. Tabbun
● Mgt of Mysthenia Gravis
2. Soman

g
○ Pathophysiologic component:
3. Sarin
■ Autoimmund D/O → adressed by
IMMUNOSUPRESSANTS
CNS ACTING
■ Progressive muscle weakness →

e
addressed by Carbamates ANTI-ALZHEIMER'S
○ Dx: Edrophonium (Tensilon®) – “Tensilon test” 1. Tacrine
○ Tx: Carbamates– Neostigmine, Ambenonium, 2. Galantamine
Pyridostigmine, etc 3. Rivastigmine
● Mgt of Glaucoma – ↓IOP 4. Donepezil

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○ Echothiophate
○ Demecarium

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● Mgt of GI atony
○ Physostigmine 4. CHOLINOLYTICS / ANTAGONIST
● Antidotes ● Classification:
○ Physostigmine – Atropine poisoning ○ Muscarinic Blockers
○ Neostigmine – Other anticholinergic poisoning ○ Nicotonic Blockers
○ Edrophonium, Neostigmine – NMB toxicity

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c. T/E MUSCARINIC BLOCKERS / ANTICHOLINERGICS
● Diarrhea
● Urination PROTYPE: ATROPINE
● Miosis ● Effects:
● Bradycardia ○ CNS Effects (toxic)
● Bronchoconstriction ■ Confusion, Agitation, Disorientation, Acute
● Emesis psychosis
● Lacrimation ■ Antidote: Physostigmine
● Sweating (general) ○ Peripheral Effects
● Salivation ■ ⊖M1: ⊖HCl production
■ ⊖M2: Tachycardia
d. Tx of Toxicity: ■ ⊖M3:
● Early detection / Short DOI (within 24 ● Exocrine gland: Dryness (Xerostomia,
hrs–potentially reversible): Cholinesterase Anhydrosis, Hyperthermia, Erythema)
reactivators–Pralidoxime, Diacetylmonoxide Depression
● Late detection / Long DOI (> 24 hrs–irreversible): ● Muscles: Relaxation (Cycloplegia,
Anticholinergic agent–Atropine mydriasis; Bronchodilation; Ileus,
constipation; Urine retention)
● Clincal Application:
REVERSIBLE AGENTS ○ Tx Symptomatic bradycardia
○ Antidote for cholinomimetic (organophosphates)
AMINO ALCOHOL poisoning (late detection)
1. Edrophonium (Tensilon®) ○ Given w/ Diphenoxylate (opioid derivative–addicting
at high doses) as antidiarrheal
CARBAMATES “-stigmine”
1. Physostigmine / Eserine OTHERS: CNS ACTING
2. Pyridostigmine A. CNS ACTING
3. Neostigmine 1. Benztropine, Biperiden, Trihexylphenidyl
4. Ambenonium ● Mgt of Extrapyramidal syndome & parkinsonism
5. Demecarium 2. Scopolamine
● Tx of motion sickness
 ● MOA: ⊖NM receptor → immediate relaxation →
B. EYE-ACTING (as mydriatics & cyclopegics) paralysis
1. Cylopentolate
2. Homatropine
3. Anistropine TOXIC EFFECTS:

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● Mydriatic - For eye exam ● General: Respiratory / Diaphragmatic paralysis
● Cyclopegics - tx of pain (eye injury) ○ Tx: Edrophonium (Tensilon), Neostigmine
● Succinylcholine: Myalgia, Myositis, Rhabdomyolysis→

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hyperkalemia, acute renal failure due to accumulation of
C. BRONCHI-ACTING (as bronchodilators) myoglobin in the blood then to kidney; (idiosyncratic)
a. SAMA (Short-Acting Muscarinic Antagonist) Malignant hyperthermia
1. Ipratropium ○ Tx: Dantrolene

g
2. Oxytropium ● Tubocurarine: ↑ degranulation of H2 in the mast cell →
b. LABA (Long-Acting Muscarinic Antagonist) anaphylactoid rxn
1. Tiotropium [Tagal = long] ○ Tx: EPI
● Mgt of bronchial asthma, COPD

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D. GASTRIC GLAND- ACTING (as Antacid)
1. Pirenzepine

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2. Telenzepine

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E. GI TRACT & URINARY BLADDER-ACTING
1. Methscopolamine
2. Glycopyrrolate
3. Hyoscine-N-Butyl-Bromide HNBB (Buscopan®)
4. Dicycloverine
5. Oxybutinin
6. Scopolamine

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● For urine incontinence & hypermotility disorder

ANTINICOTINICS
NN RECEPTOR BLOCKER / GANGLIONIC BLOCKER
● Obsolete antihypertensives
1. Hexamethonium
2. Trimethaphan
3. Mecamylamine

NM RECEPTOR BLOCKER / NEUROMUSCULAR

BLOCKERS (NMB)
● Uses: Skeletal muscle relaxant
● Clinical uses:
○ Anesthetic adjuncts to relax skeletal muscle
prior to surgery
○ Tx of spastic disorder (ex: spastic cerebral
palsy)

A. Depolarizing NMB / Irreversible NMB /

Noncompetitive NMB
1. Succinylcholine
● MOA: promotes irreversible NM receptor activation
→ 2 phases of effect:
○ Initial: depolarizing → contraction
○ Final: desensitizing phase → worn out muscle
→ relaxation
B. Non-depolarizing NMB / Reversible NMB /
Competitive NMB
a. Isoquinoline: “-curium” (ex: Atracurium);
Tubocurarine
b. Steroidal: “-curonium” (ex: Pancuronium)
 OF -cu

Hematologic Drugs
ACTIONMOLECULAR HANISM

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DRUGS: COAGULATION D/O
● Bleeding – Hemorrhage

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● Clotting – Thrombosis

PHYSIOLOGY OF CLOT FORMATION

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A. EVENTS
1. CELLULAR EVENTS: Platelets / Thrombocytes
a. Platelet migration & Aggregation

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b. Components:
i. Pro-aggregants: CLOT PATHWAYS INVOLVED IN BLOOD COAGULATION
● TXA2 CASCADE
● ADP
● 5-HT

n
ii. Anti-aggregants: BLEED
● PGI2 (prostacyclin)

ia
● PGE1
● cAMP
iii. Glycoproteins: CLOT – binding to
endothelial injury
● GPIA - binding of platelet to
COLLAGEN
● GPIB - binding of platelet to VON
WILLEBRAND FACTOR

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● GPIIB/IIIA - interplatelet binding via
Fibrinogen (bridge b/n platelets)
c. End product: 1° Hemostasis / White Thrombus / 1. Extrinsic: IIIa, VIIa
Platelet Plug 2. Intrinsic: VA, VIIIA, IXA
d. Problem: clot is unstable due to Fibrinogen (weak ● Convergence– common pathway: X → Xa
bridge)
XA → II (prothrombin) → IIA (thrombin)
2. PROTEIN EVENT: Clotting Factors IIA → I (fibrinogen) → IA (fibrin→ deposits onto platelet plug
a. Blood Coagulation Cascade and glues platelet together; attacts other cells esp RBC to
b. Goal: “to strengthen the weak bridge” deposit into the platelet plug (red thrombus)
● Activate fibrinogen → fibrin (polymer)
c. Product: 2° hemostsis / Red thrombus
i. Stable clot
B. REGULATORY MECHANISM
Proteins–Clotting Factors: PLASMIN
1. Zymogen – initially (inactive) (ex: I) ● Serine protease enzyme
2. Active – (ex: Ia) ● IA form: Plasminogen
● Plasminogen → Tissue Plasminogen Activator →
Plasmin
● Responsible for facilitating FIBRONYLSIS → bleeding
ANTICLOTTING FACTORS: PROTEIN C & S
INDIRECT ACTING ANTICOAGULANT / THROMBIN
● Interfere with coagulation cascade INHIBITORS
● MOA: Destroy clotting factors which activate

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1. Antithrombin III (ATIII) prothrombin (II) (technically, XA up)
● Directly inactivates activated clotting factors (IIa,
IXa, Xa, XIa, XIIa, XIIIa) Parenteral: Emergency
● Blocks IIa → ⊖1A → still a weak bridge → prone to

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dissolution → bleeding

2. Protein C & S
● Vitamin K-dependent anti-clotting factors

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● Attenuate the blood clotting cascade by proteolysis
of two co- factors Va and VIIIa (intrinsic) →
⊖convergence → bleeding .

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1. Heparin - heterogenous mixture of sulfated
DRUGS mucopolyssacharides

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A. ANTITHROMBOTICS → BLEEDING a. Forms of Heparin (based on size)
● Prevent clot formation → bleeding ● High Molecular Weight / Unfractionated /

ia
○ 1st event Cellular event – ANTIPLATELET Regular Heparin
● Low Molecular Weight Heparin
○ 2nd event / Coagulation Cascade –
1. Enoxaparin
ANTICOAGULANTS 2. Dalteparin
3. Tinzaparin
a. ANTICOAGULANT 4. Fondaparinux
5. Fraxiparin
● Interefere the blood coagulation cascade by actin on 6. Danaproid
different clotting factors (end: ⓧ1a)

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Criterion UFH / HMWH LMWH
DIRECT ANTICOAGULANT / THROMBIN INHIBITORS MOA Binds and forms an Binds to XA more
● MOA: Blocking directly IIa (thrombin) → bleeding active complex to selectively
Antithrombin III
(accelerates ATIII action
by 1000x)→ inhibits CF
XA, IIA
ROA Parenteral Parenteral
Prevention: SQ Prevention &
Treatment: IV (bolus, Treatment: SQ
infusion)
Monitoring aPTT (activated partial None
thromboplastin time) if
Parenteral:
1. Hirudin - natural substance from leech saliva (Hirudo
medicinalis) – ↑ risk hypersensitivity Application
in
❎
given IV INFUSION
✅
2. Lep1rudin - recombinant form of Hirudin; 1st line agent
for HIT pregnancy
3. Bivalirudin - prevention/tx of acute thrombosis
post-angioplasty b. Clinical uses:
● After the conduct of PTCA–Percutaneous ● When initiating anticoagulation therapy
Transluminal Coronary Angioplasty ○ Due to IMMEDIATE bleeding effect
4. Argatroban - alternative for HIT ○ Used at the start of warfarin therapy maxl 5
days only
Oral: ● Mgt of coagulative disorders:
1. Ximelagatran – withdrawn ○ Pulmonary embolism
2. Dabigatran (Pradaxa®) ○ Acute coronary syndrome
● Alt to Warfarin in the mgt of: ○ Deep vein thrombosis DVT
○ Stroke prophylaxis in px with atrial fibrillation ○ Venous thromboembolism VTE
○ Vascular thromboembolic d/o ● Anticoagulation is necessary during pregnancy
○ Deep vein thrombosis (LMWH)
● Advantages of Dabigatran (vs Warfarin)
○ No significant drug-food interaction c. T/E:
○ No PT-INR monitoring required ● Bleeding– intracerebral hemorrhage (most serious)
○ Safer >> warfarin ○ Antidote: Protamine sulfate [MOA:
○ Pricey than warfarin neutralization]
● T/E: bleeding ○ In every 100U Heparin = 1 mg Protamine SO4
(IV)
 ● Heparin-Induced Thrombocytopenia (HIT) –
immune-mediated thrombosis & thrombocytopenia E. T/E
→ clotting Initial Chronic
○ Tx: Lepirudin (FLA), Argatroban (alt) Cutaneous Bleeding
● Hairless, reversible alopecia necrosis Antidote: Vit K1 (phytonadione)

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● Long term: mineralocorticoid deficinecy Purple toe syndrome (beyond 3
● Osteoporosis (long-term) – ↑Ca resorption (Ca in wk use)
the bone is transferred to blood → ⓧCa for
strength in the bones) F. C/I

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● ↑ clearing of postprandial lipemia by causing the ● Pregnancy (teratogenic–depends on w/c trimester)
release of lipoprotein lipase from tissues ○ 1st: nasal hypoplasia & depressed nasal
bridge
d. Major Contraindications ○ 2nd: –
● Active bleeding ○ 3rd: hemorrhagic disorder of newborns

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● Genetic disorders (hemophilia / Xmas disease)
● Menstruation G. Monitoring Tests
● Preexisting thrombocytopenia ● PT-INR: Prothrombin time - International
Normalized Ratio

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● If less than → ↓warfarin (↑risk of thrombosis)
Oral: Maintenance ● If greater than → ↑warfarin (↑risk of bleeding)
a. XA Inhibitors Category PT-INR
● “-Xaban” Most px 2-3
● No monitoring is required
Px w/ prosthetic heart 2.5 - 3.5

n
1. Apixaban
valves
2. Rivaroxaban

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b. Coumarin derivatives
H. D/I [↑PT INR → bleeding, ↓PT-INR → clotting]
a. Pharmacokinetic DI
↑PT INR → bleeding ↓PT-INR → clotting
Enzyme INHIBITION Enzyme INDUCTION
Drug DISPLACEMENT ⊖Warfarin absorption (+Bile
from plasma proteins acid sequestrants except
(Pyrazolone derivatives) colesevelam)

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b. Pharmacodynamic DI
↑PT INR → bleeding ↓PT-INR → clotting
[A] + other Anticoagulant [A] + Green leafy veggies
[P] + Broad spectrum Abx

1. Warfarin – only clinically usefull coumarin derivatives

A. MOA: Inhibits hepatic synthesis of Vitamin
K-dependent clotting factors–X, IX, VII, II →
bleeding
○ Site of action: liver (manufactures clotting
factor) b. ANTIPLATELET
○ Synthesis: via VKERC (Vitamin K Epoxide
Reductase Complex)
○ Vit K-dep. CF – CF that requires Vit K
Hepatic Synthesis Warfarin Influence
Liver: (+) VKERC → Liver: (-) VKERC →
reactivation of ↑ ↓Hydroquinone →
Hydroquinone (active Vit ↓1972 → ⊖Ia → bleding
K) → ↑X,IX,VII,II → Ia
formation → clotting

B. Additional MOA:
○ Inhibit protein C & S (⊖bleeding effect) →
Clotting

C. Onset of action:
○ Initial: Clotting (max: 5 days)
■ Remedy: co-administer w/ Heparin
○ Final: Bleeding (> 5 days)
● Targets the “1st event / cellular events”
D. Use: Chronic anticoagulation
○ Chronic atrial fibrillation
○ Prostethic heart valve TXA-2 SYNTHESIS INHIBITOR
○ Rheumatic heart disease
○ Deep vein thrombosis
○ Venous thromboembolism
 1. Tirofiban
2. Abciximab
3. Eptifibatide

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B. FIBRINOLYTICS

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1. Aspirin (< 325 mg/day) (↓dose = ↑ efficacy)
● MOA: ⊖COX in the platelet via irreversible inhibition of

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COX on AA → ⓧ Prostaglandin → ↓TXA-2 → bleeding
● Clinical Use:
○ 1st line antiplatelet (in 1° & 2° prevention of Acute
thrombotic events)

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ADP INHIBITORS ● Plasminogen activator
A. Reversible ● Hasten the conversion of plasminogen to plasmin
1. Ticagrelor ● Clinical uses: for Emergency Cases

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B. Irreversible: Thienopyridines “-clop ○ ST Elevation MI (STEMI)
○ Massive pulmoembolism
○ Acute ischemic stroke

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○ Central DVT
● Toxic Effects: Bleeding
● Antidote: Tranexamic acid – ⊖Plasminogen activator →
clotting

THROMBOLYTIC AGENTS
1. Streptokinase

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● Isolated form β-hemolytic streptococci
● ↑ risk of hypersensitivity
1. Ticlopidine (250mg bid) ○ Tx: Diphenhydramine (IV)
● Alt to Aspirin for stroke prophylaxis 2. Urokinase
● T/E: Cause low platelet count → ● From mammalian kidneys
Thrombocytopenia, Neutropenia 3. Anistreplase
2. Clopidogrel (75 mg OD) ● APSAC–Anisoylated Plasminogen Streptokinase
● Not neutropenia & thrombocytopenia effect Activator Complex
● Alt agent of Aspirin in the mgt of Coronary Artery
Disease Tissue Plasminogen Activator (TPA)
4. Alteplase - natural TPA
5. Reteplase - recombinant TPA
PDE/ADENOSINE UPTAKE INHIBITORS
● MOA: PDE is responsible for the metabolism of
cAMP to AMP → ↑cAMP, ↑PGI2 (anti-aggregants)
● Actions: Anti-aggregant → bleeding, vasodilation
● Clinical uses:
○ General application: Antiplatelet (in C. PROTHROMBOTIC → CLOTTING
combination with other APs)
■ + Aspirin
■ + Clopidogrel VITAMIN K
○ ● Supports X, IX, VII, II production
1. Dipyridamole (Persantin®) - Dx agent in ● Forms:
Pharmacologic Stress Test ○ Vit K1 - phytonadione – clinically useful
● Effect on coronary artery: Coronary Vasodilation → ■ prevents hemorrhagic disorder of newborn
“Coronary Steal Phenomenon” does not target the ■ bleeding caused by Vit K deficiency
heart but by relaxing the coronary arteries → heart (nutritional, metabolic, warfarin poisoning)
will undergo reflex tachycardia → heart is stressed ○ Vit K2 - menaquinone; found in human tissues
2. Cilostazol (Pletaal®) – Mgt of intermittent Claudication and is synthesized by intestinal bacteria / flora
○ Vit K3 - menadione – water soluble; ineffective in
warfarin overdosage

GP IIB / IIIA RECEPTOR ANTAGONIST ε-AMINOCAPROIC ACID = TRANEXAMIC ACID

● MOA: Inhibit interplatelet binding ● MOA: Antifibrinolytic
● Clinical use: Prevention/Treatment of Acute Thrombosis ● Uses:
post angioplasty (same with Bivalirudin) ○ Fibrinolytic poisoning
● T/E: Bleeding ○ Prev/tx of post-procedural bleeding
● A synthetic inhibitor of fibrinolysis
 ● An adjunctive therapy in hemophilia
● As therapy for bleeding from fibrinolytic therapy,
● Prophylaxis for rebleeding from intracranial aneurysm
● Has been used in patients with postsurgical
gastrointestinal bleeding and postprostatectomy
receptor-mediated endocytosis
● Primarily CHOLESTEROL–waxy fat carried through
the blood by lipoproteins
● Carries cholesterol TOWARDS the heart
● Exert atherogenic effect: conveys lipids into the

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bleeding and bladder hemorrhage secondary to artery walls
radiation- and drug-induced cystitis 5. HIGH DENSITY LIPOPROTEIN
● Protective lipoprotein through reverse cholesterol
transport

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APROTININ ● Carries cholesterol AWAY from the heart
● ⊖Plasmin ● Major vehicle for the transport of cholesterol from
● Given to minimize bleeding in px who underwent CABG the peripheral tissues to the liver for use or
(Coronary artery bypass graft) excretion
● Exert several antiatherogenic effects:

g
○ retrieval of cholesterol from the artery wall
○ inhibit the oxidation of atherogenic
lipoproteins
DRUGS FOR DYSLIPIDEMIA

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LIPIDS
● Biomolecules that are soluble in organic solvents and
insoluble in water.
● Insoluble in water; must be incorporated in the blood
(aqueous in nature) to be distributed

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○ Must be combined with proteins to be distributed
● Types:

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○ Hydrolyzable – can be broken down into simpler
molecules by hydrolysis through an enzyme
(Lipoprotein lipase)
■ Triglycerides – upon hydrolysis, yields FFA and
glycerol
● Has ESTER functional group–hydrolyzable
○ Non-hydrolyzable – cannnot be broken down into
simpler molecules by hydrolysis
■ Cholesterol – a steroid

1.

2.
CHYLOMICRON
● Largest lipoprotein

intestine) le
MAJOR GROUPS OF LIPOPROTEINS

● Primarily TAGS (80-90%

● Originate in the intestine from exogenous dietary fat
(from the food we eat; synthesized in the small

● Responsible for the transport of dietary lipids into

circulation
VERY LOW DENSITY LIPOPROTEIN
● Primarily TAGS (50-70%)
● Derived in the liver; endogenous
● Secreted by liver and export triglycerides to
peripheral tissues
3. INTERMEDIATE DENSITY LIPOPROTEIN
● Intermediate in the catabolism of VLDL to LDL
● Aka “VLDL Remnant” because it is the remnant afer
the depletion of TAGS (derivative of VLDL)
● Ave. cholesterol cont: 30%
● Ave. TAGs cont: 40%
4. LOW DENSITY LIPOPROTEIN
● Product of intravascular metabolism of the TAG-rich
lipoprotein, VLDL (Remnant of VLDL but devoid of
TAGs)
● Catabolyzed in hepatocytes and other
 LIPID LOWERING AGENTS
HMG-CoA REDUCTASE INHIBITORS FIBRATES / FIBRIC ACID DERIVATIVES
● MOA: Block reduction of HMG-CoA to Mevalonic Acid 1. Gemfibrozil – t1/2 = 1.5 hrs
(targets de novo synthesis) 2. Clofibrate

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● Reduce LDL level (alone or in combination with resins, 3. Fenofibrate – t/12 = 20 hrs
niacin, ezetimibe) 4. Bezafibrate
● Liver will be "pushed" to utilize its alternative method; 5. Ciprofibrate
thus ↑HDL levels & ↓ Blood LDL ● MOA: Peroxisome Proliferator Activated Receptor -

t
● Reduce cholesterol synthesis (Up-regulate low-density Alpha Agonist
lipoprotein (LDL) receptors on hepatocytes) ○ ⨁ LPL → ↓ TAGs
● T1/2 = 1-3 hours → taken HS at peak of De novo ○ ⨁Apo A-I, Apo A-II → ↑HDL
synthesis, except Atorvastatin (T1/2=14 hrs) and ○ ⊖APOCIII → ↓VLDL, ↓serum TAG, LDL

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Rosuvastatin (T1/2 = 19 hrs) ● Uses:
● Absorption enhanced by food ○ 1st line: HyperTAGS
● Rosuvastatin is the most efficacious agent for severe ○ Mgt: Metabolic syndrome
hypercholesterolemia ○ In hypertriglyceridemias in which VLDL predominate

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● Uses: and in dysbetalipoproteinemia
○ 1st line in the mgt of HYPERCHOLESTEROLEMIA ○ May be of benefit in treating the
○ For stabilization of atheromatous plaque (4-6mos) hypertriglyceridemia that results from treatment with
● T/E: viral protease inhibitors

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○ Hepatic dysfunction (AST & ALT is necessary) ● T/E:
○ Myositis, rhabdomyolysis ○ Rhabdomyolyss
○ Teratogenic

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○ ↑risk of bile stones / cholesterol gallstone
● Ex: “-statins” ○ Clofibrate – Hepatobiliary CA

NICOTINIC ACID

●
MOA:

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○ Inhibits the release and synthesis of VLDL
○ Mobilization of FFA by enhancing Lipoprotein
Lipase activity → to reduce TAGS
○ ⊖ HDL catabolism → ↑HDL
○ ⊖LP(a) lipoprotein → ↓lipoproteiNemia → ↓risk of

Uses:
angina pectoris

○ Alt to fibrates: HyperTAGs

○ Mgt of lp(a) LipoproteiNemia
○ Useful in patients with combined hyperlipidemia and
in those with dysbetalipoproteinemia
1.
2.
3.

●
●

●
BILE ACID BINDING RESIN / SEQUESTRANTS
Cholestyramine
Colestipol
Colesevelam–antidiabetic (unknown MOA)

Taken PO; non absorbed→ promote adsorption

MOA: Bile acid will adhere to the surface of bile acid
sequestrants → promote excretion & inhibit biliary
recycling →
↓reabsorption of bile acid → ↑bile acid synthesis → lipid
converts more cholesterol into bile which exits the body
→ cholesterol worn out → ↓blood cholesterol, ↓LDL.
↑HDL, ↑TAGS, ↑VLDL
● ! The most effective agent for increasing HDL ● Uses:
● T/E: ○ add ons to statins for hypercholesterolemia
○ Hepatotoxicity ○ Antidote for oral poisoning (except colesevelam)
○ Erythema (flushing) ○ Used in combination with Niacin if used to tx px with
■ Associated with ProstaglandinD2 → relieved by LDL elevations in person with combined
NSAID hyperlipidemia
■ Reduced by taking aspirin half our earlier than ○ Used in relieving pruritus in px who have
niacin cholestasis and bile salt accumulation
Ibuprofen OD mitigates flush ○
● T/E:
○ Steatorrhea, bloating, constipation
○ Vit ADEK Malabsorption
○ ↑risk of bile stones
○ ↑TAGs

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○ Colesevelam is Pregnancy Category B

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STEROL ABSORPTION INH: EZETIMIBE
● MOA: ⊖Niemann-Pick-C1-Like1 Transporter– transporter
responsible for the passage of fats from small intestine
towards the blood; allows entry of cholesterol from SI to

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blood
● Selective inhibitor of intestinal absorption of phytosterols
and cholesterol
● Uses:

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○ Co-administration w/ statins for
hypercholesterolemia (also in px with
phytostererolemia)
■ Ex: Simvastatin + Ezetimibe (Vytorin)

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● T/E: myositis (rare), Hepatic d/f (low incidence)

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Others:
1. Lomitapide - Inhibits microsomal triglyceride
transfer protein (MTP, plays an essential role in the
addition of triglycerides to nascent VLDL in liver,
and to chylomicrons in the intestine)
2. Mipomersen - An antisense oligonucleotide that
inhibits Apo B- 100 synthesis; Available only for use
in homozygous familial hypercholesterolemia

le
through a restricted (REMS) program

Combination Therapy:
1. Fibrates + BAS – Useful in treating patients with familial
combined hyperlipidemia who are intolerant of niacin or
statins (T/E: cholelithiasis)
2. Statins + BAS – Useful in the treatment of familial
hypercholesterolemia but may not control levels of VLDL
in some patients with familial combined
hyperlipoproteinemia
3. Niacin + BAS – Effectively controls VLDL levels during
therapy of familial combined hyperlipoproteinemia or
other disorders involving both increased VLDL and LDL
levels
4. Statins + Niacin – An efficacious and practical
combination for treatment of familial combined
hyperlipoproteinemi
5. Statins + Ezetimibe – Highly synergistic in treating
primary hypercholesterolemia and has some use in the
treatment of patients with homozygous familial
hypercholesterolemia who have some receptor function
6. Statins + Fenofibrate – Complementary in the
treatment of familial combined hyperlipoproteinemia and
other conditions involving elevations of both LDL and
VLDL
 Cardiovascular Drugs ANTIHYPERTENSIVE DRUGS

DIURETICS

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➔ Drugs that can enhance urinary excretion of Na+ ions
DRUGS FOR HYPERTENSION
and H2O
➔ ↑Na & H2O in the urine = ↓Na & H2O in the blood →

t
INTRODUCTION TO BLOOD PRESSURE ↓BV → ↓Preload → ↓SV → CO → ↓BP
For cellular survival, O2 and nutrients is necessary via the ➔ Site of action: Kidney tubule
blood. Blood is stagnant thus requires a pressure (external
strength).

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↑Pressure applied = ↑movement of blood

Factors contributing to Pressure:

1. Heart

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● Ventricular Contraction: Systole
● Ventricular Relaxation: Diastole
2. Blood vessel (2)
● Arteries – distributes OXYGEN-RICH blood from
heart → organs

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○ Provides greatest pressure → ↑ movement
○ [AWAY]

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● Veins – disrtributes OXYGEN-POOR blood from
organs → heart
◆ Proximal Convoluted Tubule (PCT)
○ Provide the least pressure → ↓ movement
◆ Distal Convoluted Tubule (DCT)
○ [VALIC]
◆ Loop of Henle
● Thick Ascending Limb (TAL)
FACTORS AFFECTING BLOOD PRESSURE ● Thin Descending Limb (TDL)
◆ Collecting Duct

le
Hydraulic equation: (all are directly proportional to BP)
𝐵𝑃 = 𝐶𝑂 𝑥 𝑆𝑉𝑅
Classifications (2) → Diuresis (Na & H2O)
1. Cardiac Output 1. Natriuretics – Na excretion
➔ Volume of the blood pumped out by the heart per minute a. CAIS – PCT
➔ Unit: vol/min b. Loop – TAL
➔ CO = HR x SV c. Thiazide – DCT
➔ Factors:
d. K-Sparing – CD
◆ HR Heart Rate – Chronotropy
● ⨁Chronotropy → ↑CO → ↑BP 2. Aquaretics – H2O excretion
◆ SV Stroke Volume – volume of the blood pumped a. Mannitol
out by the heart in every contraction / beat b. Vasopressin Modifiers
● ⨁SV → ↑CO → ↑BP
● Determinants of Stroke volume:
○ Inotropy (strength) A. Natriuretics: CARBONIC ANHYDRASE INH
◆ ⨁Inotropy → ↑SV → ↑CO → ↑BP
○ Preload (Venous retourn / End Diastolic
Volume) ● Sulfonamide-like →
◆ Volume of the blood received by the sulfonamide-associated t/e
heart at the end of relaxation ○ Blood – hemolytic
◆ ↑Preload (↑blood welcomed by the vein → ↑
blood to be ejected) → ↑SV → ↑CO → ↑BP anemia
◆ Factors: ○ Skin – SJS
● Venous Tone – M found in the ● MOA: ⓧ Carbonic anhydrase
veins ○ Targets: Kidneys, Eyes,
○ ↑Veins tone → Venoconstriction →
↑blood will be received by the heart Brain
(at every relaxation) – ↑Preload → ■ PCT – ⊖reabsorption of Na & HCO3 ions
↑SV → ↑CO → ↑BP
● Blood Volume – Na+ & H2O in ● Short-lived natriuresis→ NMT 3 days
the blood ● ∴ not clinically useful anti-HTN
○ ↑Na in the blood → H2O follows → ● HCO3 loss is continuous → ↓HCO3
↑blood volume → ↑Preload → ↑SV →
↑CO → ↑BP (basic) in the blood → Metabolic
acidosis
2. Systemic Vascular Resistance / Afterload ● S/E: Metabolic acidosis
➔ Pressure required for the blood to be ejected by the ■ Ciliary bodies – ⊖aqueous humor
heart
production → ↓IOP → Anti-Glaucoma
➔ Factor:
◆ Tone of the Arteries – narrowness of the artery
● ↑Tone → narrow → ↑SVR → BP
 ■ Choroid plexus – ⊖cerebrospinal fluid ● Anion poisoning
production → ↓swollen head size ➔ S/E:
● Clinical Uses: ◆ Electrolyte imbalance (HYPO ALL)
○ Mgt of Glaucoma – 1st line agent in Open-Angle ◆ Sulfonamide-associated t/e

t
Glaucoma ◆ Ototoxicity (greatest risk: Ethacrynic acid)
○ Induce urinary alkalinization (in the tx of WA ◆ Metabolic related toxic effects (Hypokalemic
poisoning– Aspirin, Phenobarbital) metabolic alkalosis) hyperGLU

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○ Tx of Metabolic Alkalosis (remove high amounts ● HyperGlycemia
of HCO3 in the blood) ● HyperLipidemia
○ Acute Mountain Sickness – swollen head when ● HyperUricemia
climbing at high altitude places ● HyPOmagnesemia
○ Catamenial Seizure – type of epilepsy ➔ D/I:

g
manifested by women during onset of ◆ Aminoglycosides
menstruation (Acetazolamide) ◆ Cisplatin
● T/E:

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○ Hyperchloremic Metabolic acidosis Sulfonamides:
○ Sulfonamide-assoc. T/E (hemolytic anemia, SJS) 1. Furosemide the only one with venodilating effect
● C/I: 2. Bumetanide
○ COPD – acidotic by default
○ Chronic liver disease – NH3 & HCO3 competition Phenoxyacetate

n
for excretion; NH3 will not be excreted → 3. Ethacrynic Acid highest risk of ototoxicity
accummulate in the brain → encephalopathy

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🌟
Sulfonylurea
1. Acetazolamide ( Diamox®) – Catamenial seizure 4. Torsemide
2. Dorzolamide
3. Brinzolamide
4. Dichlorphenamide
C. Natriuretics: THIAZIDE DIURETICS

le
B. Natriuretics: LOOP DIURETICS ➔ Sulfonamide-like
➔ MOA: ⓧ NaCl Co-transporter in
the DCT → ↓ Na, Cl but ↑ Ca
➔ Aka High Ceiling Diuretics ◆ ⊖ reabsorption of Na & Cl →
(↑ dose = ↑ effect) (others HYPOnatremia &
provide maximal effect HYPOchloremia
despite inc. dose) ◆ Less effective than loop
➔ Have the highest efficacy in (loop can inhibit Na, K and
mobilizing (lowering blood Cl whereas Thiaizide can
conc) Na+ and Cl− from the only inhibit Na & Cl)
body ➔ Effects:
➔ Sulfonamide-like ◆ Natiuresis: within 2 weeks
➔ MOA: ● If > 2 WKS: Diuretic breaking Phenomenon
ⓧNa-K-2Cl-Co-Transporter (NK2Cl) in the TAL → ↓ (no diuretic action anymore)
Na, K, Cl, Mg, Ca ● As compensation, after 2 weeks,
vasodilation will occur
◆ 1° action: ⊖ Monovalent ion reabsorption (Na, K,
◆ Vasodilation: beyond 2 weeks
Cl) ◆ ⨁CA Reabsorption → ↑Ca HYPERcalcemia
◆ 2° Action: ⊖ Divalent cations (Mg, Ca) ◆ ↑ expression of COX → ↑PGE2 conc → ↑
➔ Effects: diuresis
◆ 1° action = most effective ● D/I: NSAIDS
◆ 2° action ➔ Uses:
◆ ↑ expression of COX → ↑PGE2 conc → ↑ ◆ 1st line agent for HTN (Others: CAT CCB,
diuresis ACEi/ARBs, Thiazide)
● D/I: NSAIDs ◆ Adjuncts in the mgt of Heart failure
◆ Venodilation = ↓Preload – FUROSEMIDE ◆ Mgmt of Nephrolithiasis due to idiopathic
hypercalciuria
➔ Uses:
● (↑Ca (urine) in the kidneys → some are not
◆ Edematous condtions: fully excreted → crystallizes in the kidney →
● Heart failure nephrolithiasis)
● Acute Pulmonary Edema ● Since Thiazide ↓Ca reabsorption → ↓Ca in
◆ Nonedematous Conditions: the urine → ⓧcrystallization of Ca
● Hyperkalemia ◆ DOC for Nephrogenic DI (paradoxical)
● Hypercalcemia (loop diuretics do not ● Vasopressin / ADH deficiency
● Polyuria
generally cause hypocalcemia
➔ T/E:
● Acute renal failure ◆ Electrolyte imbalance (HYPO–ALL except Ca)
 A. AQUARETICS: MANNITOL
◆ Sulfonamide-associated t/e
◆ Metabolic related toxicity: HYPERGLU
● HyperGlycemia ➔ Creates an osmotic gradient
● HyperLipidemia in the water permeable sites
● HyperUricemia

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of the kidney tubule
◆ PCT, TDL
True Thiazides (w/ Benzothiadiazide) ➔ MOA: Mannitol undergoes
1. Chlorthiazide rapid glomerular filtration

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2. Hydrochlorothiazide (concentrates in urine) →
stays in urine as it is
Thiazide-like (not Benzothiadiazide but same MOA) impermeable → water will undergo osmosis →
1. Chlorthalidone aquaresis
2. Indapamide ➔ Use:

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3. Metolazone ◆ Mgt of inc. incranial pressure (Cerebral edema)
➔ T/E:
◆ Dehydation
D. Natriuretics: K-SPARING DIURETICS ◆ HYPOVOLemia (extremely ↓ blood volume)

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◆ HYPERNATRemia

➔ MOA:
◆ Direct Action B. AQUARETICS: ANTIDIURETIC HORMONES
Mineralocorticoid
(Aldosterone) Receptor

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Antagonism –
Spironolactone,

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Eplerenone
◆ Epithelial Na+ Channel SYMPATHOPLEGICS [CO, SVR]
(ENaC) Inhibitors –
Effects:
Amiloride, Triamtere
➔ Effects: 1. Tachycardia : ↑CO
◆ Natriuresis: ⊖ Na+ reabsorption 2. Vasoconstriction: ↑SVR
● ⊝ Na ion efflux
◆ ⓧK+ secretion → K remains in the blood → A. Centrally Acting: 𝝰-2 AGONIST
HYPERkalemia

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1. Methyldopa
● Direct action mineralocorticoid R
2. Clonidine
antagonism → no ENAC opening → ↓Na
3. Guanfacine
reabsorption → K saved
4. Guanabenz
➔ Prevent K ion secretion by blocking the action of
aldosterone in the collecting tubules (actions are
dependent on renal prostaglandins) B. Peripherally Acting: Adrenal Neuronal Blockers
➔ Uses: Acts on the presynapse (storage and release)
◆ Mgt of Diuretic induced hypokalemia (loop & 1. Reserpine
Thiazide) 2. Guanthedine
◆ Mgt of Hyperaldosteronism 3. Guanadrel
◆ Adjuncts for HF 4. Bretylium
◆ Hepatic cirrhosis; symptomatic mgt in women
with PCOS– specific to Spironolactone
➔ T/E: C. GANGLIONIC BLOCKERS
◆ HYPERkalemia 1. Hexamethonium
◆ Gynecomastia (Spironolactone to men)
2. Trimethaphan
◆ Loss of libido (Spironolactone)
◆ Infertility (Spironolactone) 3. Mecamylamine
◆ ↑risk of Renal stone formation (triamterene)
D. ALPHA-1 BLOCKERS “-ZOSIN”
● VASODILATION
Ex:
1. Prazosin
Aldosterone Antagonist:
2. Doxazosin
1. Spironolactone – diuretic of choice for px w/
Hepatic cirrhosis; symptomatic mgt in women with 3. Terazosin
PCOS (anti-androgen, anti-acne) (if edema is caused
by heart or other organ, Loop and thiazide is used)
E. BETA BLOCKERS “-OLOLS”
2. Eplerenone
● BRADYCARDIA
ENaC Inhibitrs
3. Amiloride 1. Celiprolol
4. Triamterene 2. Bisoprolol, betaxolol
3. Esmolol
4. Atenolol, acebutolol
5. Metoprolol
 DIRECT VASODILATORS [SVR] b. MIXED ARTERIOLAR VASODILATOR
● Target: Arteries (relax arteries) → ↓SVR
● Mechanisms of Vasodilation: ➔ Relax the ARTERIES & VEINS
1. ↑Nitric oxide levels → ↑Guanylyl Ex:
cyclase enzyme for conversion

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1. Nitrovasodilators
of GMP to become cGMP → 2. Na Nitroprusside
vasodilation ● Structure:
a. Ex: Hydralazine, ○ Nitro group = MOA

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Sodium Nitroprusside, (↑NO→↑cGMP)
○ Cyanide = toxic
Nitrovasodilators
➔ Clinical uses:
◆ 1st line for Hypertensive emergency (must be
2. K Channel Openning → hyperpolarization → freshly prepared)

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vasodilation ● Shelf life: 24 hrs
a. Ex: Minoxidil, Diazoxide ● Prone to photodegradation
3. L-Type Ca ion (heart, arteries) Blockade ➔ T/E:
a. Ex: CCB ◆ Accumulation of CN → ⊖ Cytochrome oxidase

e
(Complex IV in ETC) → ATP synthesis ⓧ
4. D1 Activation → renal vasodilation
a. Ex: Fenoldopam
5. Endothelin Antagonist → blockade of potent
vasoconstrictor “-sentan” c. CALCIUM CHANNEL BLOCKER

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a. Ex: Bosentan, Tezosentan
6. Alpha 1 Receptor Blockade → vasodilation
a. Ex: “-zosins”

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a. DIRECT ARTERIOLAR VASODILATOR

➔ Relax the ARTERIES only

◆ Feedback toxicity (reflex mechanism) when

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given as monotherapy
● Reflex Tachycardia – remedy: + B-blocker
● Peripheral edema – remedy: + Diuretics or
+ ACEIs or +ARBS

➔ Classification:
◆ Structure (→ Site of action) :
a. Dihydropyridines: “-dipines”
Ex: ○ Vasoselective (arteries) (feedback T/E)
b. Non-dihydropyridines
Drug Name Clinical Use T/E ○ Cardioselective (heart(
Hydralazine ● Hypertension in ● SLE ○ Verapamil – most cardioselective
pregnancy ○ Diltiazem – 50:50 (balanced, intermediate
● Adjunct in HF (in activity)
combination with
ISDN only for ◆ Duration of Action:
African-America a. Intrinsically SA:
n px) ○ All Non-DHP– Verapamil, Diltiazem
Minoxidil ● Alt of HTN crisis ● Hirsutism / ○ Majority of DHP (except LAL)
Hypertrichosis b. Intrinsically Long Acting:
Diazoxide ● Alt for HTN crisis ● ⊖insulin release ○ Lercarnidipine
● Mgt for → ○ Amlodipine
Hypoglycemia Hyperglycemia ○ Lacidipine
secondary to c. Modified Long Acting: Intrinsically short-acting,
insulinoma but have been made available as modified
release formulations
○ Felodipine XR

➔ Relax the ARTERIES only
◆ For SHORT ACTING DHP ONLY since it is
vasoselective: Feedback toxicity (reflex
mechanism) when given as monotherapy
● Reflex Tachycardia – remedy: + B-blocker
Angiotensin Converting Enzyme Actions:
1. Conversion of inactive Ang I → active Ang II → ↑SVR,
BV
2. Inactiving Bradykinin → Inactive Bradykinin
● Active bradykinin: ↑NO, ↑PGI2 → vasodilation

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● Peripheral edema – remedy: + Diuretics or ● Inactive: Vasoconstriction → ↓SVR
+ ACEIs or +ARBs

toxicity ∴ better used✅

◆ If LONG ACTING – not associated with feedback
b. DRUGS → REDUCE BV & SVR

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➔ Classes (2):
➔ Uses: 1. Inhibitors of Synthesis of Ang II (enzyme)
◆ 1st line for HTN I. Renin inhibitor – Aliskeren
◆ Tx of angina pectoris II. ACE Inhibitor – “-pril”
◆ Mgt of Arrhythmia

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● Ang II – ↓
Ex:
● Bradykinin – ↑
Dihydropyridines (DHP)

2. Inhibitors of Action of Ang II (receptor)

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Nondihydropyridines
1. Verapamil I. Angiotensin Receptor Blocker
2. Diltiazem ● “-sartan”, Salarasin

➔ Clinical Uses:

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◆ 1st line for HTN
ANGIOTENSIN ANTAGONISTS [SVR, BV] ◆ Base treatment components in HF px (default) (Can
● Targets the RAAS pathway be used safely in ischemic heart disease patients)

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a. RAAS Pathway
● Renin-Angiotension-Aldosterone-System Pathway
● Cascade of reaction from renin enzyme → Angiotensin II
→ Aldosterone
● Responsible for long-term BP regulation
● Triggers → Renin secretion:
◆ 1st line: albuminuria
◆ Mgt: CKD w/ or w/o DM ( ACEIs exert a
renoprotective effect)
◆ Most effective in conditions associated with high
renin activity
General rule: Never taken concomitantly
➔ 1st line: ACEI (economical adv)

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➔ 2nd line: ARBs (if in conflict w/ ACEI)
○ B1 Activation in juxtaglomerular cells
○ Renal hypotension
➔ Toxic Effects:
○ Renal hypoperfusion
◆ ACEI only: (↑Bradykinin)
● Angiotensinogen (liver) → Renin → Angiotensin I
● Dry cough
(inactive) → Angiotensin Converting Enzyme / Kininase
● Angioedema
II) → Angiotensin II (active)
◆ Shared:
● Hypotension
Effects of Angiotensin II in the body:
● Hyperkalemia (due to Aldosterone blockade)
1. ↑ Release of NE from vesicles via exocytosis →
↑sympathetic effect: 𝝰1 - Vasoconstriction; β1 -
➔ C/I:
tachycardia → ↑SVR
◆ SBP <100 mmHG [indicative for hypotension]
2. Aldosterone secretion (fr: adrenal cortex) → ↑ Blood Na
◆ Preexisting hyperkalemia
& H2O reabsorption → ↑ Blood volume
◆ Pregnancy (2nd and 3rd trimester of pregnancy)
3. Vasopressin release (fr: posterior pituitary gland) →
● Renal dysgenesis / renal malformation
↑H2O → ↑Blood volume
● Fetal hypotension
● Anuria

DRUGS FOR ANGINA PECTORIS
● Chest pain due to reduced oxygenation
● D/I: PDE-5 Inh (tx of Erectile d/f) (additive)
○ Sildenafil, Tadalafil, Vardenafil
◆ Throbbing / Vascular HA
◆ Tolerance – Monday disease (workers making
bombs)

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CONCEPT
1. Coronary Artery – blood vessel that SUPPLIES oxygen Ex:

t
to the heart Nitroglycerin, ISMN, ISDN, Amyl nitrite
2. Heart – RECEIVES / DEMANDS for the oxygenated
VSA ➔ Amyl nitrite (inh)
blood
SA ➔ NTG (SL) tab
➔ ISDN (SL) tab

g
Mismatch / Imbalance = ANGINA PECTORIS IA ➔ NTG (SR) tab PO
➔ ISDN tab PO
Presentation of Mismatch: ➔ NTG Transdermal patch
LA ➔ ISDN SR Tab
↑ O2 DEMAND ↓ O2 SUPPLY

e
➔ ISMN SR tab
Effort Angina/ Classic Prinzmetal Angina / Variant
Angina Angina / Vasospastic
Angina / Angina Inversa
● Precipitated by ● Coronary artery

n
PHYSICAL exertion or VASOSPASM → CA
EMOTIONAL stress narrows → ↓supply of BETA BLOCKERS
oxygenated blood to

ia
heart
➔ ⊖B1 → ↓Stress → ↓O2 Demand → FOR EFFORT
ANGINA

➔ 1st line MAINTENANCE agents for Effort angina

ANTI-ANGINAL DRUGS ➔ Combined with High Dose Nitrates to mask reflex
● Goals: tachycardia
○ To REDUCE O2 demand

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○ To ENHANCE O2 supply
● Classes: CALCIUM BLOCKERS
1. Nitrovasodilators = Organic Nitrates
2. B Blockers
3. CCBs A. Nondihydropyridines
➔ Cardioselective → ↓O2 Demand → FOR EFFORT
ANGINA
NITROVASODILATORS / ORGANIC NITRATES ➔ Alternative for Effort Angina

➔ MOA: serves as substrate for NO synthase to

become Nitric Oxide → ↑cGMP → Vasodilation B. Long-Acting DHP (LAL)
◆ RNO2 (substrate) → NO synthase → NO ➔ Vasoselective → ↑O2 Supply → FOR PRINZMETAL
ANGINA
➔ Effects (2): Dose-dependent ➔ Monotherapy is enough (because they are LA DHP)
◆ Low-dose (SL): Venodilation → ↓Preload →
↓SV → ↓workload → ↓stress on heart → ↓O2
demand → FOR EFFORT ANGINA C. Short-Acting DHP
➔ FOR PRINZMETAL ANGINA if and only if:
◆ High-dose (IV): Arteriolar Vasodilation → ◆ Combined with B-Blockers
Coronary artery vasodialtion → ↑ O2 supply → ◆ in MR preparations
FOR PRINZMETAL ANGINA
● As it affects arteries, ⨁feedback toxicity:
Reflex tachycardia → ↑O2 demand; remedy:
⨁B-blocker

➔ Clinical Uses:
◆ For Angina Pectoris
● Low dose - EFFORT
● High dose + Bblocker - PRINZMETAL
◆ Alt for Hypertensive emergency & Acute
Pulmonary Edema
◆ ISDN: Adjunct for HF with Hydralazine (For
African-American px)
◆ Amyl nitrite - CN poisoning

➔ T/E:
◆ Hypotension
 DRUGS FOR HEART FAILURE Beta-1 Agonist [ENHANCE FORMATION]
➔ Uses:
● Heart fails to meet the demand ◆ Mgt of Acute HF & exacerbation of Congestive
HF

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2 Pathophysiologic Components of HF: ◆ IV
1. ↓ Myocardial contractility
2. ↑ Work load (↑preload, ↑afterload) ➔ MOA: 𝞫1 Activation → ⨁AC → ↑ cAMP → ↑Inotropy,

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↑Chronotropy
DRUGS FOR HEART FAILURE
Ex:
1. Inotropic Agents – to ↑Myocardial contraction 1. Dobutamine
2. Unloader Medication – to ↓ Cardiac workload 2. Dopamine

g
INOTROPIC AGENTS
Bipyridines / Phosphodiesterase 3 Inhibitors [INHIBIT

e
METABOLISM]
Cardiac Glycosides ➔ Uses:
◆ Mgt of Acute HF & exacerbation of Congestive
➔ MOA: ⃠ Na-K-ATPase Pump (NAP) → ⃠ NCX Opening HF
→ ⊖Ca extrusion → ↑Ca ◆ IV
➔ (Intracellular) Sodium goes out, (extracellular)

n
➔ MOA: ⊖ enzyme PDE3 (metabolizes cAMP → AMP)
Potassium goes in; Sodium goes back in in exchange → ↑ cAMP → ↑Inotropy, ↑Chronotropy
of Calcium via the Sodium-Calcium Exchanger (NCX)

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➔ Ca - ↑ → contraction
Ex:
➔ Na - ↑ → hypernatremia
1. Inamrinone
➔ K - ↓ → Hypokalemia
2. Milrinone
➔ Effects:
◆ Mechanical Effect: ⊖NAP → ⨁ Inotropy
◆ Electrophysiologic Effect: (Dose Dependent)
● Therapeutic Dose: Atria
UNLOADER AGENTS
○ ↑Parasympathetic activity →

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Bradycardia / (-) Chronotropy ● 1st line for Heart Failure
● Toxic Dose: Ventricle ● Reduce afterload and/or preload
○ Enhanced automaticity → Tachycardia / ● Given in combination always
(+) Chronotropy
○ Tx for Digoxin-Induced VTach:
Lidocaine ACEI/ ARBS
➔ Uses: ➔ Base treatment component
◆ Adjunct for HF (moderate-severe; not FLA) ◆ ↓BV → ↓Preload
◆ Mgt of atrial fibrillation ◆ ↓SVR → ↓SVR/Afterload
➔ T/E:
◆ Narrow TI (start low & go slow) → requires Diuretics
Therapeutic Drug Monitoring (TDM)
➔ ↓BV → ↓Preload
◆ Cardiac T/E → Ventricular tachycardia
➔ Loop Diuretics, Thiazide Diuretics, or both
● Conditions that ↑ risk:
➔ Spironolactone–important in px taking Digoxin in case
○ HYPO K, Mg, O
of Hypokalemia
○ HYPER Ca
◆ Extracardiac T/E:
● N&V (most common)
Vasodilators
● Yellow-Green vision
➔ ISDN (low dose: VEINS) + Hydralazine (arteries)
➔ Mgt of T/E: ◆ ISDN - ↓Preload
◆ Correct all electrolyte imbalance ◆ Hydralazine - ↓Afterload
◆ Lidocaine (IV) for VTach ➔ Amlodipine + Prazosin
◆ Specific Antidotes: Digitoxin-Binding Antibodies ➔ Nesiritide
● DigiBind ◆ Brain natriuretic peptide (BNP) analogue
● DigiFab ◆ ↑cGMP → vasodialtion
◆ Natriuresis
◆ Endothelin Antagonist
Ex:
● Bosentan, Tezosentan
1. Cardiac Glycosides
a. Digoxin
b. DIgitoxin–withdrawn
Beta Blockers
➔ General: B Blockers are C/I ❗️❗️
➔ Block receptor in the Kidney: ⊖Renin → ⓧRAAS
Pathway → ↓Afterload, ↓Preload
➔ Bisoprolol, Carvedilol, Nebivolol, Metoprolol
Succinate

tt
eg
ian
le
 CLASS III: POTASSIUM BLOCKERS
DRUGS FOR ARRHYTHMIA
● Goals: Sotalol A Beta blocker
1. Na Channel Blockade
Amiodaron Iodine-containing (32% I2)

t
2. Inhibition of Sympathetic activity
Uses:
3. Prolongation of effective refractory period
● 1st line for Vtach
4. L-Type Channel Blockade
● Mgt of Atrial fibrillation

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Vaughan-Williams Classification
T/E:
Class ●Hepatotoxicity
Na Channel Blockade Na Channel I ●Iodine cont. →
Blockers Wolf-chaikoff effect
Inhibition of Sympathetic Beta blockers II

g
○ <10-14 days:
activity HYPOthyroidism
Prolongation of effective K Channel Blockers III ○ > 14 days:
refractory period HYPERthyroidism
L-Type Channel Blockade Calcium Channel IV

e
● Induction of pulmonary
Blockers fibrosis
Dronedarone Devoid of I2 → ⓧWolf-Chaikoff,
ⓧPulmonary fibrosis
Bretylium
Dofetilide

n
CLASS I: Na CHANNEL BLOCKERS
Ibutilide

ia
Criterion IA IB IC
Extent of Na+ Moderate Weak Strong
Channel Block
CLASS IV: NON-DHP CCB CHANNEL BLOCKERS
Effect in Action Prolong Shorten No effect
Potential
Duration
Verapamil 1st line for Chronic Paroxysmal
Examples: “A Double “Baby Too “More Fries
Quarter Much Love Please Supraventricular Tachycardia
Pounder” makes you Cheese” Extracardiac T/E: Constipation

le
Pregnant”
Disopyramide Tocainamide Moricizine
Quinidine Mexilitine Flecainide
Procainamide Lidocaine Propafenone
Phenytoin Encainide MISCELLANEOUS

IA: Adenosine 1st line for Acute Paroxysmal

Disopyramide Anticholinergic (xerostomia, urine Supraventricular Tachycardia
retention) S/E: Bronchospasm (adenosine
Quinidine Cinchonism (Tinnitus, HA, ↑Bronchial tone)
Dizziness)
Digoxin Mgt of Atrial Fibrillation
Procainamide SLE
MgSO4 1st line for Torsades de pointes
IB
Tocainide
Mexiletine Oral congener of Lidocaine
Lidocaine 1st Line Digoxin-ind. VTach (IV)
Phenytoin Anticonvulsant / Antiepileptic

IC
Moricizine
Flecainide
Propafenone
Encainide

CLASS II: BETA BLOCKERS

Penbutolol
Esmolol
Acebutolol
 ● Hypothalamus → RH → Anterior Pituitary Gland →
SH → PEG → PH
Endocrine Pharmacology Negative
Stimulus (↑PH)
↓PH
Response
↓RH = ↓SH = ↓PH
Positive ↑PH ↑RH = ↑SH = ↑PH

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INTRODUCTION a. Negative Feedback Mechanism
● MAJOR REGULATORY MECHANISM

t
ENDOCRINE SYSTEM ● if there is excess of target organ hormone, they will
● A ductless system (not connected) go to the brain and will tell brain to stop stimulation.
● Endocrine glands – member organs ● Ex: Thyroid Gland
○ Central Endocrine Glands ○ H → APG → Thyroid Gland → Cells

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○ Peripheral Endocrine Glands ○ Thyrotropin RH → Thyrotropin → T3, T4
○ Stimulus: Conc of Peripheral Hormones–T3, T4
Classification of Endocrine Glands: ○ Response: ⓧTRH release
Central Endocrine Glands Peripheral Endocrine

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Glands Smmary: AXIS
Loc is in the brain Loc is outside the brain H APG PEG PH
Hypothalamus Thyroid Thyrotropin Thyrotropin / Thyroid T3, T4
Pituitary Gland Adrenal cortex Releasing TSH Gland
● Anterior PG Pancreas

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Hormone
● Posterior PG Sex organs (testes, ovary)
Corticotropin Coticotropin Adrenal Cortisol
Releasing Adrenocorti- Cortex

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● Hypothalamus – master gland
Hormon cotropic
● Anterior Pituitary Gland – aka Adenohypothesis (CRH) Hormone
● Posterior Pituitary Gland – aka Neurohypothesis (ACTH)
Gonadotropin Gonadotropins: Ovaries Estrogen
● Function: endocrine hormone regulation Releasing FSH Testis Progesterone
● Endocrine hormone – endogenous compounds that hormone LH Testosterone
are produced by specific cells (needs to be incorporated (GnRH)

le
& circulated in the blood) Growth Growth Hormone Liver Somatomedins
● Systemic effect Hormone RH / Somatotropin (insulin-like
growth
factors-1 IGF1)
Growth
ENDOCRINE HORMONE REGULATION Hormone ⊖GH, TSH
Inhibiting
PHYSIOLOGIC PROCESSES hormones
1. Circadian Rhythm / Sleep Wake Cycle / Diurnal Cycle GHIH /
● Scheduling of hormone release Somatostatin
● “24 hour cycle in hormonal release”
● Ex: b. Positive Feedback Mechanism
○ Upon waking up = ACTH, CORTISOL ● Rare
(catabolic hormone) provides energy by ● Ex: Ovulation – movement of matured egg cell from
breaking down macromolecules the ovary to the fallopian tube (→ pregnancy)
○ Ex: Deep sleep = GROWTH HORMONE → ○ H → APG →
growth ○ GnRH → FSH → ↑ Estrogen → GnRH → LH
2. Feedback Mechanism → Progesterone
● Concept: Concentration of peripheral hormone ○ Estrogen – egg cell maturation (occurs in the
(Stimulus) → Response initiated by Hypothalamus ovary)
● Response is either: ○ Progesterone – ovulation
○ To NEGATE – Negative Feedback
Mechanism
○ To SUPPORT – Positive Feedback
Mechanism
● Hypothalamus – stimulate all endocrine gland by
releasing its own version of hormone, “Releasing
Hormones”
● Anterior Pituitary Gland – release its own version
of hormone once signal from Hypothalamus is
received, “Stimulating Hormone / -tropin”
● Peripheral Endocrine Glands – (different from
each EG) produces “Peripheral Hormone”
 ● HYPOprolactinemia (↓PRL)
○ Ⓧ Lactation (GO action is inhibited)
HYPOTHALAMIC & PITUITARY HORMONES &
● HYPERprolactinemia (↑PRL)
AGENTS
○ Prolactinoma – tumor in anterior gland →
affects PRL release (excessive)

t
○ Drug-induced
HYPOTHALAMIC HORMONES: GnRH ■ Ex: 1st gen Antipsychotic agent (DA
blockers)

t
Drugs: GnRH Analogues – “-relin” ● DA blocks PRL → PRL dominates

⬆️
○ S/Sx Amenorrhea - Galactorrhea Syndrome
Drugs: ■ Galactorrhea – excessive milk

⬇️
➔ Gonadorelin production

g
⬆️
➔ Goserelin ■ Amenorrhea – absence of mentruation
➔ Buserelin ■ Infertility
➔ Nafarelin ○ Tx: Bromocriptine (D2 Agonist)
➔ Tritprelin

e
➔ Histerelin GROWTH HORMONE (SOMATOTROPIN)
➔ Leuprolide
a. Regulation of Release
● H → APG → Organs
Effect: Manner of Administration
● GHRH → Somatotropins

n
1. Intermittent / Pulsatile – POSITIVE
● GHRH – stimulates production of Somatotropins
● Stimulatory
● GHIH – inhibits production of Somatotropins
● ↑ FSH = ↑Estrogen

ia
● ↑H secretion = ↑Progesterone
● Clinical use: Mgt of of hypothalamic hypogonadism b. Physiologic Effects
2. Continuous / Sustained – NEGATIVE ● Liver: Somatomedins secretion → IGF1
● ROA: IM Depot ○ Linear body growth
● Inhibitory → inhibit APG secretion of FSH and LH ○ Organ size
● ↓FSH = ↓Estrogen ○ Lean body mass
● ↓LH secretion = ↓Progesterone ● Muscle: ↑ CHON synthesis

le
● Clinical Use: Mgt of Hormone Excess States ○ Growth of muscle
(Breast CA, Endometrial CA, Endometriosis, ● Adipocytes
Prostate CA) ○ Stimulate TG hydrolysis in adipose cell → ↑ FFA
→ weight loss
T/E: (IM Depot–Contrinuous) ● Other cells:
● Female: Masculinizing effect (Hirsutism, Acne) ○ ⊖ Glucose uptake (into the cell) ↑ Hepatic glucose
● Male: Feminizing effect (Gynecomastia, loss of output in the blood → HYPERglycemia
libido)
c. Clinical Conditions
1. Deficiency
a. Onset:
ANTERIOR PITUITARY HORMONES i. Pre-puberty: Pituitary Dwarfism
● Originates from Adenohypothesis ii. Post-puberty: ↑Cardiovascular death risk (No
● Follow the hypothalamic - pituitary portal axis system visible physical feature but ↑ cardiovascular
● Ex: Prolactin, Growth Hormone mortality)

⚠️
b. Tx: (depends on defective gland)
i. Hypothalamic defect: GHRH
PROLACTIN / PRL

⚠️
● Exogenous GHRH
a. Regulation of Release ii. Pituitary defect: Somatotropin
● H → APG → Mammary Gland ● Somatropin – recombinan IGF1
● TRH stimulates PRL release ○ Mgt of Prader-Willi Syndrome
● DA inhibits PRL release ○ Mgt of Turner Syndrome
○ Mgt of Idiopathic Short Stature
b. Physiologic Effects: ● Mecasermin – IGF-1 Agonist for px
● TOP (Mammary Gland) Effects: GO! unresponsive to Somatropin
○ Breast development (size of breast = lactation
ability) Drugs:
○ Milk production / Lactation ➔ Hypothalamic Defect
● BOTTOM (Sex organ) Effects: STOP! ● Exogenous GnRH
○ ⊖ Ovulation → infertility
○ ⊖ Spermatogenesis → infertility ➔ GH Antagonist
● Somatropin
c. Conditions: ● Mecasermin
 b. Effects
2. Excess
a. Onset: Drugs:
i. Pre-puberty: Pituitary Gigantism ➔ Oxytocin
ii. Post-puberty: Acromegaly (lateral growth) ◆ Nasal spray: stimulate milk let-down

t
● External: Facial (coarsened), ◆ IV: Oxytocic (induce labor)
Macrognathia (prominent jaw), Thickened ● T/E: Uterine tetany
lips, Wide-spaced lips, Large tongue ➔ Atociban

t
(macroglossia), Broadened nose, ◆ Oxytocin Antagonist
Prominent jaws and forehead, Enlarged ◆ Tocolytic – Uterine relaxant
joints, enlarged fingers
● Internal: Cardiomegaly (fetal)

g
b. Tx: VASOPRESSIN
i. Somatostain Analogue
● MOA: ⊖GH, TSH, Gastrin, Insulin, a. Effects
Receptors:
Glucagon

e
1. V1 - Vasoconstriction
● Application:
2. V2 - Rebasorption of H2O in renal tubule (save)
○ ⊖GH – Acromegaly
○ Tumors (Hypersecretion)
■ ⊖Insulin – Insulinoma b. Clinical Conditions
■ ⊖Glucagon – Glucagonoma 1. Deficiency – DIABETES INSIPIDUS (DI)

n
■ ⊖Gastrin – Zollinger-Ellison ● S/Sx:
Syndrome ○ Polyuria (Inability to conccentrate urine → very

ia
○ Bleeding esophageal varices – as dilute urine / too many urine)
vasoconstrictor → ⓧblood loss ○ Polydipsia (extreme thirst → due to
ii. Pegvisomat – GH Antagonist dehydration)
○ For px unrespsonsive to Somatostatin ○ HYPERnatremia
analogue ● Types:
Drugs: Central / Neurogenic DI Nephrogenic DI
➔ Somatostatin Analogue ABSOLUTE lack of RELATIVE lack of

le
● Ocreotide Vasopressin Vasopressin (Resistant
● Lanreotide – long acting (Hypothalamic defect) Receptor)
Vasopressin Agonists Thiazide Diuretics
➔ GH Antagonist (paradoxical)
● Pegvisomat
Drugs:
➔ Vasopressin Agonists
Summary: GH ● Non-selective VA:
Criterion Deficiency Excess ○ Vasopressin
● Vasopressin II - Selective Agonist
Applicable Dwarfism Gigantism
Diseases Cardiac mortality Acromegaly ○ Desmopressin
Drugs GHRH Ocreotide
Somatropin Lanreotide
Mecasermin Pegvisomat 2. Excess – SIADH Syndrome of Inappropriate
Antidiuretic Hormone Secretion
● S/sx:
○ Highly concentrated urine or TOO LITTLE
POSTERIOR PITUITARY HORMONES URINE
○ ↑ H2O Reabsorption→ HYPERVOLEMIA
● From neurohypothesis
○ Hypervolemia → ↑BV → ↑BP → HTN
● Do not follow an axis
○ Na in the blood become diluted with H2O →
● H → PPG → Cells
HYPOnatremia
● Synthesis → Storage, release → Cells
● Tx:
● Hormone synthesized by H is the same hormone all
Drugs:
through out
● PPG only stores and releases these hormones to cells ➔ Non-selective V Antagonist:
● Conivaptan
● Demeclocycline – a TCN
OXYTOCIN
➔ Selective V2 Antagonist
a. Effects ● Tolvaptan
● Stimulate milk let-down (vs. Prolactin that produces the
milk)
○ Main stimulus: Nipple suckling
● Uterine contraction (Oxytosis)
Summary:
Criterion Deficiency Excess
Disease DI SIADH
Drugs V Agonists V Antagonist

t
(-pressin) (-vaptan)
NonSelective Vasopressin Conivaptan
Demeclocycline

t
V II Selective Desmopressin Tolvaptan

eg
ian
le
 CONDITONS
THYROID HORMONES ANTI-THYROID AGENTS
HYPOTHYROIDISM
● Deficiency in TH
PHYSIOLOGY

t
REGULATION OF THYROID HORMONE RELEASE ● Causes:
● TRH → TSH → T3, T4 ○ Post-procedural (thyroidectomy, radioactive iodine
therapy RAI) in developed countries

t
● T3 - Triiodothyronine; 4x more potent
● T4 - Tetraiodothyronine or Thyroxine ○ Iodine deficiency in underdeveloped countries
○ Autoimmune– HashimOto’s Disease
○ Drug-Induced (Anti-thyroid agents, Amiodarone
BIOSYNTHESIS OF T3 & T4

g
● Types:
Types TRH TSH T3, T4

e
Primary (TG Defect) ↑ ↑ ↓
Secondary (Pituitary ↑ ↓ ↓
Defect)
Tertiary (Hypothalamic ↓ ↓ ↓

n
Defect)

ia
● S/Sx: Hypometabolic & Hyposympathetic
○ Slowness in movement
○ ↑ sleeping time
● Site: Thyroid follicular cell TFCs ○ Cold intolerance
○ Regulatory Mechanism: Wolf-Chaikoff Effect ○ Weight gain despite decreased appetite
■ Stimulus: ↑Blood Iodide ○ Severe: Myxedema Coma
■ < 10-14 days: ⊖Symporter
● ↓ Iodide uptake → ↓T3, T4 → ● Tx: Thyroid Supplementation

le
HYPOthyroidism Drugs:
■ > 14 days: ⨁Symporter ● Thyroxine
● ↑ Iodide uptake → ↑ T3, T4 → ○ L-thyroxine – preparation of choice
HYPERthyroidismm ○ D-thyroxine – 4% biological activity of
● RM: Iodide (I- L-isomer
● Liothyronine – 3-4x more potent than
Steps (5) L-thyroxine
a. Active Uptake of Iodide via Na+-I- Symporter
● From the systemic circulation, NIS allows entry
of Na and I into the TFC
b. Peroxidase-Catalyzed Reactions (3)
HYPERTHYROIDISM
● Peroxidation of Iodide to a Molecular Iodine
● Causes:
○ I- → I2
○ Autoimmune: GravE’s disease
● Organification / Iodination – addition of
○ Hyperfunctioning nodules: mass on the thyroid
Iodine to the Tyrosine residues of
producing excessive T3 & T4
Thyroglobulins– complex CHON (w/ Tyr) found
○ Drug-Induced: Amiodarone & Iodides (triggers
in TFC
Wolf-Chaikoff Effect on long term basis)
○ Monoiodotyrosylthryoglobulin (MIT)
○ Diiodotyrosylthyroglobulin (DIT)
● S/Sx: Hypermetabolic & Hypersympathetic
● Coupling reaction – TG is still connected
○ Weight loss despite ↑ appetite
○ T3-TG = 1 MIT + 1 DIT
○ Heat intolerance
○ T4-TG = 1 DIT + 1 DIT
○ ↑ sweating
c. Proteolysis via Protease
○ ↑ irritability
○ T3 + TG (liberated)
○ Tachycardia
○ T4 + TG (liberated)
○ Palpitation
d. Release into systemic circulation
○ Ratio: 1 (T3) : 4 (T4)
● Tx: Anti-thyroid agents
e. Peripheral conversion of T4 in the blood
1. Thioamides
○ T4 → T3 via deiodinase
● MOA: ⊖Peroxidase Inhibitor
○ ↑potent [T3]
● Addtl MOA of PTU: ⊖Peripheral conversion of
T4 to T3
 Criterion PTU Methimazole
DOA Short Long = Matagal
Onset F/Past Slow
Use Emergency Maintenance
states (thyroid Therapy

t
storm,
hyperthyroid

Safety ✅ crisis)
Pregnant ❎ Pregnant

t
(Aplasia cutis)
T/E Hepatitis Obstructive
jaundice
General T.E Hypothyroidism
Agranulocytosis (↓B, E, N**) →

g
Fever, Oral ulcer, sore throat

2. Anion Inhibitors

e
● MOA: ⊖ Na-I Symporter → ⃠ Iodide uptake
● Use: DOC for Amiodarone-induced Hyperthyroidism
● T/E: Aplastic anemia

n
3. Iodides

ia
● MOA: activate Wolf-Chaikoff Effect → for
hyperthyroidism during short-term use
○ Initial mgt (short term)
● Use: Mgt of Thyroid storm (for initial mgt only
● T/E: Iodism–rhinitis, conjunctivitis, sialadenitis

4. RAI
● Ex: I131 – emits 𝞫 radiation → TFC death

le
● Preferred tx for Hyperthyroidism except during
pregnancy
● T/E Hypothyroidism

5. Beta Blockers
● Symptomatic mgt of sympathetic (Tachycardia,
palpitation)
● ⊖Peripheral conversion of T4 to T3

6. Dexamethasone
● ⊖Peripheral conversion of T4 to T3

Drugs:
1. Thioamides
● PTU
● Methimazole (Tapalin®) / Thiamazole
(Tapazole®)
● Carbimazole
2. Anion Inhibitors
● Perchlorate
● Pertechnetate
● Thiocyanate
3. Iodides
● SSKI
● Lugol’s Solution
4. RAI
● I131
5. Beta-blocker
● Propranolol
● Carvedilol
6. Dexamethasone
 ADRENOCORTICAL HORMONES SYNTHETIC GCs (DRUGS)
DOA:
STRUCTURE OF ADRENAL GLAND 1. Short Acting GC: Hydrocortisone, Cortisone;

t
Prednisone, Prednisolone; Meprednisone,
In the adrenal cortex: Meprednisolone
1. Zona Glomerulosa: Mineralocorticoids 2. Intermediate Acting GC: Triamcinolone,
2. Zona Fasciculata: Glucocorticoids Fluocinolone, Paramethasone

t
3. Zone Reticularis Androgens 3. Long Acting GC: Betamethasone, Dexamethasone

MINERALOCORTICOID Drugs:
➔ Short Acting

g
Site: Zona Glomerulosa
● Hydrocortisone, Cortisone
Major: Aldosterone
● Prednisone, Prednisolone
● Meprednisone, Meprednisolone
EFFECTS

e
➔ Intermediate Acting
● Loc: Kidnet Tubule ● Triamcinolone
● Reabsorption of: Na & H2O, HCO3- ● Fluocinolone
● Secretion of: K, H, Cl ● Paramethasone
➔ Long Acting

n
CONDITIONS ● Betamethasone
1. Excess – HYPERALDOSTERONISM ● Dexamethasone

ia
● S/Sx:
○ HYPERnatremia USES
○ HYPOvolemia → HTN A. Adrenal
○ Metabolic Alkalosis ● D/x: Cushing Syndrome – DEXAMETHASONE Test
“Dexa Test”
○ HYPOkalemia ● Tx: GC Deficiency & Excess
○ HYPOchloremia ○ Addison’s Disease – Deficiency

le
○ Cushing Syndorme – Excess
● Tx: Mineralocorticoid Antagonist (K-Sparing B. Non-Adrenal
Diuretics) ● Allergy
Drugs: ● Collagen-vascular D/O (SLE)
➔ Spironolactone ● Eye D/O
➔ Eplerenone ● Respiratory D/O
● Infecctions
2. Deficiency – HYPOALDOSTERONISM ● Systemic inflammations
● S/sx:
○ HYPOnatremia C. Fetus
○ HYPERvolemia → HYPOTension ● Stimulation of lung maturation in fetus (esp in
○ Metabolic acidosis premature cases) (Respiratory Distress Syndrome)
○ HYPERkalemia
○ HYPERchloremis TOXIC EFFECTS
● GC Excess → Cushing Syndrome
● Tx: Fludrocortisone –salt retaining agent ○ Moon face
Drugs: ○ Buffalo hump
➔ Fludrocortisone ○ Truncal obesity
○ Thinning of skin
○ Easy bruising

GLUCOCORTICOID
○ Osteoporosis
Major: Cortisol ○ Hypokalemia
○ Hypertension
EFFECTS ○ Hyperglycemia

Physiologic Pharmacologic
● Catabolism oof CHO, ● Anti-infllamatory
CHON, lipids → energy ● Immunosuppression
● CV function ● Catabolism of bones &
● Immunity joints
● ⊖ mitosis
●
 PANCREATIC HORMONES & DRUGS FOR DIABETES INSULIN PREPARATION
MELLITUS Majority are administered SQ
Except Regular Insulin– IV

t
PANCREATIC HORMONES
1. Insulin a. Classes
2. Pancrease

t
Criterion Insulin Glucagon
Origin 𝞫 - cells 𝝰 - cells
Stimulus for release Fed state Fasted state
Response Hypoglycemia Hyperglycemia
Metabolism
✅
Anabolic
🚫
Catabolic

g
Glycogenesis
Glycogenolysis 🚫
✅ ✅
🚫
Lipogenesis
🚫 ✅

e
Lipolysis

3. Incretins
● ↑ secretion of Insulin
● Anorexiant effect (appetite supprent)

n
● Slow down GET → busog effect
● Needs to be activated in px with DM

ia
● Ex: Based on DOA
○ Glucagon-like Peptide 1. Rapid-Acting
■ A potent stimulant of insulin synthesis and ● Insulin Lispro
release and beta cell mass ● Insulin Aspart
■ It inhibits glucagon secretion ● Insulin Glulisine
■ It slows gastric emptying time 2. Short Acting
■ It has an anorexic effect ● Regular Insulin – only IV administered Insulin

le
■ A potential therapeutic agent for type 2 3. Intermediate Acting
diabetes ● Isophane / Neutral Protamine Hagedorn NPH
■ Requires continuous SC infusio Insulin
■ Exenatide- its analog 4. Long Acting
○ Gastrin-insulinotropic peptide ● Insulin Glargine (peakless insulin)
● Insulin Detemir
4. Amylin
● Anorexiant effect (appetite supprent) Based on Requirements
● Slow down GET → busog effect a. Demand Insulin – used to control post-prandial
hyperglycemia (administered multiple times/day
before meals)
i. Ex: RA (LAG) & SA (Regular) Insulin
DRUGS FOR DIABETES MELLITUS b. Basal Insulin – used to control normal blood
Diabetes melltius –is defined as an elevated blood glucose glucose within 24 hrs (sustained effect;
associated with absent or inadequate pancreatic insulin administered once or twice a day max)
secretion, with or without concurrent impairment of insulin i. Ex: IA (NPH), LA (GD)
action

T1DM T2DM
Insulin dependent DM Non-Insulin dependent DM
ABSOLUTE lack of insulin RELATIVE lack of insulin
Complete destruction of B Resistance to the action of
cells insulin combined with a
Severe or absolute insulin relative deficiency in insulin
deficiency secretion
Requires exogenous insulin
for survival
Tx: Tx:
Insulin Oral AD Agents
Pramlintide
 b. Clinical Uses
● Mainstay tx of T1Dm
● Mgt of T2DM (when T2DM px develops T1DM)
SULFONYLUREAS
● ↑ Generation # = ↑ Potency → ↓ dose, ↓ S/E

t
c. Toxic Effects
● Hypoglycemia A. 1st Generation SU
○ S/Sx: 1. Chlorpropramide – longest t1/2 (used w/
caution in px with hepatic & renal insufficiency)

t
■ Tremors
2. Tolbutamide – shortest t1/2; preferred for use in
■ HA
elderly (tanda); S/E: cardiotoxicity
■ Tachycardia 3. Tolazamide
■ Palpitation 4. Acetohexamide
■ Sweating

g
■ Tremolousness B. 2nd Generation SU
■ Hostility 1. Glibenclamide = Gliburide
■ Nausea 2. Gliclazide
3. Glipizide

e
■ Hunger
4. Glimepiride
■ May progress convulsion and coma if untreated
○ T/E: Glucose
● Lipodystrophy – atrophy of the SQ fatty tissues MEGLITINIDE
○ To delay, rotate injection sites ● Modulates beta cell insulin release by regulating

n
● Allergy – Hypersensitivy- local or systemic urticaria due potassium efflux
to histamine release
1. Repaglinide

ia
● Immune insulin resistance – Low titer of IgG anti-insulin
2. Nateglinide
antibodies leads to insulin resistance-lupus
erythematosus Uses:
● “Demand insulin”
● T1DM
● Control post-prandial hyperglycemia (30 min
before breakfast)
ORAL ANTIDIABETICS

le
T/E:
● Hypoglycemia
● Weight gain
● Disulfiram-like reactions

Drugs
➔ 1st Gen:
● Chlorpropramide
● Tolbutamide
● Tolazamide
● Acetohexamide
➔ 2nd Gen:
● Glibenclamide = Gliburide
● Gliclazide
Insulin Secretagoues
● Glipizide
● ↑ Insulin secretion from 𝞫 cells of pancreas to the blood ● Glimepiride
→ HYPOGLYCEMIA
● MOA: K- Channel 🚫 in the 𝞫 Cells of the pancreas
➔ Meglitinide
● Repaglinide
● Nateglinide

Biguanides

● 🚫 K Channel (inhibitory) → depolarization → Ca

Channel opening → Ca2+ intrusion → mobilize Insulin
→ Insulin fusion to CM → Release of Insulin
● ↑ Insulin in blood → HYPOglycemia
●
○ 🚫
MOA: Activates AMP-Activated Protein Kinase
Absorption of glucose from GIT to Blood
○ Glucose uptake to cell
ALPHA - GLUCOSIDASE INHIBITORS
● MOA: Alpha-Glucosidase Inh blocks simplication of
non-absorbale, complex CHO to absorbable, simple
○ Stimulate glycolysis (→ Pyruvate formation) sugar
🚫
○ Stimulate Glycogenesis ( → Glycogen formation)

t
○ Inhibit Gluconeogenesis ( Glucose)
● ↑ Glucose utilization
● The only EUGLYCEMIC agent

t
● Clinical uses:
○ 1st line for T2DM
○ Mgt of Pre-DM (borderline result)

● T/E:

g
○ Diarrhea → resolved if: (a) chronic use; (b) MR
prep ○ Nonabsorption → ↓ Blood glucose
○ Weight loss ● Should be taken at the first bite of each meal
○ Lactic acidosis ● Uses: Alt for T2D

e
● T/E: Flatulence
GIT
Glucose ❎
Blood

Glucose →
Cell

Glucose → Pyruvate
Drug:
➔ Acarbose
(Glycolysis) ➔ Voglibose

n
➔ Miglitol
Glucose → Glycogen

🚫Gluconeogenesis

ia
INCRETIN-BASED DRUGS
Drugs: Classes:
● Metformin 1. INCRETINMIMETICS – GLP-1 AGONIST
● Phenformin ● Administered SQ
a. Exenatide

le
● Metformin ● Synthetic analog of
● Phenformin – withdrawn due to lactic acidosis glucagon-like-polypeptide (GLP-1) •
Potentiation of glucose mediated insulin
secretions
● Suppression of post-prandial glucagon
release
● Slows gastric emptying
THIAZOLIDINEDIONES / INSULIN SENSITIZERS ● Central loss of appetite
● MOA: PPAR-𝜸 Agonist ● njectable adjunctive therapy (Type 2 Dm)
with:
○ Metformin
○ Metformin plus Sulfonylureas
● ADVERSE EFFECTS:
○ Nausea
○ Vomiting
○ Diarrhea
○ Weightloss
○ Necrotizing and hemorrhagic
pancreatitis
b. Liraglutide
c. Lixisenatide

2. DIPEPTIDYLPEPTIDASE-4 INHIBITORS – “-gliptin”

● MOA: DPP-4 Inh blocks conversion of active
○ ↑ Glu utilization Incretin to its inactive form
○ ↑FA utilization
● Uses: Alt for T2DM
● T/E: Hepatotoxicty (requires ALT & AST monitoring)

Drug:
➔ Pioglotizone
➔ Rosiglitazone – withdrawn due to cardiotoxicity

a. Sitagliptin (Januvia®)
b. Vidagliptin (Galvus®)
c. Linagliptin (Trajenta®)
d. Saxagliptin (Onglyza®)
e. Teneligliptin (Glipten®)
● Uses: ● T/E: N&V
○ T2DM as Monotherapy ○ N& V
○ In combination: w/ Biguanides (metformin): ○ Hypoglycemia
Janumet ○ Weight loss
○ In combination w/ SGLT-2 Inh: Glyxambin ○ Anorexia

t
● T/E: N&V, Hypoglycemia, Weight loss

Drug:

t
➔ GLP-1 Agonist
● Exenatide
● Liraglutide
● Lixisenatide
➔ DPP-4 Inhibitors

g
● Sitagliptin (Januvia®)
● Vidagliptin (Galvus®)
● Linagliptin (Trajenta®)
● Saxagliptin (Onglyza®)
● Teneligliptin (Glipten®)

e
🚫
SGLT-2 INHIBITORS “-GLIFLOZIN”

n
● MOA: Sodium-Glucose-Linked-Transporter-2
found in the PCT of the kidneys which is responsible

ia
for 90% reabsorption of glucose → ⊖ Glu
reabsorption, 90% excreted → glucoresis →
Hypoglycemia

le
● Clinical use: Mgt of T2DM
○ Monotherapy: Dapagliflozin (Forxiga®),
Empagliflozin (Jardiance®)
○ w/ Metformin: Dap + Met = Xigduo® ; Empa +
Met = Jardiance Duo®
○ w/ DPP4 inh: Empagliflozin + Lina = Glyzambi

● T/E:
○ Fungal infection

Drugs
➔ Dapagliflozin
➔ Empagliflozin
➔ Luseogliflozin
➔ Canagliflozin

AMYLIN ANALOGUE: PRAMLINTIDE

● MOA:
● Injectable antihyperglycemic agent
○ SC: Abdomen and thigh
● Modulates postprandial glucose level
● pproved for pre-prandial use in persons with Type 1
and 2 DM
● Administered in addition to insulin
● Suppress glucagon release
● Delays gastric emptying
● Has CNS mediated anorectic effect

● Clinical use: The only non-insulin injectable

 2. ANDROGEN ANTAGONIST
GONADAL HORMONES ● Bicalutamide, Flutamide
● Uses: tx of Prostate CA
1. Estrogens (Estradiol)
2. Progestins (Progesterone0 ● Cyproterone acetate

t
3. Androgens (Testosteron) ● Tx of excessive sexual drive in men
Drugs:
➔ Bicalutamide
DRUGS FOR ESTROGENS & PROGESTINS

t
➔ Flutamide
HYPOTHALAMUS ➔ Cyproterone acetate
1. GnRH Analogues “-relin”
● Intermittent administration: Positive feedback (for

g
hypogonadism)
● Continuous administration (IM depot): Negative
feedback (for hypergonadism–CA & endometriosis)

e
ANTERIOR PITUITARY GLAND
2. Clomiphene – ↑ FSH, LH → ↑Estrogen, Progesterone
● Ovulation inducer
3. OCP– ↓FSH, LH → ↓Estrogen, Progesterone

n
● Contraception
4. Danazol → ↓ Progesterone

ia
● Contraception

OVARY

🚫
5. Mifepristone – Progesterone Antagonist
● Contraceptive; Abortifacient
6. Anastrazole, Letrozole – Aromatase Inh (enz that
converts androgen to estrogen)

le
● ↓ Estrogen conc

SERMs: SELECTIVE ESTROGEN RECEPTOR

MODULATOR
● Partial agonist (alone–agonist; w/FA–antagonist)
7. Tamoxifen
● Estrogen (+) breast CA
8. Raloxifene
● Tx of osteoporosis (⊖bone resorptio)

DRUGS FOR ANDROGENS

1. 5-𝝰-REDUCTASE INHIBITORS

🚫
● MOA: 5-𝝰-Reductase Inhibitors
● Conversion of Testosterone → 5-dihydrotestosterone
(5-DHT)
● 5-DHT – 10x more active than Testosterone
● To lessen androgen effect, block stronger product
formation
● Clinical use:
○ Mgt of BPH (reduces the size of the prostate)
Drugs:
➔ Finasteride
➔ Dutasteride
 ● Mast Cells, Basophils – ↑HISTAMINE
DEGRANULATION leading to ↑Histamine conc
Autacoid Pharmacology
🚫
3. H3 Receptor / Autoregulatory
● CNS Presynapse – AUTOREGULATION: further

t
release of Histamine → modulate histamine effects
AUTACOID
● Endogenous compounds 4. H4 Receptor

t
● Local hormones (vs Endocrine that must be distributed ● Inflammatory Cells (ex: Neutrophils) –
→ systemically acting) INFLAMMATION via chemotaxis (Neutrophil
○ Produced by virutally all cells movement from blood to tissue)
○ No distribution needed

g
● Ex: BESH DRUGS
○ Bradykinin
1. AGONISTS
○ Eicosanoids
1. Histamine
○ Serotonin

e
● Obsolete
○ Histamine
● Pulmonary Challenge Test (provocative test for
bronchi) (substituted at present by Methacholine)
HISTAMINE
● Test for Gastric Secretory function
BIOSYNTHESIS ● Determination of Adequacy of HCl secretion

n
1. Location:
● Mast cells – Effector cells during allergy 2. Betahistine (Serc®)

ia
● Basophils – Effector cells during allergy ● H1 Receptor Agonist
● Parietal cells ● H3 Receptor Antagonist
● CNS ● Mgt of Endolymph associated with vertigo
2. Process: ○ Endolymph – Fluid in the inner ear
● Precursor: Histidine ■ Ex: Meniere’s Disease
● Enzyme: L-histidine decarboxylase
● Process: Decarboxylation 3. Impromidine

le
● Product: Histamine ● Investigational drug
3. Mechanism of Release: Degranulation
Calcium Dependent Calcium Independent 2. ANTAGONISTS
Degranulation Degranulation
a. Physiologic / Functional Antagonist
AnaphylaXIS AnaphylaCTOID
IgE mediated (IgE Dru-induced MTG (Morphine, 1. Epinephrine
fixation to mass cells) Tubocurarine, Guanethedine) ● A1 Agonist – Vasoconstriction → HTN
● B2 Agonist – Bronchodilation → easy breathing

EFFECTS b. Pharmacologic Antagonist – ANTIHISTAMINES

A. RECEPTOR
A. H1 ANTIHISTAMINES
● Generally are anti-allergy
Receptor General Response
H1 Allergy 1ST GENERATION
H2
H3
Acidity; Allergy
Inhibitory receptor ➔ Lipophilic → ⨁ brain →
➔ Majority
🚫
➔ Aka Classical AH, Sedating AH
wakefulness → Sedation
H4 Inflammation
1. Ethanolamine
1. H1 Receptor ● Most sedating, most effective
● Blood Vessel – VASODILATION: ↓BP → Diphenhydramine Also used for Dystonia
anaphylactic shock (Benadryl®) (torticollis–twisting of neck)
● Bronchi – BRONCHOCONSTRICTION: DOB/SOB Dimenhydrinate – salt form of Diphenhydramine
● Sensory nerve endings – PRURITUS, PAIN Doxylamine Sleeping Aid
● Capillary endothelium –WHEAL: contraction- → (Unisom®)
shrinkage of endothelium → creates spaces in the Carbinoxamine
cell → fluid from the blood escapes through the
endothelium into the tissue → wheal (characteristic 2. Ethylenediamine
bump on skin; local edema) Pyrilamine GI upset; mild sedation only
● Brain – WAKEFULNESS / ALERTNESS Tripelennamine

2. H2 Receptor 3. Piperazine
● Parietal cell of Stomach – HCl PRODUCTION: ⨁ ● Tx of motion sickness
Meclizine
Proton Pump; activation peaks at night
(Bonamine®)
 Cyclizine SEROTONIN
Hydroxyzine Prodrug of Cetirizine
(Iterax®) BIOSYNTHESIS
1. Locations
4. Alkylamines
● Enterochromaffin cells – on small intestine; >90% of

t
● Components of Cold medications
○ Relieves symptoms of cold medications 5-HT are synthesized here
○ Includes: ● Platelets (as a pro-aggregant)
■ Analgesic (Paracetamol) ● Stomach

t
■ Nasal decongestant (𝝰1-agonist– ● Brain
Phenylephrine, Mixed acting–PPA) 2. Process:
■ Anti-H1 ● Precursor: L-tryptophan
Chlorphenamine ● Reactions:
Brompheniramine w/ PPA: Nasatapp®

g
○ Hydroxylation (Hydroxylase)
5. Phenothiazine ○ Decarboxylation (Decarboxylase)
Promethazine Anaesthetic adjunct: to induce ● Product: 5-Hydroxytryptamine (5-HT)
(Phenergan®) pre-operative sedation

e
6. Piperidine
Cyproheptadine 🚫
🚫 H1 Receptor
EFFECTS

🚫 M3 Receptor a. RECEPTOR
5-HT1,2
🚫

n
Receptor Location Effect
Mgt of Serotonin Syndrome 5-HT1A CNS Presynapse ● Further release of 5-HT
(hyperthermic dx)
5-HT1B/1D Cerebral blood ● Cerbreal vasoconstriction

ia
vessel ● Anti-migraine
2ND GENERATION 5-HT2A/2B Smooth muscles ● Contraction
➔ Originally 1st generation agent
Uterus ● Oxytocis
1. Piperazines – Less Sedating Cerebral BV ● Vasoconstriction
Cetirizine (Virlix®, Bronchial SM ● Bronchoconstriction
Zyrtec®, Alnix®) Platelet ● Aggregation (clot)
Levocetirizine w/ Monteluklast: Zykast®, 5-HT3 Chemoreceptor ● Nausea & Vomiting

le
(Allerzet®) Coaltria® Trigger Zone CTZ (emesis)
5-HT4 GIT ● Peristalsis → BM
2. Piperidines – True Non-Sedating
Loratadine (Claritin®, Most applicable for Px (pilot,
Allerta) drivers, machine operators)
DRUGS
Desloratadine with allergy requiring mental
(Aerius®) alertness 1. AGONISTS
Fexofenadine From modifications of
(Telfast®) Terfenadine (cardiotoxic) Drug Name Type of R Clinical Use
Agonist
3. Newer Agents Buspirone Partial 5-HT1A Anxiolytic (therapeutic
Bilastine (Bilaxten®) effects after 2 weeks)
Ebastine w/ Betamethasone: Sumatriptan Full 5-HT1B/1D Anti-migraine
Co-aleva® Inhibit inflammation of
Naratriptan
meninges
ozlmitriptan A/E: Increase in BP
B. H2 ANTIHISTAMINES C/I: Hypertensive Px
Cimetidine Prototype Cisapride Partial 5-HT4 Mgt of IBS
Least potent (high dose) Tigaserod (predominant
Enzyme inhibitor Prucalopride Full constipation)
Anti-androgenic
Famotidine faMOSTidine Most potent
Nizatidine Almost 100% bioavailability 2. ANTAGONISTS
Ranitidine
Drug Name Type of Clinical Use
Applications: Allergy & Acidity Agonist
➔ Mgt of Acid Peptic Disease Cyprohepatadine 5-HT1,2 Mgt Serotonin Sydnrome
➔ Mgt of Acute GI ulcer bleeding Ondansetron Anti-emetic in CA
➔ Adjuncts for allergic reaction Granisetron 5-HT3 chemotherapy
Palonosteron

🌟
T/E: Cimetidine Ketanserin 5-HT2A/2B Antihypertensive
➔ Enzyme inhibitor = D/I Alosetron– used in Mgt of IBS w/ predominant symptom is
➔ Antiandrogenic = loss of libido, gynecomastia diarrhea
 EFFECT
3. ERGOTS
● From Claviceps purpurea Organ Effect Eicosanoid
● Target: 𝝰1, DA, 5-HT2 Blood vessel Vasoconstriction TXA2
Vasodilation PGI2

t
○ Mixed action on 5-HT2
■ Agonist – Ergotamine, Ergonovine Injured tissue Inflammation PGE2 (major)
PGI2 (↑BF w/ Neutrophil)
■ Antagonist – Methysergide
LTD4
Ergotamine Vasoselective

t
Bronchial Bronchoconstriction LTC4, LTD4 (SRSAs)
𝝰, 5-HT2 Anti-migraine Muscle Bronchodilation PGE series
Ergonovine Agonist Uteroselective
Uterine Muscles Oxytosis PGE series
Post-partum hemorrhage
Dysmenorrhea PGF
Anti-migraine
Stomach Cytoprotection (thick PGE series (vs Gastrin,
Methysergide 5-HT2 Prophylaxis for Migraine HA

g
mucosal lining, ACh, M3 that ↑Acidity)
Antagonist ↓acidity)
Platelet Aggregation (clot) TXA2
● T/E: 🚫Aggregation PGI2, PGE1

e
⬇️
1. GI disturbances (most common) (bleed)
2. Vasospasm → gangrene (most serious) Eyes IOP PGF2𝝰
3. Retroperitoneal fibrosis (unique)

n
DRUGS / PROSTAGLANDIN ANALOGUES
EICOSANOIDS

ia
Drug PG Effect Clinical Use
BIOSYNTHESIS Analogue
● Eicosanoids – products of eicosanoic acid metabolism Misoprostol PGE1 Cytoprotection Tx of NSAID
○ Eicosanoic Acid – Polyunsaturated FA (multi DB); (Cytotec®) induced-ulcer
Arachidonic Acid Abortifacient
○ Metabolism Epoprostenol PGI2 Vasodilation Mgt of Primary
■ COX – Cyclooxegenase (systemic) Pulmonary HTN
Dinoprostone PGE2 Cervical Therapeutic
■ 5-LOX - 5-Lipooxygenase

le
ripening abortion
Alprostadil PGE1 Vasodilation Tx of Erectile
(local) dysfunction as male

Latanoprost
Carboprost
PGF2𝝰 ⬇️IOP urethral suppository
Tx of Glaucoma

Prostanoids:
1. Prostaglandin (PG) – derived from Semen
2. Prostacyclin (PGI2)
3. Thromboxanes (TXA2)

Leukotrienes (LE)
1. LTB4: Chemotactic Factor
2. LTC4, LTD4: SRSAs Slow Reacting Substances of
Anaphylaxis → Bronchoconstriction
 RHEUMATOLOGIC DRUGS
RHEUMATOLOGIC DISORDERS
t
● Affect the musculoskeletal (muscles, bones, joints,
ligaments, tendon) system
● Features:
t
○ AUTOIMMUNE – self-reactive immune cells (B & T)
■ Rheumatoid Arthritis
● Chronic/Systemic inflammation
● Affects synovium
g
● Arthritis (multiple, symmetrical)
● Symmetrical, HAND involvement
● Morning Joint stiffness (1 hr)
■ Systemic Lupus Erythematosus
e
● Usually affects women > men
● MALAR rash – Butterfly-shape rash
● Photosensitivity (sunlight)
● Renal complication (Nephritis)
■ Ankylosing Spondylitis
n
● Fusion of the spine: Bamboo spine
● Affects men > women
ia
● Enthesitis (inflamm)
● Sacrolitis (inflamm of sacro illac joint)
○ INFLAMMATORY – Non-specific immune response
against and adverse stimulus
■ Cardinal signs: Rubor (redness), Calor (heat),
Tumor (swelling), Dolor (pain), Functio laesa
(loss of function)
le
❌ ❌
■ Osteoarthritis – non-inflammatory
Rheumatologic disorder; rubor, calor
● Morning joint stiffness (~5min)
○ METABOLIC
■ Gouty Arthritis
● ↑ body stores of Uric acid → goes to joints
→ attacked by inflammatory cells
● Big toe: Monoarticular arthritis
RHEUMATOID DRUGS
ANALGESICS
● Induces ANALGESIA–loss of pain perception
A. NON-NARCOTIC ANALGESICS
a. Acetaminophen, USP / Paracetamol, BP
➔ Weak COX inh in the periphery
➔ Uses: Analgesic, Antipyretic
◆ Analgesic of choice (1st line) in Osteoarthritis
◆ Antipyretic effect is better than analgesic effect
➔ No anti-inflammatory effect even at higher doses
❌
➔ Advantages:
◆ vs ASA: HYPERURICEMIA effect
◆ Safe in pregnancy, children, lactating moms
➔ T/E: Hepatotoxicity
◆ Risk factors:
● > 4 g/day
● Preexisting liver disease
● Concomitant use of CYP1A2 inducers
b. Nonsteroidal Anti-Inflammatory Drugs NSAID
● All are weak organic acids except Nabumetone
🚫
○ Nabumetone – the only prodrug NSAID
● MOA: COX inhibition → PG synthesis
○ Isoforms of COX
■ COX 1
● Constitutive / Homeostatic Enzyme
● PGs for maintenance
○ Cytoprotection
■ If blocked, mucosal lining will
thin & ↑HCl production
❌
○ Renal vasodilation = ↑ diuresis
■ If blocked, diuresis
■ COX 2
● Inducible Enzyme
● PGs for pain & inflammation
● PGs due to adverse stimuli (physica
injury)
Classifications:
1. NON-SELECTIVE
A. Aspirin & Salicylates
● Prototype NSAID
● The ONLY Irreversible NSAID
Pharmacodynamics – dose dependent; COX inh
1. Analgesic – < 600 mg/day
2. Anti-inflammatory –3.2 - 4 g/day
3. Antipyretic – 0.3 - 1.2 g/day
4. Antiplatelet – < 325 mg/day
5. Anticancer – potential use
Toxicology – includes other NSAID
1. GI effects (gastritis , GI ulcer bleeding)
(Non-selective only)
● Tx: PPI, Misoprostol
2. Reversible decrease in GFR (all NSAID):
Nephrotoxic
3. NSAID-induced bronchial asthma (due to
switch of AA metabolism to favor LOX pathway
→ ↑LT → ↑SRSA → Bronchoconstriction
● Tx:
○ Zileuton – 5-LOX Inh
○ Montelukast, Zafirlukast – LTD4
Antagonist
4. Hyperuricemia → C/I: Gout
● Ex: ASA, Tolmetin, Salicylates
5. CNS Effects
● ASA & Salicylates
○ Mild: Salicylism (tinnitus, hyperthermia,
hyperventilation)
○ Severe: Hallucinations, acid-base
imbalance
○ Fatal: Respiratory depression
6. Reye’s Syndrome
● ASA + Child w/ viral infection
● Fatal: hepatic failure, encephalopathy
B. Pyrazolone Derivatives
1. Phenylbutazone
2. Dipyrone
3. Sulfinpyrazone – not an NSAID
● Uricosuric agent (concentrates UA in the urine)
➔ Powerful analgesic & anti-inflammatory
➔ Withdrawn due to:
◆ Hematotoxicities:
● Agranulocytosis (↓BEN)
● 🌟
gastritis)
Longest half-life

● Thrombocytopenia (↓Platelet) → bleeding

● Aplastic Anemia (↓RBC, WBC, Platelet)

t
—most serious H. Pyrrole Alkanoic Acid Derivative
◆ Nephrotoxicities: 1. Tolmetin
● Acute tubular necrosis ● C/I in Gout
● Anasarca (massive edema)

t
● Nephrotic syndrome (massive albuminuria)

2. COX-2 INHIBITORS
C. INDOle Derivatives

g
1. Indomethacin A. Preferrentially selective
1. Meloxicam
Uses:
➔ Mgt of Patent Ductus Arteriosus B. Highly selective / Specific:
◆ Ductus Arteriosus – blood vessel seen in fetus;

e
1. Celecoxib
serves as connecting vessel between two major 2. Etoricoxib
blood vessels–Aorta (↑O2) and Pulmonary Artery 3. Valdecoxib – withdrawn
(↓O2); closure is necessary to not impair 4. Rofecoxib – wthdrawn
oxygenation of the fetus
◆ Patent = open
🚫 ➔ Adv: Not associated with GI effects

n
◆ Opening is PG mediated → must COX Inh → ➔ T/E: ↑risk of acute thrombotic events → clotting → MI
Closure (emergency type of Angina pectoris), Stroke (clot in

ia
➔ Tx in pain in Acute Gout the brain)
➔ Mgt Barter’s Syndrome (indomethacin can fix
electrolyte imbalance in renal tubule)

D. PROpionic Acid Derivatives a. NARCOTIC ANALGESICS

1. Ibuprofen (Medicol®, Dolan®) ● Narcosis (at toxic doses)
2. Naproxen ○ Stupor – lethary / weakness
3. Ketoprofen ○ Insensibility

le
4. Flurbiprofen
General Pharmacology
➔ Analgesic & Anti-inflammatory
➔ Added Antipyretic: Ibuprofen, Naproxen ➔ Sources: Papaver spp
➔ Ibuprofen – safest NSAID in children ◆ Morphine – Papaver somniferum
➔ Naproxen – fever of malignancy ◆ Thebaine – Papaver bracteatum
◆ APAP → ASA → Naproxen (⨁CA)
➔ 🌟MOA:
◆ Mixed action → Activation of Opioid Receptors
E. Phenylacetic Acid Derivatives
● Mimicry – agonist
A. True Phenylacetates ● ↑ Release of opioid peptides
1. Sulindac – Sulfonamide-like (hemolytic anemia, SJS) ○ Endorphins
2. Alcofenac ○ Endomorphins
3. Diclofenac – Diclofenac Na (Voltaren) Diclofenac K ○ Dinorphins
(Cataflam) ○ Enkephalins
◆ Opioid receptors
B. Acetic Acid Derivatives
1. Ketorolac – Tx of acute pain post-operation ● Mu (μ)– majority
2. Etodolac ● Kappa (k) – additional analgesia in women
3. Nabumetone – the only prodrug NSAID; not a weak ● Delta (δ) – spinal analgesia
organic acid
➔ Effects:
◆ CNS – Analgesia, Addiction, Miosis, Cough
F. Fenamates / Fenamic Acids suppression, Respiratory depression, Convulsion
1. Mefenamic Acid
◆ Peripheral
2. Meclofenamic Acid
3. Flufenamic Acid ● CVS: Bradycardia except Meperidine,
Venodilation
➔ Analgesic only ● Biliary Tract: Biliary contraction except
➔ Not useful in inflammation Meperidine
➔ Never given in children, give Ibuprofen ● GIT: Constipation
● Uterus: Tocolysis
● Mast Cell: Anaphylactoid rxn; Pruritus
G. OXICAM Derivatives
1. Piroxicam
● Provides greatest risk in GI effects (ulcer &
➔ Clinical Uses: ● Semi-synthetic Morphine Derivatives –
◆ Tx of pain (visceral pain) Hydromorphone, Oxymorphone
● Mild: Tramadol ○ 8-12x more potent than Morphine
● Moderate: Codeine & company ○ Equal efficacy for severe pain
● Severe: Morphine & friends ● Semi-syntheetic Codeine Derivative –

t
Somatic pain – musculoskeltal pain; NSAID
Visceral pain – internal organs pain; Narcotics
Neuropathic pain – + nerves; Anti-convulsants
Hydrocodone, Oxycodone
○ 8-12x more potent than Codeine
○ Equal effiacy vs Codeine for Moderate

t
pain
● Synthetic
◆ Mgt of acute pulmonary edema – Morphine
● Methadone
◆ General Anesthetic adjuncts – Fentanyl (IV)
○ Same efficacy vs Morphine
◆ Anti-diarrheals – Diphenoxylate, Loperamide

g
○ Good OBA, Longer DOA → Less rapid
◆ Anti-tussives – Dextrometorphan
development of tolerance
○ Used to wean-off morphine or heroine
➔ T/E:
addicts

e
◆ Respiratory depression (greatest threat)
● Meperidine / Pethidine (Demerol®
● Necessitates antidotal therapy–Naloxone
○ No cardiac & biliary effects (no biliary colic
◆ Addiction (manifested by withdrawal symptoms)
& bradycardia)
● Frequent yawning
○ Toxic metabolite: Normeperidine → pass
● Hyperventilation
through BBB → seizure

n
● Mydriasis
● Levorphanol
● Rhinorrhea
○ 5-7x more potent than morphine

ia
● ↑ Hostility
○ Undergoes Isomerism → Dextro-isomer
◆ Tolerance (develops >2-3 wks exposure)
○ Dextromethorphan – cough suppressant,
◆ Anaphylactoid Rxn
anti-tussive
● Tx: Epinephrine
● Fentanyl
○ 100x more potent than morphine
➔ C/I
○ IV administered General anesthetic to
◆ Pregnancy (crosses through the placenta → baby
induce Opioid combination

le
becomes addicted as well → upon delivery,
withdrawal will occur)
◆ Px with head trauma (further enhance ↑ICP values)
State
Neurolept ✅ ✅
Dromperidol Fentanyl
❌
N2O

◆ Do not combine a PA w/ a FA → ↓ analgesia

Analgesia
Neurolept
Anesthesia
✅ ✅ ✅
● Loperamide & Diphenoxylate
🌟
Specific Agents
○ Anti-diarrheal
1. BASED ON SOURCES
○ Loperamide – devoid of narcotic properties
A. OpiaTes – naTural
○ Diphenoxylate – ⨁addiction
● Morphine – standard of comparison as
■ Remedy: Coadminister with Atropine
analgesics
to lessen addiction tendency
○ Poor oral BA = undergoes extensive FPE
● Tramadol
○ 25-30% OBA
○ Derivative of codeine
○ For severe pain
○ Weak μ agonist → for mild pain
● Codeine – standard of comparison as
● Pentacozine
anti-tussive
○ Partial 𝝟 agonist
○ Less effiacy compared from Morphine (for
○ Given alone: 𝝟 agonist
pain)
○ w/ FA: μ Antagonist
○ For moderate pain
● Thebaine – precursor in Naloxone formation
2. BASED ON PHARMACODYNAMICS
A. Strong Full Agonists – used in the tx of severe
B. Opioids – semi-synthetic, synthetic
pain; comparable effect with Morphine
● Semi-synthetic
● Fentanyl
● Heroine – Diacetylmorphine / Diamorphine
● Oxymorphone
○ Equal efficacy vs Morphine
● Heroin
○ Drug of abuse (vs Morphine–clinically
● Meperidine
useful)
● Hydromorphone
● Apomorphine
● Methadone
○ Same structure with Morphine
● Levorphanol
○ Not analgesic (no affinity at μ receptor)
B. Mild to Moderate Full Agonist – used in the tx of
○ DA Reuptake Inhibitor → ↑DA
moderate pain; comparable effect with Codeine
○ DA-2 Agonist → ↑DA effects
● Codeine
○ Mgt of Parkinsonism (↓DA)
 ● Oxycodone ● MOA: 🚫 Dihydroorotate dehydrogenase → ⊖
● Hydrocodone Ribonucleotide synthesis → Arrest cell cycle
● Tramadol
C. Partial Agonists – has D/I with full agonist 5. Mycophenolate Mofetil

🚫
● Pentazocine ● Prodrug → Mycophenolic Acid

t
● Nalbuphine ● MOA: Inosine Monophosphate Dehydrogenase
● Butorphanol ● Maximum dose: 6 mg
● Buprenorphine

t
D. Full Antagonist – antidote for Narcotic poisoning 6. Gold Compounds

🌟
● Naloxone ● Contains elemental Gold
● Naltrexone ● Preparations:
● Nalorphine ○ Parenteral: Aurothiomalate, Aurothioglucose

g
● Nalmefene ○ Oral: Auranofin
● Levallorphan ● Obsolete due to toxicity and questionable effiacy
● T/E: Hypersensitivity, Nephrotic syndrome
DMARDS

e
● Disease Modifying Antirheumatic Drugs
● Immunosuppressant B. BIOLOGIC AGENTS
● Full effect occurs when taken after a long period of ● Product of Recombinant technology
time– 6-12 months ● HMW

n
○ Aka SAARDs– Slow Acting Anti-rheumatic drugs ● Monoclonal antibodies

🚫
🚫

ia
Abatacept T-Cell Activation
A. NON-BIOLOGIC AGENTS / Rituximab B-Cell depleting agent (Target CD20
● Conventional
● Small MW Tocilizumab
Anakinra
🚫
B Lymphocyte)

🚫IL-6 mediated signalling

IL-1 neutralizing agent
1. Methotrexate MTX Adalimumab
● 1st line DMARD Infliximab
Etanercept 🚫Tumor Necrosis Factor-Alpha
🚫 🚫
● Uses: CA (100mg/day), RA (7.5-20mg/wk)
Certolizumab

le
● MOA: AICAR Transformylase; Thymidylate
Golimumab
synthetase → ⊖DNA synthesis →
⊖hyperproliferation of synovial cell → ⊖ Inflammation
● T/E: Hepatotoxicity (dose-dependent); common in
GLUCOCORTICOIDS
CA treatment
1. SYSTEMIC
● Rescue Drug: Leucovorin / Folinic Acid
○ PO: Mgt of RA
■ Prednisolone (Pred®)
2. Anti-malarials
■ Dexamethasone (Decilone®)
● Chloroquine, Hydroxychloroquine (Plaquenil®)
■ Methylprednisolone (Medrol®)
● 2nd line DMARDs
○ IV – life threatening SLE (pulsatile administration
🚫
● MOA:
(1000mg IV for 3 days)
○ T-Lymphocyte responses to mitogens →
■ Methylprednisolone (Solu-Medrol®)
🚫
⊖hyperproliferation of synovial cell

🚫
○ Chemotaxis
2. LOCAL
○ DNA and RNA synthesis
● For OA
● T/E:
● ROA: Intrasynovial
○ Derived from cinchona → Cinchonism
● DOA: every 4-6 months
■ Tinnitus, HA, Diziness
● S/E: since intrasynovial → could destroy joints
○ Optic neuritis

3. Sulfasalazine ANTI GOUT AGENTS

● Prodrug → Sulfapyridine and 5-Aminosalicylate Gout: ↑ body stores of uric acid → joints → “foreign bodies”
○ Sulfapyridine – RA → attack inflammed cells
○ 5-Aminosalicylate / 5-ASA / Mesalamine –
IBD (no DMARD property; a COX-inh → Acute Gout
anti-inflammatory) ● Acute monoarticular arthritis
● T/E: ● Big toe: PODAGRA of Gout
○ Sulfapyridine – Sulfonamide-associated T/E ● Problem: joint arthritis (pain & inflammation)
○ Mesalamine – GI effects (gastritis, ulcer) ● Drugs → relieve symptoms

🚫Tubulin
4. Leflunomide Drug MOA Notes
● Prodrug → A77-1726 Colchicine Polymerization 1st line for Acute
→ ⊖ Microtubule Gout
 synthesis → ⊖
Chemotaxis of T/E: Watery
Neutrophils Diarrhea, Bloody
Diarrhea, Peripheral

🚫COX ❎ neuropathy

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NSAIDs Aspirin, Tolmetin,
Salicylates

✅Indomethacin,

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Ibuprofen
Glucocorti- Immunosuppression Used for NMT 5
coids days
Chronic Gout
● UA deposition on kidney and joint

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● Forms:
1. Gouty Nephropathy – ⨁ renal UA stones
2. Chronic Tophaceous Gout – ⨁tophi (inflammatory

e
bumps; subcutaneous deposits of monosodium
urate MSU crystals → bukol in the joints →
deformed)

● Steps for Treatment

n
1. Give Colchicine alone on first 2-3 wks of therapy
(to stabilize pain manifestation)

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2. Take Colchicine + Hypouricemics after 2-3 weeks
(to lower UA levels)

Hypouricemic Agents
● Lower blood UA level
● Concept: Enzymes
○ Xanthine Oxidase

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■ Responsible for oxidation of Xanthine &
Hypoxanthine → Uric Acid
○ Urate Oxidase / Uricase
■ Responsible for Uric Acid conversion to
Alantoin which is readily excreted in the urine

Drugs MOA Notes

Allopurinol 🚫XO
Purine analogue
1st line for Chronic
Tophaceous Gout
Febuxostat Non-purine analogue
Peglovicase Recombinant Uricase – absent in
Rasburicase Uricases mammals; exogenous
administration only
Uricosuric Agents ↑ Excretion of T/E: Renal uric acid stone
(Sulfinpyrazone, UA formation
Penicillamine, Remedy: frequent
Probenecid) hydration
 PSYCHOTICS

CNS Pharmacology SCHIZOPHRENIA

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INTRODUCTION
↑DA, ↑5-HT,
● Components: Brain & Spinal Cord
● Brain – command center

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● Central – drugs that acts on or can enter the CNS ● Hereditary
● Mode of communication: Release of Neurotransmitters– ● Biology theory: ↑DA, ↑5-HT, ↓Glutamate
chemicals responsible for the the transmission of signals ● Symptoms:
● Types: ○ Positive Symptoms – not present in normal person

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■ Hallucinations – sensory misperceptions
(auditory – most common)
Inhibitory Excitatory & Inhibitory
Dopamine, GABA Acetylcholine, NE ■ Delusions – fixed false belief
Glycine Opioid Glutamate, Serotonin ● Paranoia / persecutory

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● Grandeur
○ Inhibitory NTs: DoGaGo ■ Disorganized thoughts / speech
■ Dopamine ■ Bizarre behavior
■ GABA – main inhibitory NT in the Brain ○ Negative Symptoms – may be present in normal
thus difficult to detect

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■ Glycine – main inhibitory NT in the spiNal cord
■ Opioid ■ Alogia – low verbal output
■ Anhedonia – inability to feel pleasure

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○ Both Excitatory* & Inhibitory NTS *primarily
■ Acetylcholine ■ Avolition – lack of motivation/drive
■ NE ■ Asociality
■ Glutamate – primary excitatory NT ■ Flattening of affect – monotonous
■ Serotonin

DRUGS: ANTIPSYCHOTICS / NEUROLEPTICS / MAJOR

TARGET ACTIONS TRANQUILIZER

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1. Ion channels A. FIRST GENERATION / CLASSICAL /
Stimulatory Inhibitory
🚫
TRADITIONAL / TYPICAL ANTIPSYCHOTICS

🚫 🚫
VGIC ● MOA: D2 Receptors
Na+, Ca2+ K-, Cl-
🚫
Opening ● Additional MOA: Anti-HAM ( Histamine, Alpha-1,
Muscarinic) → ↑Side effects → Disadvantage
a. PiSo, MiCo – CATIONS ● Use: For the tx of POSITIVE SYMPTOMS (cannot tx
b. PhIClo, SulIBiO – ANIONS negative)

● Ex: NA
○ Since Na & Ca is primarily found in the
extracellular fluid → once channel opens →
undergo diffusion (high to low conc) → Na &
Ca enters → cell will become positively
charged → “Depolarization”
■ DeCaNaPositive
○ Since K is primarily found in the intracelular
fluid → once channel opens → undergo
diffusion (high to low conc) → K exits → cell
will become negatively charged →
“Hyperpolarization”
○ Since Cl is primarily found inthe extracellular
fluid → once channel opens → undergo
diffusion (high to low conc) → Cl enters → cell
will become negatively charged →
“Hyperpolarization”
■ HyKCl
2. Neurotransmission
● Fates: (Mechanisms of Termination of effect)
○ Binding to a receptor
○ Metabolism by MAO & COMT
○ Reuptake into presynaptic terminal
○ Passive diffusion into the SC
Drugs:
➔ Phenothiazine “-azine”
◆ Aliphatic – “-promazine” (Chlorpromazine)
◆ Piperazines – “- phenazine” (Fluphenazine)
◆ Piperidines – “-redazine” (Thioridazine)
➔ ButyrOphenones “-peridOl”
◆ Haloperidol, Droperidol
◆ Used for Manic phase, Huntington’s disease,
Tourette’s Syndrome, Phencyclidine Intoxication,
➔ Thioxanthenes “-thix-”
◆ Thiothexene
◆ Rarely used
Potency: BP PTA
● Butyrophenones = Piperazines > Piperidines >
Thioxanthene > Aliphatics
● Most potent: Butyrophenones = Piperazines
● ↑ Potency = ↑D2 Receptor affinity, ↓HAM Receptor
affinity
● Most likely to cause EPS – ↑DA receptor
● Most likely to cause sedation – ↑ HAM receptor
○ Chlorpromazine (aliphatic) – ↑ HAM receptor
○ Haloperidol (Butyrophenone) – ↑DA receptor
 ■ Sx: Fever, muscle rigidity, altered mental
B. SECOND GENERATION / ATYPICAL status, unstable vital signs
ANTIPSYCHOTICS ■ Tx: Dantrolene, Bromocriptine (D2 Agonist)
● MOA:
○ Block 5-HT > D2 Receptor B. Histamine-R Blockade

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○ Block D4 Receptor ○ Sedation (Chlorpromazine typically used as
● Use: For NEGATIVE Symptoms sleeping aid due to its greater affinity to H receptor)
● Advantage: ↓ binding to DA receptor → ↓ EPS C. Alpha-1 Blockade

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○ Clozapine – completely no EPS effect ○ Vasodilation → Orthostatic hypotension
● Efficacy: ○ Failure to ejaculate
○ Treating ⨁ Symptoms: 2nd Gen = 1st Gen D. Muscarinic-R Blockade
○ Treating ⊖ Symptoms: 2nd Gen > 1st Gen ○ Common in ↓potency Typical antipsychotics

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○ Anticholinergic effects Alice in Wonderland
Drugs: –zapine, –xapine, –peridone E. Others
➔ Clozapine ○ Seizure – clozapine
➔ Olanzapine ○ Agranulocytosis (↓BEN) → ↑risk of infection –

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➔ Loxapine clozapine
➔ Risperidone ■ Requires WBC count monitoring
➔ Paliperidone ○ Cardiac S/E:
➔ Ziprasidone ■ Myocarditis – clozapine
■ QT prolongation – Ziprasidone, Thioridazine,

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➔ Quetiapine
➔ Amisulpride Azithromycin, Quinolones

🤍 👀
➔ Molindone ○ Retinal deposits → blindness

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➔ Aripiprazole – newest, -prazole not a PPI ■ thioRIdazine (QT prolongation) is blind
○ Corneal deposits → does not cause blindness
A. Clozapine ■ Chlorpromazine
● No EPS at all ○ Weight gain
● Only antipsychotic that can ⇩ suicide risk ■ Olanzapine
● Never a 1st line ■ Common in 2nd gen antipsychotics except
● WOF: “SAM” → seizure, agranulocytosis, AMA Amisulpride, Molindone, Aripiprazole

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myocarditis ○ Risk for DM
B. Aripiprazole ■ Olanzapine
● Newest antipsychotic
● Partial D2 Agonist (on top of Anti-5HT & Anti-D4) EPS - 1st gen
● Least sedating Metabolic S/E - 2nd gen
C. Olanzapine
● WOF: Overweight / obesity, Diabetes
D. Risperidone MOOD DISORDERS
● For intractable hiccups
E. Ziprasidone
BASIC COMPONENTS
● Causes QT prolongation → arrhythmia
F. Quetiapine
NE, ↓5-HT, DA
● WOF: Sedation (quietapine→shhleep)

I. Mood vs Affect
A/E of 1st & 2nd Gen Antipsychotics Mood Affect
A. Dopamine-R Blockade Feeling expeirenced internally External expression of mood
○ EPS – Extrapyramidal Symptoms
■ ⇩DA → ⇧Acetylcholine II. Mood Regulation
● NT responsible for Mood regulation
■ Dystonia, Akathisia (managed by ↓ dose)
● 5-HT, NE, DA
■ Mgt (Goal): ↓ Acetylcholine – Centrally Acting
Anticholinergics: Biperiden (Akiniton®),
III. Mood Spectrum
Brenztropine, Trihexyphenidine
Major Depressive Disorder
○ Hyperprolactinemia
Dysthymia
■ ⇩DA → ⇧Prolactin (DA is a prolactin inhibiting Euthymia – normal mood
hormone) Hypomania
■ Galactorrhea, amenorrhea (prolactin– inhibits Mania
gonadotropin RH), infertility, libido ● Major Depressive Disorder
○ NMS – Neuroleptic Malignant Syndrome ○ Symptoms (+) 2 weeks
■ Malignant hyperthermia ○ Biologic theory: ↓NE, ↓5-HT, DA
■ Rare but life threatening idiosyncratic (Type B) ● Dysthamia
reaction to Antipsychotics ○ Mild depression
● Hypomania ■ Present with pyschotic features & phobias
○ For at least 4 weeks ● D/F Interaction
● Mania ○ Tyramine-rich foods → HTN crisis
○ Persistently elevated mood for 1 week ■ ⇧Tyramine → ⇧Catecholamines → ⇧BP
● Mixed Disorder: ■ Cheese, wine, beer, chicken liver, banana

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○ Cyclothimia – Hypomania + dysthymia
○ Bipolar disorder – mania + MDD (shift is not abrupt) Drugs:ANTI-DEPRESSANTS
➔ ATYPICAL ANTIDEPRESSANTS: SARI SEROTONIN

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🚫 🚫
ANTAGONIST & REUPTAKE INHIBITOR
DRUGS FOR DEPRESSION
● MOA: 5-HT reuptake & 5HT-2A/2B Receptor
Goal/MOA: ↑NE, DA, 5=HT ● Effect: ⇧ 5-HT
Drugs:ANTI-DEPRESSANTS ● Examples: “-zodone”

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🚫
➔ TRICYCLIC ANTIDEPRESSANTS ○ Trazodone
● MOA: Reuptake of NE > 5-HT ○ Nefazodone – w/ Blackbox warning:
● Effect: ⇧ NE, 5-HT levels Hepatotoxicity
● Additional effects: Anti-HAM ● A/E:

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● Examples: ○ Sedation (similar structure with
○ “-triptylline” (Amitryptylline, Nortriptylline) Alprazolam–Sedative hypnotic BZD)
○ “-pramine” (Imipramine, Desipramine, ○ Priapism – sustained erection
Comipramine)

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○ Doxepine
● Uses: Drugs:ANTI-DEPRESSANTS
○ Tx of Neuropathic pain – Amitryptylline

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➔ SSRI: SELECTIVE SEROTONIN REUPTAKE
○ Tx of Enuresis (bedwetting) – Imipramine
🚫
INHIBITOR
○ Tx of Insomnia (as Anti-HAM) ● MOA: Reuptake of 5-HT
○ Mgt of anxiety attacks (panic) – Imipramine ● Effect: ⇧ 5HT levels
○ Mgt of OCD – Clomipramine ● Examples:
● A/E: ○ FluFlu: Fluoxetine, Fluvoxamine
○ Wt gain (most common) ○ Paro-Ser: Paroxetine, Sertraline
○ Sedation → coma (Anti-H) ○ Citalopram & Escitalopram

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○ Orthostatic hypotension (Anti-A1) ● Uses:
○ Anticholinergic effects (Anti-M) ○ 1st line against Major Depressive Disorder
○ QT prolongation ■ All are Category C except
● Toxicities: very Narrow TI Paroxetine–Category D
○ TCA overdose (triad–3Cs) ■ Safer to use than TCAs and MAOi
■ Cardiotoxicity (QT prolongation) ○ Mgt of OCD – Fluoxetine, Fluvoxamine,
■ Convulsion Sertraline
■ Coma ○ Mgt of PDD (premenstrual dysphoric disorder)
– Fluoxetine, Fluvoxamine
Drugs:ANTI-DEPRESSANTS ○ Mgt of bulimia nervosa – Fluoxetine
➔ TETRA ANTIDEPRESSANTS ○ Mgt of Alcohol dependence
● Examples: Mama Mia Amor ● A/E:
○ Maprotiline ○ Sexual disfunction
○ Mianserine ■ Remedy: shift to another drug
○ Amoxapine ○ Sleep disturbance (insomnia–Fluoxetine)
○ Discontinuation syndrome (withdrawal → ⨁
Drugs:ANTI-DEPRESSANTS symptoms)

🚫
➔ NON-SELECTIVE MAO INHIBITORS ■ Fluoxetine – less likely to cause DS due

✅
● MOA: MAO-A & MAO-B to long t1/2

✅
○ MAO-A → NE, EPI, ACh, 5-HT, Tyramine, ■ sexual dysfunction

✅
Histamine ■ QT prolongation

✅
○ MAO-B → DA ■ HA
● Effect: ⇧ NE, EPI, ACh, 5-HT, Tyramine, ■ Insomnia
Histamine, DA levels ○ Serotonin syndrome (excessively high 5-HT)
● Examples: MPITS ■ D/I: SSRI + MAOI, Tyramine-rich,
○ Moclobemide – MAO-A selective reuptake inhibitors =
○ Phenelzine ■ Tx: Cyproheptadine
○ Isocarboxazid ● Blackbox warning: ⇧ suicidal ideality
○ Tranylcypromine ● C/I:
○ Selegiline – MAO-B selective ○ Px with serotonin syndrome → aggravation
● Uses: ○ With MAOIs and TCA
○ Mgt of ATYPICAL depression–PIT ● Efficacy:
 ○ TCA = SSRI ➔ NDRI: NORPINEPHRINE-DOPAMINE REUPTAKE

🚫
● Advantages: INHIBITORS
○ Fewer anti-HAM s/e ● MOA: Reuptake of NE, DA
○ Less likely to cause CV morbidities ● Effect: ⇧ NE, DA
○ Safer than TCAs following overdose ● Examples:

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○ Bupropion – smoking cessation
■ vs Buspirone - anxiolytic
● Advantage:

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Drugs:ANTI-DEPRESSANTS ○ Does not cause sexual dysfunction
➔ SNRI: SEROTONIN & NOREPINEPHRINE

🚫
REUPTAKE INHIBITORS
● MOA: Reuptake of 5HT & NE

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● Effect: ⇧ NE = 5-HT levels (vs TCA that NE>5HT)
ANTIMANIA & BIPOLAR DISORDER
● Examples:
○ Duloxetine – hepatotoxic
○ Venlafaxine – cardiotoxic Drugs:ANTI-MANIA & BIPOLAR DISORDER

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🚫
● Uses: muscle & nerve pain ➔ LITHIUM CARBONATE (Eskalith®)
○ Mgt of Depression in px with back pain or ● MOA: Phosphoinositide recycling
muscle pain ○ Inositol → PI → PIP → PIP2 → PLC → IP3,
○ Mgt of Fibromyalgia DAG

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○ Mgt of Diabetic Neuropathy ○ IP3 → IP2 → IP1 → Inositol
○ Mgt of Chronic musculoskeletal pain ● Effect: ⇧ IP3 → Gq linked
● A/E: ● Uses:Primary mgt of Mania and Hypomania

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○ Sexual disfunction ● Limitation:
■ Remedy: shift to another drug ○ Not as effective for rapod recyclicers
○ Sleep disturbance (insomnia) ● D/I: ↓Na → ↑Li or vv
○ Conditions that will ⇧ [Li]
■ Sodium loss
Drugs:ANTI-DEPRESSANTS ■ Thiazides (natriuretic)
➔ NASSA: NORADRENERGIC & SELECTIVE ■ ACE inhibitors (⇩Angiotensin II,

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SEROTONIN ANTAGONIST [NASSAn si MIRTA ayan ↓Aldosterone → ⇩Na retention)
■ NSAIDs → ⇩renal excretion of Li
🚫
TULOG]
● MOA: Presynaptic 𝝰2 receptors ○ Conditions that will ⇧[Li]
(autoregulatory) ■ Acetazolamide – act on PCT → ⇧H2O
● Effect: ⇧ NE excretion → ⇧Na in the blood
● Examples: ■ eeXanthine diuretics – same
○ Mirtazapine ■ Osmotic diuretic – same
● Advantage: ■ Na supplementation
○ Does not cause sexual dysfunction ● A/E: Occurs at normal doses
● AE/SE: ○ Fine tremors – movement disorder
○ Highly sedating ○ Polyuria, polydipsia (due to vasopressin
deficiency)
○ N&V
Drugs:ANTI-DEPRESSANTS ● Toxicities: Occurs at higher doses
➔ RIMA: Reversible Inhibitor of MAO-A ○ Coarse tremors
● Examples: ○ Neuromuscular excitability → seizure,
○ Moclobemide hyperreflexia
● Idiosyncratic reactions
○ Thyroid enlargement (goiter)
○ Teratogenic → Ebstein’s anomaly
Drugs:ANTI-DEPRESSANTS

🚫
➔ NARI: NORADRENERGIC REUPTAKE INHIBITORS
● MOA: Reuptake of EPI
Drugs:ANTI-MANIA & BIPOLAR DISORDER
● Effect: ⇧ EPI
● Examples: ➔ VALPROIC ACID
○ Reboxetine ● Uses: Better than Li for rapid recyclers

Drugs:ANTI-DEPRESSANTS Drugs:ANTI-MANIA & BIPOLAR DISORDER

➔ CARBAMAZEPINE
● Uses: Prophylaxis of mania
 ● Metabolized to →
n-desmethyldiazepam (active)
ANXIETY
■ Flunetrazepam (Rohypnol®)
● Date rape drug
BASIC CONCEPTS ● Common name: “roofies”

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■ Chlordiazepoxide
↓GABA, ↓EPI, Cortisol ● Longest acting BZD
○ BZD Active Metabolite (NorOxa)

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I. Fear VS Anxiety ■ Nordiazepam / N-Desmethyldiazepam
Fear Anxiety ■ Oxazepam
Definite known cause Not known / Vague cause ○ BZD w/o Active Metabolite (COLA)
Due to overstimulation of ■ Clonazepam

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excitatory NTs ■ Oxazepam
■ Lorazepam
II. Types of Anxiety Disorders ■ Alprazolam
1. GAD - Generalized Anxiety Disorder

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● Excessive worrying
2. OCD – Obsessive-Compulsive Disorder Drugs: ANXIOLYTICS
● Marked by repititive action ➔ BARBITURATES “-barbital” “-bital” “-tal”
● What you are obsessed of, you act on compulsion ● MOA: GABA–pentameric Receptor binding → Cl
3. PTSD – Post Traumatic Stress Disorder

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channel will open → Hyperpolarization →
● War shock syndrome Inhibitory effect
● Common to soldiers or anyone who had undergone ○ BZD and BBTs are allosteric activators of

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traumatizing event GABAa to bind to GABA
4. Panic Disorder ○ BBT increase DURATION of Cl- channel
5. Social Phobia opening barbiDURATES
● Speech or interaction with people ● Classifications:
○ Ultra Short-Acting – Sulfur containing (very
III. Biologic Theory lipophilic → makes it short acting)
● ↓GABA, ↓EPI, Cortisol ■ Thiopental, Thiamylal, Methohexital

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■ Rapid onset of action, short DOA
IV. Drugs: ■ For INDUCTION of anesthesia
● Sedative-Hypnotics ○ Short Acting – [5,6,7-barbital]
● Calming-Sleeping ■ Pentobarbital, Hexabarbital,
Secobarbital
■ For SEDATION
○ Intermediate-Acting [Barbie tune]
ANXIOLYTICS / MINOR TRANQUILIZERS
■ Amobarbital, Butabarbital
■ For HYPNOSIS
Drugs:ANXIOLYTICS / MINOR TRANQUILIZERS ○ Long Acting
➔ BENZODIAZEPINES ■ Phenobarbital
● MOA: GABA–pentameric Receptor binding → Cl ■ As Anti-convulsant, insomnia, and Status
channel will open → Hyperpolarization → epilepticus
Inhibitory effect
○ BZD and BBTs are allosteric activators of Clinical Effects of BZDs and BBTs:
GABAa to bind to GABA 1. CNS depression (dose dependent)
○ BZD increase FREQUENCY of Cl- channel ● Tranquilizer → Sedative → hypnotic → anesthesia
opening FRENzodiazepine → respiratory depression → coma
● Examples: -zepam, -zolam, -zep- 2. Anterograde Amnesia (after giving the drug)
○ Chlordiazepoxide ● Basis of date rape drug
○ Chlorazepate ● Acceptable use: during surgery / procedure (ex:
● Classes (Based on DOA): Midazolam or Thiopental before endoscopy)
○ Short Acting: 3. Anticonvulsants
■ Midazolam, Triazolam ● Long-acting agent (Phenobarbital) & Lorazepam
■ For initiation and maintenance of sleep ● For “prevention” never treatment of ongoing attack
■ WOF: Anterograde amnesia 4. Muscle Relaxation
○ Intermediate Acting: LTO-zepam A-zolam ● Occur in high doses
■ Lorazepam, Terrazepam, Oxazepam, ● Mgt of spastic paralysis (cerebral palsy, tetani)
Alprazolam ● Diazepam
■ For seizures & insomnia 5. Tolerance & Dependence
○ Long Acting ● Tolerance – ⇩ responsiveness due to chronic or
■ Diazepam ⇧doses
○ Tachyphylaxis – acute
 ○ Tolerance – chronic
● BZD & BBT exhibit cross tolerance
● Dependence – physical or psychologic
○ Withdrawal signs:
■ Anxiety, tremors, hyperreflexia, seizures
c. Ramelteon – novel hypnotic drug
● MOA: ⨁ Activates melatonin receptor
● Use: Regulates sleep-wake cycle

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SEIZURES
Clinical Uses of BZD and BBT
1. Mgt of Anxiety attacks BASIC CONCEPTS

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2. Mgt of sleep disorders
● Clonazepam ↓Inhibitory NT, ↑Excitatory NT
● Diazepam ● Seizure – uncontrolled or abnormal electrical activity of
● Lorazepam the brain →

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● Phenobarbital ➔ uncontrolled firing of neurons
3. Mgt of seizures ➔ Imbalance between excitatory & inhibitory NTs
● Long acting BZD or BBT ● Seizure – sign; Epilepsy – disease
4. Induction of anesthesia ● WTD:

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● Ultra short acting BBT (thiopental) and Short acting ○ Remove patient from imminent danger
BZD (midazolam) ○ Remove any potential harm in the surrounding
5. Mgt of Bipolar disorder ○ Make sure that the tongue is not obstructing the
● Clonazepam airway
6. Mgt of withdrawal states

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○ Turn the head to the side
● Diazepam ○ Do not restrict the movement
7. Mgt of neonatal hyperbiliribunemia ○ Bring to the hospital if approaching 5 minutes

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● DOC: Phenobarbital
● Unconjugated bilirubin entry into the brain →
“Kernicterus” TYPES OF SEIZURE
● Phenobarbital induces glucuronidation of
🧠
1. Focal seizure / Partial Seizure – only 1 hemisphere of
uncojugated B1 to conjugated B2 the brain is involved

❎ Simple
loss of consciousness ✅ Complex
altered sensorium /

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Clinical Uses of BZD and BBT impaired of
● Additive CNS depression consciousness
● Overdosage: CV & respiratory depression (more
common with barbiturates (bc Narrow TI) ● Drugs:
● Mgt: ○ 1st line: [Car & Penny] CARbamazepine,
○ ABC – maintain airway & ventilatory support PHENYtoin
○ Flumazenil – antidote for BZDs & newer agents (Z ○ Alt: [LOV] Lamotrigine, Oxcarbazepine, Valproic
drugs) Acid
○ Urinary alkalinization – NaHCO3 to promote BBT
elimination 2. Generalized Seizure – affects both hemisphere
● Both present with impaired consciousness
Generalized Tonic Absence / Petit mal
Clonic Seizure / Grand Seizure (children)
OTHER SEDATIVE HYPNOTICS
Mal (Blank stares)
a. Z-Drugs: Zolpidem, Zaleplon, Eszopiclone Valproic Acid Ethosuximide
● MOA: only bind to GABAa receptors with 𝝰1 subunit Lamotrigine Valproic Acid
● Advantage: Topiramate
○ Minimal withdrawal symptoms
○ Have rapid onset of action with minimal effects on 3. Status Epilepticus
sleep patterns ● Medical emergency
● Use: for zzzz Insomnia ● 5 minutes or more of continuous seizure
● Antidote: Flumazenil ● Recurrent seizure without recovery
● Drug:
b. Buspirone ○ IV Lorazepam (Ativan®) DOC
● MOA: Partial agonist of 5HT1A receptor ○ Diazepam (old DOC)
● Advantage: ○ IM Midazolam, Clonazepam
○ No significant interaction with other sedative
hypnotics
○ No analgesia, no muscle relaxation
○ No euphoria, no dependence
○ No potential for abuse
● Use: Anxiolytic
 ANTI-CONVULSANTS
H. Leevetiracetam (Keppra®)
● Summary of MOA: ● MOA: Selectively bind to SV2A (synaptic vesicular
○ Na Channel Blockers: PVC protein) → prevents release of Glutamate
■ Phenytoin, Valproic Acid, Carbamazepine, ● Advantage: Does not cause DI

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Lamotrigine, Topiramate, Pregabalin,
Gabapentin I. Pregabalin, Gabapentin
○ (T-Type) Ca Channel Blockers ● MOA: Na Channel blocker

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■ Ethosuximide, Valproic Acid, Topiramate ● Use: Neuropathic pain (for herpetic neuralgia), Migraine
○ GABA-mimetics
■ Phenobarbital, Valproic Acid, Diazepam

A. Carbamazepine

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● MOA: Na Channel blocker → inhibitory
● Enzyme INDUCER
● Capable of AUTOINDUCTION – can induce its own

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metabolism
● Use: DOC for Trigeminal neuralgia – nerves that
innervates the face
● AE / SE:
○ Dose-related: requires dose adjustment

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■ Ataxia
■ Diplopia

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○ Teratogenic
■ Neural tube defects: Spina bifida
○ SJS

B. Phenytoin
● MOA: Na Channel blocker → inhibitory
● ROA: IV (never IM as it can cystallize the muscle)

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● Enzyme INDUCER
● Use: For Focal seizure
● AE:
○ Non-dose related: Nystagmus – most common
○ Dose-related: Ataxia, Diplopia
○ Cosmetic changes: Gingival hyperplasia, hirsutism
○ Idiosyncratic: SJS, blood dyscrasia
○ Teratogenic: Fetal hydantoin syndrome /
Craniofacial abnormalities
● Phosphenytoin – water soluble derivative of Phenytoin;
can be given both IV & IM

C. Valproic Acid

🚫
● Broadest spectrum
● MOA: ⇧GABA, Na, Ca conductance
● Enzyme INHIBITOR – the only anticonvulsant that is an
enzyme inhibitor

D. Phenobarbital
● Protein Bound
● Pwede sa Buntis
● Pwede sa Bata

E. Lamotrigine
● MOA: Na channel blocker
● A/E: SJS

F. Ethosuximide
● MOA: Ca (T-type) Channel Blocker
● Use: DOC for Absence seizure

G. Topiramate
● MOA: Na, Ca Channel blocker
 PARKINSONISM
Drugs: ANTI-PARKINSONISM
➔ DOPAMINE AGONISTS
BASIC CONCEPTS
● Ergot Alkaloids

t
○ MOA: Stimulate D2 Receptor in the brain
⇩DA, ⇧ ACh ○ Effects: ⇧DA
■ Bromocriptine

t
Parkinsons Disease ■ Cabergolide
● Neurodegenerative disease ■ Pergolide – withdrawn due to valvular
● Predominantly affects the substantia nigra or basal heart disease
ganglia ○ Use:

g
● No cure = symptomatic relief only ■ Less wearing off phenomenon
● Affects DA producing areas of the brain = ⇩DA → ACh ■ Longer DA
realease ■ For Hyperprolactinemia
(prolactinoma–the only PG gland tumor

e
Manifestations: “TRAPS” that could be treated medically)
● Tremors ○ AE:
● Rigidity ■ Pulmonary fibrosis
● Akinesia / Bradykinesia (slow movement(

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● Postural Instability ● Non-ergot Derivatives
● Shuffling gait (hinahatak yung paa) ○ MOA: Partial Agonist at D3 Receptors in the
brain

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○ Example:
ANTIPARKINSONISM ■ Pramipexole
■ Ropinirole
Drugs: ANTI-PARKINSONISM
➔ LEVODOPA
● A prodrug of DA (Cannot cross the BBB)
Drugs: ANTI-PARKINSONISM
● L-DOPA → L-Dopa decarboxylase → Dopamine
➔ AMANTADINE

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● Problem: Initial conversion of L-DOPA in the
periphery → ⇩DA in the body ● MOA: ⇧DA In The Synaptic Cleft
● Solution: + Carbidopa → Sinemet®, Tagamet® ● Uses:
○ MOA: L-DOPA decarboxylase in the periphery ○ Antiviral for Influenza A
○ D/I: Potentiation ○ Antiparkinsonism
● Adverse effects: ○ A/E:
○ N&V (due to DA in periphery → ileus) – ■ Levidoreticularis – couple stone appearance
minimized by addition of Carbidopa
○ Wearing off / On-Off Phenomenon (after
prolonged use of drug) – due to long half-life; Drugs: ANTI-PARKINSONISM
minimized by Carbidopa ➔ APORMORPHINE
● MOA: ⇧DA2 Agonist
● Effect: ⇧DA2 levels
Drugs: ANTI-PARKINSONISM ● Opioid derivative with no effects on opioid receptor
● Uses:
🚫
➔ COMT Inhibitors
● MOA: COMT (converts DA to 3-methyldopa) ○ Adjunct for the Off-Phenomenon of L-dopa
● Effect: ⇧DA
● Examples:
○ Tolcapone – hepatotoxic Drugs: ANTI-PARKINSONISM

🚫
○ Entacapone ➔ CENTRALLY ACTING ANTICHOLINERGICS
● Use: ● MOA: Muscarinic Receptor → ⇩excitatory
○ Given WITH L-Dopa + Carbidopa actions of ACh
○ To inhibit metabolism of metabolized DA in the ● Effect: ⇩ACh levels
brain ● Opioid derivative with no effects on opioid receptor
● Uses:
○ Adjunct for the Off-Phenomenon of L-dopa
Drugs: ANTI-PARKINSONISM ○ Also used to address EPS (tremors & rigidity)
● Examples:
🚫
➔ MAOB Inhibitors
● MOA: MAOB (selective to DA) ○ Biperiden
● Effect: ⇧DA ○ Benztropine
● Examples: ○ Trihexyphenidine
○ Selegiline
○ Rasegiline
 ● Short-Acting Benzodiazepine
○ Examples:
ANESTHESIA
■ Midazolam – causes anterograde amnesia
● Propofol
GENERAL ANESTHESIA ○ MOA: Potentiate GABA receptor → ⇧GABA →

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I. Stages of Anesthesia Inhibitory

🌟
1. Analgesia ○ Milk emulsion → Aka Milk of Anesthesia
2. Excitatory / Disinhibition stage ○ COD of Michael Jackson

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● px is delirious, enhanced reflex, very unstable ○ Most comonly used anesthetic for induction
VS) because it is highly lipophilic → rapid onset of
3. Surgical aneshesia action and recovery
● No pain reflex, unconscious, regular respiration ○ Has anti-emetic effects

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& VS ● Ketamine
4. Medullary depression ○ MOA: Block NMDA Receptor
● Cardio-respiratory depression ○ Use: For dissociative anesthesia (conscious)
● Adrenal medulla – control center of the ○ Phencyclidine PCD – causes dissociative

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lungs & heart ∴ px cannot survive w/o anesthesia, a Schedule I drug, not clinically useful
adrenal medulla ● Etomidate
○ Non-barbiturate hypnotic
II. Induction of Anesthesia ○ Causes sedation without analgesia
● Form administration to anesthesized state ○ Use: preferred for px with cardiac reserve

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● Requirement: rapid onset, short duration, rapid ● Opioid Analgesia
recovery ○ Example:

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● Induction: IV anesthetics → Propofol → ■ Morphine
Neuromuscular blocking agents to relax the ■ Fentanyl
diaphragm→ intubation ■ Sulfentanyl
● Maintenance: Inahalational Anesthetics → ○ Use: Adjuncts on induction of anesthesia
present in O2 mask worn by patients

INHALATIONAL ANESTHETICS

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LOCAL ANESTHESIA
● MAC – minimum alveolar concentration;
○ Concentration that prevents movement in response ● MOA: Na Channel Blockers
to skin incission in 50% of unpremedicated subjects ● Types:
at 100% Ester Type Amide Type
○ a measure of potency; inversely proportional Cocaine – only one with Prilocaine
○ The higher the MAC, the lower potency
vasoconstrictor effect
Procaine
● AE:
🌟
Bupivacaine
Lidocaine (Xylocaine®)

● Examples: in order of increasing potency / decreasing

○ Hypersensitivity (due to its PABA metabolite; esp for
MAC: NDSIEHM
ester type)
○ Nitrous Oxide (Laughing Gas) – weak anesthetic
○ Bupivacaine – most cardiotoxic
& potent analgesic; usually used in dental
○ Effects when given systemically:
procedures
■ CNS – seizures & CN depression
○ Desflurane – only one that causes
■ CV – vasodilation (except Cocaine)
bronchoconstriction (C/I: Asthma)
● Others:
○ Sevoflurane – for children (sweet & less pungent)
○ Lidocaine – anti-arrhthmic of choice for
○ Isoflurane – increases response of heart to
digoxin-induce arrhythmia
Catecholamines (C/I: cardiac patients)
○ EMLA® → Lidocaine + Prilocaine
○ Enflurane – for Asthmatic patient [Esthmatic]
○ + Epinephrine – local vasoconstrictor
○ Halothane – Hepatotoxic
■ minimizes systemic absorption → ⇩ risk of
○ Methoxyflurane – potent anesthetic, weak
seizure
analgesic
■ Prolong duration of action

● AE: Malignant hyperthermia

○ C/I: Succinylcholine– a DNMB
○ DOC: Dantrolene–Ca antagonist

INHALATIONAL ANESTHETICS
● Ultra Short Acting Barbiturates
○ Examples:
■ Thiopental
■ Thiamylal
■ Methohexital
 Respiratory Drugs Drugs:
➔ EXPECTORANT
● Stimulate bronchial gland to secrete water for

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DRUGS FOR COLDS easier expectoration
● Example:
COMMON COLDS ○ Guaifenesin

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● Etiology: Viral – [CAR]
○ Coronavirus, Adenovirus, Rhinovirus

Drugs: DRUGS FOR BRONCHOSPASTIC DISEASES

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➔ NASAL DECONGESTANTS / ALPHA 1- AGONIST (ASTHMA & COPD)
● Never use for MT 3-5 days → causes Rhinitis
medicamentosa (rebound congestion)
INTRODUCTION

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● Example:
○ Phenylephrine Bronchial Asthma
○ Oxymetazoline ● Inflammatory disease affecting the airways
○ Xylometazoline ● Sx: Airway hyperresponsiveness (bronchoconstriction)
● Types:

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Acute Asthma Attacks Chronic Asthma Attack
ALLERGIC COLDS Use relievers Use controllers
For acute attacks For maintenance

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Bronchodilators Anti-inflammatory
Drugs:
DOA: Short DOA: Long
➔ ANTIHISTAMINE + NASAL DECONGESTANTS

DRUGS FOR ASTHMA

DRUGS FOR COUGH
BRONCHODILATORS

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Drugs: ● MOA: Adenylyl cyclase converts AMP → cAMP =
➔ MUCOREGULATORS stimulate bronchodilation
● ⇧H2O portion of bronchial glands → easy ● Example:
expectoration
🚫
○ B2 Agonist – stimulate adenylyl cyclase
● Example:
🚫
○ Methylxanthine – Adenosine which causes
○ Ambroxol bronchoconstriction & PDE (enzyme that
○ Bromhexine
🚫
metabolizes cAMP to AMP
○ Carbocisteine (Solmux®) ○ Anti-muscarinics – ACh

Drugs: Drugs:
➔ MUCOLYTICS ➔ SABA
● Breakdown disulfide linkages between mucus ● Use: Relievers
● Example: ● 1st line RELIEVERS for BA
○ N-Acetylcysteine NAC ● 2nd line Reliever in COPD
■ Effervescent tablet, syrup ● Example:
■ Also for APAP overdose ○ Albuterol / Salbutamol
○ Metaproterenol
Drugs: ○ Perbuterol / Picoterol
➔ ANTITUSSIVES / COUGH SUPPRESSANT ○ Terbutaline
● Indication: for dry non-productive cough /
intolerable cough Drugs:
● Types: ➔ LABA

🚫
○ Peripherally Acting ● Use: Controller
■ MOA: Peripheral cough receptor ● Monotherapy in COPD
■ Ex: Levodropropizine (Levopront®) ● + Inhaled Corticosteroid in BA

🚫
○ Centrally Acting ● A/E: Palpitations, tachycardia, tremors,
■ MOA: Cough reflex center in the brain hypokalemia
■ Ex: ● Route:
● Non-narcotic: Butamirate citrate ○ Inhalational (MDI, Nebulizer)
(Sinecod®) ○ PO (SABAs)
● Opioid: Dextrometorphan ○ SQ – Terbutaline – for the tx of preterm labor
(Robitussin®), Codeine
 ● Example: Types:
○ Bambuterol ● Inhaled CS (ICS) – 1st Line CONTROLLERs for
○ Indacaterol maintenance of Asthma [BFT]
○ Formoterol ○ Example:
○ Salmeterol ■ Budesonide

t
■ Fluticasone
■ Triamcinolone
ANTIMUSCARINIC ○ A/E:

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● S/E: none ■ Local S/E: Oral thrush (gargle after each use)
● ROA: Local ■ Hoarseness (irritation on the vocal cords)
Drugs:
➔ SAMA ● Systemic Oral Corticosteroid

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● Use: Reliever ○ Example:
● 1st line RELIEVER for COPD ■ Prednisone
● Add on agent in BA ■ Prednisolone
● Example: ■ Methylprednisolone

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○ Ipratropium ○ Use: for SEVERE asthma exacerbation
○ Oxytropium ○ Never use it for MT 14 days → s/e manifests
○ A/E:
Drugs: ■ Hypertension
■ Hyperglycemia

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➔ LAMA
■ Immunosuppression
● Use: Controller

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● 1st line CONTROLLER for COPD
● Systemic Parenteral Corticosteroid
● Add on for severe asthma
○ Example:
● Example:
■ IV Methylprednisolone
○ Tiotropium
■ IV Hydrocortisone / Cortisol
○ Use: for STATUS ASTHMATICUS
○ Dose dependent
METHYLXANTHINES
○ A/E:
Drugs:

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■ Hypertension
➔ METHYLXANTHINES ■ Hyperglycemia
● Use: Alternative agents in BA ■ Immunosuppression
● A/E: Narrow TI
○ CNS overstimulation → agitation, seizures
○ Cardiac overfunctiong → palpitations, B. ANTI-LEUKOTRIENE / LEUKOTRIENE MODIFIER
tachycardia, tachyarrhythmia a. LOX inhibitor – Zileuton
○ Diuresis b. LTD4 Receptor Antagonist – Montelukast, Zafirlukast
● Example:
○ Theophylline – PO; controller ● Use: Controllers of BA especially in CHILDREN
○ Aminophylline – IV; reliever ● A/E:
○ Historical: unmasking of Churgg-Strauss Syndrome
(presentation: asthma)
MAST CELL STABILIZERS ○ Present: psychotic features, ⇧suicide ideality

🚫
● MOA: Hyperpolarization of mast cell memrbane →
degranulation of mast cell C. ANTI-IgE
● Ex: Cromones (Cromolyn Na, Nedoocromil) ● Ex: Omalizumab– a monoclonal antibody
● Uses: ● Use: for poorly controlled BA with increased IgE
○ Prophylaxis of seasonal/ allergic asthma
○ Mgt of allergic rhinitis
● A/E: Bronchospasm
○ Mgt: SABA

ANTI-INFLAMMATORY AGENTS
A. CORTICOSTEROIDS

🚫
● MOA:
○ PLA2 (Phospholipase 2),
■ Phospholipid → Phospholipase 2 →

🚫
Arachidonic acid
○ Cytokines → Late phase allergic reaction
 Drugs:
Gastrointestinal Drugs ➔ MUCOSAL PROTECTANTS
● Example:
○ Sucralfate – contains Aluminum & Sucrose

t
ACID-RELATED DISORDERS ■ A/E: Constipation
○ Bismuth subsalicylate
BASIC CONCEPTS ■ A/E: black stools & black tongue

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I. Acid secretion: Histamine, Acetylcholine, Gastrin → ○ Rebamipide (Mucosta®) – stimulate COX →
Stimulate Proton-Pump Activation ⇧PGE → cytoprotection

II. Gastroesophageal Reflux Disease

g
● Sx: Heartburn, acid regurgitation
● Clinical diagnosis
CONSTIPATION-RELATED DISORDERS
III. Peptic Ulcer Disease

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● Endoscpic disease LAXATIVES
● Causes:
○ H. pylori – #1 cause Drugs:
○ NSAIDs - #2 cuse ➔ BULK FORMING LAXATIVE

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● MOA: Absorption of water → form bulky mass –
peristalsis → poop
DRUGS

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● Example:
Drugs: ○ Psyllium

🚫
➔ PROTON PUMP INHIBITORS
● MOA: H-K-ATPase pump
● Use: 1st line for GERD & PUD Drugs:
● Decreases basal acid & stimulated acid secretion ➔ OSMOTIC LAXATIVE
● Given 30 minutes before breakfast (being ● MOA: ⇧Osmotic pressure → attract water →

le
prodrugs) peristalsis
● Example: ● Example:
○ Omeprazole, Esomeprazole, Pantoprazole, ○ Lactulose (NMT 3 days)
Lansoprazole ● Use: for tx of Hepatic Encepalopathy (problem in
the brain present in px with liver failure)
● Lactulose promote excretion of NH3
Drugs:

🚫
➔ H2 Blocker
● MOA: H2 Drugs:
● Decreases basal acid secretion only ➔ STIMULANT LAXATIVE
● Given at bed time ● MOA: Stimulate the walls of the intestine directly
● Cimetidine – enzyme inhibitor; gynecomastia → smooth muscle contration → peristalsis
● Example: ● Example:
○ Cimetidine, Ranitidine, Famotidine, ○ Senna
Nizatidine ○ Castor oil
○ Bisacodyl (Dulcolax)
● A/E: should not be given for a long time
Drugs: ○ Senna - melanosis coli
○ Bisacodyl - atonic coli (cannot contract)
🚫
➔ M1 Blocker
● MOA: M1
● A/E: Alice in Wonderland
● Example: Drugs:
○ Pirenzepine, Telenzepine ➔ STOOL SOFTENERS / ANIONIC SURFACTANTS
● MOA: ⇩ Surface tension → allow water to
penetrate
Drugs: ● Example:
➔ ANTACID ○ Senna
● MOA: → Neutralization ○ Castor oil
● Types: Systemic & Nonsystemic ○ Bisacodyl (Dulcolax)
○ Systemic – can be asborbed by the body ● A/E: should not be given for a long time
■ NaHCO3 ○ Senna - melanosis coli
○ Nonsystemic ○ Bisacodyl - atonic coli (cannot contract)
■ Al(OH)3, Mg(OH)2