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MBBS 2nd Prof Pharmacology - Complete Answers

VERY SHORT QUESTIONS (3 Marks Each)

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• Reduces bioavailability of the drug (e.g., morphine, propranolol, lignocaine have high first-pass effect)
• Drugs with high first-pass metabolism require higher oral doses than parenteral doses
• Drugs like lignocaine, GTN cannot be given orally because of extensive first-pass metabolism
• Sublingual/rectal/parenteral routes bypass the first pass effect

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1. Enalapril - converted to enalaprilat (active) in the liver
2. Levodopa - converted to dopamine in the brain

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• Drugs with narrow TI (e.g., digoxin, lithium, warfarin, phenytoin) require careful dose titration and monitoring
• Narrow TI drugs have a small difference between therapeutic and toxic doses
• Used to determine how safely a drug can be used clinically
• Guides individualization of drug dosage

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• WHO defines it as activities relating to adverse drug reactions (ADRs)
• Involves spontaneous reporting systems (e.g., Yellow Card in UK, Vigibase globally)
• Aims to improve patient safety
• Identifies previously unknown ADRs post-marketing
• In India: IPC (Indian Pharmacopoeia Commission) runs the PvPI (Pharmacovigilance Programme of India)

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1. Thalidomide - causes phocomelia (limb reduction defects/seal limbs)
2. Valproic acid - causes neural tube defects (spina bifida)

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1. Drug-induced Cushing's syndrome - from prolonged corticosteroid therapy
2. Agranulocytosis - caused by carbimazole or clozapine therapy

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1. Glaucoma (open-angle and acute angle-closure) - reduces intraocular pressure by opening the trabecular meshwork
2. Dry mouth (Xerostomia) - in Sjogren's syndrome and post-radiation xerostomia
3. Diagnostic - pilocarpine iontophoresis (sweat test) for cystic fibrosis

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• Myasthenia gravis is caused by autoantibodies against nicotinic ACh receptors (NMJ), reducing available receptors
• Neostigmine is an anticholinesterase (reversible inhibitor of acetylcholinesterase)
• It inhibits the breakdown of ACh at the NMJ → increases ACh concentration
• The accumulated ACh competes more effectively with antibodies for the reduced number of receptors
• Result: improved neuromuscular transmission and muscle strength

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1. Donepezil (drug of choice) - long acting, once daily
2. Rivastigmine - also inhibits BuChE; available as patch
3. Galantamine - also a nicotinic receptor allosteric modulator
4. Tacrine - earliest but hepatotoxic, no longer used

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• Organophosphate (OP) compounds cause irreversible inhibition of acetylcholinesterase by phosphorylation
• Pralidoxime (2-PAM) is an oxime that reactivates AChE by attacking the phosphorus atom and removing the phosphate group from the enzyme
• This must be done before "aging" (permanent covalent bond formation, within 24-48 hrs)
• After reactivation, AChE resumes breakdown of ACh, reversing toxidrome
• Oximes are used alongside atropine (atropine treats muscarinic effects; oximes treat both muscarinic and nicotinic effects)

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1. Trihexyphenidyl (Benzhexol) - most commonly used
2. Biperiden
3. Procyclidine

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• Malignant hyperthermia is a life-threatening hypermetabolic crisis triggered by inhalational anesthetics (halothane) and succinylcholine
• Involves uncontrolled release of calcium from SR via ryanodine receptors → muscle rigidity, hyperthermia, rhabdomyolysis
• Dantrolene acts peripherally by blocking Ca2+ release from the sarcoplasmic reticulum (ryanodine receptor antagonist)
• Reduces muscle hypercontraction → lowers temperature
• Dose: 2.5 mg/kg IV, repeat every 5 min, up to 10 mg/kg

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1. No ganglionic blockade - d-TC blocks autonomic ganglia causing hypotension; pancuronium does not
2. No histamine release - d-TC releases histamine causing bronchospasm, hypotension; pancuronium does not
3. Longer duration of action - pancuronium has longer, more predictable duration
4. Cardiovascular stability - pancuronium causes mild tachycardia (due to vagal block) but maintains BP better than d-TC

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• α1 stimulation → vasoconstriction → raises BP; reduces angioedema and urticaria
• β1 stimulation → positive inotropic and chronotropic effect → improves cardiac output
• β2 stimulation → bronchodilation → relieves bronchospasm
• Also inhibits further mediator release from mast cells
• Dose: 0.5 mg IM (anterolateral thigh)

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1. Vasoconstriction - adrenaline (α1) causes local vasoconstriction, reduces blood flow at injection site
2. Slows absorption of lignocaine into systemic circulation → prolongs duration of local anesthesia (from 30 min to 60-90 min)
3. Reduces systemic toxicity - slower absorption keeps plasma levels low
4. Reduces bleeding in surgical field

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• Cardiogenic shock = heart failure with low cardiac output and tissue hypoperfusion
• Dobutamine is a synthetic catecholamine with selective β1 agonist activity
• Increases myocardial contractility (positive inotropic) without significant increase in heart rate
• Does NOT significantly increase BP (unlike dopamine at high dose)
• Does NOT increase SVR (unlike noradrenaline), so afterload is not increased
• Result: increased cardiac output and improved tissue perfusion
• Used when cardiac output is low but BP is not severely low

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• BPH causes urinary obstruction due to smooth muscle contraction in prostate and bladder neck (mediated by α1A receptors)
• Tamsulosin and Silodosin are selective α1A adrenergic receptor antagonists
• α1A receptors predominate in prostate, urethra, and bladder neck (vs. α1B in blood vessels)
• Blockade of α1A → relaxation of smooth muscle → decreases urinary resistance → improves urine flow
• Advantage: Selective for α1A → minimal vasodilation → less hypotension compared to non-selective alpha-blockers (prazosin)

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1. Start with a very low dose (0.5 mg) at bedtime
2. Take the first dose at night before sleeping (patient is recumbent)
3. Gradually titrate the dose upward (go low, go slow)
4. Avoid concomitant diuretics with the first dose

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1. Bronchial Asthma/COPD - Propranolol blocks β2 receptors in bronchi → bronchospasm → can be life-threatening
2. Diabetes mellitus (insulin-treated) - Blocks β2-mediated glycogenolysis (warning signs of hypoglycemia like tachycardia are masked); prolongs hypoglycemia

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• β1 blockade (heart) → reduces heart rate and myocardial contractility → reduces cardiac output
• Renin suppression → block β1 receptors on JGA → reduces renin → reduces Ang II and aldosterone → reduces fluid retention
• Central action → reduce sympathetic outflow (especially with lipid-soluble agents like propranolol)
• Pre-synaptic β blockade → reduces noradrenaline release
• Drugs: propranolol, atenolol, metoprolol, bisoprolol

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1. Topical anesthesia before venipuncture or IV cannula insertion in children
2. Before lumbar puncture, skin grafting
3. Post-herpetic neuralgia
4. Topical anesthesia for minor dermatological procedures
5. Before circumcision in neonates

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1. Propranolol (β-blocker) - drug of choice for prophylaxis
2. Topiramate (anticonvulsant)
3. Valproate/Sodium valproate (anticonvulsant)
4. Amitriptyline (TCA)
5. Flunarizine (calcium channel blocker)
6. Methysergide (serotonin antagonist - used with caution due to retroperitoneal fibrosis)
7. Candesartan/Lisinopril (newer options)

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• Ergotamine is a partial agonist at 5-HT1B/1D receptors and also has α-adrenergic agonist activity
• 5-HT1B/1D agonism → causes vasoconstriction of dilated intracranial blood vessels → relieves migraine
• Also inhibits release of neuropeptides from trigeminal nerve terminals
• Used for acute migraine attacks, not prophylaxis
• Given orally or sublingually; often combined with caffeine (Cafergot) for better absorption
• Limitations: Nausea, vomiting, ergotism (peripheral vasoconstriction), contraindicated in ischemic heart disease, pregnancy, peripheral vascular disease
• Largely replaced by triptans now

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• Platelets play a key role in coronary thrombosis that causes MI
• Aspirin irreversibly inhibits COX-1 in platelets → blocks thromboxane A2 (TXA2) synthesis
• TXA2 promotes platelet aggregation and vasoconstriction
• Platelets have no nucleus → cannot regenerate COX → aspirin effect lasts platelet lifetime (7-10 days)
• Low dose (75-150 mg) selectively inhibits platelet COX-1 without significantly inhibiting vascular endothelial prostacyclin (PGI2) synthesis
• PGI2 is anti-aggregatory - preserving it is beneficial
• Net result: reduced platelet aggregation → reduced clot formation → reduced risk of MI

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• In paracetamol overdose, normal glucuronidation and sulfation pathways are saturated
• Excess paracetamol is metabolized by CYP2E1 to a toxic reactive metabolite NAPQI (N-acetyl-p-benzoquinoneimine)
• NAPQI depletes hepatic glutathione and binds to liver cell proteins → hepatocellular necrosis
• N-Acetylcysteine (NAC) acts by:
  1. Replenishing glutathione (NAC is a glutathione precursor/substitute)
  2. Directly conjugates with and detoxifies NAPQI
  3. Enhances sulfation pathway
• Most effective within 8-10 hours of ingestion; given IV or orally

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• Methotrexate is a DMARD (Disease Modifying Antirheumatic Drug) and is the anchor drug for RA
• Mechanism: Inhibits dihydrofolate reductase (DHFR) → reduces folate availability → inhibits purine and pyrimidine synthesis → inhibits proliferation of rapidly dividing inflammatory cells (T lymphocytes)
• Also inhibits aminoimidazolecarboxamide ribonucleotide (AICAR) transformylase → increases adenosine → anti-inflammatory
• Benefits:
  • Reduces synovitis, joint inflammation, pain
  • Slows radiographic progression (joint erosion)
  • Improves functional capacity
• Adverse effects: Hepatotoxicity, myelosuppression, mucositis, pneumonitis (supplement with folic acid)

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• Gout is caused by hyperuricemia → monosodium urate crystal deposition in joints
• Allopurinol is a xanthine oxidase inhibitor
• It is a structural analog of hypoxanthine; it is converted to alloxanthine which inhibits xanthine oxidase
• Xanthine oxidase converts hypoxanthine → xanthine → uric acid
• Inhibition → reduced uric acid synthesis → lowered serum and urinary uric acid
• Used for prophylaxis of gout (chronic/tophaceous gout, recurrent attacks)
• NOT used during acute attacks (can worsen by mobilizing crystals)
• Also used in tumor lysis syndrome (to prevent hyperuricemia from massive cell breakdown)

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SHORT QUESTIONS (5 Marks Each)

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• 100% bioavailability - drug delivered directly into circulation
• Rapid onset of action - useful in emergencies
• Accurate and precise dose titration possible
• Suitable for large volumes of fluid/drug
• Suitable for drugs destroyed by oral route (e.g., insulin, heparin)
• Can be used in unconscious patients
• Irritant drugs can be given (diluted in blood)

• Requires sterile technique - risk of infection/septicemia
• Irreversibility - cannot retrieve drug once given
• Risk of air embolism, thrombophlebitis
• Requires trained personnel
• Expensive and inconvenient
• Risk of too rapid administration - anaphylaxis, cardiac toxicity
• Not suitable for oily or insoluble preparations

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• Faster absorption than subcutaneous (rich blood supply)
• Moderately rapid onset
• Can administer depot preparations (e.g., depot antipsychotics, medroxyprogesterone)
• Suitable for moderate volumes (up to 5 mL)
• Can be self-administered
• Suitable for drugs that irritate SC tissue

• Painful - especially repeated injections
• Risk of abscess, nerve injury (sciatic nerve in gluteal region)
• Cannot be used in bleeding disorders (hematoma)
• Requires aseptic technique
• Absorption variable (depends on muscle blood flow)
• Inadvertent IV injection possible

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• Bypasses first-pass metabolism - high bioavailability
• Rapid absorption from highly vascular sublingual area
• Rapid onset - suitable for emergencies (e.g., GTN in angina, 2-3 min onset)
• Patient can self-administer easily
• Convenient, painless
• Drug not destroyed by gastric acid or digestive enzymes

• Limited to potent drugs (small amount absorbed)
• Only lipid-soluble, small molecules absorbed
• Food/drink must be avoided
• Saliva may wash away drug if swallowed
• Not suitable for all drugs
• Irritation of oral mucosa with repeated use

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• Rapid onset due to large alveolar surface area and rich blood supply
• Local action in lungs with minimal systemic effects (e.g., bronchodilators)
• Avoids first-pass metabolism
• Lower doses needed compared to oral route
• Titratable effect (for anesthetic gases)

• Requires special devices (MDI, spacers, nebulizers)
• Poor patient technique leads to ineffective drug delivery
• Oral/pharyngeal candidiasis with inhaled steroids
• Systemic absorption can occur (especially with high-dose steroids)
• Not suitable for drugs that irritate airways
• Coughing or bronchospasm may be triggered
• Drug must be in particulate size 1-5 microns for alveolar deposition

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• Sustained drug delivery over hours to days (e.g., GTN 24 hrs, fentanyl 72 hrs, nicotine patch)
• Bypasses first-pass metabolism
• Maintains constant plasma levels - avoids peaks and troughs
• Painless, convenient, good patient compliance
• Can be removed if side effects occur
• Suitable for drugs with short half-lives requiring continuous release

• Limited to highly potent, lipid-soluble drugs (e.g., GTN, fentanyl, scopolamine, nicotine, estradiol)
• Skin irritation and contact dermatitis
• Slow onset - not useful in emergencies
• Absorption varies with skin thickness, blood flow, temperature
• Expensive
• Only small doses can be delivered

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1. Liposomes - phospholipid vesicles that encapsulate drug; targeted delivery, reduced toxicity (e.g., liposomal amphotericin B, liposomal doxorubicin)
2. Nanoparticles - nano-sized particles for targeted delivery across BBB and to tumors; biodegradable; improved bioavailability
3. Osmotic Drug Delivery (OROS) - tablet with osmotic core and small laser-drilled hole; delivers drug at constant rate (e.g., nifedipine GITS, glipizide GITS)
4. Transdermal patches - matrix or reservoir systems for sustained delivery (GTN, fentanyl, nicotine)
5. Implants - subdermal implants for sustained release (e.g., levonorgestrel implants for contraception, etonogestrel)
6. Bioadhesive systems - adhere to mucous membranes for sustained local release
7. Niosomes - non-ionic surfactant vesicles, similar to liposomes but more stable
8. Prodrug systems - chemical modification to improve delivery/specificity

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1. First-pass metabolism - extensive hepatic/gut wall metabolism reduces bioavailability (e.g., morphine F = 30%, propranolol F = 25%)
2. Solubility - drug must dissolve in GI fluids; lipid-soluble drugs are better absorbed; poor solubility (BCS Class II drugs) reduces bioavailability
3. Physicochemical properties - molecular size, ionization (pH of GI tract affects absorption of weak acids/bases per Henderson-Hasselbalch equation)
4. Pharmaceutical formulation - particle size, excipients, tablet coating, disintegration and dissolution rate affect absorption
5. GI factors - gastric emptying rate, intestinal motility, presence of food, P-glycoprotein efflux transporters, gut bacteria (affect absorption significantly)

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1. Volume of distribution - highly protein-bound drugs have low Vd; they are confined to plasma
2. Drug interactions - displacement from protein binding sites can transiently increase free drug levels (e.g., warfarin displaced by phenylbutazone → bleeding risk)
3. Hypoalbuminemia - in liver disease, nephrotic syndrome - reduced binding → increased free drug → toxicity (e.g., phenytoin, warfarin)
4. Drug persistence - protein binding acts as a reservoir, prolonging drug action
5. BBB and placental transfer - protein-bound drugs cannot cross; affects drug distribution to CNS/fetus
6. Renal drug filtration - only free drug is filtered at glomerulus; protein-bound drug is not filtered

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1. Oxidation (most common) - catalyzed by microsomal CYP450 enzymes (CYP3A4, CYP2D6, etc.) in liver
   • Hydroxylation, N-dealkylation, O-dealkylation, deamination
   • e.g., Paracetamol → NAPQI; Phenytoin → p-hydroxy phenytoin
2. Reduction - less common
   • Nitroreduction, carbonyl reduction
   • e.g., Chloramphenicol → amino derivative
3. Hydrolysis - by esterases (plasma, liver, gut)
   • Esters and amides hydrolyzed
   • e.g., Aspirin → salicylic acid; Succinylcholine → succinylmonocholine (plasma cholinesterase)

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1. Drug interactions - rifampicin reduces efficacy of oral contraceptives (contraceptive failure), warfarin (reduced anticoagulation), oral hypoglycemics
2. Autoinduction - carbamazepine induces its own metabolism
3. Loss of efficacy of co-administered drugs requiring higher doses
4. Tolerance - some sedatives (barbiturates) lose effect via self-induction
5. Activated prodrugs may be over-activated (cyclophosphamide)
6. Takes 1-2 weeks to develop; reverses slowly after stopping inducer

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1. Toxicity/adverse effects - cimetidine inhibits warfarin metabolism → bleeding; erythromycin inhibits terfenadine → QT prolongation/torsades
2. Drug interactions - most clinically important type of interaction
3. Immediate onset - no lag period unlike induction
4. Beneficial interactions - ritonavir "boosting" of other antiretrovirals; probenecid slows penicillin excretion
5. Grapefruit juice inhibits CYP3A4 in gut wall - increases bioavailability of many drugs (statins, cyclosporine)

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1. Dosing frequency - drugs with short t½ require more frequent dosing (e.g., penicillin 6-hourly); long t½ drugs given once daily (e.g., amlodipine, atorvastatin)
2. Time to steady state - steady state is reached in 4-5 half-lives regardless of dose
3. Drug washout time - drug is essentially eliminated in 4-5 half-lives (useful for stopping drugs before surgery, switching medications)
4. Accumulation - drugs with long t½ (e.g., amiodarone t½ = weeks) accumulate with repeated dosing
5. Duration of action - correlates with t½ for most drugs
6. Loading dose requirement - drugs with long t½ require loading doses to rapidly achieve therapeutic levels (e.g., digoxin, amiodarone)

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• Rate = k × C (where k = elimination rate constant, C = concentration)
• Constant fraction (not constant amount) eliminated per unit time
• Half-life is constant and independent of dose/concentration
• Plasma concentration-time graph is exponential (straight line on semi-log plot)
• Applies to most drugs at therapeutic concentrations
• The higher the concentration, the faster the absolute rate of elimination
• Examples: most drugs including aspirin (at low doses), digoxin, gentamicin

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1. Slow absorption - depot preparations (IM depot antipsychotics), controlled release formulations, transdermal patches
2. High plasma protein binding - bound drug acts as reservoir, slowly released as free drug is eliminated
3. High lipid solubility - extensive tissue distribution and storage in fat (e.g., thiopentone redistributes from brain to fat)
4. Reduced metabolism - liver disease, enzyme inhibition, genetic slow acetylators
5. Reduced renal excretion - renal impairment, alkaline urine (reduces ionization of basic drugs, promotes tubular reabsorption)
6. Enterohepatic circulation - drug excreted in bile, reabsorbed from intestine repeatedly (e.g., morphine glucuronide, some statins)

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1. Age - neonates (immature liver/kidney metabolism), elderly (reduced renal/hepatic function, altered Vd, polypharmacy)
2. Body weight/composition - obese patients - lipid-soluble drugs have higher Vd; loading doses based on ideal body weight
3. Sex - hormonal differences affect drug metabolism; women have more fat, less plasma proteins for some drugs; CYP3A4 activity higher in women
4. Genetic factors (Pharmacogenetics) - slow/fast acetylators, CYP2D6 poor metabolizers affect drug response and toxicity
5. Disease states - liver disease (reduced metabolism), renal disease (reduced excretion), cardiac failure (reduced hepatic blood flow), hypothyroidism/hyperthyroidism
6. Drug interactions - enzyme induction/inhibition, protein binding displacement, synergism, antagonism

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• β2 agonist (salbutamol) → Gs → bronchodilation
• α1 agonist (phenylephrine) → Gq → vasoconstriction
• Muscarinic M2 → Gi → reduced HR in heart

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• Lipid-soluble ligand diffuses across cell membrane → binds to receptor → receptor-ligand complex enters nucleus → binds to hormone response elements (HREs) on DNA → alters gene transcription → new protein synthesis

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1. Receptor Tyrosine Kinases (RTKs):
   • Ligand binds → receptor dimerizes → autophosphorylation of tyrosine residues → intracellular signaling cascade (PI3K/Akt/MAPK pathways)
   • Examples: Insulin receptor, EGF receptor, PDGF receptor, VEGF receptor
   • Clinical: Imatinib inhibits BCR-ABL tyrosine kinase (CML treatment)
2. Receptor Guanylyl Cyclase:
   • Ligand binds → produces cGMP
   • Example: ANP (Atrial Natriuretic Peptide) receptor → cGMP → vasodilation, natriuresis
3. JAK-STAT receptors (cytokine receptors):
   • Associated with JAK (Janus kinase) → activates STAT transcription factors
   • Examples: Erythropoietin receptor, growth hormone receptor, prolactin receptor, cytokine receptors (IL-2, IFN)

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1. Additive synergism (Addition/Summation): Combined effect = sum of individual effects (1+1 = 2)
   • Example: Two beta-blockers given together; two CNS depressants (alcohol + benzodiazepine)
2. Potentiation (Supra-additive synergism): Combined effect > sum of individual effects (1+1 > 2)
   • Example: Trimethoprim + Sulfamethoxazole (Co-trimoxazole) - both block folate synthesis at different steps
   • Example: Levodopa + Carbidopa - carbidopa blocks peripheral DOPA decarboxylase → more levodopa reaches brain
   • Example: Probenecid + Ampicillin
3. Mechanisms:
   • Same receptor (additive)
   • Different receptors/pathways converging on same effect
   • Pharmacokinetic interaction (probenecid reduces penicillin excretion)

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1. Pharmacological/Receptor Antagonism:
   • Competitive (Reversible): Antagonist competes with agonist for same receptor site; surmountable by increasing agonist dose; shifts dose-response curve to right (e.g., atropine blocks muscarinic receptors; naloxone blocks opioid receptors; propranolol blocks β receptors)
   • Non-competitive (Irreversible): Antagonist binds irreversibly; cannot be overcome; reduces Emax (e.g., phenoxybenzamine blocks α receptors)
2. Chemical Antagonism: Direct chemical combination neutralizes the drug
   • e.g., Protamine + Heparin (forms inactive complex); Dimercaprol + heavy metals
3. Physiological/Functional Antagonism: Two drugs act on different receptors producing opposite effects
   • e.g., Histamine (bronchoconstriction) vs. Adrenaline (bronchodilation); insulin vs. glucagon
4. Pharmacokinetic Antagonism: One drug reduces blood levels of another
   • e.g., Rifampicin induces warfarin metabolism → reduced anticoagulation

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1. Slow/Fast Acetylators (NAT2 gene):
   • Drugs metabolized by N-acetyltransferase: INH, dapsone, hydralazine, procainamide
   • Slow acetylators → accumulate drug → more side effects (INH neuropathy, SLE with hydralazine, procainamide)
   • Fast acetylators → less drug effect; need higher doses
2. CYP2D6 polymorphism:
   • Poor metabolizers → codeine not converted to morphine (no analgesia); adverse effects with antidepressants
   • Ultra-rapid metabolizers → excess morphine production from codeine → toxicity
3. G6PD deficiency:
   • X-linked; oxidant drugs cause hemolysis (primaquine, dapsone, nitrofurantoin)
4. Pseudocholinesterase deficiency:
   • Succinylcholine is normally hydrolyzed rapidly; in deficiency → prolonged neuromuscular blockade ("scoline apnea")
5. HLA-B*5701: Abacavir (HIV drug) hypersensitivity - screen before use

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• Reversible inhibitor of acetylcholinesterase (AChE) - quaternary ammonium compound
• Also has direct stimulant action on nicotinic NMJ receptors
• Inhibition of AChE → accumulation of ACh at muscarinic and nicotinic junctions

1. Myasthenia gravis (diagnosis and treatment)
2. Reversal of non-depolarizing neuromuscular blockade (with atropine)
3. Post-operative urinary retention and paralytic ileus
4. Atony of urinary bladder
5. Diagnosis: Tensilon (edrophonium) test for MG

• Muscarinic: SLUD (salivation, lacrimation, urination, defecation), bronchospasm, bradycardia, hypotension, increased GI motility, miosis
• Nicotinic: Muscle fasciculations, weakness, paralysis (at high doses)
• Treatment of overdose: Atropine (for muscarinic effects)

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1. Remove from exposure - remove contaminated clothing, wash skin
2. Supportive care - ABC, oxygen, mechanical ventilation if needed, IV fluids
3. Atropine (anticholinergic)
   • Blocks muscarinic effects only
   • Large doses IV (2-4 mg every 5-10 min) until secretions dry up ("atropinization")
   • Does NOT reverse nicotinic effects
4. Pralidoxime (2-PAM) - oxime/reactivator
   • Reactivates AChE before "aging" (must be given within 24-48 hrs)
   • Reverses both muscarinic and nicotinic effects
   • Dose: 1-2 g IV over 15-30 min, then infusion
5. Benzodiazepines - for seizure control (diazepam IV)
6. Dialysis - not useful (OP compounds are highly lipid soluble)

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• Hyperthermia, dry skin and mouth, flushed skin, mydriasis, delirium/hallucinations, urinary retention

1. Supportive care - maintain airway, IV fluids, temperature control (cooling), catheterize for urinary retention
2. Activated charcoal if ingestion is recent (within 1-2 hours)
3. Physostigmine (specific antidote)
   • Tertiary amine AChE inhibitor - crosses BBB
   • Reverses both peripheral AND central anticholinergic effects (delirium, coma, seizures)
   • Dose: 1-2 mg slow IV; repeat if needed
   • Atropine should be kept ready to reverse physostigmine-induced bradycardia
4. Diazepam for agitation and seizures
5. Cooling measures for hyperthermia
6. Avoid phenothiazines (also have anticholinergic effects)

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• Non-depolarizing (competitive) neuromuscular blocking agent
• Competitive antagonist at nicotinic NMJ receptors - competes with ACh
• Blocks ion channel opening → muscle paralysis
• No fasciculations
• Reversed by AChE inhibitors (neostigmine + atropine)

1. Surgical muscle relaxation (intubation, abdominal surgeries)
2. Facilitation of mechanical ventilation in ICU
3. Electroconvulsive therapy

1. Tachycardia and hypertension (vagolytic effect - blocks cardiac muscarinic M2 receptors)
2. No histamine release (advantage over d-TC)
3. Prolonged action in renal failure (renally excreted)
4. Potentiated by aminoglycosides, volatile anesthetics, hypokalemia, hypothermia

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• Depolarizing neuromuscular blocking agent
• Mimics ACh at NMJ nicotinic receptor - binds and causes prolonged depolarization (Phase 1 block)
• Causes initial fasciculations then persistent depolarization → flaccid paralysis
• NOT reversed by neostigmine (actually worsened)
• Hydrolyzed by plasma pseudocholinesterase (short duration ~5 min)

1. Rapid sequence induction/intubation (ultra-short onset <60 sec, shortest action)
2. Emergency airway management
3. ECT - to reduce fractures

1. Muscle fasciculations → post-op myalgia
2. Hyperkalemia - dangerous in burns, trauma, paraplegia (K+ efflux from fasciculations)
3. Malignant hyperthermia (with halothane)
4. Prolonged apnea in pseudocholinesterase deficiency
5. Bradycardia, increased intraocular pressure, increased intragastric pressure
6. Phase 2 (dual) block with high/repeated doses

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• Activates all adrenergic receptors: α1, α2, β1, β2
• α1: vasoconstriction, mydriasis
• β1: ↑HR, ↑contractility
• β2: bronchodilation, vasodilation in skeletal muscle, glycogenolysis

1. Anaphylaxis (drug of choice) - 0.5 mg IM
2. Cardiac arrest (IV during CPR)
3. Combined with local anesthetics (prolongs LA action)
4. Bronchial asthma (acute - SC/nebulizer)
5. Open-angle glaucoma (reduces IOP)
6. Epistaxis (local hemostasis)
7. Superficial bleeding (topical)

• Hypertension, tachycardia, palpitations, arrhythmias
• Anxiety, tremor, headache
• Pallor → flushing
• Pulmonary edema
• Hyperglycemia (β2 → glycogenolysis)
• Contraindicated in halothane anesthesia (sensitizes heart to arrhythmias)

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• Cardiogenic shock, acute heart failure (with low BP)
• Acute renal failure (low dose - controversial)
• Septic shock (medium-high dose)

• Nausea, vomiting
• Tachycardia, arrhythmias
• Hypertension (high doses)
• Vasoconstriction, tissue necrosis on extravasation
• Should not be used in tachyarrhythmias or pheochromocytoma

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• Non-selective: Phentolamine (reversible), Phenoxybenzamine (irreversible)
• Selective α1: Prazosin, Terazosin, Doxazosin
• Selective α1A: Tamsulosin, Silodosin
• α2 selective: Yohimbine

1. Hypertension (prazosin, doxazosin)
2. BPH (tamsulosin, silodosin - improve urinary flow)
3. Pheochromocytoma (phenoxybenzamine - pre-op preparation)
4. Raynaud's phenomenon
5. Peripheral vascular disease
6. Hypertensive emergencies (phentolamine)
7. Scorpion envenomation

1. Postural hypotension (especially first dose)
2. Reflex tachycardia (non-selective)
3. Fluid retention - edema
4. Nasal congestion
5. Retrograde ejaculation (α1A blockers)
6. Dry mouth (less common)

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1. Hypertension
2. Angina pectoris (reduces oxygen demand)
3. Arrhythmias (AF, SVT, ventricular arrhythmias)
4. Heart failure (carvedilol, bisoprolol, metoprolol - in stable HF)
5. Post-MI (reduces mortality)
6. Hyperthyroidism (symptom control - propranolol)
7. Migraine prophylaxis (propranolol)
8. Anxiety/tremor (propranolol)
9. Portal hypertension/esophageal varices (propranolol - reduces portal pressure)
10. Pheochromocytoma (only after alpha-blockade)
11. Glaucoma (timolol eye drops)

1. Bradycardia, heart block
2. Bronchospasm (avoid in asthma)
3. Cold extremities, Raynaud's
4. Mask hypoglycemia symptoms
5. Fatigue, lethargy, depression
6. Impotence
7. Dyslipidemia (↑TG, ↓HDL)
8. Withdrawal syndrome if stopped abruptly (rebound hypertension, angina)

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• Local anesthetic: Blocks voltage-gated Na+ channels → prevents Na+ influx → prevents action potential generation and conduction → nerve block
• State-dependent blockade (preferentially blocks open/inactivated channels)
• Antiarrhythmic (Class Ib): Preferentially blocks Na+ channels in ischemic/depolarized tissue; shortens APD; used for ventricular arrhythmias

1. Local anesthesia - infiltration, nerve block, topical, spinal, epidural
2. Ventricular arrhythmias - especially post-MI ventricular tachycardia/fibrillation (IV)
3. Status epilepticus (second line, IV)
4. Topical - pharynx for endoscopy/intubation

• CNS (early): Perioral numbness, tinnitus, dizziness, confusion
• CNS (severe): Seizures, coma, respiratory arrest
• Cardiovascular: Hypotension, bradycardia, heart block, cardiac arrest (at high doses)
• Methemoglobinemia (rare)
• Allergic reactions (rare with amides)

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1. Allergic conditions - allergic rhinitis, urticaria, angioedema
2. Anaphylaxis (adjunct, not first-line - adrenaline is first)
3. Motion sickness (promethazine, diphenhydramine - 1st gen cross BBB)
4. Nausea/vomiting - promethazine
5. Pruritus (itching)
6. Common cold - reduce rhinorrhea
7. Premedication - promethazine
8. Insomnia - diphenhydramine (1st gen sedation used therapeutically)

• 1st generation: Sedation (most common), anticholinergic effects (dry mouth, urinary retention, constipation, blurred vision), paradoxical CNS excitement in children, tachycardia, QT prolongation (terfenadine - withdrawn)
• 2nd generation: Minimal sedation, no significant anticholinergic effects, headache, occasionally cardiac (terfenadine, astemizole - withdrawn due to QT)

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• Selective agonist at 5-HT1B and 5-HT1D receptors (serotonin receptors)
• 5-HT1B: Causes vasoconstriction of dilated meningeal/cranial blood vessels - relieves migraine
• 5-HT1D: Inhibits release of inflammatory neuropeptides (substance P, CGRP) from trigeminal nerve terminals - reduces neurogenic inflammation
• Does NOT prevent migraine (acute treatment only)

1. Acute migraine attack (drug of choice for moderate-severe attacks)
2. Cluster headache

1. "Triptan sensations" - tingling, flushing, warmth, pressure in chest/throat/neck
2. Nausea, dizziness
3. Chest tightness (coronary vasoconstriction)
4. Hypertension

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• Irreversibly inhibits cyclooxygenase (COX-1 and COX-2) by acetylating a serine residue
• Reduces synthesis of prostaglandins, prostacyclin (PGI2), and thromboxane A2 (TXA2)
• COX-1 inhibition → ↓TXA2 in platelets → anti-platelet
• COX inhibition → ↓PGE2, PGI2 → anti-inflammatory, analgesic, antipyretic

1. Low dose (75-150 mg): Antiplatelet - MI prophylaxis, secondary prevention of stroke, ACS
2. Analgesic dose (325-650 mg): Headache, fever, musculoskeletal pain
3. Anti-inflammatory dose (>2 g/day): Rheumatoid arthritis (historical), Kawasaki disease
4. Acute MI management
5. Preeclampsia prevention (low dose)

1. GI irritation, peptic ulceration, bleeding (COX-1 inhibition → ↓protective PGs in stomach)
2. Increased bleeding time (anti-platelet)
3. Aspirin-sensitive asthma (inhibits COX → shunts arachidonic acid to lipoxygenase → ↑leukotrienes → bronchospasm)
4. Reye's syndrome (in children with viral infections - hepatic encephalopathy)
5. Salicylate toxicity (tinnitus, hearing loss, hyperventilation, metabolic acidosis)
6. Uricosuric (low dose) / antiuricosuric (medium dose) effects

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• Anti-TNFα: Infliximab, Etanercept, Adalimumab (risk: reactivation of TB - screen before use)
• Anti-IL-6: Tocilizumab
• Anti-CD20: Rituximab
• Anti-CD80/CD86 (T cell costimulation): Abatacept
• JAK inhibitors: Tofacitinib, Baricitinib (targeted synthetic DMARDs)

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Quick Navigation Guide

• Q1-6: General Pharmacology basics (first-pass, prodrug, therapeutic index, pharmacovigilance, teratogenicity, iatrogenic disease)
• Q7-14: Cholinergic pharmacology (pilocarpine, neostigmine, anticholinesterases, oximes, anticholinergics)
• Q15-17: NMJ drugs (muscle relaxants, dantrolene, pancuronium)
• Q18-27: Adrenergic pharmacology (adrenaline, lignocaine+adrenaline, dobutamine, nasal decongestants, beta-2 agonists, tamsulosin, prazosin, propranolol, beta blockers)
• Q28-36: Autacoids/PNS (EMLA, antihistamines, migraine, aspirin, COX-2, NAC, methotrexate, allopurinol)

• Q1-6: Routes of drug administration
• Q7-16: General pharmacology (bioavailability, protein binding, biotransformation, enzyme induction/inhibition, half-life, kinetics, factors modifying drug action)
• Q17-23: Receptor types (GPCR, nuclear, ion channel, enzyme-linked, synergism, antagonism, pharmacogenetics)
• Q24-29: Cholinergic drugs (physostigmine vs neostigmine, OP poisoning, belladonna poisoning, atropine substitutes)
• Q30-37: Adrenergic drugs (pancuronium, succinylcholine, adrenaline, dopamine, alpha/beta blockers, lignocaine)
• Q38-42: Autacoids (antihistamines, prostaglandins, sumatriptan, aspirin, DMARDs)

• For 3-mark questions: aim for 3-4 key points with a brief definition
• For 5-mark questions: include mechanism, uses (at least 3-4), and adverse effects in a table format where possible
• Mnemonics like SLUD (salivation, lacrimation, urination, defecation for cholinergic toxidrome) and dose-dependent dopamine effects are frequently asked and easy marks