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PHARMACOLOGY CHEAT SHEET — MISSING TOPICS

PAPER 1 + PAPER 2

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═══ PAPER 1 ═══

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1. BETA BLOCKERS — Classification & Drug Interactions

• Non-selective (β1 + β2): Propranolol, Nadolol, Timolol, Sotalol
• Cardioselective (β1): Metoprolol, Atenolol, Bisoprolol, Acebutolol
• With ISA: Pindolol, Acebutolol (partial agonist activity)
• α + β blocker: Labetalol, Carvedilol
• β blocker + K+ channel block: Sotalol

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4. ANTIPARKINSONIAN DRUGS — Levodopa + Carbidopa Rationale

• 95% of oral levodopa is converted to dopamine in the periphery by DOPA decarboxylase

• Peripheral dopamine → nausea, vomiting, hypotension, cardiac arrhythmias
• Only <1% crosses the BBB

• Carbidopa = peripheral DOPA decarboxylase inhibitor (does NOT cross BBB)
• Blocks peripheral conversion → more levodopa reaches brain
• Levodopa dose reduced by 75%
• ↓ Peripheral side effects (nausea, vomiting, cardiac effects)
• Faster therapeutic response

• MAO-B inhibitors: Selegiline, Rasagiline (prevent dopamine breakdown)
• COMT inhibitors: Entacapone, Tolcapone (prevent levodopa peripheral conversion)
• Dopamine agonists: Bromocriptine, Ropinirole, Pramipexole
• Anticholinergics: Trihexyphenidyl (Benzhexol) — for tremor
• NMDA antagonist: Amantadine

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6. BARBITURATES — MOA, Uses, Adverse Effects

• Ultra-short acting: Thiopentone (IV anaesthesia)
• Short acting: Pentobarbitone
• Intermediate: Amobarbitone
• Long acting: Phenobarbitone (AED)

• Phenobarbitone: Epilepsy (tonic-clonic, partial seizures)
• Thiopentone: IV induction of anaesthesia
• Pentobarbitone: Sedation (now largely replaced by BZDs)

• CNS depression, sedation, respiratory depression
• Enzyme induction (CYP450) → multiple drug interactions
• Physical and psychological dependence
• Paradoxical excitement in elderly/children
• No analgesic effect (anti-analgesic at low doses)
• Acute intermittent porphyria — contraindicated
• Hangover effect
• Overdose: No antidote (cf. BZD — flumazenil); treat supportively

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10. BIOTRANSFORMATION — Phase I & Phase II

• Add/unmask a functional group (-OH, -NH₂, -SH, -COOH)
• Reactions: Oxidation (most common, CYP450), Reduction, Hydrolysis
• Site: Liver microsomes (CYP450 enzymes), also gut, lung, plasma
• Product may be active, inactive, or toxic
• Examples:
  • Oxidation: Phenobarbitone → hydroxyphenobarbitone
  • Reduction: Chloramphenicol → amine
  • Hydrolysis: Procaine → PABA + diethylaminoethanol

• Attach endogenous molecule to drug/Phase I metabolite
• Results in inactive, water-soluble conjugate (usually)
• Reactions: Glucuronidation (most common), Sulfation, Acetylation, Methylation, Glutathione conjugation, Glycine conjugation
• Examples:
  • Glucuronidation: Morphine → morphine-6-glucuronide (active), morphine-3-glucuronide (inactive)
  • Acetylation: Isoniazid → acetylisoniazid (fast vs slow acetylators)
  • Sulfation: Paracetamol → sulfate conjugate

• Prodrugs activated by Phase I (enalapril → enalaprilat)
• Toxic metabolites: Paracetamol → NAPQI (Phase I) → depletes glutathione
• Drug interactions at Phase I (enzyme induction/inhibition)
• First-pass metabolism affects oral bioavailability

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11. FACTORS MODIFYING DRUG ACTION & FACTORS AFFECTING DRUG ABSORPTION

• Physicochemical: Lipid solubility, ionization (pKa), molecular size, formulation
• pH: Weak acids absorbed better in acidic stomach; weak bases in alkaline intestine (but most absorption from intestine due to large surface area)
• GI motility: ↑ motility → ↓ absorption time (metoclopramide speeds, opioids slow)
• Surface area: Small intestine >> stomach (villi, microvilli)
• Blood flow: ↑ splanchnic blood flow → ↑ absorption
• First-pass metabolism: Reduces bioavailability of orals (morphine, propranolol, nitrates)
• Food: Delays gastric emptying; some drugs require food (griseofulvin), some don't (tetracyclines — chelation)
• Formulation: Enteric coating, sustained release, particle size
• P-glycoprotein: Efflux pump → ↓ absorption of some drugs

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12. ANTICHOLINERGICS — Mydriasis & Tropicamide

• Iris has 2 muscles: sphincter pupillae (M3, constricts) and dilator pupillae (α1, dilates)
• Anticholinergics block M3 → sphincter paralysis → unopposed dilator → mydriasis
• Also cause cycloplegia (paralysis of ciliary muscle → loss of accommodation)

• Shortest acting muscarinic antagonist for ophthalmology
• Used for: Fundoscopy, optic disc examination, diabetic retinopathy screening
• Advantage: Rapid onset, short duration → less disruption to vision
• Contraindicated in narrow-angle glaucoma (blocks drainage → ↑ IOP)

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14. SKELETAL MUSCLE RELAXANTS

1. Depolarizing: Succinylcholine (Suxamethonium)
2. Non-depolarizing (competitive):
   • Short acting: Mivacurium
   • Intermediate: Vecuronium, Rocuronium, Atracurium, Cisatracurium
   • Long acting: Pancuronium, d-Tubocurarine

• MOA: Mimics ACh at NMJ → persistent depolarization → Phase I block (fasciculations then paralysis)
• Onset: 60 sec (fastest), Duration: 5-10 min
• Metabolized by plasma pseudocholinesterase
• Uses: Rapid sequence intubation, electroconvulsive therapy
• Adverse effects: Hyperkalemia (burned/denervated patients), malignant hyperthermia, bradycardia, increased IOP/ICP/intragastric pressure, prolonged apnoea (pseudocholinesterase deficiency)

• Non-depolarizing, intermediate acting, steroidal
• No histamine release, no cardiac effects (advantage over pancuronium)
• Metabolized in liver, eliminated in bile
• Reversed by neostigmine + atropine, or sugammadex

• Neostigmine (anticholinesterase) + Atropine (to prevent muscarinic SE)
• Sugammadex: Encapsulates rocuronium/vecuronium → rapid reversal

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15. PLASMA PROTEIN BINDING — Clinical Significance

• Drug bound to plasma protein = pharmacologically inactive (large complex, can't cross membranes)
• Only free (unbound) drug is active, distributes, metabolized, excreted
• Main protein: Albumin (acidic drugs — warfarin, phenytoin, NSAIDs), α1-acid glycoprotein (basic drugs — propranolol, lidocaine)

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17. PHARMACOVIGILANCE

• Detect new/rare ADRs
• Identify risk factors for ADRs
• Quantify risk
• Communicate safety information
• Prevent harm to patients

• Spontaneous reporting (Yellow Card/Vigibase): Voluntary reporting by healthcare professionals — most common method globally; suffers from underreporting
• Prescription event monitoring (PEM): Follow-up of patients on specific drugs
• Case-control studies
• Cohort studies
• Randomized trials (Phase IV)

• Signal generation → Signal strengthening → Signal assessment → Regulatory action

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20. PRE-ANAESTHETIC MEDICATION — Drugs & Rationale

• Glycopyrrolate preferred: Does not cross BBB (no CNS effects), longer acting, no tachycardia

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23. PARENTERAL ROUTES OF DRUG ADMINISTRATION

• No first-pass metabolism
• Reliable bioavailability
• Useful in unconscious/vomiting patients
• Rapid onset
• Useful for drugs destroyed in GI tract (insulin, heparin)

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26. PROSTAGLANDIN ANALOGUES — Obstetric & Gynaecological Uses

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27. SUCCINYLCHOLINE APNOEA — Management

• Normal: 80 (80% inhibition by dibucaine)
• Heterozygous: 40-60
• Homozygous atypical: 20 (prolonged apnoea)

1. Maintain ventilation — continue mechanical ventilation (MOST important)
2. Do NOT give neostigmine (makes it worse — further inhibits pseudocholinesterase)
3. Fresh Frozen Plasma (FFP) — contains pseudocholinesterase → provides enzyme → hydrolyzes succinylcholine
4. Monitor with nerve stimulator — wait for return of neuromuscular function
5. Genetic counseling for patient and family
6. MedicAlert bracelet for patient

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29. ALCOHOL DE-ADDICTION — Pharmacological Management

• Benzodiazepines (Chlordiazepoxide, Diazepam, Lorazepam) — first line
  • Treat/prevent seizures and delirium tremens
• Thiamine (Vitamin B1) — prevent Wernicke's encephalopathy
• Beta-blockers (atenolol) — autonomic symptoms
• Clonidine — sympathetic overactivity

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30. LIDOCAINE — Administration Techniques & Spinal Anaesthesia Complications

• Surface/topical: EMLA cream, throat spray, eye drops
• Infiltration: Direct injection into tissue
• Nerve block: Peripheral nerve (brachial plexus, femoral, dental)
• Epidural (lumbar/caudal)
• Spinal (intrathecal): Hyperbaric (heavy) lidocaine in 5% dextrose
• IV Regional (Bier's block): For limb surgery; tourniquet prevents systemic absorption
• Maximum dose: 3 mg/kg plain; 7 mg/kg with adrenaline

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32. FIXED DOSE COMBINATIONS (FDCs) — Advantages & Disadvantages

• ↑ Patient compliance (fewer tablets)
• Synergistic effects (co-trimoxazole, anti-TB drugs)
• Prevents emergence of resistance (anti-TB, HIV)
• Reduced cost
• Masks taste of unpalatable drugs
• Easier prescription
• Reduced drug abuse (analgesic combinations with antiemetics)

• Cannot adjust individual drug doses
• If ADR occurs, difficult to identify causative drug
• Patient may not need all components
• Pharmacokinetic incompatibility (different half-lives)
• More expensive than individual generics
• Irrational combinations may be harmful (e.g., steroid + antibiotic)

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33. DRUG ANTAGONISM — Types with Examples

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36. THERAPEUTIC USES OF HISTAMINE

1. Betazole (H2 agonist analogue): Test gastric acid secretion (replaced by pentagastrin)
2. Histamine phosphate: Diagnosis of pheochromocytoma (stimulates catecholamine release — now obsolete)
3. Intradermal histamine: Test for intact triple response (wheal, flare, local edema) — tests sensory nerve integrity
4. Desensitization: Subcutaneous histamine in allergic rhinitis (historical)

• Allergic conditions (urticaria, rhinitis, anaphylaxis adjunct)
• Motion sickness (promethazine, cinnarizine)
• Pruritus
• Nausea/vomiting (promethazine)
• Pre-medication (promethazine)
• Sedation (diphenhydramine)
• Vertigo (cinnarizine)
• Common cold (symptomatic)

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37. LEGAL ASPECTS OF DRUGS IN INDIA & CLINICAL TRIALS PHASE III

• Drugs & Cosmetics Act, 1940 (amended 1964, 2008): Regulates manufacture, sale, distribution, import of drugs
• Drugs & Cosmetics Rules, 1945: Schedules H, H1, X for prescription drugs; Schedule G for pharmacy-only drugs
• Schedule H: Rx-only drugs (antibiotics, steroids, psychotropics)
• Schedule H1: High-risk Rx drugs with special monitoring (fluoroquinolones, 3rd gen cephalosporins, ARVs) — require red "Rx" label
• Schedule X: Habit-forming drugs (opioids, benzodiazepines) — 2-year record keeping
• NDPS Act 1985: Narcotic drugs and psychotropic substances
• CDSCO: Central Drugs Standard Control Organisation — regulatory body
• New Drugs & Clinical Trials Rules 2019: Governs clinical trials in India

• Design: Randomized Controlled Trial (RCT), multicenter, large sample
• Sample size: 1,000-3,000+ patients
• Purpose: Confirm efficacy and safety, compare with standard treatment, establish dose regimens
• Duration: 1-4 years
• Outcome: Primary (efficacy endpoint) + secondary (safety, QoL)
• Regulatory submission: Data submitted for marketing approval (NDA/New Drug Application)
• Ethics: Informed consent, independent ethics committee, DSMB monitoring

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38. METHANOL POISONING

• Methanol → (Alcohol dehydrogenase) → Formaldehyde → (Aldehyde dehydrogenase) → Formic acid
• Formic acid → metabolic acidosis + optic nerve toxicity

• Latent period (6-24 hrs): Initially similar to ethanol intoxication
• Severe metabolic acidosis (high anion gap)
• Visual symptoms: "Snowstorm vision," blurring, optic disc hyperemia → blindness (formate accumulates in optic nerve)
• CNS depression, coma
• Putamen necrosis (MRI finding)

1. ABC + supportive care
2. Sodium bicarbonate — correct metabolic acidosis
3. Ethanol (or Fomepizole): Competitive substrate for alcohol dehydrogenase → blocks methanol metabolism (ethanol has 10-20x higher affinity)
   • Fomepizole (4-MP): ADH inhibitor — drug of choice, fewer side effects than ethanol
4. Folinic acid/Folic acid: Enhances formate metabolism to CO₂ + H₂O
5. Hemodialysis: Remove methanol and formate (if severe acidosis, visual impairment, high levels)
6. Treat optic nerve inflammation: Steroids (controversial)

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41. COMPETITIVE vs NON-COMPETITIVE ANTAGONISM

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42. CARBONIC ANHYDRASE INHIBITORS — Uses & Adverse Effects

1. Glaucoma (open-angle) — reduces aqueous humour production (CA inhibition in ciliary body) — MOST IMPORTANT USE
2. Altitude sickness (AMS) — prophylaxis and treatment (causes metabolic acidosis → stimulates respiration)
3. Epilepsy — adjunct (absence seizures), related to metabolic acidosis
4. Metabolic alkalosis — to alkalinize urine, excrete HCO₃⁻
5. Cystinuria, Uric acid stones — alkalinize urine to increase solubility
6. Pseudotumour cerebri — reduces CSF production
7. Periodic paralysis (hypokalemic)
8. Idiopathic intracranial hypertension

• Metabolic acidosis (hyperchloremic)
• Hypokalemia
• Drowsiness, paresthesias (numbness/tingling of extremities — very common)
• Renal calculi (Ca²⁺ phosphate — alkaline urine)
• Allergic reactions (sulfonamide derivative — sulfa allergy contraindication)
• Bone marrow suppression (rare)

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44. ENZYME INDUCTION & INHIBITION

• ↑ CYP450 enzyme synthesis → ↑ drug metabolism → ↓ plasma levels of substrate drugs
• Onset: Gradual (days-weeks); reversible on stopping inducer
• Examples of inducers: CRAP GPS
  • Carbamazepine, Rifampicin, Alcohol (chronic), Phenytoin, Griseofulvin, Phenobarbitone, Smoking (CYP1A2)
• Consequences: Therapeutic failure (OCP failure on rifampicin → unintended pregnancy); need dose increase of substrate

• ↓ CYP450 enzyme activity → ↓ drug metabolism → ↑ plasma levels → toxicity
• Onset: Rapid (1-2 days); competitive or irreversible
• Examples of inhibitors: SKIM
  • Sulfonamides, Ketoconazole, Isoniazid, Metronidazole, cimetidine, ciprofloxacin, fluconazole, amiodarone, grapefruit juice (CYP3A4)
• Consequences: Drug toxicity (warfarin toxicity when metronidazole added → bleeding)

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45. ESSENTIAL MEDICINES — Definition & EML Preparation

1. Disease burden — prevalence and severity in target population
2. Evidence of efficacy — from systematic reviews, RCTs
3. Safety profile — acceptable risk:benefit ratio
4. Quality — available in assured quality formulations
5. Cost-effectiveness — affordable; comparative cost-effectiveness with alternatives
6. Pharmacokinetics — suitable for target setting (oral, stable, etc.)
7. Availability — can be produced and supplied consistently
8. Priority of health system — fits national health programme needs

• Guides procurement, supply, and rational prescribing
• Basis for national formulary
• Price control under DPCO (Drug Price Control Order)
• Reduces irrational prescribing and drug expenditure

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46. TERATOGENICITY

• Category A: Safe; Category B: Probably safe; Category C: Uncertain; Category D: Evidence of risk; Category X: Contraindicated

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47. BIPOLAR DISORDER — Management & Lithium

• MOA: Inhibits inositol monophosphatase → depletes inositol → ↓ IP3/DAG signaling; also modulates cAMP, GSK-3β
• Pharmacokinetics: 100% oral absorption, NOT protein bound, NOT metabolized, renal excretion (competes with Na⁺ in PCT — sodium depletion → lithium retention → toxicity)
• Therapeutic index: Very narrow (0.6-1.2 mEq/L therapeutic; >1.5 toxic; >2.0 severe toxicity)
• Monitoring: Serum lithium levels, renal function, thyroid function, ECG

• Early/dose-related: Tremor (fine), polyuria/polydipsia (nephrogenic DI), nausea, diarrhea, weight gain
• Long-term: Hypothyroidism (50% patients), nephrogenic DI, renal tubular damage, hyperparathyroidism
• Toxicity: Coarse tremor, ataxia, confusion, seizures, cardiac arrhythmias, coma

• Sodium depletion (vomiting, diarrhea, diuretics, low-salt diet, sweating)
• NSAIDs, ACE inhibitors, thiazides (↓ renal Li excretion)
• Dehydration

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48. WAYS TO PREVENT ADVERSE DRUG REACTIONS

1. Thorough history: Drug allergy, previous ADRs, current medications (drug interactions), comorbidities
2. Rational prescribing: Only prescribe when clearly indicated; use essential medicines list
3. Start low, go slow: Especially in elderly, renal/hepatic impairment
4. Avoid polypharmacy: Review and stop unnecessary drugs
5. Dose adjustment: In renal failure (creatinine clearance), hepatic failure, extremes of age
6. Monitoring: TDM (digoxin, lithium, phenytoin, aminoglycosides), LFTs, RFTs, CBC
7. Genetic testing: Where available (HLA-B5701 before abacavir, HLA-B1502 before carbamazepine)
8. Patient education: Signs of ADRs, when to seek help
9. Drug interactions check: Before prescribing combinations
10. Pharmacovigilance: Report ADRs; use ADR reporting systems
11. Avoid known dangerous combinations: Aminoglycosides + loop diuretics (ototoxicity); MAOIs + SSRIs (serotonin syndrome)

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50. ATROPINE SUBSTITUTES AND USES

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═══ PAPER 2 ═══

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1. COMBINED ORAL CONTRACEPTIVE PILLS (COCPs)

1. Suppress ovulation (primary): Estrogen + Progestin suppress GnRH → ↓ FSH (no follicular development) + ↓ LH surge (no ovulation)
2. Thicken cervical mucus (progestin): Sperm penetration impaired
3. Endometrial changes (progestin): Atrophic endometrium → impairs implantation

• Nausea, breast tenderness, headache (early)
• Thromboembolism (DVT, PE, stroke): ↑ clotting factors (estrogen effect) — most serious
• Hypertension (renin-angiotensin ↑)
• Weight gain, mood changes
• ↑ Risk of cervical cancer (minor)
• Amenorrhea on stopping
• ↓ Libido
• Contraindicated: Smokers >35 yrs, migraines with aura, thrombophilia, active liver disease, estrogen-dependent tumors

• ↓ Dysmenorrhea, menorrhagia
• ↓ Ovarian cancer risk (50%), endometrial cancer risk (50%)
• ↓ Benign breast disease
• Treatment of endometriosis, PCOS
• ↓ PID risk
• ↓ Iron deficiency anemia
• Acne treatment (cyproterone acetate + EE — Diane-35)

• DMPA (Depo-Provera): Medroxyprogesterone acetate 150 mg IM every 3 months; progestin only; amenorrhea common; delayed return of fertility
• NET-EN: Norethindrone enanthate 200 mg IM every 2 months
• Cyclofem: Monthly combined injectable

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2. BETA-LACTAM ANTIBIOTICS — Semisynthetic Penicillins & Aminopenicillins + Clavulanic Acid

• Many bacteria produce beta-lactamase → destroy beta-lactam ring → resistance
• Clavulanic acid = beta-lactamase inhibitor (irreversible "suicide inhibitor" — binds irreversibly to beta-lactamase and inactivates it)
• Clavulanic acid alone has minimal antibacterial activity
• Combination restores amoxicillin activity against beta-lactamase-producing organisms (MRSA — still resistant as it has altered PBP)
• Other combinations: Ampicillin + Sulbactam (Unasyn), Piperacillin + Tazobactam (Tazocin)

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3. INSULIN ANALOGUES, DKA MANAGEMENT & GLIMEPIRIDE

• Less hypoglycemia (especially nocturnal)
• More flexible meal timing (rapid-acting)
• Better pharmacokinetic predictability
• Less intra-patient variability (especially glargine vs NPH)
• Degludec — ultra-long acting, flexible timing

1. IV Fluids: 0.9% Normal saline (1L/hr initially, then titrate) — correct dehydration
2. Insulin: Regular insulin IV infusion 0.1 U/kg/hr (after K⁺ >3.5 mEq/L)
3. Potassium replacement: Add K⁺ to IV fluids (insulin drives K⁺ intracellular)
4. Bicarbonate: Only if pH <6.9 (controversial)
5. Monitor: Blood glucose hourly, electrolytes 2-4 hourly, urine ketones
6. Treat precipitant: Infection (antibiotics), missed insulin, etc.
7. Switch to SC insulin once anion gap normalised and patient eating

• Class: 3rd generation sulfonylurea
• MOA: Closes ATP-sensitive K⁺ channels in pancreatic β-cells → depolarization → Ca²⁺ influx → insulin secretion (glucose-independent)
• Also has extrapancreatic effects (↑ insulin sensitivity)
• Advantages: Once daily, lower hypoglycemia risk than glibenclamide, weight neutral (relative), can be used in mild renal impairment
• ADR: Hypoglycemia, weight gain

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4. MDR-TB DRUGS

• MDR-TB: Resistant to at least Isoniazid + Rifampicin (two most potent first-line drugs)
• Pre-XDR-TB: MDR + resistant to any fluoroquinolone
• XDR-TB: MDR + fluoroquinolone resistance (as per 2021 WHO definition)

• Bedaquiline: ATP synthase inhibitor; bactericidal; specific for TB; monitor QTc; hepatotoxicity
• Delamanid: Nitroimidazole; inhibits mycobacterial cell wall (mycolic acid synthesis); QTc prolongation
• Linezolid: Protein synthesis inhibitor (50S); bone marrow suppression, peripheral neuropathy with prolonged use
• Pretomanid (with Bedaquiline + Linezolid = BPaL regimen): For XDR-TB

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8. CEPHALOSPORINS — Generation Comparison

• MOA: Same as penicillins (PBP inhibition)
• Cross-allergy with penicillin: ~1-2% (much less than previously thought)
• Eliminated renally (dose adjust in renal failure) except ceftriaxone (biliary)
• Ceftriaxone: DO NOT mix with calcium-containing solutions in neonates (precipitation)

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10. ANTIAMOEBIC DRUGS

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11. HYPERTHYROIDISM DRUGS — Radioactive Iodine & Thyrotoxic Crisis

1. Thionamides: Propylthiouracil (PTU), Carbimazole/Methimazole
   • MOA: Inhibit thyroid peroxidase → ↓ T3/T4 synthesis; PTU also inhibits peripheral T4→T3 conversion
2. Iodides (Lugol's iodine, KI): Wolff-Chaikoff effect — ↓ hormone synthesis + release; used pre-op (↓ vascularity)
3. Radioactive Iodine (RAI, ¹³¹I)
4. Beta-blockers (Propranolol): Control sympathetic symptoms (tachycardia, tremor, anxiety)

• Taken up by thyroid follicular cells (same mechanism as stable iodide — Na⁺/I⁻ symporter)
• Emits beta particles (tissue penetration 0.5 mm) → destroys follicular cells → hypothyroidism
• Also emits gamma rays (for imaging)
• Effect in 6-12 weeks
• Contraindications: Pregnancy, breastfeeding, children (relative), large goitre with compressive symptoms
• SE: Hypothyroidism (most common, often permanent), transient thyroiditis

1. Propylthiouracil (PTU) — high dose (loading 600 mg, then 200-300 mg 6-hrly) — blocks synthesis + T4→T3 conversion
2. Iodide (Lugol's) — 1-2 hours AFTER PTU (to prevent organification of iodine) — blocks hormone release
3. Propranolol — control tachycardia, block peripheral T4→T3 conversion
4. Glucocorticoids (Dexamethasone) — block T4→T3 + anti-inflammatory
5. Supportive: IV fluids, cooling, treat precipitant (infection)
6. Cholestyramine — binds T4 in gut (adjunct)

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12. PRIMAQUINE & ARTEMISININ-BASED COMBINATION THERAPY (ACT)

• Class: 8-aminoquinoline
• MOA: Active against liver stages (hypnozoites) — generates reactive oxygen species
• Uses:
  • Radical cure of P. vivax and P. ovale malaria (only drug that eliminates hypnozoites — prevents relapse)
  • Gametocidal (especially for P. falciparum — public health use, prevent transmission)
• SE: Hemolytic anemia in G6PD-deficient patients — G6PD testing before use is mandatory
• Contraindications: Pregnancy, G6PD deficiency (relative), infants <6 months

• Why combination? Artemisinin alone has short half-life → monotherapy causes recrudescence; partner drug with longer half-life clears residual parasites
• MOA of Artemisinins: Activated by heme iron in parasite → generates free radicals → damage parasite proteins/membranes; also inhibits PfATP6 (Ca-ATPase)
• Fastest parasite clearance (within 48-72 hrs), active against all stages including gametocytes

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13. MACROLIDES — Azithromycin vs Erythromycin

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14. PURINE ANTAGONISTS / ANTIMETABOLITES

• Analogue of: Folic acid
• MOA: Inhibits dihydrofolate reductase (DHFR) → ↓ tetrahydrofolate → ↓ thymidine + purine synthesis → ↓ DNA/RNA synthesis → kills rapidly dividing cells
• Uses: ALL, NHL, choriocarcinoma (curative), breast cancer, osteosarcoma; RA, psoriasis (low dose); ectopic pregnancy; IBD
• ADR: Mucositis, myelosuppression, hepatotoxicity (chronic, cirrhosis), pulmonary fibrosis, teratogenicity
• Rescue: Folinic acid (Leucovorin) given after high-dose MTX to rescue normal cells

• Analogue of: Hypoxanthine (purine)
• MOA: Converted by HGPRT to 6-TGMP → inhibits purine synthesis de novo; also incorporated into DNA
• Uses: ALL (maintenance), IBD (Crohn's)
• ADR: Myelosuppression, hepatotoxicity, GI toxicity
• Drug interaction: Allopurinol inhibits xanthine oxidase → blocks 6-MP metabolism → ↑ toxicity (dose reduce 6-MP by 75%)

• Prodrug of 6-MP (metabolized to 6-MP in vivo)
• Uses: Transplant immunosuppression, autoimmune diseases (SLE, RA, IBD, myasthenia gravis)
• ADR: Myelosuppression, hepatotoxicity, ↑ infection risk, lymphoma
• TPMT genotyping before use — slow metabolizers get toxicity

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16. DRUGS IN SCABIES & PSORIASIS

• Corticosteroids: First line for limited disease
• Vitamin D analogues (Calcipotriol/Calcitriol): ↓ keratinocyte proliferation + ↑ differentiation; safe for face/flexures; combination with betamethasone (Daivobet)
• Coal tar: Anti-inflammatory, antiproliferative; messy
• Dithranol (Anthralin): Inhibits mitosis; irritant
• Tazarotene (retinoid): Normalize keratinocyte differentiation

• Methotrexate: Weekly dosing; monitor LFTs
• Cyclosporine: Calcineurin inhibitor; rapid onset; nephrotoxicity limits long-term use
• Acitretin (retinoid): Teratogenic (avoid in pregnancy); for pustular/erythrodermic psoriasis
• Biologics: Anti-TNF (Adalimumab, Etanercept), Anti-IL12/23 (Ustekinumab), Anti-IL17 (Secukinumab, Ixekizumab), Anti-IL23 (Guselkumab) — for refractory moderate-severe psoriasis

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19. DOMPERIDONE MOA & USES; PROKINETIC AGENTS

• Class: D2 receptor antagonist (dopamine antagonist)
• MOA: Blocks D2 receptors in upper GIT (stomach, duodenum) → reduces inhibitory dopaminergic tone → ↑ gastric motility + ↑ LES pressure; Also acts on chemoreceptor trigger zone (CTZ) — but does NOT cross BBB (unlike metoclopramide) → no extrapyramidal effects
• Uses: Gastroparesis, nausea/vomiting (PONV, chemotherapy-induced nausea), GERD, functional dyspepsia
• ADR: ↑ Prolactin (galactorrhea, amenorrhea, gynecomastia — acts on pituitary which is outside BBB), QT prolongation (cardiac concern with domperidone — black box)
• Advantage over metoclopramide: No extrapyramidal effects (doesn't cross BBB)

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22. POST-EXPOSURE PROPHYLAXIS (PEP) IN HIV

• Occupational PEP (oPEP): Healthcare workers (needlestick, splash) — risk ~0.3%
• Non-occupational PEP (nPEP): Sexual exposure, IDU, assault

• TDF (Tenofovir) + 3TC (Lamivudine) + DTG (Dolutegravir) — 28 days
• Alternative: TDF + 3TC + LPV/r (Lopinavir/Ritonavir)

1. Must start within 72 hours (every hour counts)
2. Complete full 28-day course — adherence critical
3. PEP is not 100% effective (~80% effective)
4. HIV testing: baseline, 6 weeks, 3 months, 6 months post-exposure
5. Safe sex practices during PEP period (condom use)
6. Side effects of ARVs (nausea, fatigue) — do not stop
7. Source testing (if possible) for HIV, Hep B, Hep C
8. Hep B vaccination/HBIG if not immune

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23. LEPROSY DRUGS & DAPSONE MOA/ADRs

• Class: Sulfone (structurally similar to sulfonamides)
• MOA: Inhibits dihydropteroate synthase → ↓ folate synthesis in M. leprae (same MOA as sulfonamides)
• Also: Anti-inflammatory — inhibits neutrophil myeloperoxidase → used in dermatitis herpetiformis

• Hemolytic anemia (most common, dose-related; worse in G6PD deficiency)
• Methemoglobinemia (cyanosis, chocolate-brown blood; treat with methylene blue IV)
• Agranulocytosis (rare, idiosyncratic)
• Peripheral neuropathy (rare)
• Dapsone syndrome (hypersensitivity — fever, rash, hepatitis — weeks 4-6)
• Nausea, GI intolerance

• MOA: Binds mycobacterial DNA; also anti-inflammatory
• ADR: Reddish-brown/orange skin discoloration (major cosmetic concern), GI side effects, ichthyosis

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24. METHOTREXATE — Uses & Adverse Effects

• Oncology: ALL, NHL, choriocarcinoma, osteosarcoma, breast cancer
• Rheumatology: RA (anchor drug), psoriatic arthritis
• Dermatology: Psoriasis (weekly low-dose)
• Obstetrics: Ectopic pregnancy (IM methotrexate)
• IBD (Crohn's disease — 2nd line)

• Acute: Mucositis, myelosuppression (nadir 7-14 days), nausea, elevated LFTs
• Chronic: Hepatic fibrosis/cirrhosis (monitor with liver biopsy after 1.5g cumulative)
• Pulmonary: MTX pneumonitis (hypersensitivity-type, NOT dose-related)
• Teratogenicity (Category X)
• Renal toxicity at high doses (precipitates in renal tubules — hydration + alkalinization of urine)
• Leucovorin (folinic acid) rescue for high-dose MTX

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25. DVT DRUGS & LMWH ADVANTAGES

• Heparin (UFH), LMWH, Fondaparinux, Direct oral anticoagulants (DOACs: Rivaroxaban, Apixaban, Dabigatran), Warfarin

• Examples: Enoxaparin, Dalteparin, Tinzaparin, Nadroparin

• Both bind antithrombin (AT III) → ↑ AT activity
• UFH: Inhibits both Factor Xa AND thrombin (IIa); requires chain ≥18 saccharides
• LMWH: Primarily inhibits Factor Xa (anti-Xa:anti-IIa ratio = 3:1 to 4:1); shorter chains
• Fondaparinux: Synthetic pentasaccharide — only anti-Xa (selective)

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26. H. PYLORI ERADICATION REGIMENS — Rationale

• PPI (Omeprazole 20mg BD) + Clarithromycin 500mg BD + Amoxicillin 1g BD

• PPI + Bismuth subcitrate + Tetracycline + Metronidazole (14 days)

1. H. pylori lives in mucous layer + intracellularly — no single drug penetrates adequately alone
2. PPI: Raises gastric pH above 5 → antibiotics work better (amoxicillin, clarithromycin are acid-labile or less effective in acid); also direct anti-H. pylori effect
3. Two antibiotics: Reduce resistance emergence; attack different targets simultaneously
4. Bismuth: Direct bactericidal + cytoprotection + anti-inflammatory
5. Confirm eradication: UBT (Urea Breath Test) or stool antigen test 4 weeks after completing therapy

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29. CALCINEURIN INHIBITORS — Cyclosporine & Tacrolimus

• Cyclosporine: Binds cyclophilin → complex inhibits calcineurin (phosphatase) → ↓ dephosphorylation of NFAT → ↓ NFAT nuclear entry → ↓ IL-2 gene transcription → ↓ T-cell activation/proliferation
• Tacrolimus (FK506): Binds FKBP-12 → complex inhibits calcineurin → same downstream effect as cyclosporine

• Organ transplant rejection prevention (both)
• Cyclosporine: RA, psoriasis, nephrotic syndrome, aplastic anaemia, dry eyes (topical)
• Tacrolimus: Also atopic dermatitis (topical), organ transplant (more potent than cyclosporine, preferred in liver/kidney transplant)

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30. ORS — Composition & Role in Diarrhoea

• SGLT1 transporter in small intestinal enterocytes co-transports Na⁺ + Glucose (1:1) → Na⁺ absorption even during diarrhea when secretion is high
• Na⁺ absorption → water follows osmotically → rehydration
• Glucose does NOT worsen diarrhoea (at ORS concentration); actively drives Na absorption
• KCl: Replaces potassium losses
• Citrate: Corrects metabolic acidosis (alternative to bicarbonate; more stable)

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31 & 32. HEPARIN vs WARFARIN & LMWH vs UFH

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33. INFLAMMATORY BOWEL DISEASE (IBD) — Drugs

• Mesalazine (5-ASA), Sulfasalazine (5-ASA + Sulfapyridine)
• MOA: Inhibit prostaglandin synthesis + NF-kB in colonic epithelium
• Primary use: Ulcerative colitis (limited role in Crohn's)
• Sulfasalazine ADR: Oligospermia, rash, hemolysis (sulfa component)

• Prednisolone, Methylprednisolone, Budesonide (topical ileum - minimal systemic absorption)
• For acute flares; not for maintenance (side effects)

• Azathioprine/6-MP: Steroid-sparing; maintenance; onset 3-6 months
• Methotrexate: Crohn's disease (weekly SC/IM)

• Anti-TNF: Infliximab, Adalimumab — both CD + UC
• Anti-integrin: Vedolizumab (gut-selective; blocks α4β7 integrin on lymphocytes)
• Anti-IL12/23: Ustekinumab — Crohn's
• JAK inhibitors: Tofacitinib, Upadacitinib — UC + CD

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34. IRON PREPARATIONS & ANAEMIA MANAGEMENT

• Ferrous salts (sulfate, fumarate, gluconate) — better absorbed than ferric
• Standard: Ferrous sulfate 200mg (65mg elemental iron) TDS
• Absorption: Best in fasting, acidic environment; Vitamin C enhances; tea/milk inhibits
• ADR: GI (constipation, nausea, black stools, epigastric pain)

• Iron sucrose: Safest; for dialysis patients; IV infusion
• Ferric carboxymaltose: Single high-dose infusion; fewer infusions needed
• Iron dextran: IM or IV; anaphylaxis risk — test dose required
• Low molecular weight iron dextran
• Indications: Intolerance to oral iron, malabsorption, active IBD, pre-operative (rapid correction), CKD

• Megaloblastic anaemia (folate deficiency)
• Pregnancy: 400-5000 mcg/day periconceptional — prevents neural tube defects (NTDs)
• Prevents deficiency in hemolytic states (increased RBC turnover)
• Methotrexate-induced folate antagonism

1. Confirm iron deficiency (serum ferritin, TIBC, serum iron, peripheral smear)
2. Treat underlying cause (dietary advice, GI bleed workup)
3. Oral iron for 3-6 months (2 months beyond Hb normalization to replenish stores)
4. Parenteral iron if oral fails/intolerance
5. Transfusion if severe symptomatic anaemia

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36. ANABOLIC STEROIDS — Uses & Adverse Effects

1. Aplastic anaemia (oxymetholone)
2. Cachexia (cancer, AIDS, chronic illness)
3. Turner syndrome (oxandrolone — promote growth)
4. Hereditary angioedema (stanozolol — stimulates C1 esterase inhibitor)
5. Chronic renal failure — ↑ erythropoiesis
6. Osteoporosis (limited use)
7. Delayed puberty in boys

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37. TOXICITY AMELIORATION OF ANTICANCER AGENTS

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41. AZOLE ANTIFUNGALS & ECHINOCANDINS

• Clotrimazole, Miconazole, Ketoconazole, Econazole — mainly topical (skin, vaginal candidiasis)
• Ketoconazole: Systemic use now restricted (hepatotoxicity)

• Fluconazole: Candida (mucocutaneous, systemic), Cryptococcal meningitis; narrow spectrum; CYP2C9 inhibitor
• Itraconazole: Broad spectrum — Aspergillus, Candida, dermatophytes, Histoplasma, Blastomyces, Sporothrix; capsules need food (acidic stomach)
• Voriconazole: Drug of choice for Aspergillosis; visual disturbances (hallucinations/photopsia); broad spectrum
• Posaconazole: Prophylaxis in high-risk neutropenics; Mucormycosis; broadest spectrum triazole
• Isavuconazole: Mucormycosis + Aspergillosis; IV/oral; best-tolerated

• Drugs: Caspofungin, Micafungin, Anidulafungin
• MOA: Inhibit β(1,3)-D-glucan synthase → ↓ cell wall glucan → osmotic fragility → fungicidal
• Spectrum: Candida (including azole-resistant), Aspergillus
• NOT active against: Cryptococcus (no glucan in wall), Mucor
• Advantages: Fungicidal for Candida, good safety, minimal drug interactions
• ADR: Infusion-related reactions, mild LFT elevations
• Use: First-line for invasive candidiasis, salvage Aspergillosis, empirical antifungal in neutropenic fever

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42. IMMUNOSUPPRESSANTS IN ORGAN TRANSPLANTATION

• Anti-thymocyte globulin (ATG) / Basiliximab (IL-2R antagonist, anti-CD25)

1. Calcineurin inhibitor: Tacrolimus (preferred) or Cyclosporine
2. Antiproliferative: Mycophenolate mofetil (MMF) or Azathioprine
3. Corticosteroid: Prednisolone

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43. URINARY ANALGESICS, EMPIRICAL UTI TREATMENT & RATIONALE FOR COMBINATION ANTIMICROBIALS

• Phenazopyridine (Pyridium): Azo dye; excreted in urine → local analgesic/anesthetic on urothelium; relieves dysuria; turns urine orange-red; not antibacterial; use max 2 days
• Flavoxate: Antimuscarinic + phosphodiesterase inhibitor; antispasmodic → relieves bladder spasm

• Uncomplicated cystitis (women): Nitrofurantoin (5 days), Fosfomycin (single dose 3g), Trimethoprim-Sulfamethoxazole (3 days), or Fluoroquinolone (ciprofloxacin — 3 days, use if susceptibility confirmed)
• Complicated UTI/Pyelonephritis: Fluoroquinolone (7-14 days) or Cephalosporin IV → oral step-down; guided by urine culture
• Hospital-acquired/ESBL-producing organisms: Carbapenems (imipenem, meropenem)

1. Trimethoprim + Sulfamethoxazole (Co-trimoxazole): Sequential blockade of folate synthesis — sulfonamide blocks DHPS, trimethoprim blocks DHFR → synergistic (bactericidal), prevents resistance
2. Amoxicillin + Clavulanate: As above — overcome beta-lactamase producing organisms
3. Broader coverage in polymicrobial/severe infections

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44. DRUGS FOR CONSTIPATION — MOA & Elderly Preferences

• Bulk-forming agents (isabgol) — first choice
• Lactulose or PEG — safe osmotic agents
• Bisacodyl (short term) — when quick relief needed
• Avoid: Stimulant laxatives (long-term), liquid paraffin (aspiration risk), magnesium salts (renal impairment)

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45. ANTITUSSIVES — Classification & Precautions

• Benzonatate: Anesthetizes stretch receptors in alveoli/bronchi; do not chew (numbs mouth)
• Demulcents: Honey, glycerine, linctus — soothe upper airway

1. Antitussives should NOT be used for productive cough (suppressing clears infection)
2. Use only for dry/non-productive cough
3. Codeine — dependence potential; avoid in children <12 years
4. DXM — abuse potential; serotonin syndrome when combined with MAOIs
5. Contraindicated in asthma (can cause bronchoconstriction)
6. Avoid in COPD with CO₂ retention (opioids → respiratory depression)
7. Benzonatate: Do not crush/chew — risk of oropharyngeal anesthesia, CNS effects

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47. ANTHELMINTICS & NEUROCYSTICERCOSIS TREATMENT

• Caused by Taenia solium larvae encysted in CNS
• Albendazole 15 mg/kg/day (preferred over praziquantel) — penetrates CNS better; given in 8-28-day courses
• Dexamethasone/Corticosteroids: Mandatory with albendazole — prevents inflammatory reaction from dying cysticerci (cerebral edema, seizures worsening)
• Antiepileptics (Phenytoin/Valproate): For seizure control
• Praziquantel: Alternative; drug interaction with dexamethasone (↓ praziquantel levels) and carbamazepine (enzyme induction)
• Surgery: For hydrocephalus (ventricular cysts, CSF diversion)

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48. CLOPIDOGREL — Detailed MOA & Adverse Effects

1. Clopidogrel is a prodrug — inactive until hepatic metabolism
2. CYP2C19 converts it to an active thiol metabolite
3. Active metabolite irreversibly binds P2Y12 ADP receptor on platelets
4. Blocks ADP-mediated platelet activation → ↓ GP IIb/IIIa expression → ↓ platelet aggregation
5. Effect lasts platelet lifetime (7-10 days) due to irreversible binding

• CYP2C19 poor metabolizers (loss-of-function alleles *2, *3): ↓ conversion to active metabolite → reduced antiplatelet effect → higher cardiovascular events
• FDA black box warning for poor metabolizers
• Alternative: Prasugrel or Ticagrelor (not dependent on CYP2C19)

• ACS (NSTEMI, STEMI) — DAPT with aspirin
• Post-PCI (stenting)
• Stroke/TIA secondary prevention
• PAD (peripheral arterial disease)
• Atrial fibrillation (alternative if warfarin not tolerated)

• Bleeding (most important — GI, intracranial)
• TTP (thrombotic thrombocytopenic purpura) — rare, class effect of thienopyridines
• Rash, diarrhea, GI discomfort
• Neutropenia (rare)
• Drug interaction: PPIs (omeprazole, esomeprazole) inhibit CYP2C19 → ↓ clopidogrel activation → ↓ efficacy; use pantoprazole or rabeprazole (minimal CYP2C19 effect)

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49. ALBENDAZOLE — MOA, Uses & Adverse Effects

• Binds to β-tubulin of helminth → inhibits tubulin polymerization → disrupts microtubule assembly → impairs:
  • Glucose uptake in helminths
  • Cell division
  • Transport of secretory vesicles
• Ovicidal + larvicidal + adulticidal activity

1. Intestinal nematodes: Ascariasis, hookworm, trichuriasis (whipworm), enterobiasis (pinworm), strongyloidiasis
2. Tissue infections: Neurocysticercosis (Taenia solium), Cystic echinococcosis/hydatid disease (Echinococcus granulosus)
3. Cutaneous larva migrans
4. Toxocariasis (visceral larva migrans)
5. Microsporidiosis (in HIV)
6. Giardiasis (alternative)
7. Mass Drug Administration (MDA): Deworming programs (with or without ivermectin)

• Usually well tolerated at single dose (400 mg)
• Prolonged treatment (hydatid/cysticercosis): Nausea, abdominal pain, elevated LFTs (hepatotoxicity), alopecia, bone marrow suppression
• Teratogenic in animals (Category C) — avoid in 1st trimester; contraindicated in pregnancy
• GI disturbance (nausea, diarrhea)
• Headache, dizziness

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50. CHELATING AGENTS & COPPER POISONING MANAGEMENT

1. Supportive care: IV fluids, treat hemolysis and hepatotoxicity
2. D-Penicillamine: Chelates copper → renal excretion; first-line
3. BAL (dimercaprol): If severe/parenteral chelation needed
4. Gastric lavage if early ingestion

1. D-Penicillamine — first-line (oral chelator); increases urinary copper excretion
2. Trientine — alternative if D-penicillamine intolerant (better tolerated)
3. Zinc acetate/sulfate — inhibits gut copper absorption (induces metallothionein); used for maintenance phase and presymptomatic patients
4. Tetrathiomolybdate — experimental; binds copper in gut + plasma
5. Liver transplantation — for fulminant hepatic failure

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