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PHARMACOLOGY INTERNAL EXAM ANSWERS

Legend: EW = Explain Why | D/W = Differentiate/Write | These are short notes (4-6 marks each)

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SHORT QUESTIONS (EW / D/W)

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1) EW: Thiopentone Sodium is used as an inducing agent of General Anaesthesia

• Produces unconsciousness within 30 seconds of IV injection (single arm-brain circulation time)
• Short duration of action (5-10 min) due to rapid redistribution from brain to muscle and fat
• Produces smooth, pleasant induction - no excitatory phase
• No analgesia maintained - hence used only for induction, not maintenance
• Highly lipid-soluble - crosses BBB instantly

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2) Write a short note on: Ketamine

1. Induction in haemodynamically unstable patients
2. Burn dressing in children (esp. asthmatics) - causes bronchodilation
3. Short surgical procedures
4. Analgesia in emergency settings

• Emergence delirium / hallucinations
• Increased intracranial pressure (contraindicated in head injury)
• Increased salivation (give atropine premedication)

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3) D/W: Morphine and Pethidine

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4) D/W: Phenytoin and Valproic Acid

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5) Barbiturate Poisoning

• CNS depression: confusion → stupor → coma
• Respiratory depression - most dangerous, main cause of death
• Hypotension, hypothermia
• Loss of corneal, gag reflexes
• Bullous skin lesions ("barb blisters") - characteristic

1. Airway - maintain, intubate if needed
2. Gastric lavage (within 4 hours) + activated charcoal
3. Alkalinization of urine (sodium bicarbonate IV) - increases renal excretion of long-acting barbiturates (phenobarbitone)
4. IV fluids for hypotension
5. Haemodialysis for severe cases (phenobarbitone)
6. Forced alkaline diuresis

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6) Lithium Carbonate as Mood Stabilizer

• Inhibits inositol phosphate recycling (depletes IP₃ and DAG signalling)
• Modulates serotonin and dopamine neurotransmission
• Inhibits glycogen synthase kinase-3 (GSK-3)

1. Drug of choice for Bipolar disorder (manic phase + prophylaxis)
2. Prophylaxis of recurrent mania and depression
3. Augmentation in resistant depression

• Coarse tremor, ataxia, confusion
• Cardiac arrhythmias
• Polyuria, polydipsia (nephrogenic diabetes insipidus)
• Hypothyroidism on long-term use

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7) Write a short note on: Intravenous Anaesthetics

• Rapid onset (1 arm-brain circulation)
• Mainly used for induction
• No analgesia (except ketamine)
• Recovery by redistribution

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8) EW: Diazepam is used in Status Epilepticus

• Diazepam is a benzodiazepine that acts on GABA-A receptors
• Enhances Cl⁻ influx → hyperpolarization → terminates seizure
• Fastest acting benzodiazepine when given IV - crosses BBB within seconds
• Controls seizure within 2-3 minutes
• First-line drug in status epilepticus (given IV 10 mg slowly, can repeat)

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9) Write a short note on: Carbamazepine

1. Drug of choice for Partial (focal) seizures - simple and complex
2. Trigeminal neuralgia (DOC)
3. Glossopharyngeal neuralgia
4. Bipolar disorder (alternative to lithium)
5. Diabetic neuropathy

• Diplopia, ataxia, dizziness (dose-related)
• Aplastic anaemia, agranulocytosis (rare, serious)
• Hepatotoxicity
• Syndrome of inappropriate ADH secretion (SIADH) - hyponatraemia
• Teratogenic (neural tube defects)
• Strong enzyme inducer (CYP3A4)

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10) EW: Ethanol is administered after Methanol Poisoning

• Methanol → (alcohol dehydrogenase) → Formaldehyde → Formic acid
• Formic acid causes optic nerve damage (blindness) and metabolic acidosis

• Ethanol has 10x higher affinity for alcohol dehydrogenase than methanol
• Competes with methanol for the enzyme → methanol is not metabolized to toxic products
• Methanol is then eliminated unchanged via kidneys and lungs
• This prevents formation of formaldehyde and formic acid → prevents blindness

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11) EW: Ketamine is a suitable anaesthetic in asthmatic child

1. Ketamine causes bronchodilation by releasing catecholamines (sympathomimetic action)
2. Raises plasma epinephrine and norepinephrine → beta-2 stimulation → bronchodilation
3. Maintains airway tone and airway reflexes - does NOT cause respiratory depression at normal doses
4. Can be given IM - useful in uncooperative children
5. No need for intubation in many cases

• Asthmatic patients requiring anaesthesia
• Burn dressing in children with asthma

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12) Write a short note on: Sodium Valproate

1. Blocks Na⁺ channels (like phenytoin)
2. Blocks Ca²⁺ channels (T-type) - important for absence seizures
3. Increases GABA by inhibiting GABA transaminase and succinate semialdehyde dehydrogenase

1. Drug of choice for Absence seizures + Myoclonic epilepsy
2. GTCS (Generalised Tonic Clonic Seizures)
3. Bipolar disorder (mood stabilizer)
4. Migraine prophylaxis

• Hepatotoxicity (idiosyncratic, serious)
• Weight gain
• Alopecia (reversible)
• Tremor
• Teratogenic: Neural tube defects (spina bifida) - avoid in pregnancy
• Thrombocytopenia
• Pancreatitis

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13) Write a short note on: Atypical Antipsychotic Drugs

1. Schizophrenia (positive + negative symptoms)
2. Bipolar disorder
3. Treatment-resistant psychosis (clozapine)

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14) Write a short note on: Diazepam

1. Anxiety disorders (short-term)
2. Status epilepticus (IV)
3. Insomnia (short-term)
4. Muscle relaxant (e.g., tetanus)
5. Alcohol withdrawal
6. Preanaesthetic medication
7. Procedural sedation

• Sedation, drowsiness
• Dependence and tolerance
• Anterograde amnesia
• Respiratory depression (with alcohol)

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15) Write a short note on: Morphine

1. Severe pain (post-op, MI, cancer pain)
2. Acute left ventricular failure (LVF) - reduces preload + anxiety
3. Antitussive (codeine preferred)
4. Pulmonary oedema - reduces dyspnoea

• Respiratory depression (main danger)
• Nausea, vomiting
• Constipation (most consistent side effect)
• Miosis (pinpoint pupils - sign of toxicity)
• Tolerance and dependence
• Histamine release - pruritus, hypotension
• Biliary/ureteric spasm

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16) Write a short note on: Naloxone

1. Opioid overdose/poisoning - drug of choice
2. Reversal of post-operative opioid effects
3. Diagnosis of opioid dependence (precipitates withdrawal)
4. Neonatal respiratory depression due to maternal opioids

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17) EW: Diazepam is used instead of Phenobarbitone in Insomnia

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18) EW: Disulfiram is used in Chronic Alcoholism

• Inhibits aldehyde dehydrogenase (ALDH)
• Normally: Ethanol → Acetaldehyde → (ALDH) → Acetic acid
• With disulfiram: Acetaldehyde accumulates
• Acetaldehyde causes: flushing, throbbing headache, nausea, vomiting, palpitations, hypotension (Disulfiram-Ethanol Reaction - DER)

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19) EW: Phenothiazine induces Parkinsonism

• Block D₂ dopamine receptors in the nigrostriatal pathway
• In the nigrostriatal system, dopamine normally inhibits cholinergic activity
• D₂ blockade → relative cholinergic excess → Parkinsonian symptoms

• Tremor (resting)
• Rigidity
• Bradykinesia
• Mask-like facies

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20) Write a short note on: Dopamine

1. Cardiogenic shock (moderate dose)
2. Septic shock with oliguria (low + moderate dose)
3. Acute heart failure
4. Oliguric renal failure

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21) Write on: Atracurium as Adjuvant to General Anaesthetics

• Provides muscle relaxation (general anaesthetics alone cannot produce adequate relaxation)
• Allows endotracheal intubation
• Reduces dose of GA needed
• Permits use of lower concentrations of inhalational agents - less toxicity

• Metabolized by Hofmann elimination (spontaneous degradation at body temperature/pH) - independent of kidney/liver
• Ideal for patients with renal or hepatic failure

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22) EW: Methyl Alcohol induces Blindness

1. Methanol → (Alcohol Dehydrogenase) → Formaldehyde
2. Formaldehyde → (Aldehyde Dehydrogenase) → Formic acid

• Formic acid inhibits cytochrome c oxidase in mitochondria of retinal ganglion cells and optic nerve
• This causes optic nerve demyelination and degeneration
• Presents as: blurred vision → "snowfield" vision → permanent blindness

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23) EW: Phenytoin is used in Epilepsy

• Phenytoin blocks voltage-gated Na⁺ channels in a use-dependent manner
• Preferentially binds to and stabilizes the inactive/refractory state of Na⁺ channels
• This reduces high-frequency repetitive firing of neurons in epileptic focus
• Does NOT affect resting neurons (specific for epileptogenic foci)

1. Drug of choice for Generalised Tonic Clonic Seizures (GTCS)
2. Focal/Partial seizures
3. IV phenytoin for Status epilepticus (after diazepam)
4. Post-neurosurgical seizure prophylaxis

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24) EW: Phenobarbitone is used in Neonatal Kernicterus

• Phenobarbitone induces hepatic glucuronyl transferase enzyme
• This enzyme conjugates (detoxifies) unconjugated bilirubin → conjugated bilirubin → excreted in bile
• Given to mothers before delivery or to neonates at risk
• Reduces unconjugated bilirubin levels → prevents kernicterus (bilirubin encephalopathy)

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25) EW: Levodopa is used in Parkinsonism

• Dopamine cannot cross the Blood-Brain Barrier (BBB)
• Levodopa (L-DOPA) is a precursor of dopamine that crosses the BBB via amino acid transporters
• Once inside the brain, it is converted to dopamine by DOPA decarboxylase
• This replenishes dopamine in the nigrostriatal pathway (which is deficient in Parkinson's)

• Carbidopa inhibits peripheral DOPA decarboxylase (does NOT cross BBB)
• Prevents peripheral conversion → more L-DOPA reaches the brain
• Reduces peripheral side effects (nausea, vomiting, cardiac arrhythmias)

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26) EW: Naloxone is used in Opioid Poisoning (OP)

• Pure competitive antagonist at µ, κ, δ opioid receptors
• Rapidly reverses: respiratory depression, sedation, miosis, hypotension
• Given IV - works within 1-2 minutes
• Dose: 0.4-2 mg IV

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27) Give Reason: Imidazoline nasal decongestant should NOT be used for prolonged periods and in those using non-specific MAO Inhibitors

• Act on α₁ and α₂ receptors in nasal mucosa → vasoconstriction → decongestion
• Prolonged use causes rebound congestion (rhinitis medicamentosa) - the nasal mucosa becomes dependent on the drug; without it, worse congestion occurs
• Also causes systemic absorption → hypertension, especially in children

• Imidazolines release noradrenaline from nerve terminals (indirectly)
• MAO Inhibitors block breakdown of catecholamines
• Combined effect: massive catecholamine release → severe hypertensive crisis (headache, stroke risk)

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28) Give Reason: Ketamine is the most suitable anaesthetic for burn dressing in asthmatic child

1. Bronchodilation: Ketamine stimulates catecholamine release → β₂ stimulation → bronchodilation (ideal for asthmatics)
2. IM route possible: Children are often uncooperative; IM injection works well for ketamine
3. Maintains airway reflexes and respiration: Unlike other anaesthetics, ketamine does not cause significant respiratory depression
4. Provides excellent analgesia: Burn dressings are painful; ketamine gives profound analgesia

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29) Give Reason: Ethanol is administered repeatedly and for several days in Methanol Poisoning

• Ethanol competitively inhibits alcohol dehydrogenase → prevents metabolism of methanol to toxic formaldehyde/formic acid
• Methanol has a long half-life (~24-30 hours) and is slowly eliminated by kidneys/lungs
• Ethanol itself is also metabolized within hours → blood ethanol levels fall
• To keep ethanol levels continuously high enough (100 mg/dL) to outcompete methanol for ADH, it must be given repeatedly
• Treatment continues until methanol is fully eliminated from the body (confirmed by absence of formate in blood/urine)
• The process takes several days - hence repeated and prolonged administration

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LONG QUESTIONS

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LONG Q1) Classify General Anaesthetics; their action and uses; S/Es of any 3 GAs

1. Gases: Nitrous oxide (N₂O)
2. Volatile liquids: Halothane, Isoflurane, Sevoflurane, Desflurane, Enflurane

1. Barbiturates: Thiopentone sodium
2. Phencyclidine derivatives: Ketamine
3. Phenol derivatives: Propofol
4. Imidazole: Etomidate
5. Benzodiazepines: Midazolam

• Stage I: Analgesia
• Stage II: Excitement/Delirium
• Stage III: Surgical anaesthesia (planes 1-4)
• Stage IV: Medullary depression (overdose - fatal)

• Not fully understood
• Lipid solubility theory (Meyer-Overton): Anaesthetic potency correlates with oil:gas partition coefficient
• Modern view: Act on ligand-gated ion channels - enhance GABA-A (inhibitory) and inhibit NMDA (excitatory) receptors

• Hepatotoxicity (halothane hepatitis - idiosyncratic, can be fatal on re-exposure)
• Malignant hyperthermia (rare genetic predisposition)
• Myocardial sensitization to catecholamines (arrhythmias)
• Hypotension

• Laryngospasm and bronchospasm (histamine release)
• Cardiovascular depression (hypotension)
• Tissue necrosis if injected extravascularly (highly alkaline, pH 10-11)
• No analgesia (patient may respond to pain)
• Porphyria - absolutely contraindicated

• Emergence delirium, hallucinations, nightmares (manage with diazepam premedication)
• Increased intracranial and intraocular pressure
• Increased salivation (give atropine)
• Hypertension and tachycardia

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LONG Q2) Drugs for GTCS (Generalised Tonic Clonic Seizures); MOA and S/Es of anyone

1. Phenytoin (DOC)
2. Sodium Valproate
3. Carbamazepine
4. Phenobarbitone
5. Levetiracetam
6. Lamotrigine
7. Topiramate

• IV Diazepam (first line, immediate)
• IV Lorazepam
• IV Phenytoin (after BZD, to prevent recurrence)
• IV Phenobarbitone (third line)
• IV Valproate

1. Blocks voltage-gated Na⁺ channels → reduces repetitive firing
2. Blocks T-type Ca²⁺ channels → effective in absence seizures
3. Inhibits GABA transaminase → less GABA breakdown → ↑ GABA
4. Inhibits succinate semialdehyde dehydrogenase → ↑ GABA synthesis

• Hepatotoxicity (most serious - especially in children <2 years; monitor LFT)
• Weight gain
• Alopecia (hair thinning - reversible)
• Tremor
• Teratogenic - Neural tube defects (spina bifida) - avoid in pregnancy or give folic acid supplementation
• Thrombocytopenia
• Nausea, vomiting (give with food)
• Pancreatitis

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LONG Q3) Classify Anti-epileptic drugs; Mechanism, Uses and S/Es of Carbamazepine and Valproate

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• Blocks voltage-gated Na⁺ channels (use-dependent)
• Stabilizes inactive state → reduces repetitive neuronal firing

1. DOC for Partial (focal) seizures - simple and complex
2. Trigeminal neuralgia (DOC)
3. Bipolar disorder
4. GTCS

• Diplopia, ataxia, dizziness (dose-related, common)
• Aplastic anaemia, agranulocytosis (rare, serious - monitor CBC)
• Hepatotoxicity
• Hyponatraemia (SIADH)
• Rash (Stevens-Johnson syndrome - rare, serious)
• Teratogenic
• Strong enzyme inducer (reduces efficacy of OCP, warfarin)

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LONG Q4) List Anti-parkinsonism drugs; elaborate drugs for initiation, maintenance, and late-stage Parkinsonism

• Loss of dopaminergic neurons in substantia nigra
• Dopamine ↓ → Acetylcholine relatively ↑ in striatum → symptoms
• Symptoms: Tremor (resting), Rigidity, Bradykinesia, Postural instability

1. Levodopa (+ Carbidopa/Benserazide)
2. Dopamine agonists: Bromocriptine, Pramipexole, Ropinirole, Rotigotine
3. MAO-B inhibitors: Selegiline, Rasagiline
4. COMT inhibitors: Entacapone, Tolcapone
5. Amantadine (releases dopamine + NMDA antagonist)

• Trihexyphenidyl (Benzhexol), Benztropine, Biperiden

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• Inhibit MAO-B → reduce dopamine breakdown → prolong dopamine action
• Neuroprotective - may slow disease progression
• Well tolerated, minimal side effects
• Started first in younger patients (delay levodopa to avoid long-term complications)

• Direct D2/D3 receptor agonists
• Used in early disease, especially in younger patients
• Delay need for levodopa → delay motor complications
• S/Es: nausea, somnolence, hallucinations, impulse control disorders

• Mild cases only
• Releases dopamine, anticholinergic, NMDA antagonist
• Used in early mild tremor

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• Most effective drug for Parkinsonism
• Levodopa → dopamine in brain (crosses BBB)
• Carbidopa blocks peripheral DOPA decarboxylase → more levodopa reaches brain, less peripheral SE
• Gold standard for established disease

• Wearing off - drug effect ends before next dose
• On-off fluctuations - unpredictable motor swings
• Dyskinesias - involuntary movements at peak dose

• Add COMT inhibitor (Entacapone) - prolongs levodopa action
• Add MAO-B inhibitor
• Controlled-release formulations

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1. Dyskinesias: Reduce levodopa dose + add amantadine (antidyskinetic)
2. Psychosis/Hallucinations: Clozapine or Quetiapine (low-dose atypical antipsychotics - do NOT use typical antipsychotics - they worsen Parkinsonism)
3. Deep Brain Stimulation (DBS) of subthalamic nucleus - for drug-refractory cases
4. Apomorphine (subcutaneous) - dopamine agonist; rescue therapy for severe on-off fluctuations
5. Tolcapone (COMT inhibitor) - more potent but hepatotoxic - use in late-stage refractory cases with monitoring

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• Ketamine = bronchodilator, NMDA antagonist, IM possible, preferred in asthmatics
• Thiopentone = ultra-short acting, induction only, no analgesia
• Diazepam = GABA-A enhancer, first-line in status epilepticus
• Naloxone = pure opioid antagonist, antidote for opioid poisoning, short-acting
• Ethanol in methanol poisoning = competes for alcohol dehydrogenase, prevents formic acid formation
• Phenothiazine → Parkinsonism = D₂ blockade in nigrostriatal pathway
• Disulfiram = blocks ALDH → acetaldehyde accumulates → aversion to alcohol
• Levodopa = crosses BBB (dopamine doesn't); always with carbidopa
• Valproate = broad-spectrum AED, teratogenic (NTD), hepatotoxic
• Carbamazepine = Na⁺ channel blocker, DOC for trigeminal neuralgia + focal seizures

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PHARMACOLOGY INTERNAL EXAM ANSWERS

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SECTION A: RESPIRATORY / ASTHMA

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1) Use of Salmeterol in Bronchial Asthma

• Highly lipophilic → stays bound in lipid membrane near β₂ receptor
• Duration: 12 hours (vs Salbutamol = 4-6 hrs)

1. Maintenance therapy in moderate-to-severe persistent asthma
2. Exercise-induced bronchospasm (prophylaxis)
3. COPD maintenance
4. Used in combination with Inhaled Corticosteroids (ICS) - e.g., Seretide = Salmeterol + Fluticasone

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2) Status Asthmaticus

• Severe dyspnoea, accessory muscle use
• SpO₂ <92%, PaO₂ ↓, PaCO₂ ↑ (late, bad sign)
• Unable to speak in full sentences
• Silent chest (very severe - air entry absent)

1. Oxygen - high flow to maintain SpO₂ >94%
2. Nebulized Salbutamol (2.5-5 mg) - repeated every 20 min (short-acting β₂ agonist)
3. Ipratropium bromide (nebulized) - anticholinergic bronchodilator, add to salbutamol
4. IV Hydrocortisone (200 mg) or oral Prednisolone - reduces airway inflammation
5. IV Aminophylline - if not responding to above
6. IV MgSO₄ - smooth muscle relaxant, bronchodilator
7. Mechanical ventilation if needed (ICU)

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3) Hydrocortisone in Status Asthmaticus

• Glucocorticoid → binds intracellular receptor → gene transcription changes
• Inhibits phospholipase A₂ → reduces arachidonic acid → less prostaglandins, leukotrienes (LTC4, LTD4 = powerful bronchospastic agents)
• Reduces airway mucosal edema
• Decreases mucus hypersecretion
• Restores β₂ receptor sensitivity (reverses tachyphylaxis to bronchodilators)
• Inhibits inflammatory cell infiltration

• Patient cannot use inhaler effectively
• Rapid systemic delivery needed in life-threatening situation
• Onset: 4-6 hours (delayed action - so given early)

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4) Budesonide in Asthma

• Anti-inflammatory: inhibits PLA₂ → ↓ leukotrienes, prostaglandins
• Reduces eosinophilic inflammation in airways
• Decreases bronchial hyperresponsiveness
• Reduces mucus secretion and mucosal edema

1. Prophylaxis/maintenance of persistent asthma (NOT for acute attacks)
2. Allergic rhinitis (intranasal)
3. COPD (combined with formoterol)

• Local action - minimal systemic absorption
• Low systemic side effects

• Local: Oropharyngeal candidiasis (fungal infection), dysphonia (hoarseness)
• Adrenal suppression (at high doses)
• Prevention: Rinse mouth after use, use spacer device

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5) Bromhexine

• Depolymerizes mucopolysaccharides in sputum → breaks disulfide bonds in mucus glycoproteins
• Reduces viscosity and elasticity of mucus
• Stimulates serous glands of bronchial mucosa → increases watery secretions → dilutes sputum
• Increases ciliary activity

1. Chronic bronchitis - to clear thick tenacious sputum
2. COPD exacerbations
3. Bronchiectasis
4. Can be used in asthma with mucus plugging

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6) Corticosteroids (Short Note)

1. Asthma, COPD (inhaled)
2. Allergic disorders
3. Autoimmune diseases (SLE, RA)
4. Adrenal insufficiency (replacement)
5. Organ transplant (immunosuppression)
6. Cerebral edema (dexamethasone)
7. Septic shock (hydrocortisone)

• Cushing's syndrome (moon face, buffalo hump, striae)
• Osteoporosis, avascular necrosis
• Hyperglycemia (steroid diabetes)
• Hypertension, hypokalemia
• Peptic ulcer
• Immunosuppression → infections
• Growth retardation in children
• HPA axis suppression (do NOT stop abruptly - taper)

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7) Role of Corticosteroids in Asthma

1. Inhibit phospholipase A₂ → ↓ arachidonic acid → ↓ leukotrienes (LTC4, LTD4) + prostaglandins → less bronchospasm
2. Reduce mucosal edema (anti-edema effect)
3. Decrease mucus secretion
4. Inhibit mast cell and eosinophil activity
5. Reduce bronchial hyperresponsiveness (BHR)
6. Up-regulate β₂ receptors → restore response to bronchodilators

• Inhaled (ICS) - for prophylaxis/maintenance in persistent asthma (daily use)
• Systemic (IV/oral) - for acute severe attacks and status asthmaticus

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8) Salbutamol (Albuterol)

• Onset: 1-3 min (inhaled), duration 4-6 hours

1. Acute bronchospasm - first-line reliever
2. Exercise-induced bronchospasm (EIB)
3. Status asthmaticus (nebulized)
4. Premature labour (tocolytic - IV)
5. Hyperkalemia (shifts K⁺ into cells)

• Tremor (hands) - most common
• Tachycardia, palpitations
• Hypokalemia (at high doses)
• Headache

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9) Inhalation of Salbutamol in Acute/Chronic Bronchial Asthma

• 2-4 puffs via MDI (metered dose inhaler) with spacer OR
• Nebulized salbutamol 2.5-5 mg - for severe attack, can be repeated every 20 min

• Used "as needed" (PRN) for symptom relief
• Frequent use (>2 times/week) indicates uncontrolled asthma → step up treatment
• NOT used as regular daily maintenance (use ICS for that)

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10) Terbutaline

1. Acute bronchospasm (inhaled/SC)
2. Premature labour - tocolysis (most common non-respiratory use)
3. Status asthmaticus (SC/IV)

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11) Non-Narcotic Antitussives

• Dry, unproductive cough (post-viral, allergic)
• Cough in patients where narcotic (codeine) is contraindicated (addiction-prone)

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12) Mucolytics

1. Chronic bronchitis, COPD, bronchiectasis
2. Cystic fibrosis (NAC - inhaled)
3. Paracetamol overdose antidote (IV NAC)

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13) Drug Treatment of Seasonal Asthma (Allergic Asthma)

• Salbutamol (SABA) PRN inhaler

• Inhaled Corticosteroid (ICS) - Beclomethasone/Budesonide (low dose) daily
• • Salbutamol PRN

• ICS (medium dose) + LABA (Salmeterol/Formoterol)

• ICS (high dose) + LABA + Montelukast (Leukotriene receptor antagonist) ± Theophylline

• Sodium cromoglycate - mast cell stabilizer, inhaled before allergen exposure
• Antihistamines - loratadine, cetirizine (for allergic rhinitis component)
• Montelukast - oral LTRA, good for allergic asthma + rhinitis
• Desensitization (allergen immunotherapy) - for identified allergens

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14) Role of Beclomethasone in Asthma

• Inhibits PLA₂ → ↓ leukotrienes, prostaglandins
• ↓ Mucosal edema, mucus secretion
• ↓ Bronchial hyperresponsiveness
• ↑ β₂ receptor expression

• Available as MDI (pressurized inhaler)
• Prodrug - activated in lungs to beclomethasone-17-monopropionate (active form)
• Very high local:systemic ratio - minimal systemic effects

1. Maintenance/prophylaxis of persistent asthma (all grades)
2. Allergic rhinitis (intranasal beclomethasone)
3. NOT used for acute attacks

• Oropharyngeal candidiasis
• Dysphonia
• At very high doses: adrenal suppression

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15) Sodium Cromoglycate

• Inhibits degranulation of mast cells - prevents release of histamine, leukotrienes, prostaglandins
• Blocks Cl⁻ channels in mast cells → prevents Ca²⁺ influx → no degranulation
• Has no bronchodilator activity
• Acts only on mast cells in lung mucosa

1. Prophylaxis of bronchial asthma - must be used BEFORE allergen exposure
2. Exercise-induced bronchospasm (inhaled 15-20 min before exercise)
3. Allergic rhinitis (intranasal)
4. Allergic conjunctivitis (eye drops)
5. Food allergy (oral - not absorbed, acts locally in gut)

• NOT useful in acute attack
• Needs to be inhaled regularly for weeks to show benefit
• Very safe - can be used in children and pregnant women

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16) EW: Aminophylline is used in Status Asthmaticus

1. Inhibits phosphodiesterase (PDE) → prevents breakdown of cAMP → ↑ cAMP → bronchial smooth muscle relaxation
2. Adenosine receptor antagonist - adenosine causes bronchospasm; blocking it relieves spasm
3. Stimulates respiratory centre (useful in apnoea)
4. Anti-inflammatory properties

• When salbutamol + steroids FAIL to control bronchospasm
• IV aminophylline provides additional bronchodilation through a different mechanism (additive effect)
• Also has CNS stimulant effect → stimulates respiratory centre → helps hypercapnia

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SECTION B: HORMONES / OB-GYN / DIABETES

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1) EW: Oxytocin is used for Induction of Labour, NOT Methyl Ergometrine

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2) Oral Contraceptive Pills (OCP)

1. Combined OCP - Estrogen (Ethinyl estradiol) + Progestin (Levonorgestrel/Norethisterone)
2. Progestin-only pill (Mini-pill) - Norethisterone alone
3. Emergency contraception - High-dose Levonorgestrel (within 72 hrs)

1. Inhibit LH surge → no ovulation (main mechanism)
2. Thicken cervical mucus → sperm cannot penetrate
3. Make endometrium atrophic → unsuitable for implantation
4. Impair fallopian tube motility

1. Contraception (>99% effective)
2. Dysmenorrhea, Endometriosis
3. DUB (Dysfunctional Uterine Bleeding)
4. PCOD (polycystic ovarian disease)
5. Acne (anti-androgenic progestins)

• Nausea, breast tenderness, weight gain
• Thromboembolic events (DVT, PE) - estrogen ↑ clotting factors
• Hypertension
• Decreased libido
• Cholestasis
• Contraindicated: Pregnancy, DVT history, breast cancer, smokers >35 yrs

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3) Misoprostol

1. Cervical ripening and induction of labour (vaginal/sublingual)
2. Post-partum haemorrhage (PPH) - prevention + treatment (when oxytocin unavailable)
3. Medical abortion (with Mifepristone - "abortion pill" combo)
4. Prevention of NSAID-induced peptic ulcers (Cytotec) - inhibits gastric acid, protects mucosa
5. Incomplete/missed abortion

• Uterine hyperstimulation (fetal distress)
• Diarrhoea, cramping, fever
• Nausea, vomiting

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4) Vaginal PGE-2 before Inducing Labour

• Cervical ripening - causes softening, effacement, and dilatation of cervix
• Acts on cervical collagen → collagenase activation → cervix becomes "ripe"
• Without a ripe cervix, oxytocin infusion is ineffective and causes more discomfort

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5) Use of Ethylene Estradiol and Progestin in OCPs

• Inhibits FSH → no follicle development → no ovulation
• Maintains endometrial stability (prevents breakthrough bleeding)

• Inhibits LH surge → no ovulation
• Thickens cervical mucus (most consistent barrier)
• Makes endometrium atrophic

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6) Metformin in Type 2 DM

1. Inhibits hepatic gluconeogenesis (main action - reduces liver glucose output)
2. Increases peripheral insulin sensitivity (muscle glucose uptake ↑)
3. Reduces intestinal glucose absorption
4. Does NOT stimulate insulin secretion

• No hypoglycemia (does NOT cause hypo as monotherapy)
• Weight neutral or causes slight weight loss (ideal for obese T2DM)
• Reduces cardiovascular mortality (UKPDS trial)
• Cheap, oral, well-established

• GI (most common) - nausea, diarrhoea, metallic taste (give with food)
• Lactic acidosis (rare but serious - avoid in renal failure, liver failure, heart failure, contrast dye use)
• Vitamin B12 deficiency (long-term)

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7) Human Insulin

1. Type 1 DM (absolute requirement)
2. Type 2 DM (when oral agents fail)
3. Diabetic Ketoacidosis (DKA) - only regular insulin IV
4. Gestational diabetes
5. Surgery, critical illness (any diabetic)
6. Hyperkalaemia (glucose + insulin drip)

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8) Mifepristone

• Blocks progesterone receptors in uterus → decidua degenerates → embryo detaches
• Makes uterus sensitive to prostaglandins
• Softens and dilates cervix

1. Medical abortion (up to 63 days) - given with Misoprostol (PGE₁)
2. Emergency contraception (within 72 hrs) - single dose 600 mg
3. Cervical ripening before MTP
4. Cushing's syndrome (blocks glucocorticoid receptor - mifepristone is also antiglucocorticoid)
5. Uterine fibroids (experimental)

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9) Exenatide

• Mimics GLP-1 (Glucagon-like peptide-1) - an incretin hormone
• Stimulates glucose-dependent insulin secretion (only when blood glucose is high - low risk of hypoglycemia)
• Suppresses glucagon secretion
• Delays gastric emptying → slows glucose absorption
• Reduces appetite → weight loss

1. Type 2 DM (with metformin or other agents)
2. Obesity + T2DM (ideal - promotes weight loss)

• Nausea, vomiting (most common)
• Pancreatitis (rare, serious)
• Weight loss
• Injection site reactions

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10) Miglitol (Alpha-Glucosidase Inhibitor)

• Inhibits alpha-glucosidase enzyme in intestinal brush border
• Prevents breakdown of complex carbohydrates into glucose
• Delays and reduces glucose absorption from gut
• Reduces postprandial hyperglycemia (blood sugar spike after meals)

• Flatulence, bloating, diarrhoea (most common - due to unabsorbed carbs in colon being fermented)
• No hypoglycemia as monotherapy
• If hypoglycemia occurs (with other drugs) - treat with glucose (NOT sucrose) - sucrose won't be absorbed

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11) Tolbutamide

• Binds ATP-sensitive K⁺ channels (SUR1 subunit) on pancreatic β-cells → channel closes → membrane depolarization → Ca²⁺ influx → insulin release
• Requires functioning β-cells to work

• Shortest acting sulphonylurea (6-8 hours)
• Relatively safer in elderly and renal impairment (short-acting)
• Metabolized in liver to inactive metabolites

• Hypoglycemia (main risk)
• Weight gain
• Nausea
• Rarely - sulphonylurea hepatotoxicity, haematotoxicity

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12) EW: Carbimazole is used in Thyrotoxicosis

1. Inhibits thyroid peroxidase enzyme → prevents iodination of tyrosine (organification blocked)
2. Prevents coupling of iodotyrosines → no T3, T4 synthesis
3. Has immunosuppressive effect - reduces TSH receptor antibodies (important in Graves' disease)

• Oral drug, effective antithyroid therapy
• Can be used in all age groups
• In pregnancy - prefer Propylthiouracil (PTU) in 1st trimester (carbimazole associated with aplasia cutis)

• Agranulocytosis (rare, serious - watch for fever/sore throat → stop drug, CBC)
• Rash, fever
• Hypothyroidism (over-treatment)
• Hepatotoxicity (rare)

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13) EW: Progesterone is used in DUB (Dysfunctional Uterine Bleeding)

1. In anovulatory DUB, estrogen acts unopposed → endometrium keeps proliferating → irregular heavy shedding
2. Progesterone "opposes" estrogen → converts proliferative endometrium to secretory phase → organized shedding
3. Withdrawal bleeding on stopping progesterone = controlled, predictable
4. Reduces endometrial vascularity → less bleeding
5. Long-term use → endometrial atrophy → less bleeding

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14) Oxytocin / Oxytocin in PPH

• Causes sustained uterine contraction after delivery of baby + placenta
• Contraction compresses uterine blood vessels → haemostasis

1. Oxytocin 10 IU IM (prophylactic) - given immediately after delivery of baby (Active Management of 3rd Stage Labour - AMTSL)
2. For established PPH - Oxytocin 20-40 IU in 500 mL NS IV infusion
3. Second line: Methyl ergometrine IM (not in hypertension)
4. Third line: Carboprost (PGF2α) or Misoprostol rectal

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15) Antiestrogen

1. Tamoxifen - ER+ve breast cancer (treatment + prophylaxis)
2. Clomiphene - Anovulatory infertility (PCOD) - to induce ovulation
3. Raloxifene - Postmenopausal osteoporosis + breast cancer prevention
4. Anastrozole/Letrozole - Postmenopausal breast cancer

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16) EW: Glucocorticoids are used in Inflammation

1. Induce Lipocortin (Annexin A1) → inhibits Phospholipase A₂ → ↓ arachidonic acid → ↓ ALL prostaglandins, leukotrienes, thromboxanes
2. Inhibit COX-2 expression (gene transcription suppression)
3. Stabilize lysosomal membranes → prevent enzyme release from neutrophils
4. Inhibit NF-κB → reduces expression of ALL pro-inflammatory cytokines (IL-1, IL-2, TNF-α, IL-6)
5. Reduce capillary permeability → less edema
6. Inhibit migration of neutrophils and macrophages to site of inflammation

• Rheumatoid arthritis, SLE
• Asthma, COPD
• IBD (Crohn's, ulcerative colitis)
• Acute allergic reactions
• Organ transplant rejection

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17) Role of Thiazolidinediones (TZDs) in DM

• Bind and activate PPAR-γ (Peroxisome Proliferator-Activated Receptor gamma) in nucleus of adipocytes and muscle cells
• ↑ expression of genes for insulin-sensitive glucose transporters (GLUT4)
• Reduces insulin resistance in peripheral tissues
• Redistributes fat from visceral to subcutaneous (less metabolically harmful)

• Weight gain (increased adipogenesis)
• Fluid retention → edema, worsening heart failure
• Osteoporosis (fractures - long-term)
• Hepatotoxicity (Troglitazone withdrawn for this - less with pioglitazone)
• Bladder cancer risk (Pioglitazone - long-term use)
• Contraindicated in heart failure

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18) Hormones (Short Classification Note)

• Act on cell surface receptors (cannot enter cell - hydrophilic)

• Lipophilic → cross cell membrane → intracellular receptors → nuclear transcription

• Catecholamines (Epinephrine, Norepinephrine, Dopamine) - act on cell surface receptors
• Thyroid hormones (T3, T4) - act on intracellular receptors

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19) EW: Iodides are used in Hyperthyroidism

• High doses of iodide transiently inhibit organification (iodination of thyroglobulin)
• Reduces thyroid vascularity and gland size
• Reduces iodide trapping
• Decreases release of T3/T4 from thyroid gland

1. Pre-operative preparation before thyroid surgery - given for 7-10 days to reduce gland vascularity and size (reduces surgical bleeding)
2. Thyroid storm (thyrotoxic crisis) - rapid reduction of thyroid hormone release
3. Nuclear radiation emergencies - Potassium iodide (KI) tablets to block radioactive iodine uptake

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20) Insulin Resistance

• Decreased number or affinity of insulin receptors
• Post-receptor defect in signalling (IRS-1, PI3K pathway impaired)
• GLUT4 not translocated to cell surface

1. Metformin (first-line)
2. Thiazolidinediones (pioglitazone)
3. Weight loss, exercise

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SECTION C: ANTIMICROBIALS, TB, LEPROSY, MALARIA, HIV

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1) DOTS (Directly Observed Treatment, Short-course)

1. Political/administrative commitment
2. Bacteriological diagnosis (sputum smear microscopy)
3. Short-course chemotherapy under direct observation
4. Regular drug supply
5. Recording and reporting system

• Ensures adherence (prevents missed doses)
• Prevents drug resistance development
• Ensures treatment completion
• Cost-effective

• Category I (new cases): 2HRZE + 4HR (2 months intensive + 4 months continuation)
• Drugs: H=Isoniazid, R=Rifampicin, Z=Pyrazinamide, E=Ethambutol

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2) Dapsone

• Inhibits dihydropteroate synthetase (same as sulfonamides)
• Blocks folic acid synthesis in organisms
• Also has anti-inflammatory properties (important in leprosy reactions)

1. Drug of choice for Leprosy (Hansen's disease) - in combination (MDT)
2. Lepromatous leprosy: Dapsone + Rifampicin + Clofazimine
3. Paucibacillary leprosy: Dapsone + Rifampicin
4. Pneumocystis jirovecii pneumonia (PCP) - in AIDS (alternative to co-trimoxazole)
5. Dermatitis herpetiformis

• Haemolytic anaemia (especially in G6PD deficiency)
• Methaemoglobinaemia
• Peripheral neuropathy
• Agranulocytosis
• Dapsone syndrome (hypersensitivity - fever, rash, jaundice)

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3) Cyclosporine

• Binds Cyclophilin (intracellular protein)
• Complex inhibits Calcineurin (phosphatase enzyme)
• Calcineurin normally activates NF-AT (Nuclear Factor of Activated T cells)
• NF-AT activates IL-2 gene transcription
• Result: ↓ IL-2 production → ↓ T-cell proliferation → immunosuppression

1. Organ transplant rejection (kidney, liver, heart) - cornerstone of immunosuppression
2. Autoimmune diseases - RA, SLE, psoriasis, IBD
3. Nephrotic syndrome (steroid-resistant)
4. Aplastic anaemia

• Nephrotoxicity (most serious, dose-dependent) - monitor creatinine
• Hypertension
• Neurotoxicity (tremor, seizures)
• Hepatotoxicity
• Gingival hyperplasia (like phenytoin)
• Hirsutism
• Hyperkalemia, hypomagnesemia

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4) Fluoroquinolones

• Inhibit DNA gyrase (Topoisomerase II) and Topoisomerase IV
• Prevents DNA supercoiling relaxation → DNA replication and transcription blocked → bactericidal

1. UTI, pyelonephritis (ciprofloxacin)
2. Respiratory infections (levofloxacin, moxifloxacin)
3. Corneal ulcer (topical ciprofloxacin/moxifloxacin eye drops)
4. Typhoid fever (ciprofloxacin)
5. Drug-resistant TB (moxifloxacin)
6. Anthrax prophylaxis

• GI disturbances
• Tendinitis/Tendon rupture (Achilles tendon - avoid in elderly, athletes)
• Cartilage damage - avoid in children, pregnancy (arthropathy in animal studies)
• CNS effects (dizziness, seizures)
• QT prolongation (moxifloxacin)
• Photosensitivity

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5) EW: Pyridoxine (Vitamin B6) is given with INH

• INH is a structural analogue of pyridoxine (Vitamin B6)
• Competitively inhibits pyridoxal kinase → reduces conversion of pyridoxine to active pyridoxal phosphate
• Pyridoxal phosphate is essential for GABA synthesis and myelin maintenance
• Deficiency → peripheral neuropathy (tingling, numbness, burning feet)

• Supplementing Vitamin B6 (10-25 mg/day) overcomes this competitive inhibition
• Prevents development of peripheral neuritis

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6) 3rd Generation Cephalosporins

• ↑ Gram-negative coverage (including Pseudomonas - ceftazidime)
• Cross BBB → use in meningitis (ceftriaxone/cefotaxime)
• Resistant to most beta-lactamases

1. Bacterial meningitis (ceftriaxone - drug of choice in community-acquired meningitis)
2. Severe hospital-acquired infections
3. Septicemia
4. Gonorrhea (ceftriaxone 500 mg IM - single dose)
5. Typhoid (ceftriaxone)
6. Neonatal infections

• Allergy (less than penicillin, 10% cross-reactivity)
• Pseudomembranous colitis (C. difficile)
• Hypoprothrombinemia + bleeding (cefoperazone - has MTT side chain)
• Superinfection

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7) Chloroquine and Primaquine in Benign Tertian Malaria

• Chloroquine alone eliminates blood stage → fever resolves → but hypnozoites remain → RELAPSE
• Primaquine is added to eliminate hypnozoites → radical cure (prevents relapse)

• Chloroquine: 600 mg loading → 300 mg at 6, 24, 48 hrs
• Primaquine: 15 mg/day × 14 days (check G6PD before - causes haemolysis in G6PD deficiency)

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8) Chloroquine in Autoimmune Disorders

1. Raises lysosomal pH → inhibits antigen processing in macrophages → reduces T-cell activation
2. Inhibits phospholipase A₂ → anti-inflammatory
3. Inhibits production of IL-1, TNF-α
4. Blocks Toll-like receptor signalling → less autoimmune stimulation
5. Mild immunosuppression

1. Rheumatoid arthritis (RA) - DMARDs (Disease-modifying antirheumatic drug)
2. Systemic Lupus Erythematosus (SLE) - Hydroxychloroquine is standard of care
3. Discoid lupus
4. Sjögren's syndrome

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9) Beta-Lactamase Inhibitors

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10) Fluoroquinolones in Corneal Ulcer

• Ciprofloxacin 0.3% eye drops or Moxifloxacin 0.5% eye drops
• Excellent penetration into cornea
• Broad spectrum - covers Pseudomonas (important in corneal infection), Staphylococci, Streptococci
• Bactericidal
• Ciprofloxacin - DOC for bacterial keratitis/corneal ulcer

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11) Azithromycin

• Very long half-life (~68 hours)
• Tissue concentration >> serum concentration (accumulates in phagocytes)
• Single daily dosing, 3-5 day course is sufficient
• Z-pack = 5-day course (500 mg day 1, 250 mg days 2-5)

1. Community-acquired pneumonia (atypical - Mycoplasma, Legionella, Chlamydia)
2. STIs - Chlamydia urethritis (single dose 1g), Gonorrhea (combo)
3. Pharyngitis/tonsillitis (penicillin allergy)
4. Typhoid fever (alternative)
5. Pertussis (whooping cough)
6. MAC (Mycobacterium avium complex) in AIDS

• GI disturbance (less than erythromycin)
• QT prolongation (cardiac arrhythmias)
• Hepatotoxicity (rare)

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12) EW: INH causes Peripheral Neuritis

• INH structurally similar to pyridoxine (B6)
• Inhibits pyridoxal kinase → ↓ pyridoxal phosphate
• Pyridoxal phosphate needed for GABA synthesis + myelin maintenance
• Result: peripheral neuropathy - tingling, numbness, burning sensation in hands/feet
• Prevention: Pyridoxine 10-25 mg/day with every INH-containing regimen

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13) Idoxuridine

• Analogue of thymidine
• Incorporated into viral DNA in place of thymidine
• Results in non-functional viral DNA → virus cannot replicate

1. Herpes simplex keratitis (corneal HSV infection) - topical eye drops/ointment
2. Herpes labialis (topical)

• Too toxic for systemic use (bone marrow suppression)
• Largely replaced by Acyclovir (safer)
• Still used topically for HSV keratitis

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14) Artemesinin (Artesunate)

• Contains an endoperoxide bridge
• Haemoglobin is digested by malaria parasite → releases haeme (ferrous iron)
• Fe²⁺ activates artemisinin → free radicals formed → alkylation of parasite proteins → parasite death

1. Uncomplicated P. falciparum malaria (chloroquine-resistant)
2. Severe/complicated falciparum malaria - IV Artesunate (DOC - replaces quinine)
3. Used in combination - Artemisinin-based Combination Therapy (ACT): Artemether + Lumefantrine (Coartem)

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15) Superinfection (Tetracycline-induced)

• Tetracycline is broad-spectrum - kills both Gram+ and Gram- organisms + many anaerobes
• This eliminates normal commensal flora (gut, oral, vaginal) that normally suppress opportunistic organisms
• Opportunistic organisms resistant to tetracycline overgrow

1. Oral/GI/Vaginal Candidiasis (fungal overgrowth by Candida albicans) - most common
2. Pseudomembranous colitis (Clostridium difficile overgrowth in gut)
3. Staphylococcal enterocolitis

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16) EW: Combination of Trimethoprim and Sulfamethoxazole is used in infections (Co-trimoxazole)

1. PABA → (Dihydropteroate synthetase) → Dihydrofolate
2. Dihydrofolate → (Dihydrofolate reductase) → Tetrahydrofolate (active form needed for DNA synthesis)

• Sulfamethoxazole (sulfonamide) → inhibits Step 1 (Dihydropteroate synthetase)
• Trimethoprim → inhibits Step 2 (Dihydrofolate reductase)
• SEQUENTIAL BLOCKADE → synergistic effect → total blockade of folic acid pathway
• 5x more effective combined than either alone (synergism)

• Reduces resistance development
• Bactericidal combination (each drug alone is bacteriostatic)
• Broader spectrum

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17) BCG Vaccine

1. Primary prevention of TB - especially miliary TB and TB meningitis in children (most effective)
2. Protection against leprosy (60-80% in some studies)
3. Bladder cancer (intravesical BCG - immunotherapy)
4. Given at birth in India (Universal Immunization Programme)

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18) Metronidazole

• Reduced by ferredoxin-linked electron transport (present in anaerobes and protozoa) → active nitro radical intermediate
• Causes DNA strand breakage → cell death
• Requires anaerobic/microaerophilic conditions for activation → SELECTIVE for anaerobes and protozoa

1. Amoebiasis (E. histolytica) - DOC for invasive amoebiasis (intestinal + hepatic)
2. Giardiasis (Giardia lamblia) - DOC
3. Trichomoniasis (T. vaginalis) - DOC (treat both partners)
4. Anaerobic infections - intra-abdominal, gynaecological, dental
5. Pseudomembranous colitis (C. difficile) - oral
6. Bacterial vaginosis (Gardnerella)
7. H. pylori eradication (triple therapy)

• Metallic taste (very common, characteristic)
• Nausea, vomiting, diarrhoea
• Disulfiram-like reaction with alcohol (avoid alcohol during treatment)
• Peripheral neuropathy (long-term)
• CNS effects (dizziness, seizures - high dose)

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19) Griseofulvin

• Binds beta-tubulin of fungal spindle → disrupts mitotic spindle → inhibits fungal cell division
• Fungistatic (not fungicidal)
• Accumulates in keratin (skin, hair, nails) - deposited in new keratin as it grows

• ONLY for dermatophytic infections (tinea/ringworm):
  1. Tinea capitis (scalp ringworm) - still preferred in children
  2. Tinea corporis, tinea pedis, tinea unguium (onychomycosis)
• NOT effective against Candida or systemic fungi

• Headache (most common)
• GI disturbance
• Photosensitivity
• Hepatotoxicity
• Teratogenic - contraindicated in pregnancy
• Enzyme inducer (reduces OCP efficacy)

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27) Aztreonam (Monobactam)

• Active ONLY against Gram-negative organisms (aerobic)
• NO activity against Gram-positive or anaerobes
• Does NOT cross-react with penicillin allergy (safe in penicillin-allergic patients)

1. Serious Gram-negative infections (E. coli, Klebsiella, Pseudomonas, Enterobacter)
2. UTI, septicemia, pneumonia caused by Gram-negative organisms
3. Penicillin/cephalosporin-allergic patients with Gram-negative infections

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28) EW: Combination Therapy is used in TB

1. Prevents resistance: Spontaneous mutants resistant to one drug exist in large TB bacterial populations. Combination means mutants resistant to Drug A are killed by Drug B and vice versa - probability of resistance to both simultaneously is extremely low
2. Kills different populations:
   • Rapidly dividing bacteria (cavities) - Rifampicin, INH
   • Slowly dividing/intracellular bacteria (macrophages) - Pyrazinamide, INH
   • Dormant/persisters - Rifampicin, Pyrazinamide
3. Bactericidal synergism - combination more effective than any single drug
4. Shorter treatment duration - 6 months combination vs years with monotherapy
5. Reduces bacterial load faster → less transmission

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29) Chemotherapy of TB

• Intensive Phase: 2 months - HRZE (4 drugs)
• Continuation Phase: 4 months - HR (2 drugs)
• Total = 6 months

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30) Clofazimine

• Binds mycobacterial DNA → inhibits mycobacterial growth
• Anti-inflammatory - inhibits neutrophil motility
• Generates reactive oxygen species in mycobacteria

1. Lepromatous (multibacillary) leprosy - in MDT (Multi-Drug Therapy) with Dapsone + Rifampicin
2. Lepra reactions (Type II - Erythema Nodosum Leprosum) - anti-inflammatory effect controls reaction
3. Drug-resistant TB (second-line)

• Skin discoloration (brownish-black/orange pigmentation) - most characteristic S/E; reversible but takes months
• GI disturbances
• Ichthyosis (dry, scaly skin)

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31) Didanosine (ddI) in HIV

• Prodrug → activated to ddA-TP (2',3'-dideoxyadenosine triphosphate)
• Competitive inhibitor + chain terminator of HIV reverse transcriptase
• Lacks 3'-OH → once incorporated into growing viral DNA chain → chain termination → no viral DNA synthesis

• Pancreatitis (most serious, potentially fatal - monitor amylase)
• Peripheral neuropathy
• Diarrhoea
• Hepatotoxicity

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32) Monobactam Antibiotics

• Active ONLY against aerobic Gram-negative bacteria
• No activity against Gram-positive or anaerobes
• Safe in penicillin allergy (no cross-reactivity)
• Given IV/IM

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33) Reverse Transcriptase Inhibitors in AIDS

• Act as "false nucleosides" → incorporated into HIV DNA → chain termination
• Examples: Zidovudine (AZT), Lamivudine (3TC), Tenofovir, Emtricitabine, Didanosine, Stavudine

• Bind allosteric site of reverse transcriptase (not the active site) → conformational change → enzyme inactivation
• Examples: Nevirapine, Efavirenz, Rilpivirine

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34) Lepra Reaction

• Immune system mounts response against dead M. leprae antigens after treatment
• Type 1: enhanced CMI
• Type 2: antigen-antibody complex deposition

• Continue anti-leprosy MDT drugs
• Type 1: Prednisolone
• Type 2: Thalidomide (DOC - not in women of child-bearing age: teratogenic), Clofazimine, Steroids

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LONG QUESTIONS

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LONG Q1) Drugs used in treatment of Malaria; Action, Uses and Side Effects of Chloroquine

• 4-aminoquinolines: Chloroquine, Amodiaquine
• Quinine, Quinidine
• Artemisinins: Artesunate, Artemether
• Sulphadoxine-pyrimethamine (SP)
• Atovaquone-proguanil (Malarone)
• Mefloquine

• Primaquine, Proguanil, Pyrimethamine

• Primaquine (only drug that kills gametocytes)

• Primaquine, Proguanil

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• Accumulates in acidic food vacuole of Plasmodium parasite
• Parasite digests haemoglobin → releases haeme (toxic)
• Normally haeme is detoxified by polymerization to haemozoin (malaria pigment)
• Chloroquine inhibits haeme polymerization → free haeme accumulates → toxic to parasite membrane → parasite death

1. Drug of choice for P. vivax and P. ovale malaria (blood stage)
2. Chloroquine-sensitive P. falciparum
3. Extraintestinal amoebiasis (hepatic amoebiasis)
4. Rheumatoid arthritis (DMARD)
5. SLE - Hydroxychloroquine
6. Pre-existing P. falciparum resistance common in many areas - use ACT

• Mild (therapeutic doses): Nausea, vomiting, headache, pruritus (common in dark-skinned individuals)
• Retinopathy (most serious - with long-term use; irreversible; annual eye examination needed)
• Skin pigmentation
• Haemolysis in G6PD deficiency
• Acute toxicity (overdose): Sudden cardiovascular collapse, QRS widening, VF, hypotension (very dangerous - IV diazepam + epinephrine used)
• Corneal deposits (reversible)

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LONG Q2) Drugs used in treatment of Leprosy; Treatment of Lepra Reaction

• Paucibacillary (PB): 1-5 skin lesions, smear negative
• Multibacillary (MB): >5 lesions, smear positive (lepromatous, borderline)

• Rifampicin 600 mg once monthly (supervised)
• Dapsone 100 mg daily (self-administered)

• Rifampicin 600 mg once monthly (supervised)
• Clofazimine 300 mg once monthly + 50 mg daily (self-administered)
• Dapsone 100 mg daily (self-administered)

• Prevents resistance, kills all subpopulations of M. leprae

• Dapsone: Inhibits dihydropteroate synthetase → ↓ folate synthesis
• Rifampicin: Inhibits RNA polymerase → bactericidal (most potent antileprosy drug)
• Clofazimine: Binds DNA + anti-inflammatory properties

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• Do NOT stop MDT during a reaction
• Type 1: Prednisolone 40-60 mg/day tapering
• Type 2 (ENL): Thalidomide (DOC, 100-300 mg/day) - but teratogenic; or Clofazimine (anti-inflammatory dose 100 mg/day); or Prednisolone for acute severe cases

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LONG Q3) Drugs used in treatment of AIDS; Describe HAART

1. HIV gp120 binds CD4 + CCR5 receptor → fusion → entry
2. Viral RNA released → Reverse transcriptase → viral DNA
3. Integrase → inserts viral DNA into host genome (provirus)
4. Host cell makes viral proteins → HIV protease cleaves → mature virions

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• Reduce viral load to undetectable (<50 copies/mL)
• Restore CD4 count (>500 cells/µL)
• Prevent AIDS-defining opportunistic infections
• Prevent transmission (U=U: Undetectable = Untransmittable)
• Extend and improve quality of life

• TDF + 3TC/FTC + DTG (Tenofovir + Lamivudine/Emtricitabine + Dolutegravir)
• India NACO: TLE = Tenofovir + Lamivudine + Efavirenz

• Single or 2 drugs → virus develops resistance quickly
• 3 drugs → probability of triple-resistance mutation simultaneously is astronomically low

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LONG Q4) Classify Cephalosporins; Uses and Side Effects

1. 1st gen: Surgical prophylaxis, skin/soft tissue infections, UTI
2. 2nd gen: RTI, sinusitis, otitis media
3. 3rd gen: Meningitis (ceftriaxone DOC), Gonorrhea, Typhoid, Neonatal sepsis, Severe hospital infections
4. 4th gen: Febrile neutropenia, multi-drug resistant Gram-negative infections
5. 5th gen: MRSA infections

1. Hypersensitivity (most common): Rash, urticaria, anaphylaxis (10% cross-reactivity with penicillin - use with caution in penicillin allergy)
2. Pseudomembranous colitis (C. difficile - disruption of gut flora)
3. Nephrotoxicity (mild, enhanced with aminoglycosides)
4. Hypoprothrombinemia + Bleeding (cephalosporins with MTT side chain - cefoperazone, cefamandole) - due to interference with Vitamin K
5. Superinfection - Candida, Enterococcus
6. Pain at injection site (IM)
7. Disulfiram-like reaction with alcohol (MTT group cephalosporins)

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LONG Q5) Drugs used in treatment of TB

• Fluoroquinolones: Moxifloxacin, Levofloxacin
• Injectable aminoglycosides: Amikacin, Kanamycin, Capreomycin
• New drugs: Bedaquiline (ATP synthase inhibitor), Delamanid, Pretomanid
• Cycloserine, Ethionamide, PAS (Para-amino salicylic acid)

• TB in pregnancy: Avoid Streptomycin (ototoxicity to fetus), Pyrazinamide (limited data); rest of HRZE are used
• TB in HIV: Start ART 2-8 weeks after starting TB treatment; Rifampicin is an enzyme inducer (reduces ARV levels - use Rifabutin instead)
• Drug-Resistant TB: MDR-TB (resistant to H+R), XDR-TB (MDR + fluoroquinolone + injectable resistant)

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LONG Q6) Treatment of Amoebiasis; Therapeutic Uses, S/Es and Toxicity

1. Intestinal amoebiasis - colitis, dysentery
2. Extraintestinal amoebiasis - hepatic abscess (most common), lung, brain

• Diloxanide furoate alone (luminal amoebicide)

• Metronidazole 400-800 mg 3x daily × 5-10 days
• Followed by Diloxanide furoate × 10 days (to eliminate luminal cysts)

• Metronidazole 400-800 mg 3x daily × 10-14 days
• • Diloxanide furoate × 10 days
• Aspiration if: Large abscess, no response to drugs, left lobe abscess (risk of rupture into pericardium)

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• Metallic taste
• Nausea, vomiting, GI disturbance
• Disulfiram-like reaction with alcohol (acetaldehyde accumulation → flushing, vomiting)
• Peripheral neuropathy (long-term)
• CNS: Dizziness, ataxia, convulsions (high dose/toxicity)
• Urine may turn dark brown (metabolites)
• Teratogenic (avoid in 1st trimester)

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• DOC for TB: INH + Rifampicin + Pyrazinamide + Ethambutol (HRZE × 2 months, then HR × 4 months)
• DOC for leprosy (MB): Rifampicin + Dapsone + Clofazimine
• DOC for malaria (vivax): Chloroquine + Primaquine
• DOC for amoebiasis: Metronidazole
• Aztreonam: Only Gram-negative, safe in penicillin allergy
• HAART: 2 NRTIs + 1 NNRTI/PI/INSTI
• Superinfection: Broad-spectrum antibiotics (tetracycline, ampicillin) → Candida/C. difficile overgrowth
• Co-trimoxazole synergism: Sequential blockade of folic acid synthesis
• Artemisinin: Fastest acting antimalarial, endoperoxide bridge → free radicals kill parasite
• Chloroquine in RA/SLE: Lysosomal pH ↑ → reduced antigen processing