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These are pharmacology exam notes (Paper 1). Here is the full extracted content:
Paper - 1
Q.1 (10 Marks)
ANS (Autonomic Nervous System)
- Beta-Blocker
- Classification of Anticholinergics & describe Atropine
CNS (Central Nervous System)
- Anti-epileptic - classification & Phenytoin
- Anti-psychotic - write about Chlorpromazine ADR (M. Imp)
G.P. (General Pharmacology)
- Factors affecting drug absorption
Q.2.a - Case Questions
- Parkinson's - Levodopa-Carbidopa Combination
- Myasthenia Gravis
- O.P. (Organophosphate) Poisoning
- Depression
Q.2.b - Short Notes
G.P.
- Bioavailability / Half-life
- Adrenaline
- Classification of alpha-Blockers
- Benzodiazepam / Morphine
- Curare
- Spinal Anaesthesia
- SSRI - Selective Serotonin Reuptake Inhibitor
These notes cover key pharmacology exam topics: autonomic drugs (beta-blockers, atropine, adrenaline, alpha-blockers), CNS drugs (antiepileptics, antipsychotics, antidepressants), general pharmacology concepts (absorption, bioavailability, half-life), and specific drug classes (opioids, benzodiazepines, neuromuscular blockers). Would you like detailed notes or explanations on any of these topics?
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Here is a complete explanation of every topic in your Paper 1:
PAPER 1 - Full Pharmacology Explanation
Q.1 (10 Marks) - Long Answer Questions
A. AUTONOMIC NERVOUS SYSTEM (ANS)
1. Beta-Blockers (β-Blockers)
Definition: Drugs that competitively block β-adrenergic receptors, opposing the actions of catecholamines (adrenaline, noradrenaline).
Classification
| Generation | Drugs | Selectivity |
|---|---|---|
| Non-selective (β1 + β2) | Propranolol, Sotalol, Timolol | β1 & β2 |
| Cardioselective (β1) | Atenolol, Metoprolol, Bisoprolol | Mainly β1 |
| With ISA (Intrinsic Sympathomimetic Activity) | Pindolol, Acebutolol | Partial agonist |
| With α-blocking | Carvedilol, Labetalol | α + β blockade |
Mechanism of Action
- Block β1 receptors in heart → decreased heart rate (negative chronotropy), decreased force of contraction (negative inotropy), decreased AV conduction
- Block β2 receptors → bronchoconstriction, vasoconstriction (in non-cardioselective)
Pharmacological Actions
- Heart: Reduces HR, contractility, cardiac output, O2 demand
- BP: Lowers blood pressure (exact mechanism not fully clear - reduced CO + renin release)
- Eye: Reduces intraocular pressure (timolol eye drops in glaucoma)
- Metabolic: Blocks glycogenolysis (mask hypoglycemia symptoms)
Therapeutic Uses
- Hypertension
- Angina pectoris
- Heart failure (carvedilol, metoprolol)
- Arrhythmias (supraventricular tachycardia, AF)
- Post-MI (cardioprotection)
- Hyperthyroidism (propranolol - controls symptoms)
- Anxiety, tremor (propranolol)
- Migraine prophylaxis
- Glaucoma (timolol eye drops)
- Pheochromocytoma (with alpha-blocker first!)
Adverse Effects
- Bradycardia, heart block
- Bronchoconstriction (contraindicated in asthma)
- Fatigue, cold extremities
- Masks hypoglycemia in diabetics
- Impotence
- Rebound hypertension on sudden withdrawal
Contraindications
- Bronchial asthma
- Heart block (2nd/3rd degree)
- Cardiogenic shock
- Uncontrolled heart failure
2. Classification of Anticholinergics & Atropine
Classification of Anticholinergic (Antimuscarinic) Drugs
A. Naturally occurring alkaloids:
- Atropine, Scopolamine (Hyoscine), Hyoscyamine
B. Semi-synthetic:
- Ipratropium bromide (inhaled - asthma/COPD)
- Tiotropium (long-acting, COPD)
C. Synthetic:
- Glycopyrrolate (pre-anesthetic)
- Tropicamide (mydriasis)
- Pirenzepine (peptic ulcer, M1 selective)
- Oxybutynin, Tolterodine (urinary incontinence)
ATROPINE - Detailed Description
Source: Atropa belladonna (Deadly Nightshade plant)
Chemistry: Tertiary amine ester - crosses blood-brain barrier
Mechanism: Competitive antagonist at muscarinic receptors (M1, M2, M3) - blocks acetylcholine
Pharmacological Actions (Dose-dependent):
| System | Effect |
|---|---|
| Heart | Tachycardia (blocks M2 - removes vagal tone) |
| Eye | Mydriasis (pupil dilation), cycloplegia (loss of accommodation), raised IOP |
| GIT | Reduces motility, reduces secretions (dry mouth) |
| Respiratory | Bronchodilation, reduces secretions |
| Bladder | Urinary retention (relaxes detrusor, contracts sphincter) |
| Sweat glands | Anhidrosis (dry, hot skin) - Note: sweat glands are muscarinic but sympathetic |
| CNS | Low dose: stimulation; High dose: delirium, hallucinations |
Mnemonic for Atropine toxicity: "Hot as a hare, Dry as a bone, Red as a beet, Blind as a bat, Mad as a hatter"
Therapeutic Uses:
- Pre-anesthetic medication (reduces secretions)
- Organophosphate poisoning (antidote - given with pralidoxime)
- Bradycardia and heart block
- Eye examination (mydriasis, cycloplegia)
- Irritable bowel syndrome, peptic ulcer (antispasmodic)
- Motion sickness (scopolamine preferred)
- Reversal of overdose with anticholinesterases
Adverse Effects: Dry mouth, blurred vision, urinary retention, tachycardia, constipation, hyperthermia
Contraindications: Glaucoma (narrow-angle), prostatic hypertrophy, myasthenia gravis
B. CNS (Central Nervous System)
1. Antiepileptics - Classification & Phenytoin
Classification of Antiepileptic Drugs (AEDs)
Based on Seizure Type:
| Drug | Type of Seizure |
|---|---|
| Phenytoin | Tonic-clonic, Partial |
| Carbamazepine | Tonic-clonic, Partial |
| Valproate | All types (broad-spectrum) |
| Ethosuximide | Absence seizures ONLY |
| Phenobarbitone | Tonic-clonic |
| Clonazepam | Absence, Myoclonic |
| Lamotrigine | Broad spectrum |
| Levetiracetam | Broad spectrum |
| Gabapentin | Partial seizures |
Based on Mechanism:
| Mechanism | Drugs |
|---|---|
| Na+ channel blockers | Phenytoin, Carbamazepine, Valproate, Lamotrigine |
| Ca2+ channel blockers | Ethosuximide, Valproate (T-type) |
| GABA enhancers | Benzodiazepines, Phenobarbitone, Valproate |
| Glutamate blockers | Lamotrigine, Topiramate |
PHENYTOIN (Diphenylhydantoin)
Mechanism: Blocks voltage-gated Na+ channels in the inactive state → stabilizes neuronal membrane → prevents repetitive firing. Does NOT cause CNS depression.
Pharmacokinetics:
- Zero-order (saturation) kinetics - small dose increase causes large plasma level rise
- Highly protein-bound (90%)
- Enzyme inducer (induces CYP450)
- Half-life: 22 hours (variable)
Therapeutic Uses:
- Tonic-clonic (Grand mal) seizures - Drug of Choice historically
- Partial (focal) seizures
- Status epilepticus (IV phenytoin/fosphenytoin)
- Trigeminal neuralgia
- Cardiac arrhythmias (digoxin-induced arrhythmias)
Adverse Effects:
| System | Effects |
|---|---|
| CNS | Nystagmus (earliest sign of toxicity), ataxia, diplopia, dysarthria |
| Gum | Gingival hyperplasia (characteristic) |
| Hair | Hirsutism (increased hair growth) |
| Blood | Megaloblastic anemia (folate antagonism) |
| Bone | Osteomalacia (↓ Vit D) |
| Skin | Steven-Johnson syndrome |
| Fetus | Fetal hydantoin syndrome (teratogenic) |
| Cardiovascular | Hypotension, arrhythmia (IV route) |
Drug Interactions: Enzyme inducer - reduces efficacy of OCP, warfarin, corticosteroids
2. Antipsychotics - Chlorpromazine (M. Imp)
Classification of Antipsychotics
Typical (First Generation / Conventional):
- Phenothiazines: Chlorpromazine, Thioridazine, Trifluoperazine, Fluphenazine
- Butyrophenones: Haloperidol, Droperidol
- Thioxanthenes: Flupenthixol
Atypical (Second Generation):
- Clozapine, Olanzapine, Risperidone, Quetiapine, Aripiprazole, Ziprasidone
CHLORPROMAZINE
Prototype: First antipsychotic discovered (1952); prototype phenothiazine
Mechanism of Action:
- Primary: Blocks D2 (dopamine) receptors in mesolimbic pathway → antipsychotic effect
- Also blocks: M1 (muscarinic), H1 (histamine), α1 (adrenergic), 5-HT receptors
- This multi-receptor blockade explains both effects AND side effects
Pharmacological Actions:
- Sedation (H1 blockade)
- Antipsychotic (D2 blockade)
- Antiemetic (D2 block in CTZ)
- Lowers body temperature (poikilothermia)
- Alpha-blockade → hypotension
- Antimuscarinic → dry mouth, constipation
Therapeutic Uses:
- Schizophrenia (positive symptoms: hallucinations, delusions)
- Mania
- Severe vomiting, hiccups
- Pre-anesthetic medication
- Tetanus (muscle relaxation)
- Potentiates analgesics and anesthetics
ADRs (Adverse Drug Reactions) - VERY IMPORTANT:
| Category | ADR |
|---|---|
| Extrapyramidal Effects (EPS) | Due to D2 blockade in nigrostriatal pathway |
| Acute dystonia | Involuntary muscle contractions (within hours) - Rx: Benztropine |
| Akathisia | Restlessness, inability to sit still |
| Drug-induced Parkinsonism | Tremor, rigidity, bradykinesia (weeks) |
| Tardive Dyskinesia | Repetitive involuntary movements of face/tongue - LATE, IRREVERSIBLE |
| Neuroleptic Malignant Syndrome (NMS) | Hyperthermia, rigidity, autonomic instability, FATAL - Rx: Dantrolene + Bromocriptine |
| Hyperprolactinemia | D2 block in tuberoinfundibular pathway → galactorrhea, amenorrhea, gynecomastia |
| Anticholinergic | Dry mouth, urinary retention, blurred vision, constipation |
| Cardiovascular | Orthostatic hypotension, prolonged QT interval |
| Metabolic | Weight gain, glucose intolerance |
| Sedation | H1 blockade |
| Photosensitivity | Skin |
| Agranulocytosis | (Clozapine >> Chlorpromazine) |
| Jaundice | Cholestatic |
C. GENERAL PHARMACOLOGY (G.P.)
1. Factors Affecting Drug Absorption
Absorption = movement of drug from site of administration into systemic circulation
Factors:
A. Physicochemical Properties of Drug:
- Lipid solubility: More lipid-soluble = better absorption (crosses membranes easily)
- Ionization (pKa): Unionized form is absorbed better. Weak acids absorbed in stomach (acidic pH); Weak bases absorbed in intestine (alkaline pH) - Henderson-Hasselbalch equation
- Molecular weight: Small molecules absorbed better
- Solubility: Must dissolve in GI fluid first (dissolution rate)
- Formulation: Tablet > Capsule > Liquid (dissolution rate)
B. Physiological/Patient Factors:
- GI pH: Alters ionization (antacids raise pH - affect acidic drug absorption)
- GI motility: Faster motility → less absorption time (diarrhea reduces absorption)
- Blood flow: Reduced splanchnic flow → reduced absorption (heart failure, shock)
- Surface area: Small intestine has largest surface area (villi, microvilli)
- Gastric emptying: Delayed emptying → slower absorption (meals, opioids, anticholinergics delay it)
- First-pass metabolism: High first-pass = low oral bioavailability (morphine, nitroglycerine, propranolol)
- Food: Can increase, decrease, or delay absorption depending on drug
C. Pharmaceutical Factors:
- Particle size: Smaller = better absorption (micronized drugs)
- Polymorphism: Different crystal forms have different solubilities
- Enteric coating/Modified release: Controls site and rate of dissolution
- Excipients: Can affect absorption
D. Route of Administration:
- IV = 100% bioavailability (no absorption step)
- Sublingual: Avoids first-pass (nitroglycerine)
- Transdermal: Sustained delivery (fentanyl patch)
Q.2.a - Case-Based Questions
1. PARKINSON'S DISEASE - Levodopa-Carbidopa Combination
Pathophysiology: Degeneration of dopaminergic neurons in substantia nigra → dopamine deficiency in striatum → imbalance between dopamine (inhibitory) and acetylcholine (excitatory) → clinical features
Clinical Features (TRAP):
- Tremor (pill-rolling, at rest)
- Rigidity (lead pipe, cogwheel)
- Akinesia / Bradykinesia
- Postural instability
WHY Levodopa + Carbidopa?
Levodopa alone - Problem:
- Levodopa is a precursor to dopamine
- When given orally, 95-99% is converted to dopamine in the periphery by DOPA decarboxylase
- Peripheral dopamine causes nausea, vomiting, hypotension, cardiac arrhythmias
- Only 1-2% crosses blood-brain barrier (BBB) - wastes drug, requires huge doses
Solution - Add Carbidopa:
- Carbidopa is a peripheral DOPA decarboxylase inhibitor
- It does NOT cross the BBB
- Therefore: Levodopa is NOT converted peripherally → more reaches brain → converted to dopamine in nigrostriatum
- Result: Can use 75% less levodopa, fewer peripheral side effects
- Trade name: Sinemet (Levodopa + Carbidopa)
Benefits of Combination:
- Reduced dose of levodopa needed
- Decreased nausea and vomiting
- Decreased cardiovascular side effects
- Faster onset, more consistent plasma levels
- More dopamine available in the brain
Complications of Long-term Levodopa Therapy:
- "Wearing off" effect (end-of-dose deterioration)
- "On-Off" phenomenon (unpredictable fluctuations)
- Dyskinesias (abnormal involuntary movements)
- Hallucinations, psychosis
2. MYASTHENIA GRAVIS
Pathophysiology: Autoimmune - antibodies against nicotinic acetylcholine receptors (nAChR) at neuromuscular junction → failure of neuromuscular transmission
Clinical Features: Fatigable muscle weakness, ptosis, diplopia, dysphagia; worsens with activity, improves with rest
Diagnosis:
- Edrophonium (Tensilon) test - short-acting AChE inhibitor; dramatic improvement confirms diagnosis
- Anti-AChR antibody test
- Repetitive nerve stimulation - decremental response
Treatment:
| Drug | Mechanism | Role |
|---|---|---|
| Neostigmine, Pyridostigmine | Anticholinesterase (AChE inhibitors) - prolongs ACh in NMJ | Symptomatic treatment |
| Corticosteroids | Immunosuppression | Reduce antibody production |
| Azathioprine, Mycophenolate | Immunosuppressants | Long-term maintenance |
| Plasma exchange / IVIG | Remove circulating antibodies | Crisis management |
| Thymectomy | Remove thymus (source of autoimmunity) | Disease modification |
Cholinergic Crisis vs. Myasthenic Crisis: Both cause weakness - differentiated by edrophonium test (improves in myasthenic crisis, worsens in cholinergic crisis)
3. ORGANOPHOSPHATE (OP) POISONING
Mechanism: Irreversible inhibition of acetylcholinesterase (AChE) → accumulation of ACh at all synapses
Examples: Malathion, Parathion, Sarin (nerve gas)
Clinical Features - SLUDGE + DUMBELS:
| Muscarinic Effects | Nicotinic Effects | CNS Effects |
|---|---|---|
| Salivation | Muscle fasciculations | Anxiety, restlessness |
| Lacrimation | Muscle weakness | Seizures |
| Urination | Paralysis | Coma |
| Defecation | Tachycardia | |
| GI cramps | Hypertension | |
| Emesis (vomiting) | ||
| Bradycardia, Bronchospasm, Miosis |
Treatment:
- Atropine (large doses, 2-4 mg IV every 5-10 min until secretions dry) - blocks muscarinic effects; does NOT reverse muscle paralysis
- Pralidoxime (2-PAM) - reactivates AChE if given early (before "aging") - reverses both muscarinic AND nicotinic effects
- Diazepam - for seizures
- Supportive: Maintain airway, oxygen, suction secretions
Key Point: Atropine is the mainstay; Pralidoxime must be given early (before the inhibitor-AChE complex becomes irreversible/"aged")
4. DEPRESSION
Pathophysiology (Monoamine Theory): Deficiency of serotonin (5-HT), noradrenaline, and/or dopamine in brain synapses
Classification of Antidepressants:
| Class | Drugs | Mechanism |
|---|---|---|
| SSRIs (First-line) | Fluoxetine, Sertraline, Paroxetine, Escitalopram | Block serotonin reuptake |
| SNRIs | Venlafaxine, Duloxetine | Block 5-HT + NA reuptake |
| TCAs (Tricyclics) | Imipramine, Amitriptyline, Clomipramine | Block 5-HT + NA reuptake + anticholinergic |
| MAOIs | Phenelzine, Tranylcypromine | Inhibit MAO → ↑ all monoamines |
| Atypicals | Mirtazapine, Bupropion, Trazodone | Various mechanisms |
Q.2.b - Short Notes
1. Bioavailability & Half-Life
Bioavailability (F):
- The fraction of administered drug that reaches systemic circulation unchanged
- IV bioavailability = 100% (reference standard)
- Oral bioavailability reduced by: first-pass metabolism, poor absorption, gut wall metabolism
- Measured as: F = AUC(oral) / AUC(IV)
Factors reducing oral bioavailability:
- High first-pass metabolism (morphine, propranolol, nitroglycerine)
- Poor GI absorption
- Drug degradation in GI tract
Half-Life (t½):
- Time for plasma drug concentration to fall by 50%
- t½ = 0.693 × Vd / Cl (Vd = volume of distribution, Cl = clearance)
- Clinical significance:
- Determines dosing frequency
- 4-5 half-lives to reach steady state
- 4-5 half-lives to eliminate drug after stopping
- Short t½ = frequent dosing (e.g., penicillin, 4-6 hrs)
- Long t½ = once-daily dosing (e.g., amlodipine ~35 hrs, amiodarone weeks)
2. Adrenaline (Epinephrine)
Source: Secreted by adrenal medulla (80%); also noradrenaline (20%)
Receptors: Acts on α1, α2, β1, β2, β3 receptors
Pharmacological Actions:
| System | Effect | Receptor |
|---|---|---|
| Heart | ↑ HR, ↑ force, ↑ CO | β1 |
| Blood vessels | Vasoconstriction (skin, viscera) | α1 |
| Vasodilation (muscle, coronary) | β2 | |
| Blood pressure | Systolic ↑, Diastolic ↓ (low dose), both ↑ (high dose) | |
| Bronchi | Bronchodilation | β2 |
| Metabolic | Hyperglycemia (glycogenolysis), lipolysis | β2, β3 |
| Eye | Mydriasis | α1 |
| Uterus | Relaxation (low dose) | β2 |
Therapeutic Uses:
- Anaphylactic shock (Drug of Choice - IM 0.5 mg)
- Cardiac arrest (IV)
- With local anesthetics (vasoconstrictory - prolongs action, reduces systemic toxicity)
- Bronchial asthma (acute - nebulized)
- Open-angle glaucoma (reduces IOP)
- Hemostasis in local surgeries
3. Classification of Alpha (α) Blockers
A. Non-selective (α1 + α2):
- Phentolamine (reversible; used in pheochromocytoma crisis)
- Phenoxybenzamine (irreversible, long-acting; used in pheochromocytoma pre-op)
B. Selective α1 Blockers:
- Prazosin (short-acting; hypertension, BPH)
- Terazosin, Doxazosin (longer-acting; hypertension, BPH)
- Tamsulosin, Alfuzosin (uro-selective α1A; BPH - minimal BP effect)
C. Selective α2 Blockers:
- Yohimbine (experimental; ED)
Uses of Alpha-Blockers:
- Hypertension (prazosin, doxazosin)
- Benign prostatic hyperplasia (tamsulosin, alfuzosin, prazosin)
- Pheochromocytoma (phenoxybenzamine + phentolamine)
- Raynaud's disease (phentolamine)
Side Effects: Postural hypotension, "first-dose effect" (syncope), reflex tachycardia, nasal stuffiness
4. Benzodiazepines & Morphine
Benzodiazepines
Mechanism: Enhance effect of GABA at GABA-A receptor → increased frequency of Cl⁻ channel opening → hyperpolarization → CNS depression
Classification by Duration:
| Duration | Drug | Half-life |
|---|---|---|
| Long-acting | Diazepam, Chlordiazepoxide, Flurazepam | >24 hrs |
| Intermediate | Lorazepam, Alprazolam, Oxazepam | 10-20 hrs |
| Short-acting | Midazolam, Triazolam | <6 hrs |
Uses: Anxiety, insomnia, status epilepticus (lorazepam/diazepam IV), muscle spasm, alcohol withdrawal, pre-anesthetic, panic disorder
ADRs: Sedation, anterograde amnesia, tolerance, dependence, respiratory depression (overdose)
Antidote: Flumazenil (competitive antagonist at GABA-A benzodiazepine site)
Morphine (Opioid Analgesic - Prototype)
Source: Papaver somniferum (Opium poppy)
Mechanism: Agonist at μ (mu), κ (kappa), δ (delta) opioid receptors → decreases pain perception; increases pain tolerance
Actions:
- Analgesia (best for severe/visceral pain)
- Euphoria / Sedation
- Respiratory depression (dose-dependent - most dangerous)
- Constipation (↓ GI motility) - does NOT develop tolerance
- Nausea/vomiting (stimulates CTZ)
- Miosis (pinpoint pupils - characteristic)
- Suppresses cough
- Urinary retention
- Histamine release → itching, bronchospasm
Uses:
- Severe pain (post-op, cancer, MI)
- Acute pulmonary edema (reduces preload + anxiety)
- Preanesthetic medication
- Antidiarrheal (codeine)
Morphine Overdose Triad: Coma + Pinpoint pupils + Respiratory depression
Antidote: Naloxone (opioid antagonist)
Tolerance & Dependence: Develops to analgesia, euphoria, respiratory depression; NOT to constipation and miosis
5. Curare (d-Tubocurarine)
Type: Non-depolarizing (competitive) neuromuscular blocking agent
Source: South American plant Chondrodendron tomentosum (used in poison arrows by indigenous tribes)
Mechanism: Competitive antagonist at nicotinic receptors (NMJ) → prevents ACh from binding → muscle relaxation
Features:
- Flaccid paralysis (proximal → distal, then respiratory last)
- No CNS effect (quaternary nitrogen - doesn't cross BBB)
- Causes histamine release → bronchospasm, hypotension
- Reversed by: Neostigmine (anticholinesterase) + Atropine (to block muscarinic effects of neostigmine)
Uses in Anesthesia:
- Muscle relaxation during surgery
- Facilitate endotracheal intubation
- Control convulsions (tetanus - rarely now)
Modern alternatives: Vecuronium, Rocuronium, Atracurium (fewer histamine effects)
Depolarizing blocker for comparison: Succinylcholine (causes fasciculations then paralysis, reversed by pseudocholinesterase, Phase II block with repeated doses)
6. Spinal Anaesthesia
Definition: Injection of local anesthetic into subarachnoid space (intrathecal) → blocks nerve roots in spinal cord
Drugs used: Bupivacaine (most common), Lignocaine, Ropivacaine
Level: Usually given at L3-L4 or L4-L5 (below spinal cord termination at L1-L2)
Mechanism: Local anesthetics block voltage-gated Na+ channels → prevents nerve conduction
Order of Nerve Block (most sensitive first):
- Autonomic fibers (B fibers) - first blocked
- Pain and temperature (C, Aδ fibers)
- Touch and pressure
- Motor fibers (last blocked)
Advantages:
- Awake patient, airway maintained
- Excellent muscle relaxation
- Reduced blood loss
- Reduced DVT risk
- Suitable for high-risk elderly patients
Uses: Lower abdominal, pelvic, perineal, lower limb surgeries; cesarean section
Complications:
| Complication | Cause/Management |
|---|---|
| Hypotension | Sympathetic block → vasodilation; Rx: IV fluids, vasopressors |
| Post-dural puncture headache | CSF leak; Rx: blood patch |
| High/Total spinal | LA spreads too high → respiratory paralysis; Rx: ventilate |
| Urinary retention | Bladder relaxation |
| Nausea/Vomiting | Hypotension |
| Backache | Local trauma |
7. SSRI - Selective Serotonin Reuptake Inhibitors
Mechanism: Selectively inhibit the serotonin transporter (SERT) → prevents reuptake of 5-HT from synapse → increased synaptic 5-HT levels
Drugs: Fluoxetine (Prozac), Sertraline, Paroxetine, Citalopram, Escitalopram, Fluvoxamine
Why "Selective"?: Unlike TCAs, they have minimal effect on noradrenaline, dopamine, histamine, or muscarinic receptors - hence fewer side effects
Onset: 2-4 weeks for full antidepressant effect (despite immediate SERT blockade - requires neuroplastic changes)
Therapeutic Uses:
- Depression (first-line)
- Anxiety disorders (GAD, panic disorder, social anxiety)
- OCD (fluoxetine, fluvoxamine - often higher doses needed)
- PTSD
- Bulimia nervosa (fluoxetine)
- Premenstrual dysphoric disorder
- Premature ejaculation (paroxetine)
Adverse Effects:
- Nausea, diarrhea (most common, GI - initial)
- Sexual dysfunction (decreased libido, anorgasmia) - very common, persists
- Insomnia or somnolence
- Headache
- Serotonin Syndrome (if combined with MAOIs, triptans, tramadol): agitation, hyperthermia, tremor, autonomic instability - LIFE-THREATENING
- Increased suicidal ideation in <25 year olds (black box warning)
- SIADH (hyponatremia - especially in elderly)
- Withdrawal syndrome on abrupt cessation ("discontinuation syndrome")
Drug Interactions:
- AVOID with MAOIs (serotonin syndrome - washout period needed)
- Fluoxetine is a potent CYP450 inhibitor - many drug interactions
- Paroxetine also inhibits CYP2D6
Quick Summary Table
| Topic | Key Drug | Key Point |
|---|---|---|
| Beta-blocker | Propranolol/Atenolol | Cardioselective vs non-selective |
| Anticholinergic | Atropine | "Hot, Dry, Red, Blind, Mad" - toxicity |
| Antiepileptic | Phenytoin | Gingival hyperplasia, zero-order kinetics |
| Antipsychotic | Chlorpromazine | D2 block → EPS, TD, NMS |
| Drug Absorption | Multiple factors | Lipid solubility, ionization, first-pass |
| Parkinson's | Levodopa+Carbidopa | Carbidopa prevents peripheral conversion |
| Myasthenia Gravis | Neostigmine | Anti-AChR antibodies, AChE inhibitor Rx |
| OP Poisoning | Atropine+Pralidoxime | SLUDGE symptoms, early 2-PAM |
| Depression | SSRIs | 5-HT reuptake inhibition, 2-4 wk onset |
| Bioavailability | - | AUC ratio, first-pass effect |
| Adrenaline | Epinephrine | Anaphylaxis DOC, mixed α+β |
| Alpha-blockers | Prazosin/Tamsulosin | Hypertension, BPH |
| Benzodiazepines | Diazepam | GABA-A enhancer, flumazenil antidote |
| Morphine | Opioid | Pinpoint pupils + resp depression; naloxone |
| Curare | d-Tubocurarine | Competitive NMJ block, neostigmine reversal |
| Spinal Anesthesia | Bupivacaine | Subarachnoid space, L3-L4 |
| SSRI | Fluoxetine | Serotonin syndrome with MAOIs |
This covers every topic in your Paper 1 in full exam-ready detail. If you want any specific topic explained in even more depth - mechanisms, diagrams, tables, or memory tricks - just ask!
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