Human Pathophysiology & Pharmacology 1

0 · Exam Blueprintread first

Two assessments drive the marks: the A2 concept map (40%) and the End-of-Trimester Exam (40%) (the in-class quiz, ~20%, covers Modules 1–2 only). The EOTE = 50 MCQ (half the marks) + 12 short-answer (half) and examines Modules 3–7: immunity → cancer → MSK/pain → genetics & ageing → neuro/autonomic + the pharmacology woven through.

Train both reflexes: MCQ recall = the tables & trap-facts here; SAQ = explain a mechanism in prose — walk a pathophysiological cascade or a drug's mechanism of action in 3–5 linked steps.

0b · The A2 Cascade Templateconcept-map spine

The A2 concept map (and every "explain the pathophysiology" SAQ) follows ONE colour-coded chain. Learn the shape and slot any disease in:

RF → Aetiology → Pathophysiology → ManifestationsRisk factor → aetiology/trigger → pathophysiology (step-by-step) → clinical manifestations → +1 diagnostic test +1 management

Worked (cervical cancer, the A2 case): RF = smoking, immunosuppression, multiple partners → aetiology = persistent high-risk HPV infection → pathophys = viral oncoproteins inactivate p53/Rb tumour suppressors → dysplasia (CIN) → carcinoma in situ → invasive squamous-cell carcinoma → local + lymphatic spread → manifestations = abnormal/post-coital bleeding, discharge, pelvic pain. Dx = Pap/HPV test + biopsy; Mx = surgery/radiotherapy ± chemo. (HIV co-infection accelerates it via CD4 loss.) Reuse this exact skeleton for stroke, MS, arthritis or any disease the exam throws at you.

0c · Assessment Shapewhere the marks are

The MCQ half rewards breadth (recognise the trap); the SAQ half rewards depth (explain a cascade or a mechanism of action in prose). Weight prep on immunology → cancer → MSK/pain → genetics/ageing → neuro/autonomic. (Modules 1–2 are A1 scaffolding, not on the EOTE.)

0d · Foundations (scaffold)Mod 1–2 underpin

Cell adaptation: hypertrophy = bigger cells; hyperplasia = more cells; metaplasia = reversible cell-type switch; dysplasia = disordered, pre-malignant. Necrosis = swelling + lysis + inflammation, not ATP-needing; apoptosis = shrinkage + apoptotic bodies, no inflammation, ATP-dependent.

Healing: resolution / regeneration (same tissue, needs mitosis) / repair-fibrosis (scar, loses function). 1st intention (edges approximated) vs 2nd (open gap, bigger scar). Healing needs age, nutrition (protein, vit C, zinc), oxygenation; corticosteroids impair it.

1 · Immunity · Innate vs Adaptive3.1 ⭐

Innate — non-specific, immediate, no memory. 1st line = barriers (skin, mucosa, cilia, stomach acid, lysozyme, flora); 2nd line = inflammation, fever, phagocytes, NK cells, complement, interferons.

Adaptive — specific, slower, has memory; recognises antigens. Two arms:

• Humoral = B cells → plasma cells → antibodies; hits extracellular pathogens/toxins.
• Cell-mediated = T cells; hits intracellular (viruses), cancer, transplants.

Inflammation & fever are INNATE (2nd line) — a classic MCQ trap.

1b · Immune Cellswho does what

T cells mature in the thymus; B cells in bone marrow.

1c · Primary vs Secondary Responsebasis of vaccines

Primary — 1st exposure; 1–2 week lag, mainly IgM, low titre. Secondary — re-exposure; faster, stronger, higher titre (mainly IgG) via memory cells. Vaccination exploits this.

1d · Complement & Mediatorsinnate effectors

Complement = plasma protein cascade: opsonisation (tag for phagocytosis), chemotaxis (C5a), anaphylatoxins (C3a/C5a → mast-cell degranulation), and the membrane attack complex (MAC) that lyses pathogens.

Interferons = antiviral; cytokines (TNF, IL-1, IL-6) drive fever & acute-phase response. Markers: CRP, ESR, WBC (neutrophils ↑ acute, lymphocytes ↑ viral/chronic).

1e · How Humoral Immunity WorksSAQ cascade

Antigen enters → APC (macrophage/dendritic) presents it → activates helper T (CD4) → cytokines stimulate the matching B cell → clonal expansion → plasma cells secrete antibody + memory B cells form. Antibodies then neutralise, opsonise and activate complement. This is the chain a "describe the immune response" SAQ wants.

Antibody functions: neutralisation, opsonisation (tag for phagocytes), complement activation (→ MAC), agglutination, and ADCC (flag cells for NK killing).

1f · Cell-Mediated Immunitythe T-cell arm

Intracellular antigen (virus, tumour) on the cell surface → cytotoxic T (CD8) → perforin/granzymes → apoptosis of the infected/abnormal cell. Helper T amplify; regulatory T enforce tolerance. This arm drives Type IV hypersensitivity and transplant rejection.

2 · The 5 Antibody Classes3.1 ⭐ MCQ gold

Y-shaped: 2 heavy + 2 light chains; variable region (Fab) binds antigen, constant region (Fc) = class/effector.

Mnemonic: M first, G placenta, A area-secretions, E allergy.

3 · Types of Immunity3.3 ⭐

Active = you make it (slow, lasting, memory); passive = given (immediate, temporary, no memory). "Natural/artificial" = how acquired; "active/passive" = who makes the antibody. Passive's lack of memory is a common MCQ.

3b · Vaccination3.3.3

= artificial active immunity: a harmless form of the antigen (live-attenuated, inactivated, toxoid, subunit, mRNA) primes a primary response + memory cells, so the real exposure triggers a fast, strong secondary response. Boosters top up waning memory. Herd immunity protects the unvaccinated by cutting transmission.

Newborns get natural passive cover from maternal IgG (placenta) and IgA (breast milk) until their own active immunity matures — immediate but no memory, so it fades. Antivenom and post-exposure rabies immunoglobulin are the artificial passive equivalents.

3c · Immune Drugs3.2.3 / 3.3

• Immunosuppressants — transplant/autoimmune. Calcineurin inhibitors (cyclosporine) block IL-2 → ↓T-cell proliferation; AEs: nephro/hepatotoxicity, infection.
• Monoclonal antibodies ("-mab") — single clone, highly specific; e.g. anti-TNF infliximab, trastuzumab. Target cytokines or cancer antigens.
• Corticosteroids — broad immunosuppression for all 4 hypersensitivity types, anaphylaxis, autoimmune disease.

Corticosteroids preferentially suppress cell-mediated immunity (humoral less affected) and shrink lymphoid tissue. Prolonged use → infection risk, hyperglycaemia, osteoporosis, poor healing — never stop abruptly (adrenal suppression). They act higher than NSAIDs (block phospholipase A2 → stop prostaglandins AND leukotrienes), giving broader anti-inflammatory cover.

3d · Antibody Quick-RecallMCQ drill

• Crosses placenta = IgG; first/largest = IgM.
• Secretions/breast milk = IgA; allergy = IgE.
• Antigen binds the variable (Fab) region.

4 · Hypersensitivity I–IV3.2 ⭐ classic trap

Excessive immune response that damages tissue (needs prior sensitisation). Mnemonic "ACID".

I–III antibody-mediated; IV is T-cell, delayed, NO antibody. II = Ab vs fixed cell; III = circulating complexes.

4b · Anaphylaxis3.2.2 · SAQ

Severe systemic Type I. Mast cells dump histamine into the circulation → systemic vasodilation → severe hypotension; airway oedema + bronchoconstriction → respiratory failure.

Mechanism→sign: hypotension = vasodilation; wheeze/SOB = bronchoconstriction + oedema; hives = histamine on skin. 1st-line = adrenaline (NOT antihistamine): β2 bronchodilates, α1 vasoconstricts/raises BP.

4c · Telling II from IIIboth IgG

Both use IgG, but: Type II = antibody binds an antigen fixed on a cell surface → that cell is destroyed (ABO transfusion reaction, haemolytic disease of the newborn, Goodpasture's). Type III = antibody binds a soluble antigen → circulating immune complexes deposit in vessels/joints/kidney → complement-driven inflammation (SLE, post-strep glomerulonephritis, serum sickness).

Management across types: avoid the allergen; antihistamines + corticosteroids dampen I–III; adrenaline for anaphylaxis; immunosuppressants for severe autoimmune Type II/III; Type IV (contact dermatitis) → topical steroids. Diagnosis often uses skin-prick (I) or patch testing (IV); raised total/specific IgE supports Type I.

4d · Worked SAQ · Allergyexplain it

Q. Why does a second bee sting cause anaphylaxis but the first did not?

A (cascade): 1st sting sensitises — venom drives IgE production that coats mast cells. On re-exposure, venom cross-links that IgE → mast-cell degranulation → massive histamine release → systemic vasodilation (hypotension) + bronchoconstriction + oedema = Type I anaphylaxis. Give adrenaline first.

Key word: the first exposure causes no symptoms because it only builds the IgE — symptoms need pre-formed IgE on mast cells. The same "sensitisation then re-exposure" logic underlies all four types.

4e · Hypersensitivity RecallACID drill

• I IgE/histamine, immediate; II IgG vs fixed cell + complement.
• III IgG complexes deposit; IV T cells, no Ab, delayed (only IV).

5 · Immunodeficiency & HIV3.3 ⭐

Primary = intrinsic/genetic defect (Bruton's = B cell; DiGeorge = T cell; SCID = both). Secondary (acquired) = consequence of another factor: corticosteroids/stress, malnutrition, drugs (chemo), infection (HIV, TB), cancer (leukaemia, Hodgkin's).

HIV/AIDS — HIV infects & destroys helper T (CD4+) cells; slow decline → broad immune failure (CD4 controls BOTH arms). AIDS = CD4 < 200/mm³ → opportunistic infection (candidiasis, Pneumocystis) + cancers. Mx: antiretrovirals + prophylaxis. Transmission: sexual, blood/needles, mother→child (pregnancy/birth/breastfeeding).

6 · Autoimmunity3.2.3 ⭐

Loss of self-tolerance → auto-antibodies / self-reactive T cells attack self-antigens (normally deleted in the thymus). Cannot be cured — managed with NSAIDs, corticosteroids, anti-TNF, immunosuppressants.

6b · Inflammation Recapunderpins it all

5 cardinal signs = redness, heat, swelling, pain, loss of function (vasodilation + ↑permeability + mediators). Histamine (mast cells) = early; prostaglandins = pain/fever (NSAID target). Acute = neutrophils; chronic (>2 wk) = macrophages + lymphocytes + fibrosis.

Exudate types: serous (watery — burns/blisters); fibrinous (sticky, → adhesions); purulent (pus → bacterial infection); haemorrhagic (RBCs → worst vessel damage).

6c · Microbiology ScaffoldMod 2 · infection

Bacteria = prokaryotes (no nucleus/organelles — what antibiotics exploit = selective toxicity). Classify by shape (cocci/bacilli), arrangement (clusters=staph, chains=strep), Gram stain, O₂ need.

Chain of infection: agent → reservoir → exit → transmission → entry → susceptible host (break any link). Viruses = obligate intracellular; not killed by antibacterials.

Antibiotic targets (4): cell-wall synthesis (penicillins → lysis), protein synthesis (aminoglycosides, macrolides), DNA/replication (quinolones), folate synthesis (sulfonamides). Resistance via mutation/gene transfer → stewardship. Selective toxicity = hit bacterial structures absent from human cells. Endotoxin (LPS) at high dose → septic shock; exotoxins (tetanus, botulism, diphtheria) are among the most potent toxins known. Remember: exotoxin = protein/gram-pos/heat-labile; endotoxin = LPS/gram-neg/heat-stable.

7 · Neoplasia & CancerModule 4 ⭐

Neoplasia = new, uncontrolled, autonomous growth. Benign vs malignant:

Carcinogenesis = multistep initiation → promotion → progression; needs multiple mutations passed to daughter cells.

7b · Oncogenes & Spreadgain vs loss

• Proto-oncogene → mutation = gain of function → oncogene = accelerator stuck ON.
• Tumour suppressor (p53 "guardian", BRCA1/2) → loss of function = brakes failed.

Cell cycle G1→S→G2→M; cancer = checkpoint failure (esp. G1/S). Metastasis routes: local invasion, lymphatic, haematogenous (blood), transcoelomic seeding.

Grading vs Staging: grading = how abnormal cells look; staging = how far it spread (TNM = Tumour, Node, Metastasis). AU risks: tobacco, UV, alcohol, HPV, BRCA, age.

8 · MSK & PainModule 5 ⭐

Osteoporosis — ↓bone density (resorption > formation; post-menopausal ↓oestrogen) → fragility fractures. Fracture healing: haematoma → soft callus → hard (bony) callus → remodelling. Compartment syndrome = ↑pressure in a closed fascial space → ischaemia (the 6 Ps) — emergency.

Pain cascade (SAQ): tissue injury → mediators (prostaglandins, bradykinin) sensitise nociceptors → signal via Aδ/C fibres → dorsal horn → spinothalamic tract → thalamus → cortex (perception). Nociceptive vs neuropathic vs referred.

8b · Arthritis & BPH5.2 / 4.4

OA = "wear-and-tear" cartilage loss, mechanical, asymmetrical, large weight-bearing joints. RA = autoimmune (Type III, synovium), symmetrical small joints, systemic, morning stiffness, RF/anti-CCP.

BPH = benign hyperplasia of the peri-urethral prostate (age/DHT) → obstruction (hesitancy, frequency, nocturia, weak stream). Mx: α1-blockers ("-osin", relax smooth muscle) + 5α-reductase inhibitors. Prostate cancer = peripheral zone, PSA marker, androgen-dependent.

8c · Cell-Cycle Recapwhere cancer breaks

G1 → S (DNA synthesis) → G2 → M (mitosis) → cytokinesis. Checkpoints (esp. G1/S restriction point) police DNA integrity; p53 halts or apoptoses damaged cells. Cancer = oncogene accelerator stuck ON plus suppressor brakes OFF → checkpoints bypassed → autonomous proliferation.

Cancer treatment (4.2.3): surgery (remove), radiotherapy (DNA damage, local), chemotherapy (cytotoxic, hits rapidly dividing cells → AEs: myelosuppression, hair loss, GI/mucositis, nausea), and targeted/hormonal therapy. Diagnosis: biopsy + histology, imaging, tumour markers (PSA, CA-125). The cytotoxic AEs come from hitting normal fast-dividing cells (marrow, gut, hair).

9 · Genetics & InheritanceModule 6 ⭐

46 chromosomes = 23 pairs (22 autosomes + 1 sex pair); gametes haploid (23). Patterns:

• Autosomal dominant — one mutant allele suffices; 50% risk (Huntington's).
• Autosomal recessive — needs two mutant alleles; carriers (Aa) unaffected (cystic fibrosis).
• X-linked recessive — males affected more (one X); females carriers (haemophilia).

Aneuploidy: trisomy (Down = trisomy 21) or monosomy (Turner = 45,X). Point mutation = single base change → loss or gain of function (match to tumour-suppressor vs oncogene).

9b · Congenital & Teratogens6.2

Multifactorial = genes + environment (neural tube defects, diabetes). Teratogens disrupt development — TORCH infections, alcohol (FAS), drugs, radiation, low folate (→ neural tube defect). Critical period = organogenesis (weeks 3–8).

10 · Ageing & Pharmacokinetics6.3.2 ⭐

Age changes map onto ADME:

Net: ↑levels, ↑half-life, ↑toxicity + polypharmacy → "start low, go slow."

10b · Worked · Punnettrecessive cross

Two carriers of cystic fibrosis (Aa × Aa):

Genotype 1 AA : 2 Aa : 1 aa; phenotype 3 unaffected : 1 affected. So 25% affected (aa), 50% unaffected carriers (Aa). Carriers are healthy but pass the allele on — the key autosomal-recessive MCQ.

10c · Routes & First-Passwhy route matters

Sublingual, rectal, IV, transdermal, inhaled all bypass first-pass hepatic metabolism (no portal vein) → useful for high first-pass drugs (e.g. GTN sublingual). Oral is convenient but loses bioavailability to first pass + incomplete absorption. IV = fastest onset, 100% F, but no recall once given.

10d · Genetics MCQ Trapsquick recall

• Down syndrome = trisomy 21 (extra chromosome).
• X-linked recessive (haemophilia) affects males more.
• Autosomal recessive needs two alleles; carriers unaffected.
• Oncogene = gain of function; tumour suppressor = loss of function.
• Teratogen critical period = organogenesis, weeks 3–8.

11 · Neuro PathophysiologyModule 7 ⭐

Consciousness = arousal (RAS/brainstem) + awareness (cortex); graded by GCS (eye/verbal/motor, 3–15).

Raised ICP — Monro-Kellie: the skull is a fixed volume of brain + blood + CSF; ↑one must ↓another or ICP rises. Compensation (displace CSF/venous blood) is exhausted suddenly → steep ICP rise → ↓perfusion (CPP = MAP − ICP). Cushing's triad (↑BP/wide pulse pressure, bradycardia, irregular breathing) = late herniation sign.

11b · Stroke, TBI, Neurodegeneration7.2–7.3

• Stroke: ischaemic (thrombus/embolus, most) vs haemorrhagic (bleed); thrombolysis only for ischaemic; FAST.
• TBI bleeds: extradural (arterial, lucid interval), subdural (venous), subarachnoid.
• Alzheimer's: amyloid plaques + tau tangles, ↓ACh → AChE-inhibitor Rx.
• Parkinson's: loss of dopaminergic neurons (substantia nigra) → tremor, rigidity, bradykinesia; levodopa.
• MS = autoimmune CNS demyelination; MND = motor-neuron loss, sensory spared.

12 · The ANS7.4.1 ⭐

Controls involuntary muscle/glands; two antagonistic branches via a 2-neuron chain (pre → ganglion → post).

• SNS "fight/flight", thoracolumbar (T1–L2).
• PNS "rest/digest", craniosacral (CN III, VII, IX, X; S2–S4).

ALL preganglionic + ALL PNS postganglionic = ACh on nicotinic/muscarinic; MOST SNS postganglionic = noradrenaline on α/β. Exceptions: sweat glands = cholinergic; adrenal medulla = nicotinic, dumps adrenaline.

12b · SNS vs PNS Effectsopposite actions

12c · Seizures & SCI7.2

Seizure = abnormal synchronous neuronal discharge; focal (one area) vs generalised (both hemispheres, LOC). Spinal cord injury: complete vs incomplete; spinal/neurogenic shock (loss of sympathetic tone → hypotension + bradycardia); autonomic dysreflexia above the lesion.

12d · Raised-ICP SAQexplain the spiral

Cascade: mass/bleed/oedema adds volume → CSF + venous blood displaced (compensated, ICP stays normal) → compensation exhausted → ICP rises steeply → CPP = MAP − ICP falls → brain ischaemia → more oedema (vicious cycle) → herniation. Late sign = Cushing's triad (↑BP, bradycardia, irregular breathing). Manage by lowering ICP and supporting MAP.

13 · Adrenergic Pharmacology7.4.2 ⭐ MCQ gold

NA acts on G-protein adrenoceptors, cleared by uptake-1 then MAO/COMT.

"β1 = 1 heart, β2 = 2 lungs." SABA (salbutamol) = reliever; LABA (salmeterol) = preventer. β2-agonist AEs: tremor, tachycardia, hypokalaemia. Use cardioselective (β1) blockers in asthmatics.

14 · Cholinergic Pharmacology7.4.3 ⭐

ACh → receptor → broken by acetylcholinesterase (AChE). Muscarinic (M1 gastric, M2 heart ↓rate, M3 smooth muscle/glands); nicotinic (ganglia + skeletal NMJ).

• Muscarinic agonist (bethanechol, pilocarpine) = more PNS: bradycardia, secretions, miosis ("SLUDGE").
• Antimuscarinic (atropine, ipratropium, oxybutynin) = less PNS: "can't see/pee/spit/poo" + tachycardia.
• AChE inhibitors (neostigmine; donepezil) ↑ACh → myasthenia gravis & Alzheimer's.
• Suxamethonium = depolarising NM blocker (fasciculations, irreversible); atracurium = non-depolarising (reversible by neostigmine).

14b · Drug → Receptor Logicmatch it

Examiners give a drug, ask the receptor (or vice versa). The reflex:

14c · Worked SAQ · Adrenalinemulti-receptor

Adrenaline in anaphylaxis hits several receptors at once: α1 → vasoconstriction → ↑BP (reverses hypotension); β1 → ↑cardiac output; β2 → bronchodilation + ↓mast-cell mediator release. One drug, three life-saving actions — the classic "explain why adrenaline" SAQ.

Contrast: a β-blocker would worsen anaphylaxis and bronchospasm — never give one here. Likewise non-selective β-blockers can trigger bronchospasm in asthmatics → use cardioselective β1 agents. β-blockers are also contraindicated in heart block and cardiogenic shock.

14d · Autonomic RecallMCQ drill

• SNS post = NA (α/β); PNS post = ACh (muscarinic); all pre = ACh/nicotinic.
• Atropine blocks muscarinic ("can't see/pee/spit/poo").
• AChE inhibitors ↑ ACh (myasthenia, Alzheimer's).

15 · Pharmacokinetics · ADME⭐ "body → drug"

Absorption · Distribution · Metabolism · Excretion.

Absorption & bioavailability

Enteral (oral, SL, rectal) vs parenteral (IV, IM, SC). IV = 100% bioavailability, fastest, no first-pass. Bioavailability (F) = fraction reaching circulation unchanged. Absorption depends on lipid solubility, ionisation/pH, GI motility, surface area, blood flow and food.

Distribution

Drugs bind albumin; only free (unbound) drug is active. ↓albumin / displacement → ↑free drug → interaction. Vd high = lipophilic/tissue; low = stays in plasma.

Metabolism & excretion

Liver (Phase I CYP450; Phase II conjugation) → water-soluble. First-pass: oral drug via portal vein → liver before circulation → ↓oral F. Kidney excretes; renal impairment → accumulation.

15b · Kinetic Parametersdosing

Half-life (t½) = time for conc. to fall 50%; ~4–5 t½ to clear OR reach steady state (rate in = rate out). Loading dose = reach level fast; maintenance dose = replace what's eliminated. CYP inducers ↓ levels, inhibitors ↑ levels/toxicity.

15c · Worked · Half-Lifeshow the steps

A drug with t½ = 8 h, started at 80 mg/L, no more dosing:

⇒ ~5 half-lives (40 h) to essentially clear; the same ~5 t½ on regular dosing reaches steady state. A loading dose skips this wait by filling the volume of distribution up front.

15d · ADRs & Interactions7.5.4 QUM

Type A ADR = dose-related, predictable (opioid respiratory depression); Type B = idiosyncratic/hypersensitivity, unpredictable (penicillin anaphylaxis). Interactions: PK (protein-binding displacement, CYP450 induction/inhibition, altered excretion) or PD (additive/synergistic/antagonistic). Elderly + polypharmacy = high risk. QUM = right drug/patient/dose/route/time + monitor.

Worked interaction: a CYP450 inhibitor added to warfarin (narrow TI) slows warfarin metabolism → ↑plasma warfarin → bleeding. An inducer does the opposite (↓effect, clot risk). This is why narrow-TI drugs are monitored when co-prescribed. Protein-binding displacement (e.g. by a second highly-bound drug) similarly raises free active drug. Always check renal and hepatic function before dosing in the elderly. The five rights — right drug, patient, dose, route, time — plus monitoring effect and ADRs are the safety backbone of quality use of medicines.

16 · Pharmacodynamics⭐ "drug → body"

Drugs bind receptors ("lock & key", e.g. GPCRs).

• Agonist — binds + activates (affinity + efficacy).
• Partial agonist — submaximal even when fully bound.
• Antagonist — binds, no effect, blocks agonist (affinity, no efficacy).

Competitive antagonist = same site, reversible, surmountable (↑agonist overcomes; shifts curve right, max unchanged). Non-competitive = irreversible/allosteric, insurmountable (↓max).

16b · Potency, Efficacy, TIdon't confuse

Potency ≠ efficacy: potency = dose needed (lower ED50/EC50 = left-shift); efficacy = max effect (curve height). A weaker, lower-dose drug can be more potent yet less efficacious than another — they are independent (e.g. a strong opioid vs paracetamol). ED50 = effect in 50%; LD50/TD50 = lethal/toxic in 50%.

Therapeutic indexTI = LD50 / ED50 (or TD50/ED50)
high TI = safer; narrow = monitor

Narrow-TI drugs: warfarin, digoxin, lithium, gentamicin. Tolerance = ↓response on repeat use (receptor downregulation, e.g. opioids). Tachyphylaxis = rapid tolerance over short repeated doses.

16c · Antagonist Curve Shiftsread the graph

Competitive (surmountable): shifts the dose-response curve right, same Emax (more agonist overcomes it). Non-competitive (insurmountable): lowers Emax (the plateau drops; extra agonist can't recover it). Partial agonist = own ceiling below full Emax and can block a full agonist if both present.

Therapeutic window = plasma range between minimum effective and toxic concentrations — dosing keeps the concentration-time curve inside it. A narrow window (digoxin, lithium) means small dose changes tip from ineffective to toxic → therapeutic drug monitoring.

On the concentration-time curve: Cmax (peak), Tmax (time to peak), and trough (just before the next dose). Onset = crossing MEC up; duration = time above MEC; the danger zone = above the toxic level. Repeated dosing builds toward steady state, oscillating between peak and trough within the window — keeping the trough above MEC and the peak below the toxic level is the dosing goal. Narrow-window drugs are measured at the trough to confirm safety.

17 · NSAIDs & COX1.3 / 5.3

Inhibit cyclo-oxygenase (COX) → ↓prostaglandins → anti-inflammatory, analgesic, antipyretic (+ antiplatelet for aspirin).

COX-1 = housekeeping (gastric mucosa, platelets, renal flow); COX-2 = inducible (inflammation). Non-selective NSAIDs → GI ulcers/bleed, renal impairment. Coxibs (celecoxib) spare gut but ↑cardiovascular risk.

Paracetamol = analgesic/antipyretic, NOT anti-inflammatory, gentle on stomach (central action). Corticosteroids block phospholipase A2 (stop prostaglandins + leukotrienes); AEs: hyperglycaemia, osteoporosis, infection, poor healing.

18 · Analgesic Ladder & Opioids5.3.2

WHO ladder (escalate by severity; non-opioids/adjuvants continue at every step):

1. Mild: non-opioids — paracetamol, NSAIDs.
2. Moderate: weak opioids — codeine.
3. Severe: strong opioids — morphine, oxycodone, fentanyl.

Opioids bind opioid receptors centrally → ↓pain. AEs: respiratory depression (the danger sign) + sedation, constipation, nausea, tolerance, dependence. Adjuvants: some antidepressants/anticonvulsants; local anaesthetics block Na⁺ channels.

19 · High-Yield MCQ Trap-Banklast look

• Innate = no memory; adaptive = memory (B/antibody, T/cell).
• IgM first+largest; IgG most abundant + placenta; IgE allergy.
• Hypersensitivity I IgE, II cytotoxic, III complex, IV T-cell delayed. Anaphylaxis → adrenaline.
• AIDS = CD4 < 200; HIV kills CD4 helper T.
• Benign = no metastasis; grading = looks, staging = TNM.
• Oncogene = gain; suppressor (p53/BRCA) = loss.
• IV = 100% F, no first-pass; only free drug active; ~5 t½ = cleared/steady state.
• β1 heart, β2 lungs; atropine = "can't see/pee/spit/poo"; AChE-I ↑ ACh.
• Competitive = surmountable; high TI = safer.
• Opioid danger = respiratory depression; paracetamol ≠ anti-inflammatory.

20 · CNS / Mental-Health Drugs7.5.3

• Antidepressants — SSRIs ↑ synaptic serotonin (reuptake block); SNRIs add noradrenaline.
• Anxiolytics — benzodiazepines enhance GABA (sedation, dependence risk).
• Antipsychotics — block dopamine D2 (extrapyramidal AEs).
• Mood stabiliser — lithium (narrow TI → monitor levels).
• Alzheimer's — AChE inhibitors (donepezil) ↑ ACh; Parkinson's — levodopa ↑ dopamine.

SAQ reflex: answer the verb — "differentiate" = give the contrast, "explain" = give the cascade; for any drug, state the mechanism of action + one key AE. Define a term before applying it (define metastasis, then say why it makes a tumour malignant).