General Principles: Receptor pharmacodynamics (agonism/antagonism, efficacy vs potency, spare receptors), signal transduction (GPCR, RTK, ion channels), therapeutic index, receptor desensitisation/tolerance.
Pharmacokinetics: ADME; absorption (pH/ionisation), first-pass effect, distribution (V_d), metabolism (Phase I/II; CYPs), excretion (renal/hepatic/biliary), clearance, half-life, steady-state, loading vs maintenance dosing.
Autonomic Pharmacology: Cholinergic (muscarinic/nicotinic) and adrenergic (α/β) systems; agonists, antagonists, mixed-action drugs; baroreflex interactions.
Cardiovascular: Antihypertensives, antianginals, antiarrhythmics (Vaughan–Williams), heart failure therapies (RAAS inhibitors, diuretics, SGLT2i, ARNI), antiplatelets/anticoagulants, thrombolytics.
Respiratory: β₂ agonists, antimuscarinics, inhaled corticosteroids, leukotriene modifiers, theophylline, antifibrotics.
Renal & Fluids: Diuretics (sites/actions), vasopressin agents, alkalinisers/acidifiers, fluid prescribing basics, electrolyte pharmacology.
Endocrine & Metabolic: Insulins & non-insulin agents (metformin, SGLT2i, GLP-1 RA, DPP-4), thyroid drugs, steroids & mineralocorticoids, bone agents (bisphosphonates, denosumab), reproductive pharmacology.
CNS: Sedatives/hypnotics, antidepressants, antipsychotics, mood stabilisers, antiepileptics, analgesics (opioid & non-opioid), anaesthetics, Parkinson’s therapy.
Infection & Inflammation: Antibiotic classes & PK/PD targets, antivirals/antifungals/antiparasitics (principles), NSAIDs/DMARDs/biologics.
GI & Hepatology: Acid suppression, prokinetics/antiemetics, laxatives/antidiarrhoeals, bile acids, hepatic encephalopathy agents.
Oncology & Immunotherapy: Cytotoxics (cell cycle), targeted therapy (TKIs, mAbs), immune checkpoint inhibitors, toxicity syndromes & rescue agents.
Special Populations & Safety: Pregnancy & lactation, paediatrics, older adults, renal/hepatic impairment, pharmacogenomics, UK BNF/MHRA Yellow Card/black triangle, controlled drugs.

⚙️ PD fundamentals – potency vs efficacy

Potency (EC₅₀) is the concentration achieving 50% maximal effect; efficacy (E_max) is maximal possible effect. A partial agonist has lower E_max even if highly potent, and can antagonise a full agonist at the same receptor.
Competitive antagonists shift the dose–response curve right (↑EC₅₀, E_max unchanged); non-competitive antagonists reduce E_max (insurmountable).
Desensitisation: GPCR phosphorylation & β-arrestin, receptor internalisation; explains tachyphylaxis with repeated doses (e.g., decongestants).

🧪 PK pearls – how numbers guide dosing

V_d relates dose to plasma concentration (V_d = (amount in body)/C_p); high V_d drugs are lipophilic/tissue-bound (e.g., TCAs), low V_d remain intravascular (e.g., heparin).
Clearance is the “volume cleared” per time (Cl = (rate of elimination)/C_p); t_1/2 = 0.693 V_d/Cl. Five half-lives ≈ steady-state/washout for first-order kinetics.
Capacity-limited (zero-order) elimination (e.g., phenytoin, ethanol) risks disproportionate toxicity with small dose increases; monitor levels and adjust carefully.

🧬 Pharmacogenomics – when genes matter

HLA-B*57:01 → abacavir hypersensitivity (screen prior to use). HLA-B*15:02 (certain ancestries) → SJS/TEN risk with carbamazepine.
TPMT/NUDT15 variants → azathioprine/6-MP myelotoxicity; DPD (DPYD) deficiency → 5-FU/capecitabine toxicity; UGT1A1*28 → irinotecan neutropenia.
CYP2C19 poor metabolisers → reduced clopidogrel activation; consider alternatives if high-risk indications.

📏 Core Tables & Equations

Equation	Form	Use / Memory Tip
Clearance	Cl = (Rate of elimination)/C_p	Sum organ clearances (renal + hepatic)
Half-life	t_1/2 = 0.693 V_d/Cl	5 × t_1/2 ≈ steady state
Loading dose	D_L = C_ss V_d/F	Use for rapid effect; beware toxicity
Maintenance	Rate = C_ss Cl/F	Adjust to organ function
Bioavailability	F = AUC_po/AUC_iv × Dose_iv/Dose_po	First-pass reduces F
Henderson–Hasselbalch	pH = pK_a + log [base]/[acid]	Trapping weak acids/bases in urine
Emax model	E = E_max[A]/(EC₅₀ + [A])	Potency vs efficacy separation
Therapeutic index	TI = TD₅₀/ED₅₀	Narrow TI = monitor (e.g., lithium)

🧠 Autonomic receptor map – agonists/antagonists

Receptor	Main effects	Agonists	Antagonists
α₁	Vasoconstriction, mydriasis	Phenylephrine	Doxazosin
α₂	↓NE release (presynaptic)	Clonidine	Mirtazapine
β₁	↑HR/contractility, renin	Dobutamine	Metoprolol, bisoprolol
β₂	Broncho/vasodilation, tocolysis	Salbutamol	Non-selective β-blockers
M₂	↓SA/AV node activity	Muscarine	Atropine
M₃	Smooth muscle/gland ↑, miosis	Pilocarpine	Ipratropium/oxybutynin
Nicotinic	Ganglia/neuromuscular	Nicotine	Varenicline (partial); NMJ blockers

💉 Antihypertensives – mechanisms & pearls

Class	Mechanism	Key adverse effects	Notes
ACEi (ramipril)	↓Ang II, ↑bradykinin	Cough, hyperkalaemia, angio-oedema	Renoprotective in proteinuric CKD; avoid in pregnancy/bilateral RAS
ARB (losartan)	AT₁ blockade	Hyperkalaemia	No cough; similar outcomes
CCB (amlodipine)	L-type Ca^{2 +} block	Ankle oedema, flushing	Dihydropyridines for BP; rate-limiting (verapamil) for arrhythmias
Thiazide(-like)	NaCl block DCT	Hyponatraemia, hypokalaemia, ↑uric acid	Indapamide/chlortalidone long-acting
β-blockers	β₁ antagonism	Bradycardia, bronchospasm (non-selective)	Post-MI, HFrEF (select agents)
MRA (spironolactone)	Aldosterone block	Hyperkalaemia, gynaecomastia	Eplerenone fewer endocrine effects

🩸 Antiplatelets & anticoagulants – quick grid

Drug	Target	Reversal / monitoring	Notes
Aspirin	COX-1 irreversible	Platelet transfusion if severe bleed	GI bleed risk; use PPI if high risk
Clopidogrel	P2Y₁₂ irreversible	Platelet transfusion	Prodrug (CYP2C19)
DOACs (apixaban, rivaroxaban)	Xa inhibitors	Andexanet alfa (selected), PCC	Check renal function; fewer interactions
Dabigatran	Direct thrombin	Idarucizumab	Renal clearance; dyspepsia
Warfarin	VKORC1 (II, VII, IX, X)	Vitamin K, PCC	INR monitoring; many interactions
Heparins	ATIII-mediated	Protamine (UFH > LMWH)	HIT risk (monitor platelets)

🧯 Emergency antidotes – must-know

Paracetamol: N-acetylcysteine (follow nomogram timing).
Opioids: Naloxone (titrate to respirations).
β-blocker/CCB: Glucagon / calcium, ± high-dose insulin euglycaemia therapy.
Organophosphates: Atropine + pralidoxime; decontaminate.
Digoxin: Digoxin-specific Fab fragments.
MetHb: Methylene blue (if G6PD normal).
Toxic alcohols: Fomepizole (or ethanol), dialysis as indicated.
Cyanide: Hydroxocobalamin.

🧭 Pathways & Checklists – Prescribing That Thinks

Scenario	Checklist	Why it matters
Starting a new drug	Indication → contraindications → baseline obs/labs → interactions (CYP/P-gp/QT) → patient factors (renal/hepatic, pregnancy, frailty) → counselling → monitoring plan	Prevents predictable harm; documents “indication + stop/review date” (UK practice)
Renal dosing	Estimate eGFR/CrCl → identify renally cleared drugs → adjust dose/interval → avoid nephrotoxins → monitor levels (TDM) & electrolytes	Gentamicin/vancomycin, DOACs, metformin require vigilance
QT risk	Baseline ECG if risk → avoid multiple QT-prolongers → correct K/Mg/Ca → monitor if adding macrolide/fluoroquinolone/antipsychotic/methadone	Prevents torsades; consider alternatives
Opioid initiation	Assess pain type → non-opioids first → start low/go slow → prescribe laxative + antiemetic PRN → set functional goals → review in 48–72 h	Reduces adverse events & dependence risk
Biologic DMARD	Screen TB/hepatitis → update vaccines (avoid live post-start) → counsel on infection risk → plan monitoring (FBC/LFTs)	Prevents reactivation & missed toxicity

🧑‍🏫 Exam hack: Say the mechanism, one key adverse effect, one interaction, and the monitoring-four sentences that impress markers every time.

💥 Drug–drug interactions – pattern spotting

CYP3A4 inhibitors (azoles, macrolides except azithro, protease inhibitors, grapefruit) ↑ levels of statins, DOACs, some CCBs-watch for myopathy/bleeding/hypotension.
CYP inducers (rifampicin, carbamazepine, phenytoin, St John’s wort) ↓ many drugs’ levels-loss of anticoagulation/contraception/anti-epileptic control.
Serotonergic stacking (SSRI + MAOI + triptan + tramadol + linezolid) → serotonin syndrome (agitation, hyperreflexia, clonus, hyperthermia).
Hyperkalaemia triad: ACEi/ARB + MRA + trimethoprim (amiloride-like) → check K⁺ & renal function.

📦 UK safety culture – bullets to remember

BNF is your default reference; use generic names; avoid dangerous abbreviations (e.g., “u” for units).
MHRA Yellow Card for suspected ADRs; black triangle ▼ indicates additional monitoring.
Controlled drugs: legal writing requirements; safe storage & witnessed destruction; avoid decimals for whole-number doses.

🩺 Therapeutics & Clinical Scenarios

STEMI: Dual antiplatelet (aspirin + P2Y₁₂), anticoagulation, statin, β-blocker, ACEi; primary PCI pathway. Watch bleeding & hypotension (nitrates in RV infarct).
AF stroke prevention: CHA₂DS₂-VASc & HAS-BLED; DOAC first-line in most; adjust for renal function; periprocedural holds depend on bleeding risk and eGFR.
HFrEF: Quadruple therapy (ACEi/ARB or ARNI, β-blocker, MRA, SGLT2i) unless contraindicated; diuretic for symptoms. Titrate slowly; monitor K⁺, renal function, BP.
Asthma: Reliever (SABA) + ICS backbone; add LABA → MART strategies; antimuscarinic (LAMA) in selected; biologics (anti-IgE/IL-5/IL-4R) in severe phenotypes.
T2DM: Metformin (if eGFR adequate) → add SGLT2i (HF/CKD benefit) or GLP-1 RA (CV benefit/weight). Watch DKA risk with SGLT2i during acute illness (sick-day rules).
Seizure control: Focal: lamotrigine/levetiracetam; generalised: valproate (avoid in pregnancy) or levetiracetam; status: benzodiazepine → levetiracetam/valproate/phenytoin.
Antibiotics (general): Source control + empiric per syndrome & local resistance → de-escalate. PK/PD targets: β-lactams (time>MIC), aminoglycosides (C_max/MIC), vanc (AUC/MIC).
PUD/UGIB risk on NSAIDs: Co-prescribe PPI in high-risk (age, steroids, anticoagulants, prior ulcer). Consider COX-2 selective in GI risk (balance CV risk).
Thyrotoxicosis: Thionamide (carbimazole), β-blocker for symptoms; watch agranulocytosis (sore throat/fever → stop & FBC). Radioiodine/thyroidectomy per case.

🧯 Toxicology vignettes – spot & treat

Opioid toxidrome: Miosis, hypoventilation, bradycardia → airway & naloxone titration; long-acting opioids may require infusion.
Anticholinergic toxidrome: Hot, dry, flushed, delirious, mydriasis, urinary retention → benzodiazepines for agitation; physostigmine only with expert advice.
Cholinergic toxidrome: Salivation, lacrimation, urination, defecation, GI upset, emesis + bronchorrhoea/bronchospasm → atropine until dry chest + pralidoxime.
Tricyclic overdose: Wide QRS, arrhythmia, seizures → sodium bicarbonate boluses; avoid class Ia/Ic antiarrhythmics.

🧪 Therapeutic drug monitoring (TDM) – where & why

Vancomycin: Target AUC/MIC (commonly 400–600) or troughs per local policy; adjust to renal function.
Gentamicin: Once-daily peaks/troughs or Hartford nomogram; watch ototoxicity/nephrotoxicity.
Lithium: Narrow TI; check level 12 h post-dose; toxicity with dehydration, ACEi/ARB, thiazides, NSAIDs.
Phenytoin: Capacity-limited kinetics; small dose changes → big level changes; albumin-bound (adjust for hypoalbuminaemia).

👶 Pregnancy & lactation – safer choices

Avoid ACEi/ARB, statins, warfarin (teratogenic); prefer labetalol/nifedipine/methyldopa for hypertension; LMWH for anticoagulation.
SSRIs generally compatible (sertraline often preferred); avoid sodium valproate (major teratogen).
Use BNF and local maternity guidelines; consider trimester-specific risks and lactation transfer.

🧠 Study & Exam Tips

Four sentences per drug: Mechanism → key indication → one dangerous adverse effect → one interaction/monitoring plan.
Numbers that matter: t_1/2, V_d, Cl, time to steady-state, PK/PD target (time>MIC, C_max/MIC, AUC/MIC).
Map to physiology: For adverse effects, identify which receptor/pathway explains it (e.g., β₂ agonist → tremor/hypokalaemia).
Safety first: Write “Indication + dose + route + frequency + duration + monitoring + stop/review date” every time.
Active recall: Build one-page class summaries (MOA, examples, ADRs, interactions); daily five-minute drills.

🚀 Rapid drill (answers hidden)

How many half-lives to ~95% steady-state? Ans: ~4–5.
ACE inhibitor cough mechanism? Ans: ↑Bradykinin.
Why add β-blocker to nitrate in angina? Ans: Blunts reflex tachycardia from vasodilation.
Which drugs raise lithium levels? Ans: Thiazides, ACEi/ARB, NSAIDs (↓renal clearance).
Warfarin + metronidazole effect? Ans: ↑INR/bleeding (CYP inhibition).

Final thought: Say the mechanism, predict the effect, prevent the harm. If you can follow the molecule from receptor to monitoring plan, pharmacology turns from a list into logic. 💪

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Premed Pharmacology

🔢 Key Areas of Study

📏 Core Tables & Equations

🧭 Pathways & Checklists – Prescribing That Thinks

🩺 Therapeutics & Clinical Scenarios

🧠 Study & Exam Tips

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