⚖️
General Principles
2 topics📘 Pharmacodynamics & Pharmacokinetics
- Affinity – ability to bind receptor; inversely related to Kd
- Potency – dose needed for 50% effect (EC50); leftward shift = more potent
- Efficacy – maximal effect (ceiling); full agonists = 100%, partial agonists = lower
- Competitive antagonist – shifts curve rightward (parallel), overcome by ↑ agonist
- Non-competitive antagonist – reduces efficacy (lower ceiling)
| G-protein | Effector | Second Messenger | Example Receptors |
|---|---|---|---|
| Gs | ↑ Adenylyl cyclase | ↑ cAMP | β₁, β₂, D₁, H₂, glucagon |
| Gi | ↓ Adenylyl cyclase | ↓ cAMP | α₂, M₂, D₂, opioid |
| Gq | ↑ PLC | IP₃ + DAG + Ca²⁺ | α₁, M₁/M₃, 5‑HT₂ |
📌 High-Yield
- Partial agonists act as antagonists when co-administered with full agonists
- First-pass metabolism reduces oral bioavailability; IV = 100%
- Time to steady state = 4–5 × t½ (90% at 3.3 t½)
💊 CYP450 Inducers & Inhibitors
- Inducers: rifampin, carbamazepine, phenytoin, St. John's wort, barbiturates
- Inhibitors: azole antifungals, macrolides, grapefruit, ritonavir, cimetidine
🧠 Clinical Pearl
- Loading dose = (Vd × Cp) / f ; Maintenance dose = (Cl × Cpss × τ) / f
- t½ = 0.7 × Vd / Cl
⚡
Autonomic Pharmacology
4 topics🧪 Cholinergic Pharmacology
- Synthesis: choline → ChAT → ACh → vesicle (via H⁺/ACh exchanger)
- Release: Ca²⁺-dependent exocytosis; botulinum toxin blocks SNARE proteins
- Termination: AChE hydrolyzes ACh → choline + acetate
| Receptor | Coupling | Effector | Location |
|---|---|---|---|
| M₁, M₃, M₅ | Gq | ↑ PLC → IP₃/DAG/Ca²⁺ | Glands, smooth muscle |
| M₂, M₄ | Gi | ↓ AC → ↓ cAMP | Heart, presynaptic |
| NN | Ion channel | Na⁺/K⁺ flux | Ganglia, adrenal medulla |
| NM | Ion channel | Na⁺/K⁺ flux | Neuromuscular junction |
AChE inhibitor
→
↑ synaptic ACh
→
Muscarinic + Nicotinic effects
⚠️ Exam Trap
- Physostigmine crosses BBB (tertiary amine); neostigmine does not (quaternary)
- Organophosphate toxicity: atropine for muscarinic effects + pralidoxime (2‑PAM) for AChE reactivation
💊 Key Drugs
- Direct agonists: pilocarpine (glaucoma), bethanechol (ileus/retention)
- AChE inhibitors: neostigmine (myasthenia), donepezil (Alzheimer), physostigmine (antidote)
- Antagonists: atropine (antidote, bradycardia), ipratropium (COPD), scopolamine (motion sickness)
⚡ Adrenergic Pharmacology
- Synthesis: tyrosine → (tyrosine hydroxylase) → DOPA → (DOPA decarboxylase) → DA → (DA β‑hydroxylase) → NE
- Termination: reuptake (primary), MAO (intraneuronal), COMT (synaptic)
| Receptor | G-protein | Effector | Key Effects |
|---|---|---|---|
| α₁ | Gq | ↑ Ca²⁺ | Vasoconstriction, mydriasis, bladder sphincter |
| α₂ | Gi | ↓ cAMP | ↓ NE release (presynaptic), platelet aggregation |
| β₁ | Gs | ↑ cAMP | ↑ HR, contractility, conduction, renin |
| β₂ | Gs | ↑ cAMP | Bronchodilation, vasodilation, glycogenolysis |
| β₃ | Gs | ↑ cAMP | Detrusor relaxation (overactive bladder) |
🧠 Clinical Pearl
- Epinephrine reversal: α-blockade unmasks β₂ vasodilation → BP drops
- Norepinephrine: α₁ + β₁; no β₂ (so no vasodilation)
- Dobutamine: β₁ > β₂ (inotrope in CHF)
💊 Beta Blockers
- β₁-selective: metoprolol, atenolol, acebutolol (safer in asthma)
- Non-selective: propranolol, timolol (glaucoma, migraine)
- ISA: pindolol, acebutolol (less bradycardia)
- α+β: carvedilol, labetalol (CHF, hypertensive emergencies)
🔄 ANS & Blood Pressure Control
- BP = CO × TPR
- Baroreceptor reflex: ↑ BP → ↑ PANS, ↓ SANS → ↓ HR, ↓ CO, ↓ TPR
- Renin-angiotensin: ↓ renal perfusion → renin → Ang I → (ACE) → Ang II → vasoconstriction + aldosterone
↓ BP
→
↓ baroreceptor firing
→
↑ SANS / ↓ PANS
→
↑ HR, ↑ TPR, ↑ CO
⚠️ Exam Trap
- Ganglionic blockers (mecamylamine) abolish reflex tachycardia
- Muscarinic blockers (atropine) prevent reflex bradycardia
- β₁ blockers prevent reflex tachycardia
🧠 Ocular Pharmacology
- Atropine (M antagonist) → mydriasis + cycloplegia (near vision loss)
- Phenylephrine (α₁ agonist) → mydriasis, no cycloplegia
- Pilocarpine (M agonist) → miosis, ↑ aqueous outflow (glaucoma)
🫀
Cardiovascular Pharmacology
6 topics💊 Antihypertensive Agents
| Class | Mechanism | Prototype | Key Side Effect |
|---|---|---|---|
| Thiazide | ↓ Na⁺/Cl⁻ cotransporter (DCT) | Hydrochlorothiazide | Hypokalemia, hyperuricemia |
| ACEI | ↓ Ang II production | Lisinopril | Cough, angioedema, hyperkalemia |
| ARB | AT₁ receptor blockade | Losartan | No cough (bradykinin spared) |
| CCB (DHP) | Vascular Ca²⁺ blockade | Nifedipine | Reflex tachycardia, gingival hyperplasia |
| CCB (non-DHP) | Cardiac Ca²⁺ blockade | Verapamil | Constipation, bradycardia |
| α₁-blocker | Vascular smooth muscle relaxation | Prazosin | Orthostatic hypotension |
💊 Comorbidity-Guided Selection
- Diabetes / CKD: ACEI or ARB (renoprotective)
- Heart failure (↓EF): ACEI/ARB + beta-blocker
- Post-MI: beta-blocker (mortality benefit)
- BPH: alpha-blocker (dual benefit)
- Pregnancy: methyldopa, labetalol (ACEI/ARB contraindicated)
🧠 Hypertensive Emergency
- IV agents: nitroprusside (cyanide toxicity), labetalol, fenoldopam (D₁ agonist)
- Nitroprusside toxicity: cyanide → metabolic acidosis; antidote = hydroxocobalamin + thiosulfate
💧 Diuretics
| Class | Site | Mechanism | Electrolyte Effect |
|---|---|---|---|
| Loop | TAL | Na⁺/K⁺/2Cl⁻ cotransporter | ↓ Na⁺, K⁺, Ca²⁺, Mg²⁺ |
| Thiazide | DCT | Na⁺/Cl⁻ cotransporter | ↓ Na⁺, K⁺; ↑ Ca²⁺ |
| K⁺-sparing | Collecting duct | Na⁺ channel / aldosterone antagonist | ↓ Na⁺; ↑ K⁺ |
| CA inhibitor | PCT | Carbonic anhydrase inhibitor | ↓ Na⁺, HCO₃⁻; ↓ K⁺ |
| Osmotic | Entire nephron | Osmotic retention | Water loss |
⚠️ Exam Trap
- Loop diuretics ↑ Ca²⁺ excretion; thiazides ↓ Ca²⁺ excretion
- Sulfonamide cross-reactivity: CA inhibitors, loops (except ethacrynic acid), thiazides
- Ethacrynic acid: no sulfa, greatest ototoxicity
- K⁺-sparing + ACEI/ARB = hyperkalemia risk
💊 Key Uses
- Loop: pulmonary edema, CHF, hypercalcemia
- Thiazide: hypertension, nephrolithiasis (↓ Ca²⁺ stones)
- Spironolactone: CHF, cirrhosis, hirsutism (anti-androgen)
- Mannitol: cerebral edema, glaucoma, oliguric AKI
🫀 Antianginal Agents
| Class | Mechanism | Stable Angina | Vasospastic Angina |
|---|---|---|---|
| Nitrates | ↓ preload, ↓ afterload, coronary vasodilation | ✅ | ✅ |
| Beta-blockers | ↓ HR, ↓ contractility | ✅ | ❌ |
| CCBs (DHP) | ↓ afterload, coronary vasodilation | ✅ | ✅ (preferred) |
| Ranolazine | ↓ Na⁺/Ca²⁺ overload, ↓ demand | ✅ | Limited |
⚠️ Exam Trap
- Beta-blockers are contraindicated in vasospastic (Prinzmetal) angina — can worsen spasm
- Nitrates + PDE5 inhibitors (sildenafil) = profound hypotension (contraindicated)
- Nitrate tolerance: provide 8–12 hour nitrate-free interval
🧠 Clinical Pearl
- Sublingual nitroglycerin: rapid onset (1–3 min), short duration (~30 min) — acute episode
- Isosorbide mononitrate: longer duration, chronic maintenance
⚡ Antiarrhythmic Agents (Vaughan Williams)
| Class | Mechanism | Prototype | ECG Effect |
|---|---|---|---|
| IA | Na⁺ blockade + K⁺ blockade | Quinidine | ↑ QRS, ↑ QT |
| IB | Na⁺ blockade (inactivated channels) | Lidocaine | ↓ QT (mild) |
| IC | Na⁺ blockade (potent) | Flecainide | ↑ QRS |
| II | β-blockade | Metoprolol | ↓ HR, ↑ PR |
| III | K⁺ blockade | Amiodarone | ↑ QT, ↑ QRS |
| IV | Ca²⁺ blockade | Verapamil | ↓ HR, ↑ PR |
💊 Key Agents
- Amiodarone: multi-class (I, II, III, IV); pulmonary fibrosis, corneal deposits, thyroid dysfunction
- Lidocaine: ventricular arrhythmias (post-MI); CNS toxicity (seizures)
- Adenosine: PSVT; transient asystole; antagonized by methylxanthines
- Dronedarone: similar to amiodarone, fewer thyroid/pulmonary effects; contraindicated in decompensated HF
⚠️ Exam Trap
- Class IC drugs (flecainide) contraindicated in structural heart disease (CAST trial)
- Class III drugs prolong QT → risk of torsades de pointes
- Amiodarone has a half-life > 80 days (large Vd)
💊 Heart Failure Pharmacology
- HFrEF (EF ≤ 40%): ACEI/ARB + β-blocker + aldosterone antagonist ± ARNI
- HFpEF (EF ≥ 50%): β-blockers + diuretics (symptom control)
| Drug | Mechanism | Mortality Benefit |
|---|---|---|
| ACEI/ARB | ↓ Ang II, ↓ afterload/preload | ✅ |
| β-blockers (carvedilol, bisoprolol, metoprolol) | ↓ SNS activity, ↓ remodeling | ✅ |
| Spironolactone / Eplerenone | Aldosterone receptor blockade | ✅ |
| Sacubitril/valsartan (ARNI) | Neprilysin inhibitor + ARB | ✅ (superior to ACEI) |
| Digoxin | Na⁺/K⁺-ATPase inhibitor | ❌ (symptom benefit only) |
💊 Inotropes (Acute CHF)
- Dobutamine: β₁ agonist, ↑ contractility, mild vasodilation
- Milrinone: PDE III inhibitor, ↑ cAMP, ↑ inotropy + ↓ TPR
- Dopamine: dose-dependent (low: D₁, moderate: β₁, high: α)
⚠️ Digoxin Toxicity
- Early: anorexia, nausea, vomiting
- Late: confusion, visual disturbances (yellow-green halos), arrhythmias
- Management: digoxin immune Fab (antidote), correct electrolytes
- Interactions: diuretics (↓ K⁺), quinidine, verapamil (↑ digoxin levels)
📊 Lipid-Lowering Drugs
| Class | Primary Effect | Key Adverse Effect |
|---|---|---|
| Statins | ↓↓ LDL (≥50%) | Myopathy, hepatotoxicity |
| Bile Acid Sequestrants | ↓ LDL (modest) | ↑ TG, GI distress |
| Niacin | ↓ LDL, ↑↑ HDL, ↓ TG | Flushing, hepatotoxicity |
| Fibrates | ↓↓ TG, ↑ HDL | Myositis, gallstones |
| Ezetimibe | ↓ LDL (15–20%) | GI distress |
| PCSK9 Inhibitors | ↓↓↓ LDL (50–60%) | Injection site reactions |
🧠 Clinical Pearl
- Statins are first-line for LDL reduction; high-intensity: atorvastatin 40–80 mg, rosuvastatin 20–40 mg
- Gemfibrozil + statin = ↑ myopathy risk (avoid)
- PCSK9 inhibitors: alirocumab, evolocumab — dramatic LDL reduction
⚠️ Exam Trap
- Niacin does NOT improve cardiovascular outcomes when added to statins
- Bile acid sequestrants bind other oral drugs — separate dosing (1 h before / 4 h after)
🧠
CNS Pharmacology
6 topics🧬 Dopamine Pathways & Drugs
| Pathway | Function | Dysfunction |
|---|---|---|
| Nigrostriatal | Motor control | Parkinson (↓ DA), EPS (DA blockade) |
| Mesolimbic | Reward, psychosis | Schizophrenia (↑ DA → positive symptoms) |
| Mesocortical | Cognition, affect | Schizophrenia (↓ DA → negative symptoms) |
| Tuberoinfundibular | Prolactin inhibition | Hyperprolactinemia (DA blockade) |
💊 Parkinson Disease Drugs
- Levodopa + carbidopa: gold standard; carbidopa is peripheral AAAD inhibitor
- COMT inhibitors: entacapone, tolcapone (↑ levodopa bioavailability)
- MAO-B inhibitors: selegiline, rasagiline (↓ DA metabolism)
- DA agonists: pramipexole, ropinirole (D2/D3 stimulation)
- Antimuscarinics: benztropine, trihexyphenidyl (tremor, rigidity)
⚠️ Exam Trap
- Carbidopa does NOT cross BBB — only peripheral AAAD inhibition
- Levodopa-induced dyskinesias correlate with disease duration and dose
- Antipsychotic-induced EPS: treat with diphenhydramine or benztropine
💊 Antidepressants
| Class | Mechanism | Examples | Key Side Effects |
|---|---|---|---|
| SSRI | SERT blockade | Fluoxetine, sertraline | Sexual dysfunction, GI, serotonin syndrome |
| SNRI | SERT + NET blockade | Venlafaxine, duloxetine | Hypertension (venlafaxine), hepatotoxicity (duloxetine) |
| TCA | Non-selective reuptake blockade | Amitriptyline, imipramine | Anticholinergic, cardiotoxicity, sedation |
| MAOI | MAO inhibition | Phenelzine, tranylcypromine | Hypertensive crisis (tyramine), serotonin syndrome |
| Bupropion | DA + NE reuptake inhibition | Bupropion | Insomnia, seizures (lowers threshold) |
| Mirtazapine | α₂ antagonist, H₁ antagonist | Mirtazapine | Weight gain, sedation |
⚠️ Serotonin Syndrome
- Triad: altered mental status, autonomic instability, neuromuscular excitation
- Trigger: SSRI + MAOI, SSRI + TCA, SSRI + meperidine
- Management: discontinue agents, supportive care, cyproheptadine (antidote)
🧠 Clinical Pearl
- SSRIs are first-line for depression and anxiety disorders
- MAOIs require 2-week washout when switching to/from other antidepressants
- Fluoxetine has the longest half-life → lowest withdrawal risk
💤 Sedative-Hypnotics & Anxiolytics
| Drug | GABAA Effect | Key Features |
|---|---|---|
| Benzodiazepines | ↑ frequency of Cl⁻ channel opening | Ceiling effect, flumazenil antidote |
| Barbiturates | ↑ duration of Cl⁻ channel opening | No ceiling, CYP inducer, no antidote |
| Zolpidem / Zaleplon | BZ₁ (α₁) selective agonist | Sleep onset, less cognitive impairment |
| Buspirone | 5-HT₁ₐ partial agonist | Non-sedating, delayed onset (weeks) |
⚠️ Exam Trap
- Barbiturate withdrawal can be life-threatening (seizures, delirium tremens)
- BZ withdrawal managed by gradual tapering; abrupt cessation → seizures
- Flumazenil reverses BZ effects, NOT barbiturates or ethanol
- Buspirone is NOT useful for acute anxiety or panic
⚡ Anticonvulsants
| Seizure Type | Preferred Agents | Key Notes |
|---|---|---|
| Focal (partial) | Valproic acid, phenytoin, carbamazepine, lamotrigine | Lamotrigine better tolerated long-term |
| Generalized tonic-clonic | Valproic acid, phenytoin, carbamazepine, lamotrigine | Carbamazepine may worsen absence/myoclonic |
| Absence (petit mal) | Ethosuximide, valproic acid | Ethosuximide is highly selective |
| Status epilepticus | IV lorazepam, IV diazepam, IV phenytoin/fosphenytoin | Fosphenytoin is water-soluble, faster infusion |
💊 Key Drug Features
- Phenytoin: zero-order kinetics; gingival hyperplasia, hirsutism, megaloblastic anemia
- Carbamazepine: auto-induction; SIADH → hyponatremia; aplastic anemia
- Valproic acid: broadest spectrum; hepatotoxicity, teratogenic (neural tube defects)
- Ethosuximide: T-type Ca²⁺ blockade; absence seizures only
- Lamotrigine: Stevens-Johnson risk (slow titration required)
⚠️ Exam Trap
- Do NOT use carbamazepine or phenytoin for absence seizures
- Phenytoin zero-order kinetics: small dose increments cause disproportionate toxicity
- Valproate inhibits CYP450 → ↑ lamotrigine levels
💊 Opioid Pharmacology
| Receptor | Effects | Endogenous Ligand |
|---|---|---|
| μ (mu) | Analgesia, euphoria, respiratory depression, miosis, constipation | β-endorphin |
| κ (kappa) | Spinal analgesia, dysphoria, diuresis | Dynorphin |
| δ (delta) | Analgesia, antidepressant-like effects | Enkephalins |
💊 Key Opioids
- Morphine: prototype; metabolite M6G active; renal excretion
- Fentanyl: high potency; lipophilic; transdermal, IV
- Methadone: long-acting; NMDA antagonist; maintenance therapy
- Buprenorphine: partial μ agonist; ceiling effect; lower respiratory depression
- Meperidine: anticholinergic; normeperidine → seizures; avoid in renal impairment
🧠 Clinical Pearl
- Opioid toxicity triad: miosis + respiratory depression + coma
- Naloxone is the antidote; duration shorter than most opioids → monitor for re-sedation
- Constipation and miosis do NOT develop tolerance
- Loperamide is a peripheral μ agonist (does not cross BBB) — antidiarrheal
⚠️ Exam Trap
- Meperidine is the exception to miosis (causes mydriasis)
- Mixed agonist-antagonists (pentazocine, nalbuphine) can precipitate withdrawal in opioid-dependent patients
💉 Anesthesia & Muscle Relaxants
| Agent | MAC (%) | Blood-Gas Ratio | Key Feature |
|---|---|---|---|
| Nitrous oxide | 104 | 0.5 | Very rapid onset/recovery; weak |
| Sevoflurane | 2 | 0.6 | Sweet odor; preferred for mask induction |
| Desflurane | 6 | 0.5 | Very low solubility; pungent; heated vaporizer |
💊 IV Anesthetics
- Propofol: rapid onset, antiemetic, negative inotrope; pain on injection
- Ketamine: NMDA antagonist; sympathomimetic; preserves airway reflexes; emergence delirium
- Midazolam: BZ; anterograde amnesia; respiratory depression
- Fentanyl: synthetic opioid; chest wall rigidity (rapid bolus)
🧠 Neuromuscular Blockers
- Succinylcholine: depolarizing; rapid onset (30–60 s); short duration; hyperkalemia risk; MH trigger
- Rocuronium: non-depolarizing; competitive antagonist; reversed by neostigmine
- Malignant hyperthermia: dantrolene is the antidote; trigger: succinylcholine + volatile anesthetics
⚠️ Exam Trap
- Low MAC = high potency (not fast onset)
- Succinylcholine contraindicated in burns, trauma, denervation (hyperkalemia)
- Dantrolene inhibits RyR1 (skeletal muscle Ca²⁺ release)
🦠
Antimicrobial Pharmacology
4 topics🧫 Antibacterial Agents
| Class | Mechanism | Examples | Key Adverse Effect |
|---|---|---|---|
| Penicillins | Cell wall (PBPs) | Amoxicillin, piperacillin, nafcillin | Hypersensitivity, GI |
| Cephalosporins | Cell wall (PBPs) | Ceftriaxone, cefepime | Hypersensitivity (5% cross-reactivity) |
| Carbapenems | Cell wall (PBPs) | Imipenem, meropenem | Seizures (imipenem) |
| Vancomycin | Cell wall (D-Ala-D-Ala) | Vancomycin | Red man syndrome, nephrotoxicity, ototoxicity |
| Aminoglycosides | 30S ribosome | Gentamicin, tobramycin | Nephrotoxicity, ototoxicity |
| Macrolides | 50S ribosome | Azithromycin, clarithromycin | QT prolongation, GI |
| Tetracyclines | 30S ribosome | Doxycycline, minocycline | Phototoxicity, tooth discoloration |
| Fluoroquinolones | DNA gyrase | Ciprofloxacin, levofloxacin | Tendon rupture, cartilage damage |
| Metronidazole | DNA damage | Metronidazole | Disulfiram-like with alcohol |
💊 Drug of Choice
- MRSA: vancomycin, linezolid, daptomycin
- Pseudomonas: antipseudomonal penicillins, ceftazidime, cefepime, carbapenems, aminoglycosides
- UTI: TMP-SMX, nitrofurantoin, fluoroquinolones
- STIs: ceftriaxone (gonorrhea), doxycycline/azithromycin (chlamydia), penicillin G (syphilis)
⚠️ Exam Trap
- Bactericidal + bacteriostatic combinations can be antagonistic (e.g., tetracycline + penicillin)
- TMP-SMX is DOC for Pneumocystis jirovecii and Nocardia
- Metronidazole is DOC for C. difficile colitis
🫁 Antitubercular Drugs
| Drug | Mechanism | Key Adverse Effect |
|---|---|---|
| Isoniazid (INH) | Mycolic acid synthesis | Hepatitis, peripheral neuritis (B6), SLE (slow acetylators) |
| Rifampin | RNA polymerase inhibition | Hepatitis, P450 induction, orange-red secretions |
| Ethambutol | Arabinogalactan synthesis | Retrobulbar neuritis (red-green color vision) |
| Pyrazinamide | Unknown (acidic environment) | Hepatitis, hyperuricemia (gout) |
| Streptomycin | 30S ribosome (aminoglycoside) | Ototoxicity, nephrotoxicity |
🧠 Clinical Pearl
- Standard 4-drug regimen: INH + rifampin + ethambutol + pyrazinamide
- Always give pyridoxine (B6) with INH to prevent peripheral neuropathy
- Rifampin induces P450 → reduces efficacy of OCPs, warfarin, etc.
🧫 Antifungal Drugs
| Class | Mechanism | Examples | Key Adverse Effect |
|---|---|---|---|
| Polyenes | Ergosterol binding (pores) | Amphotericin B, nystatin | Nephrotoxicity, infusion reactions |
| Azoles | 14α-demethylase inhibition | Fluconazole, voriconazole | Hepatotoxicity, CYP inhibition |
| Echinocandins | β-glucan synthase inhibition | Caspofungin, micafungin | Infusion reactions, hepatotoxicity |
| Flucytosine | DNA/RNA synthesis inhibition | Flucytosine | Bone marrow suppression |
| Terbinafine | Squalene epoxidase inhibition | Terbinafine | Hepatotoxicity, dysgeusia |
💊 Key Uses
- Cryptococcal meningitis: Amphotericin B + flucytosine (induction), fluconazole (consolidation)
- Invasive aspergillosis: voriconazole (DOC)
- Mucormycosis: amphotericin B
- Onychomycosis: terbinafine (first-line)
⚠️ Exam Trap
- Fluconazole has excellent CNS penetration; does NOT cover Aspergillus
- Liposomal amphotericin B has less nephrotoxicity than conventional
- Azoles inhibit CYP450 → multiple drug interactions
🧬 Antiviral Agents
| Virus | Drug | Mechanism | Key Adverse Effect |
|---|---|---|---|
| HSV/VZV | Acyclovir | DNA polymerase (chain terminator) | Nephrotoxicity (IV), neurotoxicity |
| CMV | Ganciclovir | DNA polymerase | Hematotoxicity, nephrotoxicity |
| HIV | NRTIs (zidovudine) | Reverse transcriptase | Hematotoxicity, neuropathy |
| HIV | NNRTIs (efavirenz) | Reverse transcriptase | CNS effects, rash |
| HIV | PIs (ritonavir) | Protease inhibition | Metabolic syndrome, CYP inhibition |
| Influenza | Oseltamivir, zanamivir | Neuraminidase inhibition | GI, bronchospasm (zanamivir) |
| HCV | Sofosbuvir | NS5B polymerase inhibition | Fatigue, headache |
🧠 Clinical Pearl
- Acyclovir resistance: most commonly due to TK deficiency
- Foscarnet: direct DNA polymerase inhibitor; nephrotoxic; used for acyclovir-resistant HSV
- HAART: combination of 3–4 drugs; never use monotherapy
- Ritonavir: used as PK booster (CYP3A4 inhibition)
⚠️ Exam Trap
- Amantadine/rimantadine no longer recommended for influenza due to resistance
- NNRTIs have a low genetic barrier — single mutation confers resistance
- Protease inhibitors are associated with metabolic syndrome (insulin resistance, dyslipidemia)
🧬
Autacoids & Inflammation
3 topics🧪 Histamine & Antihistamines
| Receptor | Coupling | Effects | Antagonist |
|---|---|---|---|
| H₁ | Gq | Vasodilation, bronchoconstriction, itch | Diphenhydramine, loratadine |
| H₂ | Gs | Gastric acid secretion, ↑ HR | Cimetidine, famotidine |
| H₃ | Gi | Presynaptic inhibition | — |
💊 Key Agents
- First-generation (sedating): diphenhydramine, promethazine, meclizine — cross BBB, anticholinergic
- Second-generation (non-sedating): loratadine, fexofenadine, cetirizine — limited CNS penetration
- H₂ antagonists: cimetidine (CYP inhibitor, anti-androgenic), famotidine (preferred)
⚠️ Exam Trap
- Cimetidine inhibits CYP450 → drug interactions; famotidine does not
- Cetirizine can cause mild sedation (unlike loratadine/fexofenadine)
- First-generation antihistamines contraindicated in elderly (anticholinergic → dementia risk)
🧠 Serotonin, Migraine & NSAIDs
| Drug | Receptor Target | Use |
|---|---|---|
| Sumatriptan (triptan) | 5-HT₁B/D | Acute migraine (vasoconstriction) |
| Ergotamine | 5-HT₂, α | Acute migraine (second-line) |
| Ondansetron | 5-HT₃ | Chemotherapy-induced nausea |
| Cyproheptadine | 5-HT₂, H₁ | Serotonin syndrome, carcinoid |
| Buspirone | 5-HT₁ₐ | GAD (delayed onset) |
💊 NSAIDs & COX Inhibitors
- Non-selective COX inhibitors: aspirin, ibuprofen, naproxen — GI ulcers, bleeding
- COX-2 selective: celecoxib — less GI toxicity, ↑ CV risk
- Acetaminophen: central COX inhibition; safe for GI/bleeding risk; hepatotoxicity in overdose (N-acetylcysteine antidote)
- Aspirin: irreversible COX-1 inhibition; antiplatelet for 7–10 days; Reye syndrome in children
⚠️ Exam Trap
- Triptans contraindicated in CAD and uncontrolled hypertension
- Ergotamine is NOT first-line; contraindicated in pregnancy, CAD, and hypertension
- COX-2 inhibitors increase cardiovascular risk (unopposed TXA₂)
🦴 Rheumatic & Inflammatory Disorders
| Drug | Mechanism | Use | Key Side Effect |
|---|---|---|---|
| Methotrexate | Folate antagonist | RA (first-line DMARD) | Hepatotoxicity, myelosuppression |
| Hydroxychloroquine | Lysosomal stabilization | RA, SLE | Retinopathy (annual eye exam) |
| Sulfasalazine | B-cell inhibition | RA, IBD | Hemolysis (G6PD) |
| Leflunomide | DHODH inhibition | RA | Hepatotoxicity, teratogenic |
| TNF inhibitors | TNF-α blockade | RA, IBD, psoriasis | Infections (TB screening) |
| JAK inhibitors | JAK-STAT inhibition | RA | Infections, thrombosis |
🧠 Gout Therapy
- Acute: NSAIDs, colchicine (microtubule inhibition), glucocorticoids
- Chronic: allopurinol (xanthine oxidase inhibitor), febuxostat, probenecid (uricosuric)
- Refractory: pegloticase (urate oxidase)
- Colchicine: narrow therapeutic index; diarrhea is dose-limiting; CYP3A4 interaction
⚠️ Exam Trap
- Do NOT start urate-lowering therapy during an acute gout flare
- Allopurinol dose adjustment in renal impairment
- Probenecid requires GFR > 50 mL/min
🩸
Hematologic Pharmacology
1 topic💉 Anticoagulants, Thrombolytics & Antiplatelets
| Drug | Mechanism | Monitoring | Reversal |
|---|---|---|---|
| Heparin | ATIII-mediated IIa/Xa inhibition | aPTT | Protamine sulfate |
| LMWH (enoxaparin) | ATIII-mediated Xa inhibition | Anti-Xa (usually not needed) | Protamine (partial) |
| Warfarin | Vitamin K antagonist (II, VII, IX, X) | PT/INR | Vitamin K, FFP |
| Dabigatran | Direct thrombin inhibitor | None (routine) | Idarucizumab |
| Rivaroxaban, apixaban | Direct Xa inhibitor | None (routine) | Andexanet alfa |
| Aspirin | Irreversible COX-1 inhibition | None | Platelet transfusion |
| Clopidogrel | P2Y₁₂ (ADP receptor) inhibition | None | Platelet transfusion |
| tPA (alteplase) | Fibrin-bound plasminogen activation | None | Aminocaproic acid, tranexamic acid |
🧠 Clinical Pearl
- Factor VII has the shortest half-life (~6 h) → warfarin affects PT/INR first
- Protein C half-life ~8 h → warfarin can cause transient hypercoagulability (skin necrosis)
- HIT: platelet drop >50% on days 5–10; stop heparin, use argatroban
- Dual antiplatelet therapy (ASA + P2Y₁₂ inhibitor) after drug-eluting stent
⚠️ Exam Trap
- Heparin does NOT cross the placenta (safe in pregnancy); warfarin is teratogenic
- LMWH has less HIT and osteoporosis risk than unfractionated heparin
- tPA for stroke: time window 3–4.5 hours; rule out hemorrhage first
🧪
Endocrine & Metabolic Pharmacology
2 topics🩸 Diabetes & Metabolic Drugs
| Class | Mechanism | Examples | Key Side Effect |
|---|---|---|---|
| Biguanides | ↑ insulin sensitivity, ↓ gluconeogenesis | Metformin | GI, lactic acidosis (renal impairment) |
| Sulfonylureas | ↑ insulin release (K⁺ channel blockade) | Glipizide, glyburide | Hypoglycemia, weight gain |
| Thiazolidinediones | PPARγ agonists | Pioglitazone, rosiglitazone | Weight gain, edema, CV risk (rosiglitazone) |
| GLP-1 agonists | GLP-1 receptor activation | Liraglutide, semaglutide | Nausea, vomiting, pancreatitis |
| DPP-4 inhibitors | ↑ endogenous GLP-1 | Sitagliptin | Weight neutral, low hypoglycemia risk |
| SGLT-2 inhibitors | ↓ glucose reabsorption (kidney) | Canagliflozin, empagliflozin | UTI, genital mycotic, osmotic diuresis |
| α-glucosidase inhibitors | ↓ carbohydrate digestion | Acarbose | Flatulence, diarrhea |
💊 Insulin Preparations
- Rapid-acting (lispro): onset 0.3–0.5 h, peak 1–2 h, duration 3–4 h
- Short-acting (regular): onset 0.5–1 h, peak 2–4 h, duration 5–7 h
- Long-acting (glargine): onset 1 h, no pronounced peak, duration ≥24 h
- Regular insulin is the only IV insulin (DKA, perioperative)
🧠 Clinical Pearl
- Metformin is first-line for Type 2 diabetes (weight neutral, no hypoglycemia)
- SGLT-2 inhibitors have cardiorenal protective effects
- Hypoglycemia management: oral glucose (conscious), IV dextrose (unconscious), glucagon (if no IV)
🦋 Thyroid & Adrenal Pharmacology
| Drug | Mechanism | Use | Key Side Effect |
|---|---|---|---|
| PTU (propylthiouracil) | Thyroid peroxidase inhibition + T₄→T₃ inhibition | Hyperthyroidism (pregnancy preferred) | Hepatotoxicity, agranulocytosis |
| Methimazole | Thyroid peroxidase inhibition | Hyperthyroidism | Agranulocytosis, aplasia cutis (pregnancy) |
| Radioactive iodine (¹³¹I) | Selective thyroid destruction | Graves disease, toxic nodules | Hypothyroidism (common) |
| Levothyroxine (T₄) | Thyroid hormone replacement | Hypothyroidism | Hyperthyroidism (overdose) |
| Dexamethasone | Glucocorticoid (long-acting) | Inflammation, cerebral edema, COVID-19 | HPA suppression, osteoporosis |
| Prednisone | Glucocorticoid (intermediate) | Inflammatory disorders | HPA suppression, weight gain |
| Fludrocortisone | Mineralocorticoid | Adrenal insufficiency (salt-wasting) | Hypertension, edema |
⚠️ Exam Trap
- PTU preferred in pregnancy (less placental transfer than methimazole)
- Thyroid storm: PTU + iodide + propranolol + glucocorticoids
- Glucocorticoid withdrawal: taper slowly to avoid adrenal crisis
- Dexamethasone has negligible mineralocorticoid activity
🫁
Respiratory & GI Pharmacology
1 topic🫁 Asthma/COPD & GI Therapeutics
| Class | Mechanism | Examples | Key Feature |
|---|---|---|---|
| SABA | β₂ agonist (short-acting) | Albuterol | Acute bronchospasm (5–15 min onset) |
| LABA | β₂ agonist (long-acting) | Salmeterol, formoterol | Never as monotherapy (↑ asthma death) |
| ICS | Glucocorticoid (inhaled) | Budesonide, fluticasone | First-line controller; thrush (rinse mouth) |
| Muscarinic antagonist | M₃ blockade | Ipratropium, tiotropium | COPD first-line; no CNS effects |
| Antileukotrienes | LTD₄ receptor antagonist | Montelukast | Exercise-induced asthma; neuropsychiatric effects |
| PDE-4 inhibitor | PDE-4 inhibition | Roflumilast | Severe COPD with exacerbations |
| PPI | H⁺/K⁺-ATPase inhibition | Omeprazole | GERD, ulcer; irreversible; B₁₂ deficiency with long-term |
| H₂ antagonist | H₂ receptor blockade | Famotidine | GERD, ulcer (less potent than PPI) |
| Misoprostol | PGE₁ analog | Misoprostol | NSAID ulcer prophylaxis; abortifacient (contraindicated in pregnancy) |
🧠 Clinical Pearl
- Asthma: SABA for acute relief; ICS for chronic control
- COPD: tiotropium (LAMA) is first-line maintenance
- Montelukast: FDA boxed warning for neuropsychiatric effects
- PPIs are the most potent acid suppressants; long-term use → B₁₂ deficiency, osteoporosis, C. difficile
⚠️ Exam Trap
- LABA monotherapy increases asthma-related death — always use with ICS
- Misoprostol is a teratogen — contraindicated in pregnancy
- Metronidazole + alcohol = disulfiram-like reaction
🌀
Neuropharmacology: Drugs of Abuse
1 topic🧠 Drugs of Abuse & Withdrawal
| Drug Class | Mechanism | Key Features | Withdrawal |
|---|---|---|---|
| Stimulants (cocaine, amphetamines) | ↑ DA, NE, 5HT (reuptake/release) | Euphoria, tachycardia, hypertension, psychosis | Depression, anhedonia (not life-threatening) |
| Depressants (BZ, barbiturates, ethanol) | GABAA potentiation | Sedation, respiratory depression (barbiturates > BZ) | Seizures, delirium tremens (ethanol, barbiturates) — life-threatening |
| Opioids | μ receptor agonism | Euphoria, miosis, respiratory depression | Lacrimation, piloerection, diarrhea (not life-threatening) |
| Hallucinogens (LSD, psilocybin) | 5-HT₂ₐ agonism | Perceptual distortions, sympathetics | No classic dependence |
| Marijuana (THC) | CB₁ receptor agonism | Sedation, euphoria, tachycardia, red eyes | Mild (irritability, insomnia) |
| PCP / Ketamine | NMDA receptor antagonism | Dissociation, nystagmus (PCP) | Not well-characterized |
💊 Clinical Management
- Opioid overdose: naloxone (repeated doses)
- BZ overdose: flumazenil (caution in chronic users → seizures)
- Barbiturate/ethanol withdrawal: benzodiazepines (diazepam)
- Stimulant toxicity: benzodiazepines, cooling measures
⚠️ Exam Trap
- Miosis is characteristic of opioids; meperidine causes mydriasis
- PCP intoxication: nystagmus (horizontal + vertical)
- MDMA toxicity: hyperthermia + hyponatremia
🎯
Oncology & Toxicology
2 topics🎯 Anticancer, Immune & Toxicology
| Drug | Mechanism | Key Toxicity | Antidote / Protection |
|---|---|---|---|
| Cyclophosphamide | Alkylating agent | Hemorrhagic cystitis | Mesna (acrolein trap) |
| Cisplatin | DNA cross-links | Nephrotoxicity, ototoxicity | Amifostine, hydration |
| Doxorubicin | Intercalation, free radicals | Cardiomyopathy (delayed) | Dexrazoxane (iron chelator) |
| Methotrexate | DHFR inhibitor | Myelosuppression | Leucovorin (rescue) |
| Bleomycin | DNA strand scission | Pulmonary fibrosis | — |
| Vincristine | Microtubule inhibition | Neurotoxicity | — |
| ATRA | Differentiation | Differentiation syndrome | Corticosteroids |
💊 Immunosuppressants
- Cyclosporine / Tacrolimus: calcineurin inhibitors; nephrotoxicity; gingival hyperplasia (cyclosporine)
- Mycophenolate: purine synthesis inhibitor (lymphocyte-selective)
- Azathioprine: prodrug → 6-mercaptopurine; myelosuppression
- Anti-TNF: infliximab, adalimumab; TB screening required
🧠 Clinical Pearl
- Log-kill hypothesis: cytotoxic drugs kill a constant fraction of cells
- Cell-cycle specific (CCS): methotrexate, 5-FU, vincristine
- Cell-cycle non-specific: alkylating agents, cisplatin, doxorubicin
🧪 Toxic Alcohols & Poisoning
| Alcohol | Toxic Metabolite | End-Organ Damage | Treatment |
|---|---|---|---|
| Methanol | Formic acid | Optic neuropathy, blindness, metabolic acidosis | Fomepizole, ethanol, folate, hemodialysis |
| Ethylene glycol | Glycolic acid → oxalic acid | Renal failure, calcium oxalate crystals, hypocalcemia | Fomepizole, ethanol, thiamine, pyridoxine, hemodialysis |
| Ethanol | Acetaldehyde → acetate | CNS depression, hypoglycemia (children) | Supportive care, thiamine, glucose |
💊 Antidotes
- Fomepizole (4-methylpyrazole): competitive ADH inhibitor; drug of choice for methanol/ethylene glycol
- Ethanol: alternative ADH substrate (second-line)
- Hemodialysis: indicated for severe acidosis (pH < 7.2), end-organ damage, or high levels (>50 mg/dL)
⚠️ Exam Trap
- Methanol → visual symptoms + anion-gap acidosis + osmolar gap
- Ethylene glycol → renal failure + calcium oxalate crystals + hypocalcemia
- Ethanol → osmolar gap alone (no significant acidosis)
- Disulfiram-like reaction: metronidazole + alcohol → ALDH inhibition → acetaldehyde buildup