FMGE Pharmacology Syllabus

List the muscarinic effects of cholinergic stimulation (parasympathetic).

DUMBELS: Diarrhea, Urination, Miosis, Bradycardia/Bronchoconstriction, Emesis, Lacrimation, Salivation/Sweating. Also accommodation for near vision and increased GI secretions/motility.

Differentiate alpha-1, alpha-2, beta-1, and beta-2 adrenergic receptor effects.

Alpha-1: vasoconstriction, mydriasis, contraction of sphincters (Gq). Alpha-2: presynaptic inhibition of NE release, decreased central sympathetic outflow (Gi). Beta-1: increased heart rate/contractility, renin release (Gs). Beta-2: bronchodilation, vasodilation, uterine relaxation, glycogenolysis (Gs).

Why does adrenaline cause a 'vasomotor reversal of Dale' after an alpha-blocker?

Adrenaline acts on both alpha (vasoconstriction) and beta-2 (vasodilation) receptors. After alpha-blockade, the unopposed beta-2 action predominates, so adrenaline causes a fall in BP instead of a rise—reversal of its pressor effect.

Which antihypertensive beta-blocker overdose is treated with glucagon, and why?

Beta-blocker overdose is treated with glucagon because it increases cardiac cAMP independently of beta-receptors (via its own receptor and adenylyl cyclase), restoring heart rate and contractility.

State the mechanism of action of benzodiazepines and barbiturates on the GABA-A receptor.

Benzodiazepines increase the FREQUENCY of chloride channel opening; barbiturates increase the DURATION of channel opening. Both potentiate GABA-mediated inhibition. Barbiturates can also directly open the channel at high doses (more dangerous).

Name the specific antidote for benzodiazepine overdose.

Flumazenil, a competitive GABA-A benzodiazepine-site antagonist. Use cautiously as it may precipitate seizures in dependent patients or mixed overdoses.

Which antiepileptic is the drug of choice for absence seizures and what is its mechanism?

Ethosuximide is the drug of choice for absence (petit mal) seizures; it blocks T-type calcium channels in thalamic neurons. Valproate is an alternative, especially if mixed seizure types coexist.

Describe the mechanism of phenytoin and one characteristic kinetic feature.

Phenytoin blocks voltage-gated sodium channels, stabilizing neuronal membranes (used for tonic-clonic and partial seizures). It shows zero-order (saturation) kinetics at therapeutic doses, so small dose increases can cause toxicity.

What is the pharmacological basis of using levodopa with carbidopa in Parkinson's disease?

Levodopa is the dopamine precursor that crosses the BBB (dopamine cannot). Carbidopa inhibits peripheral DOPA decarboxylase without crossing the BBB, increasing central levodopa availability and reducing peripheral side effects (nausea, hypotension).

Compare typical and atypical antipsychotics in terms of receptor action and side effects.

Typical (e.g. haloperidol): potent D2 blockade, high extrapyramidal side effects (EPS) and hyperprolactinemia. Atypical (e.g. risperidone, olanzapine, clozapine): block D2 and 5-HT2A, fewer EPS but more metabolic effects (weight gain, diabetes); clozapine risks agranulocytosis.

What is serotonin syndrome and which drug combinations classically cause it?

A potentially fatal hyperserotonergic state: hyperthermia, autonomic instability, neuromuscular hyperactivity (clonus, hyperreflexia), and altered mental status. Caused by combining SSRIs/SNRIs with MAO inhibitors, tramadol, linezolid, or triptans. Treat with cyproheptadine and supportive care.

Name the opioid antagonist used for overdose and the classic triad of opioid toxicity.

Naloxone (short-acting mu antagonist) reverses opioid overdose. Classic triad: respiratory depression, pinpoint (miotic) pupils, and coma/CNS depression.

What does the blood–gas partition coefficient tell you about inhalational anesthetic induction speed?

A LOW blood–gas partition coefficient (low solubility, e.g. nitrous oxide, desflurane) means faster induction and recovery, because the anesthetic rapidly raises arterial partial pressure. High solubility (e.g. halothane) gives slower onset/offset.

Define MAC (minimum alveolar concentration) of an inhalational anesthetic.

MAC is the alveolar concentration of an anesthetic at 1 atmosphere that prevents movement in response to a surgical (skin) incision in 50% of patients. It is an index of anesthetic potency—lower MAC = more potent.

State the mechanism of ACE inhibitors and their hallmark cough-causing side effect.

ACE inhibitors (e.g. enalapril) block angiotensin-converting enzyme, reducing angiotensin II formation (vasodilation, less aldosterone). They also reduce bradykinin breakdown, causing the characteristic dry cough and risk of angioedema. ARBs avoid the cough.

How does nitroglycerin relieve angina at the molecular level?

GTN is converted to nitric oxide, which activates guanylyl cyclase → increased cGMP → smooth muscle relaxation. Predominant venodilation reduces preload and myocardial oxygen demand; it also dilates coronary arteries.

List the four drug classes shown to improve survival in chronic heart failure with reduced ejection fraction.

1) ACE inhibitors/ARBs (or ARNI - sacubitril/valsartan); 2) Beta-blockers (carvedilol, bisoprolol, metoprolol succinate); 3) Mineralocorticoid receptor antagonists (spironolactone, eplerenone); 4) SGLT2 inhibitors (dapagliflozin, empagliflozin).

Describe the Vaughan-Williams classification of antiarrhythmic drugs.

Class I: Na+ channel blockers (Ia quinidine, Ib lignocaine, Ic flecainide). Class II: beta-blockers. Class III: K+ channel blockers (amiodarone, sotalol). Class IV: Ca2+ channel blockers (verapamil, diltiazem). (Unclassified: digoxin, adenosine.)

What is the mechanism of digoxin and its therapeutic effect in heart failure?

Digoxin inhibits the Na+/K+-ATPase, raising intracellular Na+, which reduces Na+/Ca2+ exchange and increases intracellular Ca2+ → positive inotropy. It also increases vagal tone (negative chronotropy), slowing AV conduction (useful in atrial fibrillation).

Match each diuretic class to its site of action in the nephron.

Carbonic anhydrase inhibitors (acetazolamide): proximal tubule. Loop diuretics (furosemide): thick ascending limb (Na-K-2Cl). Thiazides: distal convoluted tubule (Na-Cl). Potassium-sparing (spironolactone/amiloride): collecting duct. Osmotic (mannitol): proximal tubule and descending limb.

Why is furosemide called a 'high-ceiling' diuretic and what key electrolyte abnormality does it cause?

Furosemide acts on the thick ascending limb where ~25% of Na+ is reabsorbed, giving a large maximal diuresis ('high ceiling'). It causes hypokalemia, hypocalcemia, hypomagnesemia, and metabolic alkalosis; ototoxicity is a notable adverse effect.

Compare warfarin and heparin: mechanism, route, monitoring, and antidote.

Warfarin: inhibits vitamin K epoxide reductase (factors II, VII, IX, X); oral; monitor by PT/INR; antidote vitamin K (and FFP). Heparin: activates antithrombin III (inhibits thrombin & Xa); parenteral; monitor by aPTT; antidote protamine sulfate.

State the mechanism of aspirin's antiplatelet action and why its effect lasts ~7–10 days.

Aspirin irreversibly acetylates platelet COX-1, blocking thromboxane A2 synthesis. Because platelets lack a nucleus and cannot regenerate COX, the effect persists for the platelet lifespan (~7–10 days) until new platelets form.

Which statin-related adverse effect must be monitored, and what is the statin mechanism?

Statins inhibit HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis, lowering LDL. Key adverse effects to monitor: myopathy/rhabdomyolysis (check CK) and hepatotoxicity (check LFTs); risk rises with fibrate co-administration.

Explain the mechanism of metformin and its most serious adverse effect.

Metformin (a biguanide) activates AMP-kinase, decreasing hepatic gluconeogenesis and increasing peripheral insulin sensitivity; it does not cause hypoglycemia or weight gain. Most serious adverse effect: lactic acidosis (avoid in renal impairment).

Compare the onset and duration of rapid-acting versus long-acting insulin analogs.

Rapid-acting (lispro, aspart, glulisine): onset ~15 min, peak 1 h, duration 3–5 h—taken with meals. Long-acting (glargine, detemir, degludec): peakless, duration ~24 h (degludec >40 h)—provide basal coverage.

State the mechanism of sulfonylureas and their main adverse effects.

Sulfonylureas (glibenclamide, glimepiride) block ATP-sensitive K+ channels on pancreatic beta cells → depolarization → insulin release (require functioning beta cells). Main adverse effects: hypoglycemia and weight gain.

Describe the mechanism of carbimazole/methimazole and propylthiouracil in hyperthyroidism.

Both inhibit thyroid peroxidase, blocking iodination and coupling of tyrosines (thyroid hormone synthesis). Propylthiouracil additionally inhibits peripheral conversion of T4 to T3 and is preferred in the first trimester of pregnancy and thyroid storm.

Classify antibiotics by mechanism: name a class for cell wall synthesis, protein synthesis, and DNA/folate inhibition.

Cell wall synthesis: beta-lactams (penicillins, cephalosporins), vancomycin. Protein synthesis: aminoglycosides, macrolides, tetracyclines, chloramphenicol (50S/30S). DNA/folate: fluoroquinolones (DNA gyrase), sulfonamides + trimethoprim (folate synthesis), rifampicin (RNA polymerase).

Which aminoglycoside toxicities must be monitored and what is the mechanism of aminoglycosides?

Aminoglycosides (gentamicin, amikacin) bind the 30S ribosomal subunit, causing misreading of mRNA (bactericidal). Major toxicities: nephrotoxicity and ototoxicity (vestibular/cochlear); also neuromuscular blockade. They show concentration-dependent killing and a post-antibiotic effect.

Name the first-line antitubercular drugs and the characteristic toxicity of each.

Isoniazid: peripheral neuropathy (give pyridoxine), hepatitis. Rifampicin: hepatitis, orange body fluids, enzyme induction. Pyrazinamide: hyperuricemia, hepatotoxicity. Ethambutol: optic neuritis (red-green color blindness). Streptomycin: ototoxicity/nephrotoxicity.

Compare amphotericin B and azoles in antifungal mechanism.

Amphotericin B binds ergosterol in the fungal membrane forming pores (fungicidal; nephrotoxic, infusion reactions). Azoles (fluconazole, itraconazole) inhibit CYP450-dependent 14-alpha-demethylase, blocking ergosterol synthesis (fungistatic; inhibit human CYPs causing interactions).

State the mechanism of acyclovir and why it is selective for infected cells.

Acyclovir is a guanosine analog activated by viral thymidine kinase to acyclovir monophosphate (then triphosphate), which inhibits viral DNA polymerase and causes chain termination. Selectivity arises because only HSV/VZV-infected cells contain the activating viral thymidine kinase.

Which antimalarial is used for radical cure of P. vivax/ovale and what enzyme deficiency must be screened first?

Primaquine is used for radical cure (kills hypnozoites in the liver). Screen for G6PD deficiency first, as primaquine causes hemolysis in G6PD-deficient patients.

Name the drug of choice for most tissue/intestinal nematodes and its mechanism.

Albendazole/mebendazole (benzimidazoles) inhibit microtubule polymerization by binding beta-tubulin, impairing glucose uptake in helminths. Used for ascariasis, hookworm, enterobiasis, etc. For tissue filariasis/strongyloides, ivermectin (glutamate-gated Cl channels) is used.

Describe the cell-cycle specificity concept in anticancer chemotherapy with one example of each type.

Cell-cycle-specific drugs act on dividing cells in a particular phase (e.g. methotrexate/5-FU in S phase, vinca alkaloids in M phase). Cell-cycle-nonspecific drugs act on cells in any phase including resting (e.g. alkylating agents like cyclophosphamide, cisplatin).

State the mechanism and a key toxicity of methotrexate, plus its rescue agent.

Methotrexate inhibits dihydrofolate reductase, blocking tetrahydrofolate and thus DNA synthesis. Key toxicities: myelosuppression and mucositis (also hepatotoxicity, nephrotoxicity). Rescue with leucovorin (folinic acid) to spare normal cells.

Differentiate the mechanism of action of NSAIDs from paracetamol (acetaminophen).

NSAIDs inhibit cyclooxygenase (COX-1 and COX-2) peripherally and centrally, giving anti-inflammatory, analgesic, antipyretic, and antiplatelet effects. Paracetamol acts mainly centrally with weak peripheral COX inhibition—analgesic and antipyretic but minimal anti-inflammatory/antiplatelet action.

What is the antidote for paracetamol overdose and how does it work?

N-acetylcysteine (NAC) replenishes hepatic glutathione, which detoxifies the reactive metabolite NAPQI. It is most effective when given within 8–10 hours of overdose.

Compare H1 first-generation and second-generation antihistamines.

First-generation (chlorpheniramine, diphenhydramine): cross the BBB causing sedation, plus anticholinergic effects. Second-generation (cetirizine, loratadine, fexofenadine): poorly cross BBB, minimal sedation and anticholinergic effects—preferred for allergic rhinitis/urticaria.

Classify drugs used in peptic ulcer disease and acid suppression with the most potent class.

H2 blockers (ranitidine, famotidine) block histamine-stimulated acid; proton pump inhibitors (omeprazole) irreversibly inhibit the H+/K+-ATPase and are the most potent acid suppressants; antacids neutralize acid; mucosal protectives (sucralfate, misoprostol); and anti-H. pylori triple therapy.

Name the bronchodilator drug classes used in asthma and give an example of each.

Short-acting beta-2 agonists (salbutamol) for acute relief; long-acting beta-2 agonists (salmeterol, formoterol); muscarinic antagonists (ipratropium, tiotropium); methylxanthines (theophylline). Anti-inflammatory controllers include inhaled corticosteroids and leukotriene antagonists (montelukast).