Pharmacology · Short notes

Cardiovascular Drugs: Short Notes & Cheat Sheet

Antihypertensives, antianginals, heart failure drugs, antiarrhythmics, anticoagulants and lipid-lowering agents.

Short notes

Read these before you attempt the topic's MCQs.

Where diuretics act on the nephron

Loop diuretics act where the most sodium is reabsorbed, so they are the most powerful. Drugs acting before the collecting duct (1–3) cause potassium loss; group 4 spares potassium.

Antihypertensives

ACE inhibitors (captopril, enalapril, lisinopril) cause dry cough and angioedema through bradykinin, as well as hyperkalaemia. They are teratogenic and contraindicated in bilateral renal artery stenosis.
ARBs (losartan, valsartan) do not cause cough. Losartan also lowers uric acid.
Dihydropyridine calcium channel blockers (amlodipine, nifedipine) cause ankle oedema and reflex tachycardia. Verapamil and diltiazem act on the heart, and verapamil causes constipation.
Thiazides: hypokalaemia plus 'hyper' glycaemia, uricaemia, lipidaemia and calcaemia. Loop diuretics (furosemide, which blocks NKCC2) cause hypokalaemia, hypocalcaemia and ototoxicity.
Spironolactone (aldosterone antagonist) causes gynaecomastia and hyperkalaemia. Amiloride and triamterene block ENaC.
Vasodilators: hydralazine (drug-induced lupus), minoxidil (hirsutism), and sodium nitroprusside for hypertensive emergencies (risk of cyanide toxicity, treated with sodium thiosulfate or hydroxocobalamin).
Safe in pregnancy: methyldopa, labetalol, nifedipine. Avoid ACE inhibitors and ARBs.

Angina and heart failure

Nitrates dilate veins and reduce preload. Glyceryl trinitrate (GTN) is given sublingually because of high first-pass metabolism. They cause headache, tolerance needs a nitrate-free interval, and they are contraindicated with sildenafil.
β-blockers are avoided in variant (Prinzmetal) angina, where calcium channel blockers are the drugs of choice. Ivabradine blocks the If current in the SA node. Ranolazine blocks the late Na+ current.
In heart failure, these reduce mortality: ACE inhibitors, ARBs or ARNI (sacubitril–valsartan); β-blockers (carvedilol, bisoprolol, metoprolol succinate); MRAs (spironolactone, eplerenone); and SGLT2 inhibitors.
Loop diuretics and digoxin relieve symptoms but do not improve survival.
Digoxin inhibits Na+/K+-ATPase, which raises intracellular Ca2+, and slows AV conduction through vagal effects. Toxicity causes nausea, yellow-green vision and arrhythmias, and is worsened by hypokalaemia. Antidote: digoxin-specific Fab.

Antiarrhythmics (Vaughan Williams)

Class IA: quinidine (cinchonism, QT prolongation), procainamide (lupus), disopyramide (anticholinergic effects).
Class IB: lidocaine (ventricular arrhythmias; given IV only) and mexiletine. Class IC: flecainide and propafenone; avoid in structural heart disease.
Class II: β-blockers. Class IV: verapamil and diltiazem.
Class III (K+ channel blockers): amiodarone, sotalol, dofetilide, ibutilide.
Amiodarone side effects: pulmonary fibrosis, both hypothyroidism and hyperthyroidism, corneal deposits, blue-grey skin, liver injury. Its half-life is several weeks.
Adenosine is the drug of choice to end PSVT. Its half-life is under 10 seconds, it causes flushing and chest tightness, and theophylline blocks its effect.
Magnesium sulfate is used for torsades de pointes.

Anticoagulants, antiplatelets and thrombolytics

Unfractionated heparin activates antithrombin and so inhibits both thrombin (IIa) and factor Xa. Monitor with aPTT. Antidote: protamine sulfate. Risk: heparin-induced thrombocytopenia (HIT).
Low-molecular-weight heparin (enoxaparin) acts mainly on Xa and is monitored with anti-Xa levels.
Warfarin inhibits VKORC1, lowering clotting factors II, VII, IX and X and proteins C and S. Target INR is usually 2–3. It is teratogenic. Reverse it with vitamin K and prothrombin complex concentrate.
Direct oral anticoagulants (DOACs): dabigatran inhibits thrombin (reversed by idarucizumab); rivaroxaban and apixaban inhibit Xa (reversed by andexanet alfa).
Aspirin irreversibly inhibits COX-1, reducing TXA2. Clopidogrel is a prodrug that blocks the P2Y12 ADP receptor and is activated by CYP2C19. Abciximab, eptifibatide and tirofiban block GP IIb/IIIa.
Thrombolytics: streptokinase (antigenic), alteplase, tenecteplase. Tranexamic acid reverses them.

Lipid-lowering drugs

Statins inhibit HMG-CoA reductase and lower LDL the most. Risks: myopathy and rhabdomyolysis (higher with gemfibrozil or macrolides) and raised liver enzymes. They are contraindicated in pregnancy.
Ezetimibe blocks NPC1L1 and reduces cholesterol absorption. PCSK9 inhibitors (evolocumab) lower LDL sharply.
Fibrates (PPAR-α agonists) lower triglycerides the most. Niacin raises HDL the most but causes flushing (aspirin prevents it).
Bile acid sequestrants (cholestyramine) raise triglycerides and bind other drugs.

Cheat sheet

High-yield facts in one place. Cover the right-hand column and test yourself.

Signature adverse effects

Drug	Remember
ACE inhibitors	Dry cough, angioedema, hyperkalaemia
Amlodipine / nifedipine	Ankle oedema, reflex tachycardia
Verapamil	Constipation, AV block (avoid with β-blocker)
Hydralazine / procainamide	Drug-induced lupus
Minoxidil	Hirsutism
Nitroprusside	Cyanide toxicity
Amiodarone	Lung fibrosis, thyroid, cornea, blue-grey skin
Digoxin	Yellow vision; toxicity ↑ in hypokalaemia
Quinidine	Cinchonism, torsades
Statins	Myopathy, rhabdomyolysis
Niacin	Flushing, hyperuricaemia, hyperglycaemia

Antidotes and monitoring

Drug	Monitor / reverse with
Heparin	aPTT / protamine sulfate
Warfarin	INR (2–3) / vitamin K, PCC
Dabigatran	Idarucizumab
Rivaroxaban, apixaban	Andexanet alfa
Digoxin	Serum level, K+ / digoxin Fab
Thrombolytics	Tranexamic acid

Diuretic sites

Diuretic	Site and target
Acetazolamide	Proximal tubule, carbonic anhydrase
Mannitol	Proximal tubule and loop, osmotic
Furosemide	Thick ascending limb, NKCC2
Hydrochlorothiazide	Distal tubule, NCC
Spironolactone	Collecting duct, aldosterone receptor
Amiloride	Collecting duct, ENaC

Memory aids

Thiazides are 'hyper-GLUC': Hyperglycaemia, hyperLipidaemia, hyperUricaemia, hyperCalcaemia (plus hypokalaemia).
Loops lose calcium: Loop diuretics increase Ca2+ excretion (hypocalcaemia); thiazides retain Ca2+.
Heart failure mortality: 'ABMS': ACE inhibitor/ARB/ARNI, β-blocker, MRA, SGLT2 inhibitor. Digoxin and loop diuretics do not reduce mortality.

Exam traps

Enalapril is a prodrug; lisinopril is not.
Isosorbide mononitrate escapes first-pass metabolism, so it works orally; GTN is given sublingually.
Warfarin skin necrosis happens early, because protein C falls before the clotting factors do.
Clopidogrel works less well in CYP2C19 poor metabolisers and with omeprazole.
Adenosine's effect is blocked by theophylline and caffeine and increased by dipyridamole.

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