B31 Pharmacology

Question 1

Bendroflumethiazide, chlortalidone, indapamide, metolazone

Answer 1

Class: thiazide diuretics.
MOA: inhibit Na+/Cl- cotransporter in DCT, preventing sodium and water reabsorption, resulting in diuresis.
Indication: hypertension, heart failure.
Side effects/contraindications: hyponatraemia, hypokalaemia, arrhythmias, impotence.

Question 2

Furosemide, bumetanide

Answer 2

Class: loop diuretics.
MOA: inhibit Na+/K+/2Cl- cotransporter in the ascending limb of loop of Henle, inhibiting sodium and water reabsorption, promoting diuresis. Also cause dilation of capacitance veins, reducing preload in HF and improves contractility.
Indication: acute pulmonary oedema, heart failure, oedema due to renal/liver failure, resistant hypertension.
Side effects/contraindications: dehydration, hypotension, any low electrolyte states, hearing loss & tinnitus at high doses. Avoid in patients with hypovolaemia/dehydration. Affect drugs that are renally excreted e.g. lithium.

Question 3

Amiloride

Answer 3

Class: potassium sparing diuretic.
MOA: inhibit sodium reabsorption in DCT and CD, causing sodium and water excretion. Retains K+.
Indication: oedema, potassium conservation when used as adjunct to thiazide or loop diuretics.
Side effects/contraindications: hyperkalaemia, arrhythmias. Avoid in Addison’s, anuria and hyperkalaemia.

Question 4

Spironolactone, eplerenone

Answer 4

Class: aldosterone antagonists/potassium sparing diuretics.
MOA: competitive binding to aldosterone receptor in DCT, inhibiting aldosterone, increasing sodium and water excretion and potassium retention.
Indication: ascites and oedema due to liver cirrhosis, heart failure, primary hyperaldosteronism, resistant hypertension, nephrotic syndrome.
Side effects/contraindications: hyperkalaemia, arrhythmias, gynaecomastia (spironolactone). Avoid in severe renal impairment, hyperkalaemia, Addison’s, pregnancy and breast feeding.

Question 5

Bisoprolol, atenolol, propranolol, metoprolol, carvedilol

Answer 5

Class: beta blockers (B1 cardioselective, apart from propranolol and carvedilol which are non-selective).
MOA: B1 receptor antagonist reducing contractility and speed of conduction in the heart. It reduces cardiac work and oxygen demand, and increases myocardial perfusion. Slow ventricular rate in AF/re-entry SVT by prolonging the refractory period of AVN. Also reduce renin secretion in hypertension.
Indication: angina, ACS, chronic HF (bisoprolol and carvedilol), AF, SVT, hypertension.
Side effects/contraindications: impotence in men, cold extremities, fatigue. Avoid in asthma due to risk of bronchospasm, heart block and patients with haemodynamic instability.

Question 6

Amlodipine, felodipine, nifedipine, diltiazem, verapamil

Answer 6

Class: calcium channel blockers (amlodipine, felodipine, nifedipine = dihydropyridines; diltiazem, verapamil = non-dihydropyridines).
MOA: decrease Ca2+ entry into vascular and cardiac cells. This causes relaxation and vasodilation in arterial smooth muscle (dihydropyridines) and reduction in myocardial contractility and conduction, slowing HR (non-dihydropyridines).
Indication: hypertension (amlodipine), stable angina, rate control in SVT/AF/atrial flutter (diltiazem and verapamil).
Side effects/contraindications: ankle swelling, flushing, headache and palpitations (amlodipine/nifedipine). Constipation and rarely bradycardia, heart block and cardiac failure (verapamil). Verapamil/diltiazem used with caution in poor LV function and avoided in AV nodal conduction delay. Amlodipine/nifedipine avoided in unstable angina and severe aortic stenosis.

Question 7

Ramipril, lisinopril

Answer 7

Class: angiotensin-converting enzyme (ACE) inhibitor.
MOA: block ACE, preventing conversion of angiotensin 1 to angiotensin 2. This reduces cardiac after-load by inhibiting vasoconstriction, lowering BP. It also inhibits aldosterone secretion, which reduces sodium and water reabsorption, decreasing preload.
Indication: hypertension, chronic heart failure, ischaemic heart disease.
Side effects/contraindications: first dose hypotension, dry cough, hyperkalaemia. Avoid in renal artery stenosis, AKI, pregnancy/breast feeding.

Question 8

Losartan, candesartan

Answer 8

Class: angiotensin receptor blockers (ARBs).
MOA: block action of angiotensin 2 on angiotensin type 1 receptor.
Indication: used when ACEi aren’t tolerated due to dry cough. Hypertension, chronic heart failure, ischaemic heart disease.
Side effects/contraindications: first dose hypotension and hyperkalaemia. Avoid in renal artery stenosis, AKI, pregnancy/breastfeeding.

Question 9

Doxazosin, tamsulosin

Answer 9

Class: alpha blockers.
MOA: inhibit alpha 1 adrenoceptor in vascular smooth muscle, causing vasodilation.
Indication: resistant hypertension.
Side effects/contraindications: postural hypotension, dizziness, syncope. Avoid in patients with pre-existing postural hypotension.

Question 10

Simvastatin, atorvastatin, rosuvastatin

Answer 10

Class: statin
MOA: inhibit HMG CoA reductase, reducing cholesterol production from liver. Specifically reduce LDL levels.
Indication: primary prevention of cardiovascular events, secondary prevention of cardiovascular events, primary hyperlipidaemia.
Side effects/contraindications: generally safe and well tolerated. Most common adverse effects are headache and GI disturbance. Rarely myopathy and rhabdomyolysis. Rise in liver enzymes. Use with caution in patients with hepatic impairment. Avoid in pregnancy/breast feeding.

Question 11

Bezafibrate, fenofibrate

Answer 11

Class: fibrates.
MOA: decrease serum triglycerides.
Indication: hyperlipidaemia if statins are not tolerated or contraindicated.

Question 12

Ezetemibe

Answer 12

MOA: inhibits intestinal absorption of cholesterol.
Indication: hypercholesterolaemia.

Question 13

Unfractionated heparin, dalteparin, fondaparinux

Answer 13

Class: heparins (anticoagulant) and fondaparinux (synthetic anticoagulant)
MOA: bind anti-thrombin enhancing its anticoagulant effects via inactivation of thrombin and factor Xa. Fondaparinux is a specific factor Xa inhibitor.
Indication: primary prevention of DVT and PE, treatment of VTE, ACS.
Side effects/contraindications: haemorrhage, bruising at injection site, hyperkalaemia and rarely heparin-induced thrombocytopenia. Used with caution in patients with clotting disorders, severe uncontrolled hypertension and recent surgery/trauma. Withheld immediately before and after invasive procedures.

Question 14

Warfarin

Answer 14

Class: vitamin K antagonist.
MOA: inhibits vitamin K epoxide reductase, inhibiting clotting factor synthesis.
Indication: treatment and secondary prevention of VTE, anticoagulation in AF and prosthetic heart valves, ACS.
Side effects/contraindications: bleeding. Avoid in patients at immediate risk of haemorrhage and in pregnancy. Patients with liver disease are less able to metabolise warfarin, increasing risk of over-warfarinisation. CYP induces (e.g. carbamazine) increase risk of clots, whereas CYP inhibitors (e.g. macrolides) increase risk of bleeding.

Question 15

Apixaban, rivaroxaban, dabigatran, edoxaban

Answer 15

Class: direct oral anticoagulants (DOACs).
MOA: act on final common pathway of coagulation cascade. Direct inhibition of factor Xa, preventing conversion of prothrombin to thrombin (apixaban, rivaroxaban, edoxaban). Dabigatran directly inhibits thrombin, preventing conversion of fibrinogen to fibrin.
Indication: VTE (PE/DVT), AF.
Side effects/contraindications: bleeding (epistaxis, GI and genitourinary haemorrhage), anaemia, GI upset, dizziness and elevated liver enzymes. Avoid in those at risk of bleeding, pregnancy and breastfeeding.

Question 16

Glyceryl trinitrate (GTN), isosorbide mononitrate

Answer 16

Class: nitrates.
MOA: nitrates converted to NO —> increase cGMP —> reduced Ca2+ in vascular SM —> relaxation of venous capacitance vessels —> reducing preload and LV filling —> reduce myocardial oxygen demand. Also relieve coronary vasospasm and dilate collateral vessels, improving coronary perfusion.
Indication: short-acting nitrates (GTN) used in acute angina and ACS. Long-acting nitrates (isosorbide mononitrate) used in prophylaxis of angina. IV nitrates used in pulmonary oedema.
Side effects/contraindications: flushing, headaches, light-headedness and hypotension. Avoid in severe aortic stenosis and hypotension. Not be used with PDE inhibitors.

Question 17

Nicorandil

Answer 17

Class: potassium channel opener.
MOA: opens ATP-dependent potassium channels —> vasodilation via reduction in calcium influx through voltage gated channels.
Indication: prophylaxis and treatment of stable angina.
Side effects/contraindications: dizziness, headache, N+V. Avoid in severe hypotension/shock, acute pulmonary oedema and LV dysfunction.

Question 18

Ivabradine, ranolazine

Answer 18

Class: pacemaker current inhibitor (ivabradine), anti-anginal (ranolazine).
MOA: selective inhibition of If channels in heart, lowering SAN firing rate and prolongs diastolic depolarisation, reducing HR and myocardial oxygen demand (ivabradine). MOA for ranolazine is not fully understood.
Indication: angina (ivabradine & ranolazine), chronic HF (ivabradine).
Side effects/contraindications: arrhythmias and AVN block (ivabradine). Avoid in acute MI, cardiogenic shock, severe hypotension, bradycardias (ivabradine).

Question 19

Aspirin, clopidogrel, ticagrelor, dipyridamole, tirofiban

Answer 19

Class: anti-platelets.
MOA: irreversible inhibition of COX, reducing thromboxane production, therefore reducing platelet aggregation (aspirin). Anti-platelet effects of aspirin occur at low doses. ADP-receptor antagonists, preventing platelet aggregation (clopidogrel, ticagrelor).
Indication: treatment of ACS and ischaemic stroke, secondary prevention of cardiovascular events, prevention of occlusion of coronary artery stents.
Side effects/contraindications: GI irritation, peptic ulceration, haemorrhage, bronchospasm (aspirin). Avoid aspirin in children < 16 and third trimester of pregnancy. Bleeding and GI upset (clopidogrel, ticagrelor). Avoid clopidogrel and ticagrelor in patients with active bleeding. Clopidogrel is a pro-drug so efficacy may be reduced by CYP450 inhibitors e.g. omeprazole, ciprofloxacin, erythromycin.

Question 20

Alteplase, tenecteplase, streptokinase

Answer 20

Class: fibrinolytic drugs.
MOA: catalyse conversion of plasminogen to plasmin, dissolving fibrinous clots and re-canalise blood vessels.
Indication: thrombolysis in STEMI and massive PE with haemodynamic instability.
Side effects/contraindications: N+V, bruising around injection site, hypotension. Treatment stopped - serious bleeding, allergic reaction, cardiogenic shock, cardiac arrest. Avoid in risk factors for bleeding and previous streptokinase treatment (anti-streptokinase Abs).

Question 21

Digoxin

Answer 21

Class: cardiac glycoside (class V anti-arrhythmic).
MOA: negatively chronotropic by increasing parasympathetic activity, slowing conduction through AVN. Positively inotropic by inhibition of Na+/K+ ATPase pump, elevating intracellular Na+ causing Ca2+ to accumulate in the cell, increasing contractile force.
Indication: rate control in AF and atrial flutter, severe HF.
Side effects/contraindications: bradycardia, GI disturbance, rash, dizziness and visual disturbance. Avoid in second degree heart block, intermittent complete heart block, ventricular arrhythmias. Reduce dose in renal failure. Hypokalaemia can increase the risk of digoxin toxicity.