Cardiology

Question 1

ACEi

Answer 1

E.g. ramipril, lisinopril, enalapril
Use: HTN, chronic HF, IHD (secondary prevention), diabetic nephropathy/CKD with proteinuria
MOA: blocks the action of ACE to prevent the conversion of Ang I to Ang II. This prevents the effects of Ang II (vasoconstriction and aldosterone secretion), reducing after load and lowering BP. Dilation of the efferent arteriole results in reduced intraglomerular pressure (slowing CKD progression). Reducing aldosterone promotes Na+/H20 excretion which helps venous return (preload; good for HF).
Adverse effects: first-dose hypotension, dry cough, hyperK+, angioedema, anaphylactoid reactions
Cautions: avoid in renal artery stenosis and AKI. Caution in pregnancy, breastfeeding and CKD (needs monitoring).
Interactions: do not prescribe with K+ elevating drugs (K+ supplements, K+ sparing diuretics), with diuretics (hypotension), or with NSAIDs (increase HF risk).

Question 2

ARB

Answer 2

Use: HTN, chronic HF, IHD (secondary prevention), diabetic nephropathy/CKD with proteinuria when ACEi not tolerated
MOA: blocks action of Ang II on the AT1 receptor
Adverse effects: first-dose hypotension, hyperK+, renal failure
Cautions: avoid in renal artery stenosis and AKI. Caution in pregnancy, breastfeeding and CKD (needs monitoring).
Interactions: do not prescribe with K+ elevating drugs (K+ supplements, K+ sparing diuretics), with diuretics (hypotension), or with NSAIDs (increase HF risk).

Question 3

Dihydropyridine Ca2+ channel blockers

Answer 3

E.g. amlodipine, felodipine
Use: HTN, symptomatic relief in stable angina
MOA: decreases Ca2+ entry into vascular and cardiac cells, reducing IC Ca2+ conc. This causes relaxation and vasodilation in arterial SM, lowering arterial pressure.
Adverse effects: ankle swelling, flushing, headache, palpitations
Cautions: avoid in unstable angina (vasodilation increases myocardial O2 demand), severe aortic stenosis

Question 4

Loop diuretics

Answer 4

E.g. furosemide, bumetanide (oral only)
Use: relieve breathlessness in acute pulmonary oedema (with O2 and nitrates), relieve symptoms due to fluid overload in HF/renal disease/liver failure
MOA: inhibit the Na+/K+/2Cl- co-transporter in the Loop of Henle. Also causes dilation of capacitance veins, reducing preload and improving contractile function of heart muscle.
Adverse effects: dehydration, hypotension, hearing loss and tinnitus (high doses), low electrolyte state
Cautions: avoid in hypovolaemia and dehydration. Caution in hepatic encephalopathy, severe hypoK+, hypoNa+, Gout
Interactions: increases lithium levels, causes digoxin toxicity, enhances amino glycoside toxicity (oto- and nephro-)

Question 5

K+ sparing diuretics

Answer 5

E.g. amiloride
Use: hypoK+ due to loop or thiazide diuretics
MOA: inhibits Na+ reabsorption (ENaC channels), leading to Na+/H20 excretion and K+ retention. It is a weak diuretic when used alone.
Adverse effects: GI upset (alone); hypotension, dizziness, urinary symptoms (with other diuretics).
Cautions: CI in severe renal impairment, hyperK+, volume depletion. Caution in hypoK+.
Interactions: K+ elevating drugs (K+ supplements, aldosterone antagonists), digoxin and lithium dosing

Question 6

Aldosterone antagonists

Answer 6

E.g. spironolactone, eplerenone
Use: ascites and oedema secondary to liver cirrhosis, CHF (moderate or within 1 month of MI; alongside BB & ACEi/ARB), primary hyperaldosteronism
MOA: competitively binds to aldosterone receptor in the DCT, increasing Na+/H20 excretion and K+ retention
Adverse effects: hyperK+ (muscle weakness, arrhythmia, cardiac arrest), gynaecomastia (spironolactone), liver impairment/jaundice, Stevens-Johnson syndrome (T cell mediated hypersensitivity reaction, causes bullous skin eruption)
Cautions: CI in severe renal impairment, hyperK+ and Addison’s. Caution in pregnancy and lactation.
Interactions: K+ elevating drugs (K+ supplements and ACEi/ARB)

Question 7

Thiazide and -like diuretics

Answer 7

E.g. bendroflumethiazide, indapamide
Use: HTN where CCB is unsuitable (oedema/HF), add-on treatment for HTN (+ CCB + ACEi/ARB)
MOA: inhibition of Na/Cl cotransporter in DCT, preventing Na+ reabsorption, resulting in an initial fall in ECF vol. Over time, RAAS reverses this.
Adverse effects: hypoNa+, hypoK+, cardiac arrhythmias, increase plasma conc. of glucose, LDL and triglycerides, impotence
Cautions: CI in hypoK+, hypoNa+ and gout
Interactions: NSAIDs reduce its effectiveness, avoid with drugs that lower K+ (loop diuretics)

Question 8

Statins

Answer 8

E.g. atorvastatin, rosuvastatin, simvastatin
Use: primary prevention of CVD (>40 y/o with CVS risk >20%), secondary prevention of CVD, primary hyperlipidaemia
MOA: inhibit HMG CoA reductase, decreasing cholesterol production by the liver and increasing clearance of LDL cholesterol from the blood (reducing serum LDL). Indirectly reduces triglycerides and slightly increases HDL cholesterol.
Adverse effects: headache, GI disturbance, muscle, rise in liver enzymes, drug-induced hepatitis
Cautions: avoid in pregnancy and breastfeeding. Caution in hepatic and renal impairment.
Interactions: metabolism reduced by CYP450 inhibitors (amiodarone, diltiazem, itraconazole, macrolides, protease inhibitors)

Question 9

Fibrates

Answer 9

E.g. bezafibrate, fenofibrate
Use: hyperlipidaemia (if statin is CI or not tolerated)
MOA: activation of gene TFs (PPARs) which regulate gene expression of lipoprotein metabolism genes. Reduced circulating LDL and increased HDL.
Adverse effects: GI upset, rash, pruritus, dizziness, headaches, increased lithogenicity of bile (increases gallstone risk), myalgia, myositis
Cautions: CI in gall bladder disease, hypoalbuminaemia, nephrotic syndrome, photosensitivity to fibrates
Interactions: increases warfarin effect, increased risk of rhabdomyolysis with statins, increased risk of hypo with oral hypoglycaemic

Question 10

Specific cholesterol absorption inhibitor

Answer 10

E.g. ezetimibe
Use: primary and secondary prevention of CVD, Conn’s syndrome
MOA: this is a prodrug and is metabolised in the liver and intestine. Inhibits intestinal cholesterol transporter NPC1L1, acting at the brush border and reducing gut absorption
Adverse effects: diarrhoea, abdo pain, headache, angioedema
Interactions: increased risk of rhabdomyolysis with statins, increased risk of gallstones with fibrates

Question 11

Parenteral anticoagulants

Answer 11

E.g. unfractionated heparin, LMWH, fondaparinux
Use: VTE, ACS
MOA: unfractionated heparin activates antithrombin which inactivates clotting factor Xa and thrombin. LMWH and fondaparinux (synthetic compound) inhibit factor Xa.
Adverse effects: bleeding (fondaparinux has lower risk than other two), injection site reactions, heparin-induced thrombocytopenia (low platelet count and thrombosis; less likely with LMWH and Fonda)
Cautions: avoid in invasive procedures. Use UFH in renal impairment. Caution in those with clotting disorder, severe uncontrolled HTN, recent surgery or trauma.
Interactions: increased risk of bleeding with antithrombotic drugs

Question 12

Warfarin

Answer 12

Use: VTE prophylaxis, prevention of stroke in AF and after heart valve replacement
MOA: inhibits vitamin K epoxide reductase, inhibiting hepatic production of vit K-dependent coagulation factors. Takes a few days to fully activate (needs bridging with heparin)
Adverse effects: bleeding
Cautions: CI in immediate risk of haemorrhage (post-trauma or pre-surgery) and pregnancy. Caution in liver disease (cannot metabolise drug properly).
Interactions: low therapeutic index, metabolism reduced by CYP450 inhibitors (fluconazole, macrolide, protease inhibitors), metabolism increased by CYP450 inducers (phenytoin, carbamazepine, rifampicin)
INR aims: 2-2.5 (VTE prophylaxis), 2-3.0 (AF), 3-4.5 (mechanical valves)

Question 13

NOAC

Answer 13

Use: VTE prophylaxis, prevention of stroke in AF
MOA: direct factor Xa inhibitor
Adverse effects: nausea, GI upset, haemorrhage (higher risk of GI bleeding than warfarin)
Cautions: CI in active significant bleeding, antiphospholipid syndrome, RFs for major bleeding
Interactions: excretion reduced by drugs which inhibit P-glycoprotein (ketoconazole)

Question 14

Dabigatran

Answer 14

Use: VTE prophylaxis, treatment of PE/DVT, prophylaxis of stroke
MOA: selective direct competitive thrombin inhibitor
Adverse effects: nausea, dyspepsia, diarrhoea, abdo pain, haemorrhage (lower than warfarin)
Cautions: CI in active bleeding, antiphospholipid syndrome, prosthetic valves, malignancy, oesophageal varies, recent surgery, recent ulcer, recent ICH, risk of major bleeding and vascular aneurysm. Caution in elderly, <50 kg, bacterial endocarditis, bleeding disorder, gastritis, GI reflux, oesophagitis, thrombocytopenia

Question 15

Fibrinolytic agents

Answer 15

E.g. alteplase, tenecteplase (only for MI)
Use: acute ischaemic stroke, acute STEMI, massive PE with haemodynamic instability
MOA: genetically engineers t-PA. Catalyses the conversion of plasminogen to plasma, dissolving fibrous clots in occluded vessels. Tenecteplase has increased fibrin specificity.
Adverse effects: N&V, bruising at injection site, hypotension. Reperfusion of brain may result in cerebral oedema; and that of the heart can cause arrhythmias.
Cautions: CI in bleeding, ICH (must be excluded on CT), previous streptokinase Rx (development of Abs)
Interactions: anticoagulants and anti-platelets, ACEi

Question 16

Vitamin K

Answer 16

For warfarin reversal and in babies with Vit K deficiency bleeding
Less effective in liver disease

Question 17

Prothrombin complex concentrate beriplex

Answer 17

Use: major bleeding in patients on warfarin (given with vitamin K), Rx and peri-operative prophylaxis of haemorrhage in patients with factor II, VII, IX or X deficiency
Adverse effects: embolism, thrombosis
Cautions: CI in hx of heparin-induced thrombocytopenia and MI or unstable angina within 3 months. Caution in DIC, hx of MI/CHD, post-op (risk of thrombosis)

Question 18

Idarucizumab

Answer 18

Monoclonal Ab fragment

Antidote for Dabigatran, reversing anticoagulant effects

Question 19

Beta adrenoceptor blockers

Answer 19

E.g. propranolol, bisoprolol, atenolol, metoprolol, carvedilol
Use: IHD, chronic HF, rate control AF, SVT, HTN
MOA: beta-1 adrenoceptors are in the heart; beta-2 are mostly in SM of BVs and airways. Beta blockers reduce force of contraction and speed of conduction in the heart, reducing cardiac work and O2 demand, increasing perfusion. Prolongs refractory period of the AVN, slowing the ventricular rate. Restores sinus rhythm in SVT by breaking the circuit. Also reduces renin secretion, lowering BP.
Adverse effects: fatigue, cold extremities, headache, GI disturbance
Cautions: CI in asthma, heart block, and haemodynamic instability. Caution in COPD (choose B1 selective e.g. aten-, biso-, meto-), HF (low dose), hepatic failure (reduce dose)
Interactions: non-dihydropyridine CCBs (verapamil, diltiazem) as can cause HF/bradycardia/asystole

Question 20

Non-dihydropyridine CCBs

Answer 20

E.g. verapamil, diltiazem
Use: control symptoms in stable angina, control cardiac rate in SVTs
MOA: decrease Ca2+ entry into vascular and cardiac cells, reducing IC Ca2+ conc., causing relaxation and vasodilation in arterial SM, lowering arterial pressure. Suppresses cardiac conduction across AVN, slowing ventricular rate.
Adverse effects: constipation, bradycardia, heart block and HF (verapamil). Vascular and cardiac SE (diltiazem).
Cautions: poor LV function (can worsen HF). Avoid in AV nodal conduction delay
Interactions: beta blockers

Question 21

GTN and isosorbide dinitrate

Answer 21

Nitrates
Use: acute angina and chest pain assoc. with ACS (GTN), angina prophylaxis (isosorbide dinitrate)
MOA: converted to NO which increases cGMP, reduces IC Ca2+ in vascular SM cells, causing them to relax. Results in venous and arterial vasodilation. Reduces cardiac preload and LV filling (reducing cardiac work and myocardial O2 demand), relieves coronary vasospasm and dilates collateral vessels (improving coronary perfusion), and relaxes systemic arteries (reducing peripheral resistance and after load)
Adverse effects: vasodilatory effects (flushing, headaches, light-headedness, hypotension), tolerance
Cautions: CI in severe AS, haemodynamic instability and hypotension
Interactions: phosphodiesterase inhibitors (hypotensive SE worsened), caution when taking HTN meds

Question 22

Nicorandil

Answer 22

Nitrate
Use: stable angina when betablockers/CCBs are insufficient
MOA: arterial and venous vasodilation (actions as a nitrate), and by opening K+ ATP channels, leading to inactivation of voltage-gated Ca2+ channels, decreasing IC free Ca2+. Cardiac preload, systemic and coronary vascular resistance is reduced due to vasodilation. Improves myocardial perfusion, decreases myocardial work and oxygen demand.
Adverse effects: vasodilatory effects (flushing, headaches, light-headedness, hypotension), GI/skin/mucosal ulceration
Cautions: CI in poor LV function, hypotension and pulmonary oedema
Interactions: phosphodiesterase inhibitors (hypotensive SE worsened)

Question 23

Ivabradine

Answer 23

Use: angina with sinus rhythm, mild-severe chronic HF
MOA: specific sinus node It current (responsible for spontaneous depolarisation) inhibitor, slowing the firing rate of the sinus node.
Adverse effects: bradycardia, 1st degree heart block, ventricular ectopics, headache and dizziness, dose-related ocular symptoms
Cautions: CI in acute MI, cardiogenic shock, congenital QT syndrome, HR < 70 in HF, 2nd and 3rd degree heart block, sick sinus syndrome, Sino-atrial block, unstable angina, unstable or acute HF

Question 24

Ranolazine

Answer 24

Use: adjunct in stable angina
MOA: late Na+ current inhibitor (during the plateau place, some transmembrane Na+ channels remain open); this is increased in hypoxic tissues and results in a rise in IC Na+ conc., activating the reversal mode of Na/Ca exchange. This causes Ca2+ accumulation and increased diastolic myocardial tension.
Adverse effects: nausea, dyspepsia, constipation, headache, dizziness, lethargy, QT interval prolongation
Cautions: body weight <60, elderly, moderate-severe HF, QT interval prolongation
Interactions:

Question 25

Aspirin

Answer 25

Use: ACS and acute ischaemic stroke, long-term secondary prevention of thrombotic arterial events (hx of CVS, cerebrovascular disease, PAD), reduce risk of embolic stroke due to AF (if warfarin/DOACs are CI), control of mild-moderate pain and fever
MOA: irreversible COX inhibitor, reducing platelet aggregation
Adverse effects: GI irritation and ulceration (RFs = >65, previous peptic ulcer, comorbidities), haemorrhage, hypersensitivity reactions, tinnitus (high doses), OD (hyperventilation, hearing change, metabolic acidosis, confusion)
Cautions: CI in <16 (risk of Reye’s syndrome), aspirin hypersensitivity, T3 of pregnancy. Caution in peptic ulceration (prescribe PPI) and gout.
Interactions: caution when given alongside antiplatelets and anticoagulants.

Question 26

Dipyridamole

Answer 26

Use: secondary prevention of stroke, first-line following TIA, second-line following ischaemic stroke, induce tachycardia (myocardial perfusion scan)
MOA: phosphodiesterase inhibitor; has anti-platelet (prevents aggregation) and vasodilatory effects (blocks uptake of adenosine, prolonging its vasodilatory effects)
Adverse effects: vasodilatory effects (headaches, flushing, dizziness, GI symptoms), increased risk of bleeding, thrombocytopenia
Cautions: IHD, AS and HF.
Interactions: reduce adenosine dose, risk of bleeding when prescribed with other antiplatelet/anticoagulants

Question 27

Clopidogrel, ticagrelor

Answer 27

Use: ACS treatment, prevent occlusion of coronary artery stents, long-term secondary prevention of thrombotic arterial events (CVS, cerebrovascular disease, PAD), reduce risk of cardiac thrombus (in AF if warfarin/DOAC CI)
MOA: ADP receptor antagonist. Prevents platelet aggregation and reduces risk of arterial occlusion by binding irreversibly to ADP on the surface of platelets. Irreversible!
Adverse effects: bleeding, GI upset (dyspepsia, abdo pain, diarrhoea), thrombocytopenia
Cautions: CI in active bleeding. Need to stop 7/7 before surgery, caution in hepatic or renal impairment.
Interactions: effect reduced by CYP450 inhibitors (omeprazole, ciprofloxacin, erythromycin, SSRIs, antifungals)

Question 28

Tirofiban

Answer 28

Use: prevention of early MI in patients with unstable angina or NSTEMI with last chest pain <12 hours ago; given with UFH, aspirin, clopidogrel
MOA: non-peptide reversible antagonist of the GP2b/3a receptor
Adverse effects: bleeding (esp. in elderly and if low body weight), thrombocytopenia
Cautions: CI in abnormal bleeding or stroke within 30d, hx of haemorrhage stroke/intracranial disease, increased INR/prothrombin time, severe HTN, thrombocytopenia

Question 29

Adrenaline

Answer 29

Inotropic agent
Use: cardiac arrest with shockable rhythm (VF or pulseless VT), anaphylaxis, induce local vasoconstriction (e.g. during endoscopy to control bleeding)
MOA: potential agonist of alpha-1, -2, beta-1 and -2 adrenoceptors. Sympathetic response i.e. vasoconstriction of vessels, increased HR/force of contraction/myocardial excitability, vasodilation of vessels, bronchodilation and suppression of inflammatory mediator relase from mast cells
Adverse effects: adrenaline-induced HTN (cardiac arrest), anxiety, tremor, headache, palpitations (conscious patient)
Heart disease patients: adrenaline-anaesthetic prep should not be used in areas supplied by an end-artery (poor collateral supply; results in tissue necrosis) for local vasoconstriction
Dose: 1 mg IV after 3rd shock in cardiac arrest; 500 mcg IM for anaphylaxis

Question 30

Atropine

Answer 30

Antimuscarinic agent
Use: severe or symptomatic bradycardia
MOA: binds to muscarinic receptors, acts as competitive inhibitor of ACh. Increases HR and conduction, reduces SM tone and peristaltic contraction.
Adverse effects: tachycardia, dry mouth, constipation, urinary retention, ocular effects, drowsiness and confusion
Cautions: patients susceptible to angle-closure glaucoma. CI in those at risk of arrhythmias.
Interactions: effects are more pronounced when used with other antimuscarinics (TCAs)

Question 31

Flecainide

Answer 31

Class 1c anti-dysrhythmic
Use: SVTs and VA
MOA: Na+ channel blocker, slowing impulse conduction and prolongs QT interval
Adverse effects: oedema, fever, dyspnoea, CNS toxicity, -ve inotropic effect, pro-arrhythmic effects
Cautions: CI in abnormal LV function, atrial conduction defects, BBB, HF, hx of MI/VT, chronic AF

Question 32

Lidocaine

Answer 32

Class 1b anti-dysrhythmic
Use: LA, VT and VF refractory to cardioversion
MOA: Na+ channel blocker, prevents initiation and propagation of APs in nerves and muscle. In the heart, it reduces duration of AP, slows conduction velocity and increases refractory period
Adverse effects: initial stinging on local administration, neurological effects (drowsiness, restlessness, tremor, fits, little CVS toxicity), OD (hypotension, arrhythmias)
Cautions: dose reduction in states of reduced CO
Interactions: co-administration with adrenaline prolongs anaesthetic effect

Question 33

Sotalol

Answer 33

Class III anti-dysrhythmic
Use: significant cardiac rhythm disturbance
MOA: non-selective beta-adrenoceptor and K+ channel antagonist
Adverse effects: prolong QT interval, increased risk of Torsades in females, anxiety, arrhythmia, chest pain, dyspepsia, flatulence, hearing impairment, fatigue, cold extremities, headache, impotence
Cautions: CI in long QT syndrome, Torsades, asthma, heart block and haemodynamic instability. Caution in HF and hepatic failure.
Interactions: non-dihydropyridine CCBs

Question 34

Amiodarone

Answer 34

Class III anti-dysrhythmic
Use: tachyarrhythmias when other drugs/cardioversion is ineffective, cardiac arrest (VF or pulseless VT)
MOA: K+ channel blocker, antagonism of alpha and beta adrenoceptors, reduces spontaneous depolarisation, slows conduction velocity, increases resistance to depolarisation
Adverse effects: hypotension (IV), pneumonitis, bradycardia, AV block, hepatitis, photosensitivity and grey discolouration, hypo and hyperthyroidism (due to iodine content)
Cautions: avoid in severe hypotension, heart block and active thyroid disease
Interactions: increases plasma conc. of digoxin, diltiazem, verapamil
Dose for cardiac arrest: 300 mg IV after 3rd shock

Question 35

Anti-arrhythmic drug classes

Answer 35

I - Na+
II - beta blocker
III - K+
IV - Ca2+

Question 36

Adenosine

Answer 36

Use: SVT
MOA: agonist of adenosine receptors on cell surfaces, reducing frequency of spontaneous depolarisations (automaticity) and increasing resistance to depolarisation (refractoriness). This slows sinus rate, conduction velocity and increases AV node refractoriness. Allows normal depolarisation from SAN to resume control of HR (cardioversion).
Adverse effects: bradycardia, systole, feeling of impending doom
Cautions: CI in hypotension, coronary ischaemia, decompensated HF, asthma. Caution in COPD and heart transplant.
Interactions: uptake blocked by dipyridamole. Effects reduced by theophylline and caffeine.

Question 37

Digoxin

Answer 37

Use: rate control in AF and atrial flutter, in severe HF
MOA: -ve chronotrope and +ve inotrope. Increased vagal (parasympathetic) tone, reducing contraction at AVN, reducing ventricular rate (AF/flutter). Direct effect on myocytes by inhibiting Na/K ATPase, causing Na+ to accumulate in the cell and Ca2+, increasing contractile force (HF).
Adverse effects: bradycardia, GI disturbance, rash, dizziness, visual disturbance (blurred/yellow), ST segment depression.
Cautions: CI in 2nd degree heart block, with or at risk of ventricular arrhythmia. Caution in renal failure, and hypoK+/hypoMg2+/hyperCa2+ (increases risk of toxicity)
Interactions: loop and thiazide diuretics (increase risk of digoxin toxicity as they cause hypoK+), plasma conc. increased by amiodarone/CCB/spiro/quinine

Question 38

Na+ bicarbonate

Answer 38

Use: prevent or treat arrhthymias, severe metabolic acidosis, alkalisation of urine (haemolytic reactions), chronic acidotic states (renal tubular acidosis), drug intoxication, removal of earwax, severe diarrhoea
MOA: increases plasma bicarb, buffers excess H+, raises blood pH and reverses acidosis
Adverse effects: metabolic acidosis with aggressive therapy, hyperNa+
Cautions: CI in patients losing Cl- by vomiting and those receiving diuretics (loop or thiazide). Caution in congestive HF, severe renal insufficiency, oedema with Na+ retention.

Question 39

Ca2+ gluconate/chloride

Answer 39

Use: severe hyperK+
MOA: raises the myocardial threshold potential, reducing excitability and risk of arrhythmias
Adverse effects: CV collapse if given too fast IV, local tissue damage
Cautions: do not mix with Na+ bicarb

Question 40

Mg2+ sulphate

Answer 40

Use: emergency management of serious arrhythmias
MOA: not understood
Adverse effects: flushing

Question 41

Treatment of endocarditis

Answer 41

Benzylpenicillin
Amoxicillin
Gentamicin
Vancomycin
Flucloxacillin