Cardiovascular Drugs
Cardiovascular diseases (CVDs) are the leading cause of death globally, and South Africa faces a high and growing burden of hypertension, ischaemic heart disease, heart failure, and stroke. The pharmacist’s role in cardiovascular pharmacotherapy is multifaceted: ensuring appropriate drug selection and dosing, monitoring for efficacy and adverse effects, managing drug interactions, providing adherence counselling, and contributing to therapeutic drug monitoring. For the SAPC examination, candidates must demonstrate a thorough understanding of the major cardiovascular drug classes — antihypertensives, anticoagulants, antiplatelets, lipid-lowering agents, and antiarrhythmics — and the South African clinical and regulatory context.
This topic builds on pharmacodynamics (pharma-006), pharmacokinetics (pharma-003 through pharma-007), and drug interactions (pharma-008).
Antihypertensive Agents
Hypertension (defined as BP ≥140/90 mmHg, or ≥130/80 mmHg in high-risk groups) affects approximately 1 in 4 adults in South Africa and is a leading risk factor for stroke, myocardial infarction, heart failure, and chronic kidney disease. The South African Hypertension Society guidelines and the National Department of Health Essential Medicines List (EML) guide antihypertensive therapy in the public sector.
Classification of Antihypertensives
| Class | Mechanism | Examples | Notes |
|---|---|---|---|
| Thiazide diuretics | ↓ Renal sodium reabsorption → ↓ blood volume → ↓ CO; vasodilatory effect | HCTZ, chlorthalidone, indapamide | First-line; metabolic effects (K⁺, glucose, uric acid) |
| ACE inhibitors (ACEIs) | ↓ Angiotensin II → vasodilation + ↓ aldosterone → ↓ blood volume | Enalapril, lisinopril, captopril, ramipril | Cough (bradykinin); angioedema; hyperkalaemia |
| ARBs (Angiotensin receptor blockers) | Block AT₁ receptor → vasodilation + ↓ aldosterone | Losartan, valsartan, irbesartan, candesartan | Alternative to ACEI; less cough |
| Calcium channel blockers (CCBs) | Dihydropyridines (DHPs): vasodilation; Non-DHPs: cardiac effects | Amlodipine, nifedipine (DHP); verapamil, diltiazem (non-DHP) | DHPs: ankle swelling, flushing; Non-DHPs: constip., HR ↓, AV block |
| β-blockers | ↓ HR, ↓ CO, ↓ renin; some also vasodilatory | Metoprolol, carvedilol, bisoprolol, atenolol | COPD, asthma contraindications; bradycardia; fatigue |
| α₁-blockers | Block α₁-receptors → vasodilation | Prazosin, doxazosin, terazosin | ”First-dose phenomenon”; orthostatic hypotension |
| Centrally acting | Stimulate α₂-receptors in CNS → ↓ sympathetic outflow | Methyldopa (pregnancy); clonidine (not first-line) | Rebound hypertension on abrupt cessation |
| Direct vasodilators | Direct smooth muscle relaxation | Hydralazine, minoxidil (with β-blocker + diuretic) | Reflex tachycardia; lupus-like syndrome (hydralazine) |
| Potassium-sparing diuretics | Aldosterone antagonists; ↑ K⁺ retention | Spironolactone, eplerenone | Hyperkalaemia; gynaecomastia (spironolactone) |
| Renin inhibitor | Inhibits renin → ↓ Angiotensinogen conversion | Aliskiren | Less used; avoid with ACEI/ARB |
Thiazide Diuretics
Mechanism: Inhibit the NaCl cotransporter (NCC) in the distal convoluted tubule → increased sodium and water excretion → reduced blood volume and cardiac output. Also cause vasodilation through opening of calcium-activated potassium channels.
Dosing:
- Hydrochlorothiazide (HCTZ): 12.5–25 mg daily (higher doses increase metabolic side effects)
- Chlorthalidone: 12.5–25 mg daily (longer half-life than HCTZ; more potent per mg)
- Indapamide: 1.25–2.5 mg daily (also has vasodilatory properties)
Metabolic adverse effects:
| Effect | Mechanism | Clinical Relevance |
|---|---|---|
| Hypokalaemia | ↑ K⁺ excretion at distal tubule | Arrhythmia risk; ECG monitoring in cardiac patients |
| Hyperglycaemia | ↓ insulin secretion; insulin resistance | Avoid in pre-diabetes/diabetes where possible |
| Hyperuricaemia | ↓ uric acid excretion | Gout risk |
| Hyperlipidaemia | Transient ↑ cholesterol/triglycerides | Less clinically significant with low doses |
| Hyponatraemia | ↑ free water clearance | Especially in elderly |
| Hypomagnesaemia | ↓ Mg²⁺ reabsorption | Arrhythmia risk |
SA public sector: HCTZ is on the EML; chlorthalidone less commonly stocked.
ACE Inhibitors and ARBs
ACE Inhibitors:
- Inhibit angiotensin-converting enzyme → ↓ Angiotensin II → vasodilation + ↓ aldosterone
- Also inhibit bradykinin degradation → bradykinin accumulation → cough and angioedema
- Captopril: sulfhydryl group; short-acting; twice or three times daily; rare blood dyscrasias
- Enalapril, lisinopril: prodrugs (converted to active form in liver); once or twice daily
- Ramipril, perindopril: once daily; perindopril has evidence for cardiovascular outcomes reduction
Key adverse effects:
- Dry cough (10–20% of patients; due to bradykinin); resolves upon cessation
- Angioedema (0.1–0.7%; more common in African patients; contraindicated if history)
- Hyperkalaemia (especially with concurrent K⁺ supplements, K⁺-sparing diuretics, renal impairment)
- First-dose hypotension (especially with diuretic pre-treatment)
- Renal impairment (especially in bilateral renal artery stenosis; monitor creatinine)
ARBs:
- Block AT₁ receptor (angiotensin type 1) → same end result as ACEI but without bradykinin accumulation
- No cough (because bradykinin metabolism is unaffected)
- Same angioedema risk (lower than ACEI but cross-reactivity ~10%)
- Used when ACEI cause cough
ACEI/ARB Monitoring in South Africa:
- Serum K⁺ and creatinine within 1–2 weeks of initiation, then periodically
- SAHPRA warning: ACEI/ARB contraindicated in pregnancy (teratogenic — foetal renal damage)
South African population considerations:
- ACE inhibitor cough appears more common in African patients
- Angioedema more common in African patients (2–4× higher incidence than Caucasians)
- Requires explicit counselling and close monitoring
Calcium Channel Blockers
Dihydropyridines (DHPs):
- Amlodipine, nifedipine, felodipine, lacidipine
- Primarily arterial vasodilation; minimal cardiac effects
- Ankle oedema (precapillary dilation without postcapillary relaxation → fluid extravasation); often combined with ACEI which prevents this
- Flushing, headache, palpitations
Non-dihydropyridines:
- Verapamil: blocks L-type Ca²⁺ channels in heart and vessels → ↓ HR, ↓ AV conduction, negative inotropy; constipating
- Diltiazem: intermediate; some HR reduction and AV block; less constipating than verapamil
- Both contraindicated in heart failure with reduced ejection fraction (HFrEF) (negative inotropic effect)
Important interactions:
- Verapamil/diltiazem + β-blockers: additive negative inotropic and chronotropic effects → heart block, severe bradycardia, hypotension
- Amlodipine + simvastatin (avoid >20 mg simvastatin); amlodipine increases simvastatin levels via CYP3A4 inhibition
- Grapefruit juice + dihydropyridines: ↑ bioavailability of some DHPs (felodipine most affected)
β-Blockers
Classification:
| Type | Examples | Selectivity | ISA |
|---|---|---|---|
| Non-selective | Propranolol, nadolol, timolol | β₁ and β₂ blocked | No ISA |
| β₁-selective | Metoprolol, atenolol, bisoprolol | Preferentially β₁ | No ISA |
| Non-selective + α₁-block | Carvedilol, labetalol | β₁, β₂, α₁ blocked | No ISA (carvedilol); labetalol has ISA |
| ISA (intrinsic sympathomimetic) | Celiprolol, acebutolol | β₁ selective | Partial agonist activity |
Properties:
- β₁ selectivity diminishes at higher doses
- ISA: produce less bradycardia and cold extremities than non-ISA β-blockers
Indications beyond hypertension:
- Heart failure (carvedilol, metoprolol succinate, bisoprolol — “3 Bs that survive trials”)
- Post-MI (mortality reduction)
- Atrial fibrillation (rate control)
- Stable angina (anti-anginal)
- Thyrotoxicosis (symptom control)
- Migraine prophylaxis (propranolol, not specific)
Contraindications:
- Asthma/COPD (β₂ blockade → bronchoconstriction) — though cardioselective β₁ blockers used with caution
- Severe bradycardia, heart block (without pacemaker)
- Decompensated heart failure
- Prinzmetal angina (variant angina) — unopposed α-mediated coronary vasospasm
Monitoring: HR, BP, symptoms of bradycardia; assess for fatigue, cold extremities, sexual dysfunction (β-blockers can cause erectile dysfunction).
Combination Therapy
Most patients with hypertension require 2 or more agents. Fixed-dose combinations (FDCs) improve adherence:
| Combination | Rationale |
|---|---|
| ACEI/ARB + thiazide | Rationale: ACEI/ARB counteracts thiazide-induced K⁺ loss and sympathetic activation |
| ACEI/ARB + CCB | Rationale: CCB causes ankle oedema; ACEI reduces this by postcapillary vasodilation |
| β-blocker + dihydropyridine | Rationale: β-blocker blunts reflex tachycardia from DHP vasodilation |
| ACEI + ARB | NOT recommended: increased hyperkalaemia, renal impairment without added benefit |
South African EML combinations:
- Enalapril + HCTZ (Renitec Plus, etc.)
- Losartan + HCTZ (Cozaar, etc.)
- Amlodipine + valsartan (first-line combination in some protocols)
Anticoagulants and Antiplatelets
Heparin and Low Molecular Weight Heparins
Unfractionated Heparin (UFH):
- Binds to antithrombin III (ATIII) → accelerates inhibition of thrombin (factor IIa) and factor Xa
- Requires aPTT monitoring (target 1.5–2.5 × control)
- Short half-life; reversible with protamine
- Used in: acute MI, DVT/PE, atrial fibrillation, cardiopulmonary bypass, stroke
- Adverse effects: HIT (heparin-induced thrombocytopenia — paradoxical thrombosis), osteoporosis with long-term use, bleeding
Low Molecular Weight Heparins (LMWHs):
- Enoxaparin, dalteparin, tinzaparin
- Predominantly anti-Xa activity (anti-IIa:anti-Xa ratio ~1:3–4 vs UFH 1:1)
- Better bioavailability, longer half-life, dose-dependent clearance
- Monitor: anti-Xa levels in renal impairment (CrCl <30 mL/min), obesity, pregnancy
- Less HIT and osteoporosis than UFH
- Not fully reversible with protamine (protamine neutralises anti-IIa more than anti-Xa)
LMWH dosing in SA:
- Enoxaparin: 1 mg/kg SC every 12 hours for DVT/PE treatment; 40 mg daily for prophylaxis
- Renal dose adjustment: avoid or reduce dose in severe renal impairment
- In South Africa, enoxaparin is registered and available; dalteparin less commonly stocked
Fondaparinux
- Synthetic pentasaccharide; selectively inhibits factor Xa via ATIII
- Used for DVT/PE prophylaxis and treatment (in some protocols)
- No HIT (not derived from animal tissue); does not cross-react with HIT antibodies
- Excreted renally; contraindicated in severe renal impairment
- No reversal agent (though haemodialysis removes some)
Warfarin
Mechanism: Inhibits vitamin K epoxide reductase (VKOR) → prevents regeneration of vitamin K → synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and natural anticoagulants (protein C, protein S) is reduced.
Monitoring:
- INR (International Normalised Ratio) — standardises PT measurement across laboratories
- Target INR: 2–3 (DVT/PE, atrial fibrillation, mechanical heart valve in most positions); 2.5–3.5 for mechanical mitral valve
- Initiation: warfarin 4–5 mg daily for 2–3 days, then titrate to INR target
- Bridging with heparin when initiating warfarin (warfarin initially prothrombotic — protein C falls first)
Pharmacogenomics of warfarin:
- CYP2C9 polymorphisms (slow metabolisers require lower doses)
- VKORC1 polymorphisms (certain haplotypes require lower doses)
- Genetic testing can guide initial dosing but is not routine in SA
Drug interactions with warfarin (high-yield for SAPC):
| Interaction | Mechanism | Effect |
|---|---|---|
| CYP2C9 inhibitors (fluconazole, metronidazole, cotrimoxazole) | ↓ warfarin metabolism | ↑ INR → bleeding |
| CYP2C9 inducers (rifampicin, carbamazepine, phenytoin) | ↑ warfarin metabolism | ↓ INR → subtherapeutic |
| Amiodarone | CYP2C9 inhibition + ↓ thyroid metabolism | ↑ INR (warfarin dose often reduced 30–50%) |
| NSAIDs, aspirin | Antiplatelet + GI erosion + protein displacement | ↑ bleeding risk |
| Vitamin K rich foods | Antagonise warfarin | ↓ INR |
| Antibiotics (broad spectrum) | ↓ Vitamin K producing gut flora | ↑ INR |
| Cranberry juice | CYP inhibition (mechanism debated) | ↑ INR |
| Garlic, ginger, ginkgo, ginseng | Antiplatelet effects | ↑ bleeding risk |
SA context for warfarin: Warfarin is the standard oral anticoagulant in the SA public sector for mechanical heart valves, atrial fibrillation, and DVT/PE. DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) are registered but expensive and not routinely available in the public sector.
Direct Oral Anticoagulants (DOACs)
| Drug | Mechanism | Dosing | Renal Dosing | Notes |
|---|---|---|---|---|
| Dabigatran | Direct thrombin (IIa) inhibitor | 150 mg BD (or 110 mg BD in ≥80 years, GI risk) | Avoid if CrCl <30; reduce if 30–50 | Reversal: idarucizumab (Praxbind) |
| Rivaroxaban | Direct factor Xa inhibitor | 20 mg daily with food (15 mg BD if acute DVT/PE) | Avoid if CrCl <15 | No reversal agent currently in SA |
| Apixaban | Direct factor Xa inhibitor | 5 mg BD (2.5 mg if ≥80 years, ≤60 kg, or Cr ≥1.5 mg/dL) | Avoid if CrCl <15 | No reversal agent in SA |
| Edoxaban | Direct factor Xa inhibitor | 60 mg daily | Reduce to 30 mg if CrCl 15–50 | Not commonly available in SA |
DOAC advantages over warfarin:
- No routine monitoring required
- Fewer food and drug interactions
- Predictable pharmacokinetics
- Faster onset (2–4 hours vs 2–3 days for warfarin)
DOAC monitoring:
- Adherence (crucial — half-lives much shorter than warfarin)
- Renal function (all DOACs — check at baseline, annually, and with acute illness)
- Hepatic function ( Child-Pugh B/C for some)
- Periodic full blood count, renal and liver function
DOAC-specific considerations in South Africa:
- Apixaban and rivaroxaban are on SAHPRA register; limited public sector availability
- Cost remains a significant barrier to widespread DOAC use
- Warfarin remains first-line for most patients in the public sector; DOACs considered in private sector or where warfarin monitoring is challenging
Antiplatelet Agents
| Drug | Mechanism | Indications | Notes |
|---|---|---|---|
| Aspirin (acetylsalicylic acid) | Irreversible COX-1 inhibition → ↓ TXA₂ → antiplatelet | Primary prevention (controversial); secondary prevention (CAD, stroke, PAD); acute MI | Low dose (75–100 mg daily); GI bleeding risk; avoid in aspirin-exacerbated respiratory disease (AERD) |
| Clopidogrel | P2Y₁₂ ADP receptor antagonist (prodrug; requires CYP2C19 activation) | Post-MI, post-stroke, peripheral artery disease; with aspirin for acute coronary syndrome; post-stent | CYP2C19 poor metabolisers (5–10% of population) get reduced activation; omeprazole (CYP2C19 inhibitor) may reduce efficacy |
| Prasugrel | P2Y₁₂ antagonist (prodrug; more efficient activation than clopidogrel) | Acute coronary syndrome (PCI); faster, more consistent platelet inhibition | Higher bleeding risk than clopidogrel; contraindicated in stroke/TIA history |
| Ticagrelor | P2Y₁₂ antagonist (direct acting; no activation needed) | ACS (with aspirin); post-MI; stroke | Dyspnoea (common); bradycardia; not a prodrug; more potent than clopidogrel |
| Dipyridamole | PDE inhibitor → ↑ cAMP → antiplatelet | Secondary stroke prevention (with aspirin) | Headache; vasodilatory |
| Cilostazol | PDE-III inhibitor → antiplatelet + vasodilation | Intermittent claudication | Contraindicated in heart failure |
Dual antiplatelet therapy (DAPT):
- Aspirin + P2Y₁₂ inhibitor (clopidogrel, prasugrel, or ticagrelor) for 6–12 months post-ACS or post-stent
- Shorter duration (3–6 months) may be used for patients at high bleeding risk
- Prolonged DAPT (>12 months) in selected patients at low bleeding risk but high ischaemic risk
Lipid-Lowering Agents
Statins (HMG-CoA Reductase Inhibitors)
Mechanism: Competitive inhibition of HMG-CoA reductase → ↓ mevalonate → ↓ cholesterol synthesis in liver → upregulation of LDL receptors → ↓ LDL cholesterol.
Classification and dosing (SA registered statins):
| Statin | Relative Potency | CYP Metabolism | SA dosing |
|---|---|---|---|
| Simvastatin | Moderate | CYP3A4 | 10–80 mg daily (20–40 mg most patients) |
| Atorvastatin | More potent | CYP3A4 | 10–80 mg daily |
| Pravastatin | Lower potency | Not extensively CYP | 20–80 mg daily (safer with interactions) |
| Rosuvastatin | Most potent | Minimal CYP (OATP uptake) | 5–40 mg daily |
Adverse effects:
- Myopathy (myalgia → myositis → rhabdomyolysis): dose-dependent; risk increased by CYP3A4 inhibitors (erythromycin, clarithromycin, ketoconazole, grapefruit juice), gemfibrozil, renal impairment, hypothyroidism
- Hepatotoxicity: LFT monitoring recommended at baseline, 12 weeks, annually; stop if LFTs >3× ULN
- New-onset diabetes: small increase in diabetes risk, especially with higher potency statins
- CNS effects: memory loss, confusion (reversible on cessation)
SAHPRA and SA context: Simvastatin is on the EML; pravastatin preferred where drug interactions are a concern. SA private sector guidelines recommend statins for secondary prevention and in high-risk primary prevention (diabetes, familial hypercholesterolaemia).
Other Lipid-Lowering Agents
Ezetimibe:
- Inhibits cholesterol absorption in small intestine (NPC1L1 transporter)
- ↓ LDL cholesterol by ~18% as monotherapy; synergistic with statins
- Used as add-on to statins when LDL target not achieved
- Very well tolerated; minimal drug interactions
Resins/Bile Acid Sequestrants:
- Cholestyramine, colestipol — bind bile acids in intestine → ↑ LDL receptor upregulation
- ↓ LDL cholesterol; cause constipation, bloating; interfere with absorption of many drugs (separate by 2–4 hours)
- Raise triglycerides — avoid in hypertriglyceridaemia
Fibrates (bezafibrate, fenofibrate):
- PPAR-α agonists → ↑ lipoprotein lipase → ↓ triglycerides significantly; modest ↓ LDL
- Used for hypertriglyceridaemia; less effective for LDL reduction
- Gemfibrozil: inhibits glucuronidation of statins → ↑ statin levels → myopathy risk; generally avoid combination
- Fenofibrate: better with statins; fibrate-statin combination increases myopathy risk but less than gemfibrozil
PCSK9 inhibitors:
- Alirocumab, evolocumab — monoclonal antibodies against PCSK9 → ↑ LDL receptor availability
- ↓ LDL cholesterol by ~50–60%
- Subcutaneous injection (every 2–4 weeks)
- Reserved for familial hypercholesterolaemia or statin-intolerant patients in SA; very expensive; not on EML
South African Dyslipidaemia Management
SA Heart and Stroke Foundation guidelines:
- LDL-C goal depends on CV risk category:
- Very high risk (established CVD, diabetes with target organ damage): LDL-C <1.8 mmol/L
- High risk (diabetes without TOD, severe dyslipidaemia): LDL-C <2.5 mmol/L
- Moderate risk: LDL-C <3.0 mmol/L
- First-line: statin (simvastatin or atorvastatin in SA); add ezetimibe if target not achieved
- Fibrates for hypertriglyceridaemia (triglycerides >5 mmol/L to prevent pancreatitis)
Antiarrhythmic Agents
Vaughan-Williams Classification
| Class | Mechanism | Examples | Notes |
|---|---|---|---|
| I | Na⁺ channel blockers | ||
| Ia | Moderate Na⁺ block + K⁺ block | Quinidine (now rarely used), procainamide, disopyramide | Prolong QT; proarrhythmic |
| Ib | Fast Na⁺ channel dissociation | lignocaine (lidocaine), mexiletine | Shorten action potential; safe in heart disease |
| Ic | Slow Na⁺ channel dissociation | Flecainide, propafenone | Proarrhythmic post-MI; avoid in structural heart disease |
| II | β-blockers | (see β-blocker section) | Rate control; reduce sudden death post-MI |
| III | K⁺ channel blockers (prolong repolarisation) | Amiodarone, sotalol, dofetilide | QT prolongation; torsades risk |
| IV | Ca²⁺ channel blockers | Verapamil, diltiazem | Rate control; AV nodal blockade |
| V | Other mechanisms | Digoxin, adenosine, ivabradine | Various |
Class IA Antiarrhythmics
Quinidine (withdrawn from most markets):
- Class Ia + vagolytic effect + α-blockade
- QT prolongation, torsades de pointes (proarrhythmic)
- Cinchonism (tinnitus, visual disturbances)
- Drug interactions: CYP3A4 substrate; inhibits CYP2D6
- Not available in South Africa in most settings
Procainamide:
- AV nodal suppression; used for AV re-entrant tachycardias
- Lupus-like syndrome (ANA positivity, arthralgia) with long-term use
- Bone marrow suppression (agranulocytosis)
- QT prolongation
Disopyramide:
- Used for ventricular arrhythmias and atrial fibrillation (rate control)
- Significant anticholinergic effects (dry mouth, urinary retention, constipation)
- Negative inotropic effect → avoid in heart failure
Class IB Antiarrhythmics
Lidocaine (lignocaine):
- IV use only (high first-pass metabolism); used in acute ventricular arrhythmias, especially in ischaemia
- Short half-life ( bolus 1–2 mg/kg IV, then infusion)
- CNS effects at toxic levels (seizures, confusion)
- SA: available as IV injection for cardiac arrhythmias and local anaesthesia
Mexiletine:
- Oral analogue of lignocaine; oral use for ventricular arrhythmias
- Used with amiodarone for refractory ventricular arrhythmias
- GI side effects; tremor
Class IC Antiarrhythmics
Flecainide:
- Contraindicated in structural heart disease (post-MI, heart failure) — CAST trial showed increased mortality
- Used for SVT (AVRT, atrial fibrillation), Brugada syndrome
- One of the few drugs that can slow AV nodal conduction enough to control AF rate
Propafenone:
- Class Ic + β-blocking activity
- Used for atrial fibrillation, ventricular arrhythmias
- Negative inotropic effect
Class III Antiarrhythmics
Amiodarone:
- Most effective antiarrhythmic; blocks multiple channels (Na⁺, K⁺, Ca²⁺ channels) and β-receptors
- Effective in both atrial and ventricular arrhythmias
- Half-life very long (15–100 days) due to tissue deposition
- Enormous adverse effect profile:
- Thyroid dysfunction (both hypo- and hyperthyroidism — contains iodine; monitor TFTs)
- Pulmonary fibrosis (-dose-related; monitor CXR, pulmonary function)
- Hepatotoxicity (monitor LFTs)
- Corneal deposits (annual ophthalmology review)
- Photosensitivity ( sunscreen essential)
- QT prolongation (but torsades less common than other Class III agents due to minimal reverse use-dependence)
- Blue-grey skin discoloration
- GI effects
- Many drug interactions (CYP3A4 inhibitor; inhibits many enzymes); increases digoxin levels
- Used in life-threatening ventricular arrhythmias, refractory atrial fibrillation
Sotalol:
- Class III + non-selective β-blocker (Class II)
- QT prolongation; torsades risk
- Used for atrial fibrillation, ventricular arrhythmias
- Start in hospital; monitor QT and HR
- Avoid in renal impairment
Class IV Antiarrhythmics
Verapamil:
- Non-dihydropyridine CCB; slows AV nodal conduction
- Used for AV re-entrant tachycardias (AVRT, AVNRT), rate control in AF
- IV verapamil for acute SVT
- Contraindicated in WPW with AF (can accelerate conduction down accessory pathway → VF)
Diltiazem:
- Similar to verapamil; less constipating
- Available IV and oral
Other Antiarrhythmics
Digoxin:
- Positive inotrope + vagotonic effect on AV node (enhances parasympathetic tone)
- Used for rate control in AF (especially with heart failure), heart failure (less used now)
- Narrow therapeutic index (0.5–2.0 ng/mL)
- Toxicity: arrhythmias (AV block, ectopic beats), nausea, vomiting, visual disturbances (yellow-green halos), confusion
- Many interactions: amiodarone, quinidine, verapamil → ↑ digoxin levels
- Renal impairment: reduce dose
Adenosine:
- Ultra-short acting (half-life ~10 seconds); IV push
- Blocks AV node conduction → terminates AVRT/AVNRT
- Diagnostically used to unmask atrial activity in wide complex tachycardia
- Side effects: flushing, chest discomfort, bronchospasm (caution in asthma)
Ivabradine:
- I(f) current inhibitor in SA node → pure rate reduction
- Used for angina (in patients who cannot use β-blockers); heart failure (recently)
- Visual effects (phosphenes — luminous phenomena)
Heart Failure Pharmacotherapy
Reduced Ejection Fraction (HFrEF)
Medications with mortality benefit in HFrEF:
| Drug Class | Example | Mortality Benefit | Notes |
|---|---|---|---|
| ACEI/ARB | Lisinopril, enalapril, losartan | ↓ Mortality | First-line; uptitrate to target dose |
| β-blocker | Carvedilol, metoprolol succinate, bisoprolol | ↓ Mortality | Start low, uptitrate slowly; target dose |
| Mineralocorticoid receptor antagonist | Spironolactone | ↓ Mortality | eplerenone if gynaecomastia; monitor K⁺ |
| ARNI | Sacubitril/valsartan (Entresto) | Superior to ACEI | Not in SA public sector; expensive |
| SGLT2 inhibitor | Empagliflozin, dapagliflozin | ↓ Mortality | Newer; evidence in HFpEF and HFrEF |
| Hydralazine + isosorbide dinitrate | Fixed combination | ↓ Mortality (African heritage patients) | Useful in patients who cannot tolerate ACEI/ARB |
Diuretics for symptom relief (no mortality benefit):
- Loop diuretics (furosemide): for volume overload
- Thiazides: for resistant oedema
- Combinations: sequential nephron blockade (use sparingly due to electrolyte disturbances)
SA public sector HF treatment: ACEI (enalapril) + β-blocker (carvedilol or metoprolol) + loop diuretic (furosemide) as first-line; add spironolactone if EF <35% and patient symptomatic.
SAPC Examination Focus Areas
High-yield topics for the SAPC exam:
- Warfarin drug interactions — CYP2C9 inhibitors/inducers, amiodarone-warfarin, vitamin K, NSAIDs
- Heparin monitoring — aPTT for UFH; anti-Xa for LMWH in renal impairment; HIT management
- Digoxin toxicity — narrow TI, hypokalaemia risk, P-gp inhibitors (amiodarone, quinidine), signs of toxicity
- Amiodarone adverse effects — thyroid (both), pulmonary fibrosis, hepatotoxicity, QT prolongation, photosensitivity, corneal deposits
- Statin myopathy — spectrum from myalgia to rhabdomyolysis; CYP3A4 interactions; gemfibrozil
- β-blocker contraindications — asthma/COPD, decompensated HF, heart block
- ACEI adverse effects — cough, angioedema (more common in African patients), hyperkalaemia, renal impairment
- Antiplatelet agents — aspirin (irreversible COX inhibition), clopidogrel (P2Y12, CYP2C19), prasugrel, ticagrelor; DAPT duration
- DHP vs non-DHP CCBs — ankle oedema (DHP), negative inotropy (non-DHP), verapamil + β-blocker interaction
- Anticoagulation in atrial fibrillation — warfarin INR target 2–3; DOAC dosing; CHA₂DS₂-VASc score
- Thiazide metabolic effects — hypokalaemia, hyperglycaemia, hyperuricaemia, hyperlipidaemia
- Heart failure medications with mortality benefit — ACEI, β-blocker, MRA (spironolactone), ARNI, SGLT2i
Summary of Key Concepts
- Antihypertensive first-line therapy in South Africa typically includes a thiazide diuretic, ACEI/ARB, or CCB (amlodipine)
- Fixed-dose combinations improve adherence and are recommended when two agents are needed
- Warfarin requires INR monitoring; major drug interactions involve CYP2C9 enzymes and vitamin K
- DOACs are registered in South Africa but not routinely available in the public sector due to cost
- LMWHs (enoxaparin) are preferred over UFH for most indications due to better pharmacokinetics and safety profile
- Antiplatelet therapy: aspirin for secondary prevention; clopidogrel added post-ACS and post-stent
- Statins: pravastatin safer in patients with drug interactions; simvastatin on EML; monitor for myopathy and hepatotoxicity
- Amiodarone: most effective antiarrhythmic but extensive adverse effects requiring monitoring; many drug interactions
- Digoxin: narrow TI; toxicity exacerbated by hypokalaemia and renal impairment; P-gp inhibitors increase levels
- Heart failure: ACEI + β-blocker + MRA (spironolactone) for reduced EF provides mortality benefit