Class & Indications

• Class: Class IC antiarrhythmic

• Indications:

  • Supraventricular arrhythmias (e.g., atrial fibrillation, atrial flutter, AV nodal reentrant tachycardia)

  • Life-threatening ventricular arrhythmias (e.g., sustained ventricular tachycardia)

  • Prevention of paroxysmal atrial fibrillation (AF) in structurally normal hearts

  • Treatment of symptomatic premature ventricular contractions (PVCs)

Pharmacodynamics (PD)

• Molecular Target:

  • Blocks voltage-gated sodium channels (Nav1.5, SCN5A) in cardiac myocytes

  • Slows conduction velocity without significantly affecting repolarization

• Physiological Effect:

  • Prolongs phase 0 of the cardiac action potential

  • Reduces conduction velocity in atrial and ventricular myocardium

  • Increases the risk of arrhythmias in patients with structural heart disease

Key Pharmacokinetics (PK)

• Absorption: Well absorbed orally (bioavailability ~90%)

• Distribution:

  • Highly lipophilic, widely distributed

  • ~40% protein-bound

• Metabolism: Primarily hepatic (CYP2D6-mediated metabolism)

• Excretion:

  • Urine (~30% unchanged drug)

  • Half-life: ~12–27 hours (prolonged in renal or hepatic impairment)

• Steady-State: Reached in ~3-5 days

Contraindications

• Structural heart disease (e.g., previous myocardial infarction, cardiomyopathy, ischemic heart disease)

• Second- or third-degree AV block (without a pacemaker)

• Severe heart failure (NYHA Class III/IV)

• Cardiogenic shock

• Brugada syndrome

• Hypersensitivity to flecainide

Cautions

• Atrial fibrillation: Should not be used for rate control; ensure AV nodal blockade before initiation

• Renal or hepatic impairment: Requires dose adjustment

• Elderly patients: Increased risk of proarrhythmia and toxicity

• QT prolongation: Risk of torsades de pointes in susceptible individuals

• Electrolyte imbalances (hypokalemia, hypomagnesemia): Can exacerbate arrhythmias

Drug-Drug Interactions

• β-blockers & Calcium Channel Blockers: Additive negative inotropic effects

• Amiodarone: Increases flecainide plasma levels; requires dose reduction

• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine, quinidine): Increases flecainide levels

• Digoxin: Increased digoxin levels when used concurrently

• Warfarin: Potential enhancement of anticoagulation effects

Adverse Effects

• Cardiac:

  • Proarrhythmic effects (especially in patients with ischemic heart disease)

  • Ventricular tachycardia or fibrillation

  • Worsening heart failure

  • Conduction disturbances (e.g., AV block, sinus bradycardia)

• Non-cardiac:

  • Dizziness, blurred vision, headache

  • Nausea, GI disturbances

  • Fatigue, dyspnea

  • Rare: Hepatotoxicity, pulmonary fibrosis

Monitoring

• ECG Monitoring:

  • Widening of QRS complex (>25% increase may indicate toxicity)

  • PR interval and QT prolongation

  • Monitor for proarrhythmic effects

• Electrolytes: Ensure normal potassium and magnesium levels

• Renal & Hepatic Function: Regular monitoring in impaired patients

• Plasma Flecainide Levels: Consider therapeutic drug monitoring in at-risk patients

Dosing Regime

• Supraventricular Arrhythmias:

  • Initial: 50 mg twice daily

  • Titration: Increase by 50 mg every 4 days (max 300 mg/day)

• Ventricular Arrhythmias:

  • Initial: 100 mg twice daily

  • Max: 400 mg/day in divided doses

• Renal Impairment: Reduce dose, adjust based on renal function

• Hepatic Impairment: Use with caution; lower doses recommended

Important Clinical Practice Considerations

• Initiate under ECG monitoring in a hospital setting (especially in high-risk patients)

• Avoid in patients with significant structural heart disease or post-MI

• Always correct electrolyte disturbances before starting therapy

• Use AV nodal blocking agents (e.g., β-blockers) in AF to prevent paradoxical acceleration

• Reassess need for therapy regularly, especially in asymptomatic patients

• Class & indications:

  • Ace Inhibitor; hypertension, chronic heart failure, diabetic nephropathy (Type 1 diabetes); left-ventricular dysfunction post MI, reduction of risk of MI or cardiac arrest in people with coronary artery disease

• PD Molecular target

  • Angiotensin converting enzyme (ACE) responsible for converting angiotensin I into angiotensin II

• PD physiological effect

  • A prevention of this conversion prevents vasoconstriction caused by angiotensin II leading to reduced vascular tone, it inhibits aldosterone release which reduces retention of sodium and water, all leading to lowered blood pressure

• Key pharmacokinetics

  • Oral absorption is good, peak concentration is reached within one hour, Vd: 1-2.4 L/kg; enalapril is metabolized in the liver by carboxyl esterase 1 to the active metabolite analaprilgt; Approx. 2/3 is excreted unchanged as this active metabolite and the rest in faces via bile; renal excretion takes place both in the glomerular filtration and tubular secretion.

• Contraindications

  • Those with ACE inhibitor hypersensitivity; hx of angio-edema or hyperkalaemia and in renal artery stenosis or renal impairment

• Cautions

  • avoid in pregnancy due to potential abnormalities; volume or sodium depletion; stroke; aortic stenosis

• Drug-drug interactions

  • A consequence of ACEi is potassium retention therefore use consideration if taking a drug that promotes potassium retention (ie K+ sparing diuretics or K+ supplements), loop diuretics may lead to hypotension, reduced excretion of lithium may lead to toxicity (monitor levels), NSAIDs including Cox-2 inhibitors due to hyperkalaemia and reduced hypotensive action

• Adverse effects

  • headache, dizziness, loss of taste, nausea, dizziness, hypotension, rash, fever, joint pain, ACE inhibitor cough a well-know adverse effect occurring in 5-35% of administrations, can take weeks to months to develop as well as subside after stopping therapy

• Monitoring

  • Vital signs, renal function (serum creatinine, eGFR), cardiac activity (12-lead ECG), urine dipstick, serum potassium levels, complete blood count, monitor clinical signs of hypo perfusion and congestion in those with heart failure

• Dosing regime

  • Hypertension: initially 5mg OD, maintenance 20mg OD up to 40 mg in divided dose

  • Post-MI: oral, 2.5mg OD increasing over several days as tolerated, max 20mg in daily, divided doses

  • HF, LV systolic dysfunction: oral 2.5mg OD, close supervision, gradually increase to target does 10mg BD if tolerated, up to 20mg BD

  • Diabetic nephropathy: 10-20mg 1-2 times daily, monitor BP closely to titrate to max dose of 40mg daily

• Important clinical practice considerations

  • Dehydration

  • Regular monitoring of renal function

  • Regular monitoring of electrolytes

  • Risk of hypotension, risk of falls and dizziness, effects of impaired liver or renal function effecting concentration and serum levels

  • Use concomitantly with lithium in patients or other drugs with narrow therapeutic windows

  • Regular blood pressure monitoring