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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

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Glyceryl trinitrate (GTN) - Group 9

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Drug name: Enalapril

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

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Group 4: Dini, Livia, Ming, Bency