Amiodarone, Doxazosin, Nitrates, Aldosterone antagonists

What class of drug is amiodarone?

Antiarrhythmic (predominantly Class III, but with Class I, II, and IV effects)

What are the common indications for amiodarone?

Amiodarone is used in a wide range of tachyarrhythmias: AF, atrial flutter, SVT, VT and VF.

Generally used when other treatments (drugs/electrical cardioversion) are ineffective or contraindicated.

What action(s) does amiodarone have on myocardial cells?

1) Blocks Na+, K+ and Ca2+ channels.

2) Antagonises α- and β-adrenergic receptors.

What are the effects of amiodarone on the heart?

1) Reduce spontaneous depolarisation (automaticity)

2) Increase resistance to depolarisation (refractoriness)

What are the important acute adverse effects of amiodarone?

Hypotension (IV- due to solvent) and minimal myocardial depression.

What are the important chronic adverse effects of amiodarone?

Pneumonitis, bradycardia, AV block, hepatitis, photosensitivity, grey discolouration (skin) and thyroid abnormalities.

Why does amiodarone affect the thyroid?

It contains iodine which is structurally similar to thyroid hormone.

What is notable about the half-life of amiodarone?

It is extremely long (≈ 25–100 days), so ffects and interactions may persist for months after stopping.

What are the main contraindications/warnings for amiodarone?

Severe hypotension, heart block and active thyroid disease.

Which drugs have increased levels when combined with amiodarone?

Digoxin, diltiazem and verapamil.

What should be done to digoxin, diltiazem, or verapamil doses if starting amiodarone?

Halve the dose.

Why should grapefruit juice be avoided with amiodarone?

Inhibits CYP3A4 → ↑ amiodarone levels and toxicity

How should IV amiodarone be administered outside cardiac arrest

Preferably via central line, as peripheral IV can cause phlebitis.

What monitoring is required during IV amiodarone infusion?

Continuous cardiac monitoring (HR and rhythm).

What baseline tests are required before long-term amiodarone therapy?

Renal, LFTs, TFTs and chest x-ray.

When should acute amiodarone therapy usually be stopped?

Once the underlying cause of the arrhythmia has resolved.

What drug class is doxasosin?

α-blockers.

What are the main indications for doxazosin?

Benign prostatic enlargement and HTN (as add-on therapy).

MOA of doxazosin?

Block α1-adrenoceptors in smooth muscle (blood vessels, bladder neck, prostate).

Causes vasodilation → lowers BP.

Reduces resistance to urine outflow → improves LUTS.

Key adverse effects of α-blockers?

Postural hypotension, dizziness and syncope (most pronounced after first dose).

Major warning for α-blockers?

Avoid in patients with existing postural hypotension.

Important drug interactions with α-blockers?

1) Additive BP-lowering with other antihypertensives (usually aim of treatment)

2) Symptomatic hypotension with PDE-5 inhibitors (sildenafil)

How should doxazosin be taken to reduce first-dose hypotension?

Take at bedtime, especially initially.

What is the main monitoring for α-blocker therapy?

Efficacy: Improvement in LUTS or BP.

Safety: Lying and standing BP, symptoms like dizziness.

Name a short-acting nitrate and when are they used?

1) Glyceryl trinitrate (GTN).

2) In acute angina associated with ACS.

Name a long-acting nitrate and when are they used?

1) Isosorbide mononitrate.

2) As prophylaxis of angina where a a BB or CCB are insufficient/ not tolerated.

When are IV nitrates used?

Treatment of ACS, pulmonary oedema and hypertensive emergencies.

MOA of nitrates?

Converted into nitric oxide (NO) when absorbed.

NO ↑ cGMP synthesis which ↓ intracellular Ca2+ in vascular smooth muscle cells → arterial vasodilation = ↓ cardiac preload = ↓ cardiac work = ↓ myocardial oxygen demand = relieves angina.

Name some common adverse effects of nitrates.

Flushing, headache, lightheadedness, hypotension.

What is nitrate tolerance, and how can it be minimised?

Reduced symptom relief with continued use; minimised by ensuring a daily nitrate-free period (usually overnight).

In which conditions are nitrates contraindicated?

Severe aortic stenosis and hypotension.

What major drug interaction must be avoided with nitrates?

Phosphodiesterase (PDE) inhibitors (sildenafil) due to risk of severe hypotension.

What are the common indications for aldosterone antagonists?

1) Ascites and oedema due to liver cirrhosis (spironolactone)

2) Chronic HF

3) Primary hyperaldosteronism (while waiting for surgery/not an option)

MOA of spironolactone?

Competitive inhibition at mineralocorticoid receptors:

↑ sodium and and water excretion (↓BP)

↑ potassium retention.

What is the main adverse effect of aldosterone antagonists?

Hyperkalemia, which can lead to muscle weakness, arrhythmias and even cardiac arrest.

What side effect affecting men can spironolactone cause?

Gynaecomastia (enlargement of male breast tissue).

What is another rare adverse reaction of spironolactone?

-Liver impairment and jaundice.

-SJS that causes a bullous skin eruption.

When should aldosterone antagonists be avoided?

In pregnant or lactating women.

When are aldosterone antagonists be contraindicated?

Severe renal impairment, hyperkalemia and adrenal insufficiency.

The risk of hyperkalemia is increased when aldosterone antagonists are combined with which drugs??

ACE inhibitors and ARBs.

How are aldosterone antagonists generally administered?

Orally, usually once daily, with food.

How long does it take for spironolactone to show effect?

Several days; it is a relatively weak diuretic.

How is efficacy of aldosterone antagonists monitored?

By symptom improvement: reduction in ascites, oedema, or BP.

Which drug does the described side effect most likely relate to?

"Has an extensive adverse effect profile that affecting the eyes, heart, lung, liver, thyroid gland, skin, and peripheral nervous system that may persist for a month or longer after treatment discontinuation".

Amiodarone.

Which drug is most likely to cause significant postural hypotension, particularly after the first dose, due to its selective receptor blocking effects?

Doxazosin.

Who can initiate amiodarone?

By a specialist prescriber: There should always be senior involvement when deciding to prescribe amiodarone, this must never be done independently by inexperienced or non-specialist prescribers.