SN6 SHORT NOTE 5M ★ High-yield

Describe amphotericin B with its mechanism, formulations, uses and toxicity.

Pharmacology · 2nd Professional — Para-Clinical

Mechanism and Formulations

Amphotericin B is a polyene macrolide that binds ergosterol in the fungal cell membrane, forming pores through which potassium and small molecules leak, killing the cell. It is fungicidal and has the broadest spectrum of any antifungal.

Its toxicity comes from limited selectivity — it also binds human cholesterol, though with lower affinity; that single fact explains the entire adverse effect profile
Not absorbed orally; given by slow intravenous infusion over 4 to 6 hours; poor CSF penetration
Formulations — conventional deoxycholate (cheap, most nephrotoxic); liposomal amphotericin B and lipid complex (substantially less nephrotoxic, allow higher doses, but far more expensive — a genuine constraint in Indian practice)

Adverse Effects

Type	Features	Management
Infusion-related ("immediate")	Fever, rigors, chills, headache, nausea, hypotension, thrombophlebitis — from cytokine release; occur during or shortly after the infusion	Slow the infusion; premedicate with paracetamol and an antihistamine; a test dose historically; hydrocortisone if severe
Nephrotoxicity ("delayed") — dose-limiting	Reduced glomerular filtration and afferent arteriolar constriction; hypokalaemia and hypomagnesaemia from tubular loss; renal tubular acidosis; occurs in the great majority	Saline pre-loading before each dose; avoid other nephrotoxins; replace potassium and magnesium actively; switch to a lipid formulation
Haematological	Normocytic anaemia from reduced erythropoietin	Usually reversible
Cardiac	Arrhythmia if infused too rapidly, and with hypokalaemia	Infuse slowly; correct potassium

CLINICAL PEARL

Amphotericin B was nicknamed "amphoterrible" for good reason, and every part of that reputation follows from one molecular fact. It binds ergosterol strongly and cholesterol weakly — enough selectivity to be usable, not enough to be safe. The lipid formulations work by delivering the drug preferentially to fungal membranes and to reticuloendothelial tissue, reducing exposure of the renal tubule while retaining efficacy.

Uses

Life-threatening systemic mycoses — invasive candidiasis, cryptococcal meningitis (with flucytosine, then fluconazole maintenance), disseminated histoplasmosis, blastomycosis, coccidioidomycosis
Mucormycosis — the drug of choice, in high dose and always with surgical debridement and correction of the underlying immunosuppression
Invasive aspergillosis — second-line to voriconazole
Visceral leishmaniasis (kala-azar) — single-dose liposomal amphotericin B is the basis of India’s elimination programme
Empirical therapy in persistent febrile neutropenia
Topically as lozenges and oral suspension for oropharyngeal candidiasis

Applied Aspects

Pre-load with 500 mL to 1 litre of normal saline before each dose — the single most effective measure against nephrotoxicity
Measure creatinine, potassium and magnesium daily, and replace electrolytes generously; hypokalaemia is almost universal and causes arrhythmia and weakness
Never infuse rapidly; cardiac arrest has followed rapid administration, particularly in renal impairment
Distinguish infusion reactions from allergy — they are rate-related and manageable, and are not a reason to abandon the drug
Cost drives practice in India: conventional amphotericin B is a fraction of the price of liposomal, and is still widely used with careful monitoring and saline loading; the liposomal form is reserved for those with renal impairment or who cannot tolerate the conventional preparation
The mucormycosis surge during the COVID-19 pandemic in India exposed both the shortage of amphotericin B and the harm of uncontrolled diabetes and indiscriminate corticosteroid use — the pharmacology was never the limiting factor

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