Antifungal drugs

a) Drugs targeting the cell membrane

  • Amphotericin BThis drug binds to ergosterols in the cell membrane to make large pores

– This leads to the leakage of cell ions causing leakage of cell content leading to cell death

– It is a broad-spectrum antibiotic which is used for many systemic fungal infections

 

Side effects: Very low therapeutic index as also affects human membranes which have cholesterol

– Flu-like symptoms

– Nephrotoxicity

– Hypokalaemia

– Hypomagnesaemia

 

  • Nystatin – This has a similar mechanism of action to amphotericin B forming pores in the membrane

– As it is so toxic, it is only used in topical treatments (e.g. for vaginal thrush)

Side effects: Diarrhoea + Rash

 

  • Azole drugs – Itraconazole + Fluconazole + Clotrimazole + Ketoconazole

These inhibit 14a-demethylase which prevents the synthesis of ergosterol in the cell membrane

– The depletion alters fluidity and permeability causing the organism to die.

Side effects: Inhibit liver enzymes CYP450 + Hepatoxicity (especially Ketoconazole)

 

  • Terbinafine – This inhibits squalene epoxidase which inhibits ergosterol synthesis

– Commonly taken orally and used for superficial fungal nail infections

Side effects: Taste disturbance

 

b) Drugs targeting other features

  • Flucytosine [targets DNA] – This drug is transported into fungal cells and made into 5-fluoruracil.

– This then inhibits thymidylate synthase needed for thymine synthesis stopping fungi making DNA

Side effects: Vomiting

 

  • Griseofulvin [targets spindle] – Inhibits mitosis by binding to tubulin thus preventing adequate spindle formation.

– It is commonly used for dermatophyte (hair and nail) infections

Side effects: Induces cytochrome P450 + teratogenic

 

  • Capsofungin [targets the cell wall] – This prevents synthesis of the fungal cell wall causing cell death

– It is very useful in fighting candida infections

Side effects: Flushing of the face

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