ANTI FUNGAL AGENTS-II-Continued..

ANTIFUNGAL AGENTS-Continued...

 

Azoles

1.Ketoconazole:-

It is an azole compound and we will deal one by one of some of the azole compounds in this post.

An azole is a chemical compound that has a five-membered heterocyclic structure with one nitrogen atom along with any other atom other than carbon.

The following structure may give a proper explanation.

The azole compounds are all having the same mechanism of action but different therapeutic indications. They are most convenient to use for systemic infections.

Mechanism:-

The fungal cell wall is made out of ergosterol. Ketoconazole impair the synthesis of ergosterol from its parent compound lanosterol by interfering with its metabolism by the enzyme cytochrome-P-450.

Anti-Fungal Spectrum

1.Histoplasma-Most preferable

2.Candida

3.Cryptococcus

4.Blastomyces

5.Dermatophytes

Kinetics

It is highly absorbed orally.

Ketoconazole is highly absorbed in the acid medium of the stomach juice. Hence antacids may impair its absorption.

Ketoconazole is metabolized in the liver by cytochrome-P-450 and excreted in bile.

Side effects

1.Gynecomastia and decreased libido due to inhibition of testosterone and corticosteroid synthesis

2.Nausea and Vomiting

3.Liver dysfunction(interference with cytochrome-P-450)

4.Allergies

Contraindication

Do not use ketoconazole along with amphotericin-B as they antagonize each other.

2.Fluconazole:-

Fortunately when compared with ketoconazole this compound is well absorbed orally and does not need acid pH in the stomach juice for absorption. Hence antacids will not interfere with the actions of Fluconazole.

Fungal Spectrum

1.Coccidoidal meningitis-Drug of choice

2.Disseminated histoplasmosis

3.Oral and esophageal candidiasis

4.Prophylactic to relapse of cryptococcal meningitis in AIDS patients who were treated by amphotericin-B.

Side effects

1.Nausea and vomiting

2.Headache

3.Skin rash.

3.Itraconazole:-

Itraconazole is an azole compound similar to ketoconazole. Absorption of itraconazole needs acid pH similar to ketoconazole and hence it is advisable to take itraconazole along with some orange juice or cola. Food interferes with its absorption though some manufacturers put in the label can be taken with or without meals it is better to take the drug one hour before food or two our hours after food.

Antifungal Spectrum:-

Although itraconazole shows a wider spectrum in vitro this is not true in vivo due to high plasma protein-bound up.

1.Subcutaneous chromomycosis(Blastomycosis)-Drug of choice

2.Histoplasmosis

3.Cutaneous sporotrichosis

4.Candidiasis

5.Tinea

Side effects

1.GI distress

2.Hypertriglyceridemia

3.Hypokalemia