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Amphotericin

Amphotericin B

 

 

Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis.

 

 

The fungal infections it is used to treat include: aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis.

 

 

It binds with ergosterol, a component of fungal cell membranes, forming pores that cause rapid leakage of monovalent ions  of K+, Na+, H+ and Cl−, and subsequent fungal cell death. 

 

 

For certain infections it is given with flucytosine.

 

 

It is given by intravenously.

 

 

Pregnancy category US: B (No risk in non-human studies).

 

 

Bioavailability 100% (IV)

 

 

Kidney elimination half-life initial phase : 24 hours, 

 

 

second phase : approx. 15 days

 

 

Excretion 40% found in urine after single cumulated over several days 

 

 

biliary excretion is also important

 

 

Side effects include:  a reaction with fever, chills, and headaches soon after the medication is given, as well as kidney problems.

 

 

Allergic symptoms including anaphylaxis may occur.

 

 

Other serious side effects include low blood potassium and inflammation of the heart.

 

 

It relatively safe in pregnancy.

 

 

Its lipid formulation that has a lower risk of side effects.

 

 

It works in part by interfering with the cell membrane of the fungus.

 

 

Used of amphotericin B is treating a wide range of systemic fungal infections. 

 

 

Due to side effects, it is often reserved for severe infections in critically ill, or immunocompromised patients. 

 

 

It is considered first line therapy for invasive mucormycosis infections, cryptococcal meningitis, and certain aspergillus and candidal infections.

 

 

Has a low incidence of drug resistance.

 

 

It is also used for life-threatening protozoan infections such as visceral leishmaniasis and primary amoebic meningoencephalitis.

 

 

Spectrum of susceptibility

 

 

Aspergillus

 

 

Candida albicans

 

 

Candida krusei

 

 

Candida glabrata

 

 

Candida lusitaniae Intrinsically resistant

 

 

Cryptococcus neoformans

 

 

Fusarium oxysporum

 

 

 

Amphotericin B deoxycholate (ABD) is administered intravenously.

 

 

Liposomal formulations have been found to have less renal toxicity than deoxycholate,nd fewer infusion-related reactions.

 

 

They are more expensive than amphotericin B deoxycholate.[21]

 

 

An oral preparation exists but is not widely available.

 

 

Often causes, within 1 to 3 hours, serious reaction soon after infusion consisting of high fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea and tachypnea, drowsiness, and generalized weakness. 

 

 

This reaction may in part be due to histamine liberation, and increase in prostaglandin synthesis.

 

 

Initial doses should be low to prevent reactions, and increased slowly. 

 

 

Paracetamol,, diphenhydramine, and hydrocortisone have all been used to treat or prevent the syndrome.

 

 

Intravenously administered amphotericin B in therapeutic doses has is associated with multiple organ damage. 

 

 

Kidney damage is a frequent.

 

 

Less kidney toxicity has been reported with liposomal formulations and it has become preferred in patients with preexisting renal injury.

 

 

With liposomes there is a decrease in the exposure of the kidneys to amphotericin B, which explains its less nephrotoxic effects.

 

 

Electrolyte abnormalities such as hypokalemia and hypomagnesemia are also common with amphotericin.

 

 

Inncreased liver enzymes and hepatotoxicity are common. 

 

 

Pancytopenia, cardiac arrhythmias and even cardiac failure have been reported. 

 

 

Skin reactions are also possible.

 

 

Amphotericin B may facilitate entry of flucystosine into the fungal cell by interfering with the permeability of the fungal cell membrane.

 

 

The use of diuretics or cisplatin may Increase renal toxicity and increased risk of hypokalemia.

 

 

Concomitant use of corticosteroids increases risk of hypokalemia.

 

 

Other nephrotoxic drugs Increased risk of serious renal damage, and hematological changes.

 

 

Its administration is limited by infusion-related toxicities.

 

 

Infusion related side effects are thought to be a result of innate immune production of proinflammatory cytokines.

 

Nephrotoxicty is dose-dependent and duration-dependent and it is accentuated by nephrotoxic drugs.

 

Liposomal amphotericin B achieves higher intracellular concentrations than amphotericin B.

Liposomal amphotericin more effective against disseminated histoplasmosis than amphotericin B deoxycholate.

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