How much does amphotericin B
Amphotericin B is a broadly effective antifungal from the group of polyene antimycotics. The active ingredient is also used as a medication against leishmaniasis.
Amphotericin B is obtained from actinobacteria of the species Streptomyces nodosum.
3 Mechanism of Action
Like all polyenes, amphotericin B acts as a pore-forming agent in the plasma membrane of fungi. It is stored in the membrane together with ergosterol and forms a pore that is permeable for ions, which increases the membrane permeability. First and foremost, amphotericin B has a fungistatic effect, and in higher doses it is also fungicidal on fungi in all growth phases.
An increase in membrane permeability (especially for metabolites) was also found in various protozoa, with parasites that are pathogenic to humans being investigated.
4 dosage forms
4.1 Oral and topical application
Amphotericin B can be used against yeasts in the mouth and throat (e.g. oral thrush) and in the digestive tract via lozenges. Amphotericin B creams are also available against yeast infections of the skin.
4.2 Intravenous and intrathecal use
The systemic application of amphotericin B must be intravenous due to the lack of bioavailability when administered orally. Regional therapy in the CNS is possible via intrathecal administration. Sufficiently diluted solutions must be used in both forms of therapy in order to keep local irritation as small as possible.
Amphotericin B for systemic use has been available as amphotericin B deoxycholate, which is rich in side effects, since the 1960s. In particular, nephrotoxicity limits therapy with this active ingredient.
Since the 1990s, liposomal preparations of amphotericin B have been offered by the pharmaceutical industry as less nephrotoxic alternatives. The much more expensive liposomal amphotericin B has an effect comparable to that of amphotericin B deoxycholate, but the product is better tolerated due to significantly fewer side effects.
5.1 Treatment of fungal diseases
Amphotericin B is used as a topical and systemic, intravenously administered antifungal, among other things, in the treatment of:
Infections with Cryptococcus neoformans are also usually treated intravenously. Intrathecal treatment is only recommended in the case of meningoencephalitis, which is mostly caused by immunosuppression or AIDS.
Amphotericin B is used for systemic mycoses for 6-8 weeks. Because of its extensive side effects (especially nephrotoxicity), amphotericin B is usually only used when other medications have not previously been successful. The dosage and the pharmacokinetic data should be taken from the product information for the respective preparation.
5.2 Treatment against parasitic unicellular organisms
As a relevant intravenous medication against diseases caused by parasitic unicellular organisms, amphotericin B is mainly used today against
- visceral and mucocutaneous leishmaniasis
- Cutaneous leishmaniasis caused by leishmania from the subgenus Viannia
- other aggressive cutaneous leishmaniasis
used. Against the amastigotes-intracellular leishmanias of all leishmaniases in humans and in vertebrates at the same temperature, the desired effect is only achieved with high doses of amphotericin B.
The WHO approves both amphotericin B deoxycholate and liposomal amphotericin B for the treatment of all the leishmaniases mentioned. Due to the greater side effects of amphotericin B deoxycholate, only liposomal amphotericin B should be used in Germany according to the guidelines of the DTG (German Society for Tropical Medicine and International Health).
However, for reasons of cost, amphotericin B deoxycholate is widely available for free treatment in various less developed countries. Wherever pentavalent antimony is not to be used - e.g. in elderly patients, in patients with previous cardiac diseases or because an ECG control is not possible at the therapy site - amphotericin-B-deoxycholate may even be the most widely used drug for the treatment of leishmaniasis (e.g. in Latin America).
Dosages and application preferences compared to other medications are listed in Chap. 3.2 of the WHO guidelines, summarized in particular in boxes 1-4. In the majority of cases, a total dose is given, which is given differently for amphotericin B deoxycholate and liposomal amphotericin B, which is usually administered in 20 daily or two-day equally-dosed infusions.
5.2.2 Naegleria fowleri
Conventional amphotericin B deoxycholate is used intravenously or intrathecally against the rare, mostly fatal meningoencephalitis caused by Naegleria fowleri. The dosage should be according to the CDC recommendation.
6 side effects
Amphotericin B is rich in side effects. The most important side effect is nephrotoxicity. The kidney damage that occurs during treatment with amphotericin depends on the total cumulative dose. When using amphotericin B for a longer period of time, the lowest possible doses should be chosen. In addition, an increased intake of table salt during treatment with amphotericin B appears to reduce kidney damage to a moderate extent.
Other side effects of treatment with amphotericin B may include:
When used as an antifungal agent, the occurrence of some side effects can be partially prevented by slowly increasing the dose at the beginning of therapy. Combination therapy with flucytosine is also conceivable, but not with liposomal amphotericin B.
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