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Amphotericin B

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Amphotericin B is a powerful antifungal medication used to treat life-threatening infections. It belongs to a class of drugs known as polyenes. This medicine is essential for fighting systemic fungal infections that affect the entire body. It is also used to treat leishmaniasis, which is a disease caused by protozoan parasites. Because it is so vital for human health, the World Health Organization includes it on its List of Essential Medicines. Doctors often reserve this drug for critically ill patients or those with weakened immune systems.

The way this drug works is quite specific. It targets the fungal cell membrane, which is the protective outer layer of a fungus. Inside this membrane, fungi use a molecule called ergosterol. Amphotericin B binds to the ergosterol, creating tiny holes called pores. These pores cause important ions, such as potassium, sodium, and chloride, to leak out of the cell. This rapid leakage leads to the death of the fungal cell. The bond between the drug and the ergosterol is stabilized by Van der Waals interactions.

There are several different ways to prepare this medicine for patients. The original version is called amphotericin B deoxycholate, or ABD. This is often referred to as the "conventional" formulation. Because the drug does not dissolve easily in normal saline, scientists developed lipid-based formulations. These versions use fats, or lipids, to carry the medicine. One example is AmBisome, a liposomal formulation approved by the FDA in 1997. Liposomal versions are often better tolerated because they cause less damage to the kidneys.

Other specialized formulations also exist for different medical needs. Abelcet was approved by the FDA in 1995 and uses two lipids to form ribbon-like structures. Amphotec, approved in 1996, uses a complex of amphotericin and sodium cholesteryl sulfate. While most versions are given intravenously through a vein, an oral version exists. However, oral use is not very common because the drug is difficult for the body to absorb through the digestive tract. Researchers are currently testing new nanoparticle systems to improve how oral versions work.

The history of this drug began in 1955 at the Squibb Institute for Medical Research. Scientists isolated the compound from a bacterium called Streptomyces nodosus. This bacterium was found in the river bed of the Orinoco region in Venezuela. After its discovery, the medicine entered medical use in 1958. It has remained highly effective for over fifty years. This long-term success is partly due to low drug resistance. For a fungus to become resistant, it must change so much that it can no longer cause infection in a host.

Despite its effectiveness, the drug is known for causing serious side effects. Some medical professionals even use the nickname "amphoterrible" to describe its impact. Patients often experience fever, chills, and headaches within one to three hours of receiving the infusion. This reaction is sometimes called "shake and bake." The drug can also cause damage to the kidneys, which is known as nephrotoxicity. Other risks include low potassium levels, liver problems, and even inflammation of the heart, called myocarditis.

The toxicity occurs because human cells and fungal cells are somewhat similar. Both types of cells use sterols in their membranes. While ergosterol is more sensitive to the drug, human cells use cholesterol. Amphotericin B can sometimes form pores in human membranes as well. This is why the drug can cause multiple organ damage. Scientists continue to study the drug to find ways to reduce these risks. For example, a new version called AM-2-19 has been engineered to be gentler on the kidneys.

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