Why Is Amphotericin B so Toxic to Humans?
- Dr. Koralla Raja Meghanadh
- Sep 8
- 3 min read
Amphotericin B effectively treats severe fungal infections like mucormycosis. Its toxicity arises mainly from improperly purified forms, which can cause harmful side effects.
The Role of Purity in Amphotericin B's Toxicity
Amphotericin B is derived from Amphotericin, which contains A, B, C, and X. A and B are non-toxic, while C and X are harmful. Improper extraction of Amphotericin B may result in trace amounts of C and X that can harm the human body. If the extraction process, known as lyophilization, is not done properly, trace amounts of C and X can remain in the final product, leading to side effects.
The purity of Amphotericin B plays a crucial role in determining its safety. The lower the purity, the higher the risk of adverse reactions.
Different Forms of Amphotericin B and Their Toxicity
Amphotericin B is an antifungal medication available in three main forms, each with distinct toxicity profiles:
1. Conventional Amphotericin B (Amphotericin B Deoxycholate or AMBDOC)
This is the most effective form but also the most toxic. Its efficacy stems from requiring the smallest doses to kill fungi. However, toxicity can vary significantly due to the purity of the compound. Purity levels fluctuate not only between manufacturers but even between batches from the same manufacturer. This variability sometimes necessitates discarding entire batches if test doses cause adverse reactions in patients. Due to its high toxicity, AMBDOC administration demands a highly skilled medical team of experienced doctors and nurses.
2. Liposomal Amphotericin B
Liposomes are tagged with amphotericin B and this complex can not harm the human cells as human cells lack the enzyme to split this complrc and hence human cells are safe. However, fungus has the enzyme to separate the liposomes from amphotericin B and amphotericin kills that fungal cell. This variant utilizes liposomes to target fungi more specifically. Liposomes are broken down by fungi, releasing Amphotericin B directly at the infection site. While this reduces damage to human cells, the residual Amphotericin B can still be toxic. Despite its reduced toxicity, higher doses are often required compared to the conventional form.
3. Amphotericin B Lipid Complex (Amphotericin BLC)
This version primarily travels through the bloodstream to reach infected tissues. If it cannot locate infected tissues, it remains in the bloodstream with minimal side effects. However, Amphotericin BLC struggles to penetrate tissues with mild infections, limiting its effectiveness. Additionally, it requires significantly higher doses, which complicates administration.
Verdict on Amphotericin B Variants and Toxicity
Conventional Amphotericin B (AMBDOC) is the most effective variant due to its potency at lower doses, but it is also the most toxic. When a high-purity batch is available, side effects are minimized, making it a strong option under the supervision of an experienced medical team. Liposomal Amphotericin B and ABLC are less toxic alternatives, but their reduced efficacy and need for higher doses often complicate their use, limiting their advantages in severe cases.
Alternative Antifungal Options for Black Fungus
Isavuconazole, in its IV form, is a newer antifungal drug offering similar effectiveness to Amphotericin B while being safer, but the long term effects of Isavuconazole are still unknown. It is important to note that even doctors who generally prefer administering AMBDOC, use this drug in IV form for
Conclusion
Amphotericin B is not inherently toxic but can be harmful if the extraction process is improper. The purity of Amphotericin B is crucial to minimizing side effects. However, when used properly, it is a life-saver in the vital treatment for severe fungal infections like mucormycosis.
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