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How and Why Ketoconazole Works

 

The term “drug class” refers to a set of drugs that share similar characteristics. For instance, they might have a similar chemical structure, behave the same way by binding to the same target, or treat the same disease.

 

Ketoconazole belongs to the azole drug class. Other members of this class include, but are not limited to clotrimazole, econazole, miconazole, fluconazole, and itraconazole. Azoles are famous for targeting a variety of fungi, including dermatophytes like tinea and yeasts like candida and malassezia. For now, we’ll focus on ketoconazole because it’s the most widely used topical antifungal for the treatment of Malassezia yeast infections.

 

Ketoconazole, basically, works to stop fungal growth.

 

But how does it work exactly? Well think of a cell and a cell membrane. Unlike animal cells, ergosterols can be found in the cell membranes of most fungi and protozoans (for now we’ll focus on fungi cell membranes).

 

Why is ergosterol important? It helps to regulate membrane fluidity. They’re basically membrane reinforcers.

 

Antifungal drugs, like ketoconazole, work by targeting ergosterol. In fact, while ergosterol is being synthesized or made, ketoconazole inhibits it. For many fungi, this interference can lead to an increase in cell permeability, leakage of cell components and, ultimately, cell death.

 

Simply put, ketoconazole is effective because it targets ergosterol, making an otherwise impermeable cell membrane permeable. Once the membrane is permeable, cell death is almost inevitable.

 

Ketoconazole comes in two forms – oral and topical. But as of May 2016, the Food and Drug Administration advised against using oral ketoconazole tablets to treat fungal infections of the skin due to several serious side effects like toxicity, liver damage and adrenal gland problems to name a few. Yikes! You can read more about it here. For similar reasons, it has been discontinued in many other countries, as well.

 

Topical ketoconazole, however, has not been associated with these effects and is still a valuable drug for some superficial fungal infections of the skin. Nizoral A-D 1% Shampoo is an over-the-counter anti-dandruff shampoo that contains 1% ketoconazole as the active ingredient. This product can be found in some local grocery stores and on Amazon. You can read more about my personal experience with Nizoral A-D 1% Shampoo here.

 

Brand name products such as Xolegel 2% Gel (for seborrheic dermatitis), Nizoral 2% Shampoo (for tinea versicolor), Ketoderm 2% Cream (for dermatophytes and candidiasis of the skin), and Extina 2% Foam (for seborrheic dermatitis) contain prescription-strength levels of ketoconazole and, therefore, are not available over-the-counter.

 

While ketoconazole has not yet been clinically proven to treat or stop the growth of Pityrosporum (Malassezia) folliculitis specifically, it has been shown to inhibit the growth of other common fungi in the laboratory. Be sure to discuss with your doctor the possible risks and benefits of using this particular drug.

 

 

 

 

 

  1. Dufourc, E. J. (2008). Sterols and membrane dynamics.Journal of Chemical Biology,1(1-4), 63–77. http://doi.org/10.1007/s12154-008-0010-6
  2. Food and Drug Administration [Internet]. Drug Safety Communication on Nizoral (Ketoconazole) Oral Tablets; [cited 2017 Apr 8]; [about 2 p.]. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM501983.pdf
  3. Food and Drug Administration [Internet]. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/076419.pdf
  4. Rosenthal, L., Burchum, J. Feb. 2017. Lehne’s Pharmacotherapeutics for Advanced Practice Providers.

 

 

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