Nizoral Review Article
Nizoral having generic name Ketoconazole is an anti-fungal agent available in white tablets. It is basically used for the treatment of systemic fungal infections such as candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. It belongs to the class fluconazole. It is recommended not to use this drug for meningitis fungus as it penetrates poorly into cerebral spinal fluid. It is also use for the treatment of severe recalcitrant cutaneous dermatophyte infections. The recommended dosage of this medication is of 3.3 to 6.6 mg per kg. Minimum treatment duration is of 4 weeks. It is found that this drug may cause serious damage to liver.
Fungi (Kingdom Myceetae) are a group of organisms that are somewhat hard to describe. They are considered a group between groups, because of the sharing of characteristics between different organisms. For instance, some fungi are single- celled (like many bacteria are), while some are as large as plants. Some reproduce by fission (asexual reproduction), while others reproduce sexually. Continue reading...
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Fungi exist almost everywhere. In fact, some of them live as parasites inside the body of host organisms. They are a group of microbes considered to be a major medical concern because of the wide variety of infections and diseases that they cause. Some may be minor itches, but some can even be life threatening. Because of this, several drugs to fight off fungi have been developed. One such drug is Nizoral.
Nizoral is an antifungal agent belonging to the azoles, subclass imidazoles. It can be used either as a prophylactic agent or for treatment; and either via topical or oral route. It is prescribed for several fungal infections affecting the mouth, gastrointestinal tract (GIT), bladder, skin, hair, nails, and other parts of the body. Its molecular formula is C26H28Cl2N4O4.
Nizoral is a drug that has long established its effectiveness. In a review by Hume and Kerkeing (1983), it was shown that Nizoral use is effective in treating several fungal conditions.
Nizoral possesses antifungal activity against a wide variety of fungi. Topically, it is used for the treatment of dermatophyte infections like tinea pedis (foot), tine versicolor (skin), tinea manuum (hand), tinea capitis (head), tinea ungulum (nails) and tinea corporis. These dermatophyte infections are caused by fungi belonging to the Trichosporon, Epidermophyton and Microsporon spp.
Stratigos et al. in 2008 found that Nizoral is effective in the treatment of seborrheic dermatitis. In a study by Zaias and Drachman (1983), it was found that long-term use of Nizoral cream can effectively manage onychomycosis (nail fungal infection). See the figures on the right for these conditions.
Nizoral is an effective broad spectrum antifungal agent (Thienpont, et al., 1979). It is useful for the treatment of vaginal candidiasis (caused by Candida spp like C. albicans, C. tropicalis, C. parapsilosis and C. glabrata), dermatophyte infections not responding to topical treatment, and systemic infections like blastomycosis (Blastomyces dermatitidis), histoplasmosis (Histoplasma capsulatum), coccidioidomycosis (Coccidioides spp.), paracoccidioidomycosis (Paracoccidioides brasiliensis) and systemic candidiasis.
Nizoral is also used as a prophylactic therapy for immunocompromised patients (people who have a lower immune response, thus have a higher susceptibility for infection). Nizoral is effective in preventing possible fungal infections associated with these patients. In a study made by Estey and colleagues (1984), they found that Nizoral is an effective prophylactic agent for patients who are suffering from leukemia.
Mechanism of action
As an antifungal belonging to the azole group, Nizoral acts on the cell wall synthesis of fungi. The fungi cell wall is made up of ergosterol, a type of cholesterol. Ergosterol is synthesized from lanosterol, through the action of a microsomal CYP450 enzyme called 14-α-sterol demethylase enzyme. Impairment of the synthesis of ergosterol is lethal to fungi – it causes a variety of effects like:
a) accumulation of 14-α-methylsterol that subsequently disrupts the integrity of the fungal cell wall;
b) impairment of membrane-bound enzymes;
c) inhibition of the electron transport chain;
d) increasing of the permeability of the cell membrane.
Anti-Androgen and Anti-Glucocorticoid
Aside from its antifungal effects, Nizoral is also known for its anti-androgenic effects, and also as a potent inhibitor of glucocorticoid synthesis.
Androgens and glucocorticoids are compounds that are structurally similar to cholesterol – they possess a steroid nucleus. They are synthesized through the use of several enzymes found in the body, which act on cholesterol. As mentioned, Nizoral inhibits the synthesis of ergosterol, another compound similar to cholesterol. Because Nizoral inhibits enzymes that act on cholesterol, other compounds synthesized from cholesterol are also blocked, such as androgen and glucocorticoids. This results to a decrease amount of these compounds in the body. This was shown by Pont et al. in 1982, observing that glucocorticoids were virtually blocked after just 4 hours of 400 and 600mg dose administration.
In the synthesis of androgen and glucocorticoids, Nizoral specifically inhibits the enzymes P450c11, P450c17, C17, 20-lyase, and 3β-hydroxysteroid dehydrogenase, which are responsible for the cholesteorol side chain cleavage step. Though other azole antifungals have the same mechanism of action, it was found that Nizoral alone has the highest effect on human cholesterol enzymes. Other azoles are more selective for fungal enzymes.
Though these side effects are viewed as negative (due to the development of gynecomastia in men), it has found some other medical use. For example, in a study made by Evans and colleagues (2004), it was found that Nizoral is effective in preventing postoperative penile erections after surgery. This is due to the inhibition of testosterone, a type of androgen (Pont et al., 1982).
Another non fungal indication of Nizoral is the management of Cushing’s syndrome. Cushing’s syndrome is a hormonal disorder that is caused by high amounts of glucocorticoids in the body. The high levels of glucocorticoids may be caused by exogenous intake (drugs) or tumors. Because Nizoral inhibits glucocorticoid synthesis, it is effective in managing Cushing’s syndrome. According to Loli, Berselli and Tagliaferri (1986), Nizoral specifically inhibits adrenal 11β-hydroxlyase and 17,20-lyase, leading to a decrease in glucocorticoid levels.
Another condition that is currently being studied is androgenic alopecia. In a study by Pierard-Franchimont et al. (1998), it was found that Nizoral may be effective in the long term treatment of this condition. These findings were also reported by Rogers and Avram (2008).
ESTEY, E., MAKSYMIUK, A., SMITH, T., ET AL. 1984. Infection Prophylaxis in Acute Leukemia. Retrieved from
EVANS, K.C., PETERSON, A.C., RUIZ, H.E. & COSTABILE, R.A. 2004. Use of oral ketoconazole to prevent postoperative erections following penile surgery. Retrieved from
HUME, A.L. & KERKERING, T.M. 1983. Ketoconazole. Retrieved from
LOLI, P., BERSELLI, M.E. & TAGLIAFERRI, M. 1986. Use of ketoconazole in the treatment of Cushing's syndrome. Retrieved from
PIERARD-FRANCHIMONT, C., DE DONCKER, P. & Pierard, G.E. 1998. Ketoconazole Shampoo: Effect of Long-Term Use in Androgenic Alopecia. Retrieved from
PONT, A., WILLIAMS, P.L., LOOSE, D.S., ET AL. 1982. Ketoconazole Blocks Adrenal Steroid Synthesis. Retrieved from
PONT, A., WILLIAMS, P.L., SALMAN, A., ET AL. 1982. Ketoconazole Blocks Testosterone Synthesis. Retrieved from
STRATIGOS, J.D., ANTONIOU, C.H.R., KATSAMBAS, A., ET AL. 2008. Ketoconazole 2% cream versus hydrocortisone 1% cream in the treatment of seborrheic dermatitis: A double-blind comparative study. Retrieved from
THIENPONT, D., VAN CUTSEM, J., GERVEN, F., ET AL. 1979. Ketoconazole — a new broad spectrum orally active antimycotic. Retrieved from
REGERS, N.E. & AVRAM M.R. Medical treatments for male and female pattern hair loss. Retrieved from
ZAIAS, N. & DRACHMAN, D. A method for the determination of drug effectiveness in onychomycosis: Trials with ketoconazole and griseofulvin ultramicrosize. Retrieved from
Nizoral Review Article