Ketoconazole, the most commonly used imidazole, is an effective oral antimycotic drug with a broad spectrum of activity.
酮康唑是最常用的咪唑类药，也是有效的口服抗真菌药，具有广谱活性。
Pharmacokinetics
When given orally, ketoconazole is absorbed variably and distributed widely. It undergoes extensive liver metabolism and is excreted through bile and stool.
药动学
口服时，酮康唑吸收不定，分布广泛，大量经肝代谢，经胆汁和粪便排出。
Pharmacodynamics
Within the fungal cells, ketoconazole interferes with sterol synthesis, damaging the cell membrane and increasing its permeability. This leads to a loss of essential intracellular elements and inhibition of cell growth.
Can inhibit or kill
Ketoconazole usually produces fungistatic effects, but can also produce fungicidal effects under certain conditions.
抑菌还是杀菌
酮康唑通常起抑菌效应，在一定条件下也可产生杀菌效应。
Pharmacotherapeutics
Ketoconazole is used to treat topical and systemic infections caused by susceptible fungi, which include dermatophytes and most other fungi.
药物治疗学
酮康唑用于治疗易感真菌引起的局部和系统性感染，包括皮肤真菌和其他大多数真菌。
Drug interactions
Ketoconazole may have significant interactions with other drugs.
• Ketoconazole used with drugs that decrease gastric acidity, such as cimetidine, ranitidine, famotidine, nizatidine, antacids, and anticholinergic drugs, may decrease absorption of ketoconazole and reduce its antimycotic effects. If the patient must take these drugs, delay administration of ketoconazole by at least 2 hours.
• Taking ketoconazole with phenytoin may alter metabolism and increase blood levels of both drugs.
• When taken with theophylline, ketoconazole may decrease the serum theophylline level.
• Using ketoconazole with other liver-toxic drugs may increase the risk of liver disease.
• Combined with cyclosporine therapy, ketoconazole may increase cyclosporine and serum creatinine levels.
• Ketoconazole increases the effect of oral anticoagulants and can cause hemorrhage.
• Ketoconazole can inhibit the metabolism (and possibly increase levels) of quinidine, sulfonylureas, carbamazepine, and protease inhibitors.
• Ketoconazole shouldn’t be given with rifampin because serum ketoconazole levels may decrease.
ketoconazole – n. 酮康唑
imidazole – n. 咪唑类药
sterol synthesis – n. 甾醇合成
pharmacotherapeutic – a. 药物治疗学的
dermatophyte – n. 皮肤癣菌
cimetidine – n. 西咪替丁
ranitidine – n. 雷尼替丁
famotidine – n. 法莫替丁
nizatidine – n. 尼扎替丁
Test 1. Which of the following antifungal agents interacts with cytochrome P-450 dependent sterol 14 -demethylase to inhibit ergosterol synthesis in many fungal organisms, as well as in gram-positive bacteria and protozoans?
A. Amphotericin B
B. Flucytosine
C. Ketoconazole
D. Griseofulvin
2. Polymyxin antibiotics target what part of the bacterial cellular anatomy?
A. Ribosomes
B. Cell membrane
C. Cell wall
D. Nucleic acids
The mechanism of amphotericin B involves ergosterol, but the mechanism is not related to ergosterol synthesis. Amphotericin B binds to ergosterol in the cell membrane, disrupting its permeability to ions. Ketoconazole and other imidazoles interact with cytochrome P-450 to inhibit P-450 dependent synthesis of ergosterol by sterol 14-demethylase. Griseofulvin interacts with microtubular protein to inhibit fungal mitosis. Flucytosine incorporates into RNA and disrupts fungal protein synthesis. Zidovudine is used primarily as an antibiotic and not as an antifungal agent.
2. B. Cell membrane
Polymyxin antibiotics function by interfering with phospholipid function in bacterial cell membranes. After binding to lipopolysaccharide (LPS) in the outer membrane, polymyxins' hydrophobic tail causes damage to both the inner and outer membranes of Gram-negative bacteria.
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