2024年11月7日 (四) 16:29的版本

1 Systemic Antifungal Agents: Drugs for Deeply Invasive Fungal Infections

全身性抗真菌药物：治疗深侵袭性真菌感染的药物

• Amphotericin B (两性霉素 B)
• Flucytosine (氟胞嘧啶)
• Imidazoles and Triazoles (咪唑类和三唑类)
  • Ketoconazole (酮康唑)
  • Itraconazole (伊曲康唑)
  • Fluconazole (氟康唑)
  • Voriconazole (伏立康唑)
  • Posaconazole (泊沙康唑)
  • Isavuconazole (艾沙康唑)
• Echinocandins (棘白菌素)
  • Caspofungin (卡泊芬净)
  • Micafungin (米卡芬净)
  • Anidulafungin (阿尼杜拉芬净)
• Other Systemic Antifungal Agents (其他全身性抗真菌药)
  • Griseofulvin (灰黄霉素)
  • Terbinafine (特比萘芬)
• Agents Active Against Microsporidia and Pneumocystis (对小孢子虫和肺孢子虫有活性的药物)
  • Albendazole (阿苯达唑)
  • Fumagillin (烟曲霉素)
  • Pentamidine (喷他脒)

1.1 Itraconazole (伊曲康唑)

1.2 Fluconazole (氟康唑)

Dosage: Fluconazole is marketed in the U.S. as tablets of 50, 100, 150, and 200 mg for oral administration, powder for oral suspension providing 10 and 40 mg/mL, and intravenous solutions containing 2 mg/mL in saline and in dextrose solution. The daily dose of fluconazole should be based on the infecting organism and the patient’s response to therapy. Generally, recommended dosages are 50 to 400 mg once daily for either oral or intravenous administration. A loading dose of twice the daily maintenance dose is generally administered on the first day of therapy. Prolonged maintenance therapy may be required to prevent relapse. Children are treated with 12 mg/kg once daily (maximum 600 mg/day) without a loading dose. In adult patients, doses of up to 1200 mg have been safely administered in clinical trials for the treatment of cryptococcal meningitis.

剂量： 氟康唑在美国销售为 50、100、150 和 200 mg 口服片剂，口服混悬剂粉末提供 10 和 40 mg/mL，以及含有 2 mg/mL 的盐水和葡萄糖溶液的静脉注射溶液。氟康唑的每日剂量应基于感染微生物和患者对治疗的反应。通常，推荐剂量为 50 至 400 毫克，每天一次，口服或静脉给药。通常在治疗的第一天给予每日维持剂量 2 倍的负荷剂量。可能需要长期维持治疗以防止复发。儿童用 12 mg/kg 每天一次（最大 600 mg/天）治疗，无负荷剂量。在成年患者中，在治疗隐球菌性脑膜炎的临床试验中，已安全地施用高达 1200 毫克的剂量。

Adverse Effects: Side effects in patients receiving more than 7 days of drug, regardless of dose, include nausea, headache, skin rash, vomiting, abdominal pain, and diarrhea (all at 2%–4%). Reversible alopecia may occur with prolonged therapy at 400 mg daily. Rare cases of deaths due to hepatic failure or Stevens-Johnson syndrome have been reported. Fluconazole has been associated with skeletal and cardiac deformities in at least three infants born to two women taking high doses during pregnancy. Although a recent clinical study found no association between fluconazole receipt by mothers and most birth defects in their children, this study did find a statistically significant increase in tetralogy of Fallot in babies born to mothers who received fluconazole (Mølgaard-Nielsen et al., 2013). Fluconazole should be avoided during pregnancy.

不良反应： 接受超过 7 天药物的患者，无论剂量如何，副作用包括恶心、头痛、皮疹、呕吐、腹痛和腹泻（均为 2%-4%）。每天 400 毫克的长期治疗可能会发生可逆性脱发。已有罕见的肝功能衰竭或 Stevens-Johnson 综合征死亡病例报道。氟康唑与两名怀孕期间服用大剂量的妇女所生的至少 3 名婴儿的骨骼和心脏畸形有关。尽管最近的一项临床研究发现母亲接受氟康唑与其孩子的大多数出生缺陷之间没有关联，但这项研究确实发现接受氟康唑的母亲所生婴儿的法洛四联症在统计学上显着增加（Mølgaard-Nielsen 等人，2013 年）。怀孕期间应避免使用氟康唑。

Drug Interactions: Fluconazole is an inhibitor of CYP3A4 and CYP2C9. Fluconazole’s drug-drug interactions are shown in Tables 61–4, 61–5, and 61–6. Patients who receive more than 400 mg daily or azotemic patients who have elevated fluconazole blood levels may experience drug interactions not otherwise seen.

药物相互作用： 氟康唑是 CYP3A4 和 CYP2C9 的抑制剂。氟康唑的药物相互作用如表 61-4、61-5 和 61-6 所示。每天接受超过 400 毫克的患者或氟康唑血液水平升高的氮质血症患者可能会出现其他情况未见的药物相互作用。

1.3 特比萘芬 (Terbinafine)

Terbinafine is a synthetic allylamine, structurally similar to the topical agent naftifine (see discussion that follows). It inhibits fungal squalene epoxidase and thereby reduces ergosterol biosynthesis.

特比萘芬是一种合成烯丙胺，在结构上类似于外用剂萘替芬（见下面的讨论）。它抑制真菌角鲨烯环氧化酶，从而减少麦角甾醇的生物合成。

ADME: Terbinafine is well absorbed, but bioavailability is about 40% due to first-pass metabolism in the liver. The drug accumulates in skin, nails, and fat. The initial t1/2 is about 12 h but extends to 200 to 400 h at steady state. Terbinafine is not recommended in patients with marked azotemia or hepatic failure. Rifampin decreases and cimetidine increases plasma terbinafine concentrations.

ADME：特比萘芬吸收良好，但由于肝脏中的首过代谢，生物利用度约为 40%。该药物在皮肤、指甲和脂肪中积累。初始 t1/2 约为 12 小时，但在稳态下延长至 200 至 400 小时。不推荐将特比萘芬用于明显氮质血症或肝功能衰竭的患者。利福平降低血浆特比萘芬浓度，西咪替丁增加血浆特比萘芬浓度。

Therapeutic Uses: Terbinafine, given as one 250-mg tablet daily for adults, is somewhat more effective than itraconazole for nail onychomycosis. Duration of treatment varies with the site of infection but typically ranges between 6 and 12 weeks. The efficacy for the treatment of onychomycosis can be improved by the simultaneous use of amorolfine 5% nail lacquer (amorolfine is not approved for use in the U.S.). Terbinafine is also effective for the treatment of tinea capitis and has been used for the off-label treatment of ringworm elsewhere on the body.

治疗用途： 特比萘芬，成人每天一片 250 毫克片剂，比伊曲康唑对指甲甲真菌病更有效。治疗持续时间因感染部位而异，但通常在 6 至 12 周之间。同时使用 5% 阿莫罗芬指甲油可以提高治疗甲癣的疗效（阿莫罗芬在美国未获批使用）。特比萘芬对治疗头癣也有效，并已用于身体其他部位的癣的超说明书治疗。

Adverse Effects: The drug is well tolerated, with a low incidence of GI distress, headache, or rash. Very rarely, fatal hepatotoxicity, severe neutropenia, Stevens-Johnson syndrome, or toxic epidermal necrolysis may occur. Systemic terbinafine therapy for onychomycosis should be postponed until after pregnancy is complete.

不良反应：该药物耐受性良好，胃肠道不适、头痛或皮疹的发生率较低。极少数情况下，可能会发生致命的肝毒性、严重的中性粒细胞减少、Stevens-Johnson 综合征或中毒性表皮坏死松解症。甲癣的全身性特比萘芬治疗应推迟到妊娠完成后。

2 Topical Antifungal Agents (外用抗真菌药)

• Topical Imidazoles and Triazoles (外用咪唑类和三唑类)
  • Clotrimazole (克霉唑)
  • Econazole (益康唑)
  • Efinaconazole (艾氟康唑)
  • Miconazole (咪康唑)
  • Luliconazole (卢立康唑)
  • Terconazole and Butoconazole (特康唑和布托康唑)
  • Tioconazole (噻康唑)
  • Oxiconazole, Sulconazole, and Sertaconazole (奥昔康唑、磺康唑和舍他康唑)
  • Ketoconazole (酮康唑)
• Structurally Diverse Antifungal Agents (结构多样的抗真菌剂)
  • Ciclopirox Olamine (环吡酮乙醇胺)
  • Haloprogin （盐丙蛋白）
  • Tolnaftate (托萘酯)
  • Naftifine (萘替芬)
  • Terbinafine (特比萘芬)
  • Butenafine (布特萘芬)
  • Tavaborole (他伐硼罗)
  • Nystatin (制霉菌素)
  • Undecylenic Acid (十一烯酸)
  • Benzoic and Salicylic Acids (苯甲酸和水杨酸)