2024年11月7日 (四) 15:45的版本

蓝皮圣经第 14 版 (2022) 精要

Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 14th Edition

1 Ch61 Antifungal Agents

抗真菌剂

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)
• 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 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。

Topical Antifungal Agents (外用抗真菌药)

• Topical Imidazoles and Triazoles (外用咪唑类和三唑类)
• Individual Agents (单体药）
  • 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)