Azoles – Antifungals

00:00 Take a look at this particular diagram.

00:03 We're going to start of with the azole antifungals.

00:06 The right down at the bottom here.

00:08 Now azole antifungals are often used in systemic infections.

00:12 And they have a variable oral bioavailability.

00:14 Some of them are actually intravenous only.

00:17 Now inducers of cytochrome P450 such as rifampin may actually decrease the bioavailability of some these agents.

00:28 So it is important to be aware that ketoconazole and other azole antifungals can be effected by inducers of cytochrome.

00:36 In terms of toxicity, common toxic reactions include vomiting, diarrhea, rash and heptatotoxicity.

00:44 Ketoconazole is a particularly bad drug for drug interaction and steroid blocking effects because it has lots of systemic effects as well as it's antifungal effect.

00:58 In terms of how these agents work, they inhibit ergosterol formation.

01:02 So ergosterol is going to be very important for the development of the cell wall within the fungal organisms.

01:09 It reduces the membrane permeability and it allows leakage of cations and nutrients out of the fungal cell.

01:18 Resistance is due to widespread use.

01:21 And we're starting to see it more and more.

01:23 It's usually because the susceptible enzymes that azoles act on, are either becoming reduced or changed.

01:32 Ketoconazole is considered a narrow spectrum antifungal.

01:36 More adverse events than other azoles.

01:39 So it's falling out of favor.

01:41 The patients that we use it on are usually patients who have chronic oral candidiasis.

01:47 And sometimes patients who have dermatological fungal infections.

01:51 I've mentioned to you before that it is a strong inhibitor of cytochrome P450.

01:57 And may increase the level of other drugs.

02:00 And inducers like rifampin may actually reduce ketoconazole levels.

02:05 Now a newer agent is fluconazole.

02:08 It's the drug of choice in most esophageal infections and oropharyngeal candidiasis.

02:13 A single oral dose often eliminates completely vaginal candidiasis.

02:19 Cryptococcal meningitis can also be treated with fluconazole, though it's typically reserved for consolidation and maintenance therapy after the initial combination of amphotericin and flucytosine.

02:30 In terms of other agents you can see them here, Canesten is the most well known azole antifungal.

02:38 Its generic name is clotrimazole.

02:41 It's a topical antifungal agent that works quite well topically or vaginally but it doesn't have a lot of use systemically.

02:49 It's often combined with a steroid like betamethasone used to treat Tinea corporis or Tinea cruris or Tinea pedis.

03:00 Itraconazole is a wide spectrum azole antifungal.

03:04 And it's often the drug of choice for infections like Blastomyces and Sporothrix schenckii.

03:11 It's the drug of choice for other types of infections as well.

03:15 Now it's an alternate drug of choice for aspergillosis, for coccidiomycoses, Cryptococcus and Histoplasma.

03:25 Voriconazole is a relatively new azole antifungal.

03:29 It has a slightly wider spectrum than the Itroconazole does.

03:32 And it may actually be better than amphotericin B.

03:35 I'm going to cover amphotericin B later.

03:39 Up to 30% of patients will develop visual blurring of unknown cause with this agent.

03:44 This is an important question, issued for you to know for questions because we often ask this particular question on exams.

03:54 Posaconazole is the broadest spectrum triazole out there.

03:59 It works against most species including Candida and Aspergillus.

04:05 It's the only azole with activity against Rhizopus and mucormycosis which may not be that commonly seen but it's something important to remember if you see a patient with mucor.