SATURDAY

November 8

SESSION 3

1:45 – 2:00

AZOLES IN DERMATOLOGY

Geert Cauwenbergh

The azole drugs that are covered in this presentation belong to the imidazale and the triazole classes. Contrary to general thinking, these agents have not only had an impact on the treatment of fungal infections in Dermatology. They can be classified in 3 groups:
1. Azoles with antifungal and/or antibacterial effects (against Gram + bacteria)
2. Azoles with antifungal and anti-inflammatory effects
3. Azoles without antifungal effect but with retinoid mimetic effects

The first category covers the molecules like miconazole, econazole, terconazole, itraconazole and azoline. Ketococonazole is a member of the 2nd category
The 3rd group encompasses elubiol, liarozole and rambazole.

Although at first sight, these classes seem clearly differentiated, the reality is that one has evolved from the other. Miconazole, because of its combined inmhibitory effects on P450 isozymes and its inhibitory effects on peroxidase enzymes in micro-organisms, was able to combine antifungal and antibacterial effects. The search for improved oral bio-availability resulted in drugs that lost the antibacterial effects at therapeutic concentrations, but yielded new observations in humans (e.g. 5-LO inhibition) that resulted in suppression of chronic inflammation.

Finally, side effect observations with these oral agents have hinted towards retinoid mimetic effects. Further exploration using modern medicinal chemistry techniques, has resulted in the RAMBA category; Retinoic Acid Metabolism Blocking Agents. These drugs hold the potential to replace the synthetic retinoids as well as retinoic acid, because they appear to cause less cumulative and long lasting toxicity when given orally, and less irritation when applied topically.

In summary, the azoles covered in the last 25 years have had a profound impact on dermatological disease. Through serendipity, careful observation and intense interaction with the clinicians treating the patients, we have been able to build the chemical class of the azoles into one of the chemical classes that today affects many dermatological diseases.