Case 22

1. Case 22 Kongkrapun Pajeenboorawun, sec.c Phramacology A

2. Case: • Paolo, 17y/o, male, single who loves to play basketball, came to the clinic because of irregular whitish spots spread over his back and chest. • He described the spots to be slightly itchy and some of the lesions have round, reddish borders. • He suspected that he got this condition by using towels from his barkadas during and after basketball games. • Working diagnosis: TINEA CORPORIS

3. Tinea corporis • Tinea corporis, on the other hand, is a common superficial fungal infection of the body surface that affects persons of all ages, but particularly children. • Predisposing factors include exessive heat and humidity, exposure to infected animals, and chronic dermatophytosis of the feet or nail. • The most common type of tinea corporis is an expanding, round, slightly erythematous plaque with an elevated scaling border.

4. Tinea. A, Characteristic plague of tinea corporis. Routine histology (B) shows the picture of mild eczematous (spongiotic) dermatitis, and periodic acid-Schiff stain reveals deep red hyphae and yeast form (c) within the stratum corneum.

5. Tinea corporis • Tinea corporis (ringworm) is the name used for infection of the trunk, legs or arms with a dermatophyte fungus. • In different parts of the world, different species cause tinea corporis. In New Zealand, Trichophyton rubrum (T. rubrum) is the most common cause. Infection often comes from the feet (tinea pedis) or nails (tinea unguium) originally. • Microsporum canis (M. canis) from cats and dogs, and T. verrucosum, from farm cattle, are also common.

7. Inflammatory tineacorporis

8. 1.Give the 2 antifungal agent to treat the condition. • Topical antifungal agent. Topical azoles Econazole, Ketoconazole, Clotrimazole, Miconazole, Oxiconazole, Sulconazole Topical Allylamines Naftitine, terbinafine, and the related benzylamine butenafine • Systemic antifungal agent. Systemic azoles Fluconazole, Itraconazole,Ketoconazole

9. 2. Discuss the mechanism of action of these drug. Azoles : (Topical azoles and systemic azoles) • Inhibit the enzyme lanosterol 14-alpha-demethylase, a cytochrome P-450–dependent enzyme that converts lanosterol to ergosterol. • Inhibition of this enzyme results in unstable fungal cell membranes and causes membrane leakage. • The organism is unable to reproduce and is slowly killed by fungistatic action.

10. Azoles (cont.) • Adult Dose: Gently massage into affected and surrounding skin areas bid for 2-6 wk • Pediatric Dose: Apply as in adults • Contraindications: Documented hypersensitivity • Pregnancy: C - Safety for use during pregnancy has not been established. • Precautions: Not for treatment of systemic fungal infections; avoid contact with the eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy

11. Azoles (cont.) • Clotrimazole, is a broad-spectrum, antifungal agent used for the treatment of superficial infections caused by species of pathogenic dermatophytes. • The mechanism of action involves inhibition of the synthesis of ergosterol, a major sterol in the fungal cell membrane. • This leads to instability of the cell membrane and eventual death of the fungus

12. Azoles (cont.) • Miconazole, a potent antifungal agent, labilizes rat liver lysosomes. The effect of miconazole depends on the drug/lysosome ratio and is influenced by the pH of the incubation media, being minimal at alkaline pH. The effect of miconazole on the lysosomal • Ketoconazole 2% cream (Nizoral) -- Imidazole, broad-spectrum antifungal agent indicated for topical treatment of tinea corporis. Inhibits synthesis of ergosterol (main sterol of fungal cell membranes), causing cellular components to leak; result is cell death.

13. Azoles (cont.) • Fluconazole (Diflucan) -- Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. • Has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. • Available as tab for oral administration, as powder for oral susp, and as a sterile solution for IV use. • Has fewer adverse effects and better tissue distribution than older systemic imidazoles.

14. Allyamines • Inhibit squalene epoxidase that converts squalene to ergosterol. • This causes squalene, a substance toxic to fungal cells, to accumulate intracellularly and leads to rapid cell death. • Allylamines bind effectively to the stratum corneum because of their lipophilic nature. • They also penetrate deeply into hair follicles. • The substituted pyridone ciclopirox is another topical antifungal agent that causes membrane instability by accumulating inside fungal cells and interfering with amino acid transport across the fungal cell membrane.

15. Allyamines (cont) • Naftifine 1% cream or gel (Naftin) -- Broad-spectrum antifungal agent that appears to interfere with sterol biosynthesis by inhibiting the enzyme squalene 2,3-epoxidase. • This inhibition results in decreased amounts of sterols, causing cell death. • If no clinical improvement occurs after 4 wk, reevaluate patient.

16. Allyamines (cont.) • Terbinafine 1% cream (Lamisil) -- Fungicidal activity; synthetic allylamine derivative that inhibits squalene epoxidase, a key enzyme in sterol biosynthesis of fungi, resulting in deficiency in ergosterol that causes fungal cell death. • Use until symptoms significantly improve

17. 3.What lab procedures would you need to confirm your diagnosis & guide your treatment? • A potassium hydroxide (KOH) examination of skin scrapings may be diagnostic. • A KOH test is a microscopic preparation to visualize fungal elements removed from the skin's stratum corneum. • The sample should be taken from the active border of a lesion because this region provides the highest yield of fungal elements. A KOH preparation from a vesicular lesion should be made from the roof of the vesicle. • The KOH helps dissolve the keratin and leaves fungal elements intact, revealing numerous septate, branching hyphae amongst epithelial cells. A counterstain, such as chlorazol black E or Parker blue-black ink, may help visualize

18. Lab Studies (cont.) • A fungal culture is often used as an adjunct to KOH for diagnosis. • Fungal culture is more specific than KOH for detecting a dermatophyte infection; therefore, if the clinical suspicion is high yet the KOH result is negative

19. Lab Studies (cont.) • A few culture mediums are available for dermatophyte growth. • Sabouraud agar containing neopeptone or polypeptone agar and glucose is often used for fungal culture. However, it does not contain antibiotics and may allow overgrowth of fungal and bacterial contaminants. • Mycosel, a commonly used agar, is similar to Sabouraud agar but has antibiotics. • Commonly, dermatophyte test medium (DTM) is used. It contains antibacterial (ie, gentamicin, chlortetracycline) and antifungal (ie, cycloheximide) solutions in a nutrient agar base. • This combination isolates dermatophytes while suppressing other fungal and bacterial species that may contaminate the culture.

20. Lab Studies (cont.) • Following culture inoculation, potential fungal growth is monitored for 2 weeks. • Positive culture results vary depending on the medium used. • DTM contains phenol red solution, which causes a color change from straw-yellow to bright-red under alkaline conditions, indicating a positive dermatophyte culture result. However, the color makes identification of culture morphology (particularly pigmentation) difficult. • Sabouraud or Mycosel agar should be used to assess gross and microscopic colony characteristic

21. 4. Side effects to watch out when giving the drugs. • Systemic therapy may be indicated for cases of tinea corporis that are extensive, those that involve patients who are immunocompromised, or those that are not responsive to topical therapy. • Most of the topical agents are safe as long as they are used properly and the only side effect may be hypersensitivity.

22. Side effects(cont.) • Clotrimazole & Miconazole • SIDE EFFECTS: The most commonly noted side effects associated with clotrimazole and miconazole are local redness, stinging, blistering, peeling, swelling, itching, hives, or burning at the area of application.

23. Side effects(cont.) • Oral ketoconazole: has a risk of hepatitis in less than 1 in 10,000 cases. • Oral Itraconazole: cytochrome P-450 activity allows for the potential of interactions with other commonly prescribed drugs. • Oral terbinafine: the potential for cytochrome P-450 drug interactions with this agent is less.

24. Side effects(cont.) • Itraconazole (Sporanox) • Rare cases of reversible idiosyncratic hepatitis reported; monitor hepatic enzyme test values in preexisting hepatic function abnormalities; concomitant administration of antacids or gastric acid secretion suppressors may decrease absorption

25. Side effects(cont.) • Fluconazole (Diflucan) • Associated with rare cases of hepatotoxicity, anaphylaxis, and exfoliative skin disorders; concomitant cisapride administration may cause torsade de pointes.

26. Side effects(cont.) • Terbinafine (Lamisil) • Rare cases of hepatobiliary dysfunction, including cholestatic hepatitis, may occur; changes in ocular lens and retina have been reported, but significance is unknown; transient decreases in absolute lymphocyte count have been observed in controlled clinical trials; isolated cases of reversible severe neutropenia have been reported.

27. Thank you