Therapy for Fungi and Viruses- Antifungals, Antivirals, and Antiretrovirals

2. Chapter 5 Therapy for Fungi and Viruses

3. Chapter 5 Topics • Fungi and Antifungals • Viruses and Antivirals • Antiretrovirals

4. Learning Objectives • Understand the differences between fungi and viruses and why the drugs to treat them must have very different mechanisms of action. • Differentiate antifungals, antivirals, and antiretrovirals by their indications, therapeutic effects, side effects, dosages, and administration. • Use antifungal, antiviral, and antiretroviral terminology correctly in written and oral communication. • Define differences in mechanisms of action of antibiotics, antifungals, antivirals, and antiretrovirals.

5. Fungi and Their Characteristics Fungus • Single-cell organism • Lack of chlorophyll • Rigid cell wall and nucleus • Reproduction by spores

6. Discussion In what ways are fungal cells similar to human cells? How are they different?

7. Discussion In what ways are fungal cells similar to human cells? How are they different? Answer: Human cell membranes contain cholesterol, and cell membranes of fungi contain ergosterol.

8. Fungi and Their Characteristics

9. Antifungals How They Work • Prevent synthesis of ergosterol • Because human cells use cholesterol, human cells are affected minimally

10. Antifungals Dispensed in Two Forms • Topical Agents • Systemic Agents

11. Drug List Antifungals • amphotericin B (Abelcet, AmBisome, Amphocin, Amphotec, Fungizone) • butenafine (Mentax) • caspofungin (Cancidas) • ciclopirox (Loprox, Penlac) • clotrimazole (Gyne-Lotrimin, Mycelex-7) • clotrimazole-betamethasone (Lotrisone) • fluconazole (Diflucan) • flucytosine (Ancobon) • griseofulvin (Fulvicin P/G, Gris-PEG)

12. Drug List Antifungals • itraconazole (Sporanox) • ketoconazole (Nizoral) • miconazole (Lotrimin AF, Monistat Derm, Monistat 3) • nystatin (Mycostatin) • sertaconazole (Ertaczo) • terbinafine (Lamisil) • terconazole (Terazol) • voriconazole (VFEND)

13. Antifungal Side Effects • Serious side effects have been reported, even for topical agents. • Pay close attention to dosing regimen to avoid overdosing.

14. amphotericin B (Fungizone) • Used for blood-born, life-threatening fungal infections • Infused slowly, not piggybacked, and not mixed with normal saline • Blood levels of drug monitored and vitals monitored during infusion • During treatment, monitor electrolytes, BUN, serum creatinine, temperature, CBC, fluid input and output • Side effects: renal toxicity, anemia, fever, chills, shaking, headache

15. voriconazole (VFEND) • Alternative to amphotericin B • Can be started IV and switched to oral • Can cause liver toxicity and blurred vision

16. fluconazole (Diflucan) • Oral form used for vaginal or oral candidiasis • IV used for patients who cannot tolerate oral • Commonly prescribed medication • Side effects: headache, rash, GI upset

17. itraconazole (Sporanox) • Fungal infections of nails • Capsule taken twice a day with a fatty meal and taken with a cola to increase stomach acidity and increase absorption • Not in conjunction with antacids or H2 blockers • Can cause liver toxicity • Capsules not substituted for oral solution due to absorption issues

18. terbinafine (Lamisil) • Kills fungus instead of just inhibiting growth • Oral form taken once daily • Six weeks for fingernails • Twelve weeks for toenails • Pulse dosing works well • Topical form for athlete’s foot, jock itch, and ringworm • Do not use vaginally • Do not exceed four weeks

19. Antifungal Dispensing Issues Lamisil, Lomotil, and Lamictal look alike. Use dose and dosage form to help keep these drugs from being dispensed incorrectly. Warning!

20. grisefulvin (Fulvicin P/G, Gris-PEG) • Fungal infections of the hair, skin, and nails • Take with a fatty meal • Avoid exposure to sunlight • Dizziness and drowsiness are side effects, as well as passing headache

21. clotrimazole(Gyne-Lotrimin, Mycelex-7) • Effective against oral candidiasis • Supplied as a troche • Available as OTC vaginal cream • Topical form is the DOC for ringworm

22. clotrimazole-betamethasone (Lotrisone) • Cream and lotion • Commonly prescribed medication

23. miconazole(Lotrimin AF, Monistat Derm, Monistat 3) • Treatment of vulvovaginal candidiasis • Available OTC

24. nystatin(Mycostatin) • For patients with oral candidiasis • Often used in liquid form, swish and swallow

25. ciclopirox (Loprox, Penlac) • “Nail polish” treats nail tissue infections • Do not take in combination with other oral antifungals • Dispensed in amber-colored container • Apply at bedtime to avoid exposure to light

26. Viruses and Their Characteristics Virus • Does not have components of a cell • Unable to replicate outside of a living host cell A virus infecting a bacterium.

27. Viruses and Their Characteristics Most viruses are spread through the following routes: • Direct contact • Ingestion of contaminated food and water • Inhalation of airborne particles • Exposure to contaminated body fluids/equipment

28. Viruses and Their Characteristics • Parts of a virus particle, virion • Nucleic acid consisting of either DNA or RNA, not both • Capsid (protein shell) that surrounds and protects the nucleic acid • Naked virus • Virus without an envelope covering the capsid

29. Stages of Viral Infection • Virus attaches to a cell receptor.

30. Stages of Viral Infection • Virus attaches to a cell receptor. • Cell membrane indents and closes around the virus, thus the virus penetrates the cell.

31. Stages of Viral Infection • Virus attaches to a cell receptor. • Cell membrane indents and closes around the virus, thus the virus penetrates the cell. • Virus escapes into cytoplasm.

32. Stages of Viral Infection • Virus attaches to a cell receptor. • Cell membrane indents and closes around the virus, thus the virus penetrates the cell. • Virus escapes into cytoplasm. • Virus uncoats, shedding its covering and releasing DNA or RNA into cell nucleus.

33. Stages of Viral Infection • Virus attaches to a cell receptor. • Cell membrane indents and closes around the virus, thus the virus penetrates the cell. • Virus escapes into cytoplasm. • Virus uncoats, shedding its covering and releasing DNA or RNA into cell nucleus. • Virus thus converts nuclear activity in the cell to viral activity and reproduces new viral particles.

34. Discussion Provide an example of a common viral infection and the symptoms of this condition.

35. Discussion Provide an example of a common viral infection and the symptoms of this condition. Answer: The flu (influenza). Symptoms include malaise, myalgia (muscle pain), headache, chills, fever.

36. Viral Classification Two ways that viral infections are classified • Duration and severity • Infection

37. Viral Classification • Duration and severity • Acute: quickly resolves with no latent infection such as common cold and flu • Chronic: protracted course with long periods of remission interspersed with reappearance such as herpes virus infection • Slow: progressive course, ultimately ending in death

38. Viral Classification • Infection • Local: affects tissues of a single system, such as the respiratory tract, the eye, or the skin • Generalized: has spread or is spreading to other tissues by way of bloodstream or tissues of the CNS

39. Virus and Cell Interaction A virus can damage a host cell in the following ways: • Kill the host cell • Alter the cell • Incorporate into the genetic material of the host cell • Divide when the host cell divides

40. Virus and Cell Interaction Immunoglobulin antibody that may prevent an organism from attaching to a cell receptor and may destroy the organism

41. Virus and Cell Interaction Interferon a substance that exerts virus-nonspecific but host-specific antiviral activity by inducing gene coding for antiviral proteins that inhibit the synthesis of viral RNA

42. Virus and Cell Interaction Vaccination • Exposes the patient to a component of a virus or a similar strain that does not produce infection. • When a vaccinated patient encounters the actual virus, the infection cannot develop.

43. Discussion Who should receive an influenza vaccine?

44. Discussion Who should receive an influenza vaccine? Answer: High-risk patients such as healthcare workers, nursing home residents, public safety workers, individuals over 65 years old, immunocompromised patients.

45. Antivirals Prevent virus cell replication without interfering with host cell’s normal function.

46. Drug List Antivirals Systemic Agents • acyclovir (Zovirax) • amantadine (Symmetrel) • cidofovir (Vistide) • famciclovir (Famvir) • foscarnet (Foscavir) • ganciclovir (Cytovene)

47. Drug List Antivirals Systemic Agents • oseltamivir (Tamiflu) • ribavirin (Copegus, Rebetol, Virazole) • rimantadine (Flumadine) • valacyclovir (Valtrex) • valganciclovir (Valcyte) • zanamivir (Relenza)

48. Drug List Antivirals Ocular Agent • ganciclovir (Vitrasert)

49. Therapeutic Uses of Antivirals • Cytomegalovirus (CMV) retinitis • Herpes simplex • Herpes simplex keratitis • Herpes zoster (shingles) • Influenza prophylaxis • Varicella (chicken pox)

50. Antiviral Side Effects Range from mild to severe. • Mild: headache • Severe: renal disorders