Antivirals and antifungals

This presentation was used for lecture class of BSN

1. Antimicrobial agents: Antivirals and Antifungals Dr. Pravin Prasad M.B.B.S., MD Clinical Pharmacology Lecturer, Lumbini Medical College 28 February, 2019 (16 Falgun 2075), Thursday

2. By the end of the class BSN 1 st year students will be able to: Classify: Antiviral agents Antifungal agents Explain the mechanism of action of acyclovir and fluconazole List the uses and adverse effect of acyclovir and fluconazole

3. Antiviral agents Used against viral infections Antivirals required for: Immunocompromised individuals Infection with high morbidity/mortality Targets of anti-viral agents: Viral enzymes, virus directed enzymes Virus specific steps

4. Anti-viral agents: Classification Anti-herpes drugs Idoxuridine, Acyclovir, Valacyclovir Anti-influenza drugs Amantadine, Oseltamivir Anti-Hepatitis drugs/Non-selective antiviral drugs Primarily for Hepatitis B: Lamivudine, Tenofovir Primarily for Hepatitis C: Ribavirin, Interferon alpha

5. Antiretroviral agents: classification Class Drugs Nucleoside reverse transcriptase inhibitors (NRTIs) Zidovudine, Lamivudine, Didanosine, Stavudine, Abacavir, Emtricitabine, Tenofovir Non-nucleoside RTI (NNRTIs) Nevirapine, Efavirenz, Delavirdine Protease Inhibitors (- navir ) Rito navir , Lopinavir, Azatanavir , Indinavir, Nelfinavir, Saquinavir, Amprenavir

6. Antiretroviral agents: classification Class Drugs Entry (fusion) inhibitors Enfuvirtide CCR5 receptor inhibitor Maraviroc Integrase inhibitors Raltegravir

7. Acyclovir: Mechanism of Action Herpes virus specific thymidine kinase Cellular kinases 1 2 Inhibits herpes virus DNA polymerase competitively Gets incorporated into viral DNA Early termination of lengthening of viral DNA DNA polymerase inhibited irreversibly

8. Acyclovir: Uses Herpes simplex infections: Genital (Primary, Recurrent) Mucocutaneous Encephalitis Keratitis Varicella zoster infections: Herpes zoster Chickenpox

9. Acyclovir: Adverse effects Dose dependent decrease in GFR Intravenous: Rashes, sweating, fall in BP Oral: Headache, nausea, malaise Topical: Stinging and burning sensation after each application Lethargy, disorientation, hallucinations, convulsions, coma Reversible Seen at higher doses

10. Zidovudine Is used for treatment of HIV/AIDS Belongs to Nucleoside reverse transcriptase inhibitor group Other drugs: Stavudine, Lamivudine, Didanosine, Tenofovir

11. Anti-retroviral agents: targets of drugs

12. Zidovudine: Mechanism of action Gets phosphorylated intracellularly Inhibits viral Reverse Transcriptase enzyme ds DNA cannot form Viral DNA not available for incorporation in host cell DNA Gets incorporated into proviral DNA and terminates chain elongation Prevents infection of new cell

13. Zidovudine: Uses As a component of Highly active anti-retroviral therapy (HAART) Post-exposure prophylaxis Prevention of Mother to child transmission

14. Zidovudine: Adverse effects Most common: Anaemia, Neutropenia Side effects that diminishes later: Nausea, anorexia, abdominal pain Headache, insomnia Myalgia High dose: Myopathy, neurotoxicity

15. Antifungal agents Used in fungal infection Fungal infection mostly associated with use of: Broad spectrum antibiotics Corticosteroids, Immunosuppressants Dentures, indwelling catheters and implants Antifungal antibiotics: obtained from fungi like Streptomyces, Penicillium

16. Antifungal agents: Classification Antibiotics: Amphotericin B, Griseofulvin, Caspofungin Antimetabolite: Flucytosine Azoles Imidazole: Clotrimazole, Econazole, Ketoconazole Triazole: Fluconazole, Itraconazole Allylanimes : Terbinafine Others: Benzoic acid, Ciclopirox olamine

17. Fluconazole Broad spectrum antifungal agent Dermatophytes, Candida, Cryptococcous Nocardia, Leishmania Has largely replace ketoconazole: Greater efficacy, longer half life, fewer side effects Resistance common Mucor

18. Fluconazole: Mechanism of Action Acts on fungal cell membrane

19. Fluconazole: Mechanism of Action Inhibits fungal enzyme lanosterol 14-demethylase Conversion of lanosterol to ergosterol affected Abnormal membrane Lanosterol Ergosterol Lanosterol 14-demethylase Fluconazole

20. Fluconazole: Uses Coccididal meningitis, Cryptococcal meningitis Systemic candidiasis Mucocutaneous candidiasis Fungal keratitis Tinea infection Except tinea unguim Aspergillosis Mucormycosis

21. Fluconazole: Adverse effects Common, dose and duration related: Nausea, vomiting, abdominal pain Rash Headache Not recommended in pregnant and lactating mothers

22. Conclusion Antiviral agents are classified on the basis of virus against which they are primarily active Acyclovir acts by inhibiting viral DNA polymerase and getting incorporated into viral DNA, causes decrease in GFR Zidovudine is active against HIV, is a component of HAART Fluconazole is a broad spectrum antifungal, however not effective against aspergillus and mucor

23. Any queries? Next class: Drugs used for the management of Hypertension Assignment: Find out if there is someone in your family taking medicines for hypertension Generic name, dosage form, strength and frequency Thank you.