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 1st
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

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)
Ritonavir, 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
Acyclovir
Acyclovir
Mono-
phosphate
Acyclovir
Triphosphate
1. Herpes virus specific
thymidine kinase
2.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

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
Muco
r

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
Aspergillosi
s
Mucormyco
sis

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

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