Antivirals

Question 1

Aciclovir

Answer 1

–When phosphorylated inhibits viral DNA polymerase

–Herpes simplex –genital herpes, encephalitis

–Varicella zoster –chicken pox & shingles

Question 2

Oseltamivir (‘Tamiflu’) / Zanamivir

Answer 2

–Inhibits viral neuraminidase
–Influenza A & B

Reversible inhibitors of NA enzyme that cleaves the sialic-acid receptor-HA bond between host-cell and virus

Effective against Inf A and B and amantadine/ rimantidineresistant strains

Resistance produces a less fit virus and is relatively infrequent, at present.

Adverse effects (oseltamivir): generally well-tolerated, some nausea, vomiting, abdominal discomfort (10-15% of patients), also rashes (rarely SJS), headaches

Adverse effects (zanamivir): again well-tolerated, though reported bronchospasm, pulmonary oedema, respiratory arrest (rarely), exacerbation of underlying airways disease in some patients

Question 3

What are the mechanisms behind Anti-retrovirals

Answer 3

Nucleoside reverse transcriptase inhibitors

Non-nucleoside reverse transcriptase inhibitors

Protease inhibitors

Entry inhibitors

HIV integrase inhibitors

Question 4

Amantadine/Rimantadine

Answer 4

Anti-influenza drugs

Inhibit the ion channel M2 function of influenza A (NOT B) viruses, preventing normal pH-mediated uncoatingand disassembly

Found later to have an anti-Parkinson’s effect also

Resistance arises readily with single aa substitutions with little affect on viral fitness.

Adverse effects at low dose: nervousness, lightheadedness, difficulty concentrating, confusion, insomnia, nausea and loss of appetite.

CNS effects are much more serious in renal impairment or high doses: delirium, hostility, hallucinations, tremor, seizures, coma.

Cardiac arrhythmias and death can occur (c.f. tricyclic antidepressant overdoses)