Antivirals Flashcards
Which Drugs can be used to treat Herpes?
- Aciclovir
- Ganciclovir
- Cidofovir
- Foscarnet
What is the mechanism of action of Aciclovir?
- Phosphorylated by thymidine kinase
- Then phosphorylated twice by the cells to form active aciclovir triphosphate
- Competes with dGTP as a substrate for viral DNA polymerase as well as acting as a chain terminator
What are the side effects of Aciclovir?
- Some nephrotoxicity
- CNS symptoms (lethargy, confusion, tremor, myoclonus, hallucinations, delirium, seizures, autonomic symptoms, coma, extrapyramidal signs)
What is the mechanism of resistance of aciclovir?
Resistance arises via:
- Absent/reduced TK enzyme
- Altered TK substrate target
- Altered DNA polymerase
What is used to treat Influenza A & B drugs gained?
- Oseltamavir (orally)
- Zanamivir (inhaler/intranasal)
What is the mechanism of action of influenza A & B drugs gained?
Neuraminidase inhibitor - blocks release of newly assembled influenza virions from the host cell
How is resistance against influenza A & B drugs gained?
Mutation of Neuraminidase enzyme (often less infective: “less fit virus”)
What are examples of use of oseltamivir and zanamivir?
Can be used prophylactically to prevent infection or within 48 hours of infection to reduce intensity and duration of symptoms. Yearly vaccinations for those at risk
When is Aciclovir used?
Aciclovir only effective during acute phase of viral infection where patient is symptomatic. Not during latent phase. Wont prevent new outbreak, only help to control time/severity of outbreak.
What is ganciclovir used for?
Currently used for CMV retinitis in immunocompromised and CMV prophylaxis in
transplant patients.
What is the mechanism of action of Ganciclovir?
Analogue of acyclovir (10-50 times greater activity against CMV) acts in same way but is phosphorylated using different enzyme - not thymidine kinase
What are ADRs of ganciclovir?
- Myelosupressive (severe dose dependent neutropenia)
- Carcinogenic/teratogenic
- Renally cleared so accumulates in renal failure.
What is Lamivudine used to treat?
- HIV
- Hep B
How does Lamivudine work?
Reverse transcriptase inhibitor
How does SOFOSBUVIR work?
Blocks action of HCV viral polymerase to prevent production of new virus
What is Interferon Alpha used for?
-Used mainly in the treatment of Hep B/C
What is the mechanism of action of Interferon Alpha?
-Immunomodulatory effect
What are adverse effects of Interferon Alpha?
- Flu-like illness
- Fever, chills
- Headache
- Malaise
- Myalgia
- Arthralgia
- Nausea
- Vomiting
- Diarrhoea
What is the Ribavirin used for?
-Used in treatment of chronic hepatitis C (in combination with interferon alpha) and treatment of infants with severe RSV infection
What is the mechanism of action of Ribavirin?
-Guanosine analogue: inhibits guanosine triphosphate formation preventing viral messenger RNA capping. Essentially prevents assembly of viral genome/DNA
What are ADRs of Ribavirin?
- Transient anaemia
- Teratogenic
How is HIV treated?
2 NRTIs and 1 of:
- NNRTI
- Protease inhibitors
- Integrase inhibitors
- Fusion inhibitors
What is the mechanism of action of HIV Drugs?
NRTI: Inhibit DNA polymerase
NNRTI: Active without further phosphorylation. Non-competitive inhibitors of HIV reverse transcriptase – bind at different sites to the
NRTI but have same effect = therefore can be used as combination therapy. Only work on HIV-1 not HIV-2
Protese inhibitor: Block the cleavage of viral polyproteins by HIV protease enzyme, preventing the production of viral proteins for the formation
of final mature virions
Intergrase Inhibitors: Prevent integration of HIV DNA provirus into host cell genome
Why is antiviral drug resistance testing needed?
- To optimise the clinical outcomes, quality of life, longevity of the patient
- To save costs and adverse effects of ineffective therapy
- To reduce the pool of drug resistant viruses in the population that may transmit between individuals, reducing the effectiveness of standard therapy
When is antiviral drug resistance testing used?
-Evidence of therapeutic failure: could be due to resistance, poor compliance, as baseline prior to starting new medication
How is antiviral drug resistance testing done?
- Incubate suspected drug resistant virus with varying concentrations of the drug of interest in a culture
- Look for graded response compared to a wild-type virus, e.g. enzyme-activity changes, PRNT
- Can then look at specific sequencing/genotype of the mutation
