Antiviral Agents Flashcards
1
Q
Describe the steps of viral replication
A
- Attachment - virus particles (virions) attaches to specific receptors on the cell surface
- Penetration - direct fusion of the virions with the cell membrane or through endocytosis and pH-mediated fusion
- Uncoating - virion disassembles, freeing RNA/DNA and nucleic acids needed for replication
- Replication/protein synthesis - viral proteins and messages and expressed
- Assembly - new virions containing viral nucleic acid are formed
- Release - new virions are released from the cell via lysis of the cell or intra/extracellular budding
2
Q
Differentiate between antivirals and antibacterials in terms of prescribing and mechanism
A
- Antiviral drugs differ from antibiotics in that antivirals do not kill the existing viruses
- Only act to prevent the replication of new viruses
- Relies on the body’s immune system to kill the existing virus
- Immunocompromised patients have difficult clearing viruses, thus are prone to viral infections even with antivirals taken
- Antivirals are rarely given empirically - normally confirm the presence of the virus before starting treatment
- Less broad-spectrum
3
Q
Describe which steps of viral replication can be targeted by drugs
A
- Fusion/entry inhibitors - prevent fusion of virions with cell membrane and thus entry into cell
- Reverse transcriptase inhibitors - prevents replication and synthesis of viral DNA from RNA
- Integrase inhibitors - prevents assembly by preventing viral DNA from integrating into the host DNA
- Protease inhibitors - prevent budding and release of the virions
4
Q
State the drugs used to treat influenza A and B, and the mechanism and resistance of these drugs
A
- Oseltamivir (Tamiflu) - taken orally, Zanamivir - inhaled/intranasally
- Mechanism - neuraminidase inhibitor - blocks release of newly assembled influenza virions from the host cell
- Resistance - mutation of neuraminidase enzyme creating an unfit virus whereby the virus becomes resistant to the antiviral however it becomes less effective in replicating
- Note that yearly vaccinations for those at risk (elderly, respiratory disease, immunocompromised) of influenza is preferred approach
5
Q
State the drugs used to treat Herpes virus HSV 1/2, VZV, and the mechanism and resistance of these drugs
A
- Aciclovir - IV, oral or topical cream
- Mechanism - DNA analogues which are phosphorylated by viral thymidine kinase and act as terminators
- Inhibits viral DNA synthesis
- Resistance - thymidine kinase enzyme mutation in the virus prevents binding to aciclovir - cannot add false substrate to viral DNA
- Aciclovir only effective during acute phase of viral infection where patient is symptomatic - not during latent phase
6
Q
State the drug used to treat Herpex virus CMV, and the mechanism and ADR of this drug
A
- Ganciclovir - IV and crosses blood-brain barrier
- Used in CMV retinitis in immunocompromised and CMV prophylaxis in transplant patients
- Mechanism - same mechanism as aciclovir but not through thymidine kinase enzyme
- ADR - myelosuppressive, carcinogenic, teratogenic, accumulates in renal failure, nephrotoxic
7
Q
State the drugs used to treat hepatitis B and their mechanism
A
- Lamivudine, adeflorvir - oral
- Used in HIV and hepatitis B
- Mechanism - reverse transcriptase inhibitor (false substrate and chain terminator)
- Causes mutation to a less violent strain
8
Q
State the drugs used to treat hepatitis C and their mechanism
A
- Sofosbuvir
- Mechanism - blocks action of hepatitis C viral polymerase to prevent production of new virus - Ribavirin - oral, IV
- Used in treatment of chronic hepatitis C and severe respiratory syncytial virus (RSV) infection in infants
- Mechanism - guanosine analogue - inhibits guanosine triphosphate formation and thus preventing RNA to DNA transcription
- ADR - transient anaemia, teratogenic
- Resistance - rare
9
Q
Describe the used of interferon alpha as treatment
A
- IM injection
- Used mainly in treatment of hepatitis B/C
- Mechanism - immunomodulatory effect - stimulate proteins to enhance cellular resistance to viral infection
- ADR - flu like illness, fever, chills, headache, malaise, myalgia, arthralgia, nausea, vomiting, diarrhoea
10
Q
State the drugs used to treat HIV
A
- Nucleoside reverse transcriptase inhibitors (NRTIs)
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- Protease inhibitors
- Fusion inhibitors
- Integrase inhibitors
- Receptor inhibitors
11
Q
Explain the action and ADRs of NRTIs
A
- Zidovudine
- Mechanism - inhibit DNA polymerase - cannot replicate DNA
- ADRs - hyperlactataemia, lactic acidosis, hepatomegaly, steatosis
12
Q
Explain the action of NNRTIs
A
- Nevirapine
- Mechanism - non-competitive inhibitors of HIV reverse transcriptase to prevent DNA replication
- NNRTIs commonly given with NRTIs as combination therapy
- NNRTIs not active against HIV-2
13
Q
Explain the action of protease inhibitors
A
- Ritonavir
- Mechanism - block cleavage of viral polyproteins by HIV protease enzyme, preventing the production of viral proteins for the formation of final mature virions
14
Q
Explain the action of fusion inhibitors
A
- Enfuvirtide - used in combination therapy with other HIV drugs
- Mechanism - interfere with fusion process between HIV and receptor
- Not active against HIV-2
15
Q
Explain the action of integrase inhibitors
A
- Raltegravir
- Mechanism - prevent integration of HIV DNA provirus into host cell genome
