Pharm - Antivirals

Question 1

Main difference between RNA viruses and retroviruses

Answer 1

RNA viruses generate viral proteins without involving the host nucleus (except: influenza)

RNA retroviruses contain reverse transcriptase, integrates into host genome then produces viral particles

Question 2

Viral DNA polymerase inhibitors - name, MoA, resistance, side fx, use

Answer 2

Acyclovir is phosphorylated intracellularly by a viral thymidine kinase (specific). The ACV-TP nucleoside analogue prevents chain elongation by binding/inactivating the viral DNA polymerase

Resistance - absent or low viral thymidine kinase.
Side fx - nausea, headache, GI, rash, renal insufficency/CNS effects (rare)
Use - herpresvirus

Question 3

Neuraminidase Inhibitors - name, MoA, resistance, side fx, use

Answer 3

Zanamivir - analogue that inhibits neuraminidase of influenza A and B. Causes 1. Viral aggregation at cell surface (NA digests Hemagglutinin (HA) receptors which hold the virus to the cell)
Causes 2. Reduced spread of virus within resp tract due to increased clumping

Resistance - mutations at or outside sialic acid binding site VERY LITTLE
Side fx - inhalation well tolerated. Wheeze/bronchospasm reported w/o disease, acute deterioration with disease
Use - Influenza A + B

Question 4

Nucleoside reverse transcriptase inhibitor (NRTI) - name, MoA, resistance, side fx, use

Answer 4

Tenofovir alefenamide - HIV reverse transcriptase converts viral RNA to proviral DNA, then integrates. Fully phosphorylated analogues competitively inhibit native nucleotides, and terminate elongation of proviral DNA

Resistance - mutations at reverse transcriptase
Side fx - headache, GI, rash, fatigue, affected by inhibitors/inducers of P-glycoprotein
Use - adults, children, mothers, PrEP

Question 5

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) - name, MoA, resistance, side fx, use

Answer 5

Etravirine - allosteric (non-competitive) inhibition by direct binding to hydrophobic pocket of HIV-1 reverse transcriptase. Inhibits RNA and DNA-dependent polymerase activity.

Resistance - less resistance than typical of the class, requires multiple mutations in reverse transcriptase
Side fx - GI, rash, nausea, hypertriglyceridaemia
Use - children, adults HIV

Question 6

Protease inhibitors (PIs) - name, MoA, resistance, side fx, use

Answer 6

Darunivir - nonpetidic PI inhibits dimerisation and catalytic activity of HIV protease. Inhibits cleavage of HIV-encoded polyproteins, preventing maturation of the infectious viral particles. Increase oral bioavailability by inhibiting CYP3A4 - PK enhancer ritonavir/cobistat.

Resistance - requires multiple resistance mutations to achieve high level resistance.
Side fx - GI, rash (10% sulfa moiety), hypertriglyceridaemia, hypercholestreolaemia, hepatotoxicity.
Use - HIV1+2 in combination

Question 7

Integrase strand transfer inhibitors (INSTIs) - name, MoA, resistance, side fx, use

Answer 7

Raltegravir - blocks catalytic activity of HIV-encoded integrase, preventing integration (strand transfer) into the host chromosome. Essential component of virus living in and remaining latent

Resistance - mutations close to integrase active site
Side fx - well tolerated. Headache, nausea, fatigue
Use - HIV1+2 children, adults

Question 8

Name four goals of cART therapy

Answer 8

1. Reduce viral load
2. Restore CD4 - i.e. immune function
3. Reduce complications from HIV
4. Reduce transmission of HIV

Question 9

Types and names of drugs included in PrEP

Answer 9

2 NRTIs
Tenofovir disoproxil
Emtricitabine

High intracellular conc prevents infection at submucosal cells
Well tolerated - GI, if any