Antiviral Drugs Part 2

Question 1

Mechanism - Ganciclovir

Answer 1

Guanosine analog
More active against CMV 
5' monophosphate by CMV phosphokinase
Triphosphate by cellular kinases 
Inhibits viral DNA poly

Question 2

Clinical uses - Ganciclovir

Answer 2

#1 for CMV retinitis 
Disseminated infections - colitis and esophagitis

Question 3

Side effects - ganciclovir

Answer 3

Bone marrow suppression - leukopenia, thrombocytopenia, neutropenia, renal toxicity
MORE TOXIZ THAN ACYCLOVIR

Question 4

Mechanism - Cidofovir

Answer 4

Cytosine analog
No phosphorylation required
Cmv retinitis and HPV & pox virus infections (molluscum contagiosum)
Acyclovir resistant HSV

Question 5

Side effects- cidofovir

Answer 5

Nephrotoxicity

Question 6

Mechanism & clinical use - vidarabine

Answer 6

Arabinose in place of ribose
Phosphorylated by C.K. To triphosphate
Inhibits viral DNA poly
HSV-1 infections —> encephalitis, keratitis
Less effect and more toxic than acyclovir

Question 7

Mechanism & clinical use - idoxuridine

Answer 7

Iodine atom replaces methyl group of thymidine
Triphosphate by C.K.
Too toxic for systemic used; topical treatment for keratoconjunctivitis
- because formation of faulty progeny DNA and mRNA due to mismatched pairing

Question 8

Mechanism & clinical use - trifluoridine

Answer 8

3 F atoms instead of H atoms on methyl group of thymidine

D.O.C for keratoconjunctivitis; topical use only

Question 9

Mechanism & clinical use - Foscarnet

Answer 9

Pyrophosphate analog
Prevents extension of DNA strand by preventing removal of phosphate from dNTP; inhibits addition of next dNTP
Viral DNA poly inhibition in all herpes viruses
CMV Retinitis and acyclovir resistant mutants of HSV-1 & VZV

Question 10

Side effects - Foscarnet

Answer 10

Nephrotoxicity, electrolyte abnormalities (hypo/hyper kalemia, calcemia, phosphatemia, magnesemia)
Can lead to seizures

Question 11

Inhibitors of retroviruses - nucleoside (7)

Answer 11

Zidovudine
Lamivudine
Stavudine
Abacavir
Tenofovir
Didanosine
Emtricitabine

Question 12

Inhibitors of retroviruses - non nucleoside inhibitors (5)

Answer 12

Delavirdine
Efavirenz 
Nevirapine
Etravirine
Rilpivirine

Question 13

Mechanism - NRTIs

Answer 13

Inhibits DNA synthesis by reverse transcriptase of HIV
All are chain terminators
All need to be phosphorylated

Question 14

Zidovudine side effects

Answer 14

Bone marrow suppression (anemia) and myopathy

Question 15

Lamivudine - clinical effects and use & side effects

Answer 15

Reduces viral load and increases CD4 count in combination with ZDV
Used also for chronic Hep B infections
Neutropenia, pancreatitis and peripheral neuropathy

Question 16

Emtricitabine & Didanosine & Stavudine

Answer 16

FTC —> derivative of 3TC
Prophylaxis pre/postexposure in combination with tenofovir

ddI —> metabolized to ddATP; those who are intolerant or resistant to ZDV
Pancreatitis and peripheral neuropathy

D4T —> advanced AIDS, intolerant/resistant to other therapies

Question 17

Abacavir - combination & side effects

Answer 17

Used in combination with a protease inhibitor (Daru/rito) or ZDV+3TC
Side effects —> liver damage and hypersensitivity reactions in those that have HLA-B*5701 mutation

Question 18

Tenofovir - analog, clinical uses, side effects

Answer 18

Adenosine monophosphate analog
Those who are resistant to other treatment/ those starting treatment
SHOULD be used in combination with other HIV drugs
Side effects—> liver damage, lactic acidosis and renal failure

Question 19

Mechanism, side effects & contraindications- NNRTIs

Answer 19

Do not chain terminate
Do not require phosphorylation
Bind near active site of reverse transcriptase (conformational change)
NOT USED AS MONOTHERAPY; used with NRTIs
Rash and hepatotoxiticity
Vivid dreams and CNS symptoms (dizziness, insomnia, headaches) —> efavirenz

Delavirdine and efavirenz contraindicated in pregnancy