Antiviral Drugs Part 2 Flashcards
Mechanism - Ganciclovir
Guanosine analog More active against CMV 5' monophosphate by CMV phosphokinase Triphosphate by cellular kinases Inhibits viral DNA poly
Clinical uses - Ganciclovir
#1 for CMV retinitis Disseminated infections - colitis and esophagitis
Side effects - ganciclovir
Bone marrow suppression - leukopenia, thrombocytopenia, neutropenia, renal toxicity
MORE TOXIZ THAN ACYCLOVIR
Mechanism - Cidofovir
Cytosine analog
No phosphorylation required
Cmv retinitis and HPV & pox virus infections (molluscum contagiosum)
Acyclovir resistant HSV
Side effects- cidofovir
Nephrotoxicity
Mechanism & clinical use - vidarabine
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
Mechanism & clinical use - idoxuridine
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
Mechanism & clinical use - trifluoridine
3 F atoms instead of H atoms on methyl group of thymidine
D.O.C for keratoconjunctivitis; topical use only
Mechanism & clinical use - Foscarnet
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
Side effects - Foscarnet
Nephrotoxicity, electrolyte abnormalities (hypo/hyper kalemia, calcemia, phosphatemia, magnesemia)
Can lead to seizures
Inhibitors of retroviruses - nucleoside (7)
Zidovudine Lamivudine Stavudine Abacavir Tenofovir Didanosine Emtricitabine
Inhibitors of retroviruses - non nucleoside inhibitors (5)
Delavirdine Efavirenz Nevirapine Etravirine Rilpivirine
Mechanism - NRTIs
Inhibits DNA synthesis by reverse transcriptase of HIV
All are chain terminators
All need to be phosphorylated
Zidovudine side effects
Bone marrow suppression (anemia) and myopathy
Lamivudine - clinical effects and use & side effects
Reduces viral load and increases CD4 count in combination with ZDV
Used also for chronic Hep B infections
Neutropenia, pancreatitis and peripheral neuropathy
Emtricitabine & Didanosine & Stavudine
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
Abacavir - combination & side effects
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
Tenofovir - analog, clinical uses, side effects
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
Mechanism, side effects & contraindications- NNRTIs
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
