Antivirals + HIV drugs Flashcards
What are the 5 subclasses or anti-retrovirals?
Nucleoside reverse inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, CCR-5 Antagonists, Fusion inhibitors
What are the two mechanisms of action for antivirals?
viral DNA chain termination and incorporation into viral DNA polymerase
What is the mechanism of Acyclovir?
Acyclovir is activated by viral thymidine kinase to a triphosphate and causes both inhibition of viral DNA polymerase and chain termination
What is Acyclovir used to treat?
Treatment for CMV retinitis, Herpes I and II, Varicella Zoster, prophylaxis for immunocompromised
What are adverse effects of Acyclovir? Specifically, which patients should avoid?
GI issues, headache, decreased BP, tremors and seizures. Reduces efficacy of anti-seizure drugs.
What enzyme is required to activate ganciclovir?
Viral thymidine kinase
What is ganciclovir used to treat?
CMV infections prophylaxis and treatment, CMV retinitis
What is the mechanism of ganciclovir?
inhibits DNA polymerase and causes chain termination
What are the side effects of ganciclovir? Which patients need to be careful with this drug?
blood dyscrasias (reduction in WBC, platelet), seizures, hepatic dysfunction.
What is the mechanism of Cidofovir?
does not require viral kinase! Uses host kinases so active against viruses that are Ganciclovir and acyclovir resistant. Activated diphosphate inhibits DNA polymerase.
What conditions if Cidofovir used to treat?
CMV retinitis, mucocutaneous HSV infections, genital warts, adenovirus, HPV
What are the adverse effects of Cidofovir?
IV drug. Dose dependent nephrotoxicity. Additive nephrotoxicity with amphotericin B and aminoglycoside antibiotics.
What is mechanism of Foscarnet?
Does not need to be phosphorylated in body for activation. Inhibits viral RNA polymerase, DNA polymerase, and HIV reverse transcriptase.
What is Foscarnet used to treat?
alternate in prophylaxis and treatment of CMV.
What are the adverse effects of Foscarnet?
FoscarNOT: Nephrotoxicity, NO calcium, Neuro
What are the Nucleoside Reverse Transcriptase inhibitors?
Abacavir, didanosine, Emtricitabine, tenofovir, zidovudine
What is the mechanism for the NRTIs?
These are prodrugs converted to triphosphate by host kinases. These block reverse transcriptase (RNA-dependent DNA polymerase).
What are the side effects of Abacavir?
hypersensitivity reactions
What are the side effects of Didanosine?
pancreatitis
What are the side effects of emtricitabine?
GI, hyperpigmentation on palms and soles of feet
What are the side effects of tenofovir?
GI issues, asthenia (weakness), and headache
What is the side effect of Zidovudine?
bone marrow suppression (AZT)
What are the non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Delavirdine (prototype), Efavirenz, Etravirine
What is the mechanism of non-nucleoside reverse transcriptase inhibitors (NNRTIs)
inhibit reverse transcriptase but are not prodrugs like NRTIs (do not need to be phosphorylated). Bind different sites from nucleotides and nucleosides.
What are the adverse effects of non-nucleoside reverse transcriptase inhibitors (NNRTIs)?
Delavirdine - causes skin rash in 20% (teratogenic in animals)
Efavirenz - CNS dysfunction, skin rash
Etravirine - rash, N/D, hepatic dysfunction, increase in levels of cholesterol and transaminases
What are the protease inhibitors?
Atanzanavir, Darunavir, Fosamprenavir, Indinavir
What is the mechanism of the protease inhibitors?
assembly of HIV virions is dependent on a viral protease to cleave precursor polyproteins. Protease inhibitors block the active site of the HIV-1 protease, preventing formation of structural proteins of the mature virion core.
What are adverse effects of protease inhibitors
Think similar effects as Cushings Syndrome: disorders of carbohydrate and lipid regulation, hyperglycemia, insulin resistance, hyperlipidemia, buffalo hump (30-50% incidence), gynecomastia, truncal obesity.
What are the Entry Inhibitors?
Maraviroc and Enfuviritide
What is the mechanism of the Maraviroc?
Binds CCR-5, transmembrane chemokine receptor, to prevent viral attachment on T cells, macrophages, etc.
What are the side effects of Maraviroc?
cough, diarrhea, muscle and joint pain, increased transaminases (AST and ALT)
What is the action of Enfuviritide?
binds gp41 subunit on the viral envelope, preventing conformation changes required for fusion of viral and cellular membranes.
What are adverse side effects of enfuviritide?
hypersensitivity at injection site
What are the integrase inhibitors?
Raltegravir
What is the mechanism of Raltegravir?
inhibits final step of strand transfer from viral DNA to host DNA by binding integrase. Prevents HIV DNA inserted into host cell DNA.
What are adverse effects of Raltegravir?
GI issues, muscle pain, increase creatine kinase, rhabdomyolysis. Can also cause depression with suicidal ideation (careful!)
