Antiviral Drugs Flashcards
Immunization
33
Most effective “treatment” (prevention) when available
Active vs. Passive
Active = vaccination
Passive = inject Ig
Amantadine
33
Antiviral
Tx: Prophylaxis of influenza A (primary use, but recently influenza strains amantidine-resistant), Also therapy for influenza A = reduces fever in 50% pts and illness duration by 1-2 days if given within first 2 days of illness
NOT influenza B
Side Effects: CNS effects (slurred, anxiety, confusion, depression)
Mechanism: Blocks viral uncoating by interfering with influenza A M2 ion channel protein
Oseltamivir
33
Antiviral
Tx: Uncomplicated influenza A and B (must be given w/in 48 hrs of symptom onset), Influenza prophylaxis
Side Effects: Bronchitis, N/V/D
Mechanism: Competitive inhibitor of influenza neuraminidases (NA); interferes with viral release and viral penetration
Pharmacology: Prodrug
Tamiflu
Trifluridine
33
Antiviral
Tx: Herpes simplex types 1 and 2 (HSV-1 and HSV-2)
Side Effects: N/A
Mechanism: Thymidine analog that interferes with DNA synthesis
Pharmacology: Form = ophthalmic ONLY
Acyclovir
33
Antiviral
Tx: IV = Rx of choice for serious systemic herpes simplex (HSV), Severe initial genital herpes
Oral = Primary genital herpes, Primary herpetic gingivostomatosis
Topical = some effect when applied early to primary genital herpes
Misc = Chickenpox
Side Effects: Generally well-tolerated, Rash, Itching, N/V, HA, Fatigue
Mechanism: Acts as competitive inhibitor of dGTP and as a DNA chain terminator (inhibits herpes DNA polymerase 10-20x more than host cell DNA polymerase = selectivity)
Pharmacology: Phosphorylated form produced 40-100x faster in infected cells by herpes thymidine kinase (TK)
Famciclovir
Famciclovir
33-02-01
Antiviral
Tx: Acute herpes zoster (shingles = latent chickenpox virus, localized and < 3 days duration), Treatment and suppression of recurrent genital herpes
Side Effects: Similar to acyclovir
Mechanism: Similar to acyclovir = prodrug converted to penciclovir, tri-Pi to active rx, and inhibits viral DNA pol
Pharmacology: Better absorbed than acyclovir
Valacyclovir = famciclovir analog, can reduce genital herpes transmission risk
Penciclovir
33-02-06 Antiviral Tx: Recurrent herpes of the lips and face Side Effects: Mechanism: Very similar to acyclovir Pharmacology: Form = topical
Ganciclovir
33-02-10
Antiviral - Anti-CMV
Tx: Cytomegalovirus (CMV) retinitis and prophylaxis for transplant pts
Side Effects: Bone marrow suppression
Mechanism: Acyclic nucleoside (guanosine) analog, similar to acyclovir (except mono-Pi is catalyzed by CMV protein kinase)
Pharmacology:
CMV in IC pts
HIV: most common cause of retinitis and visual loss
Solid organ transplants: single most common viral infxn after solid organ transplantation, often from donor organ
Anti-CMV rx will slow progression of CMV retinitis but they will NOT cure it
Best CMV retinitis strategy = prevention, effective anti-HIV rx regimens to try to get CD4 counts > 150
Foscarnet
33-02-14
Antiviral - Anti-CMV
Tx: CMV retinitis, Acyclovir-resistant herpes simplex
Side Effects: Renal damage, Electrolyte imbalance, Seizures
Mechanism: Inhibits CMV DNA polymerase by binding to its pyrophosphate binding site (does NOT require conversion to triphosphate form to be active)
Pharmacology: Compared to gancyclovir, higher % pts on foscarnet must be taken off due to side effects
Lamivudine
33-02-20 Antiviral Tx: Hepatitis B Side Effects: N/V Mechanism: Nucleoside analog (Pi by cell enz to active) that inhibits reverse transcriptase domain of heptatitis B DNA polymerase Pharmacology:
33-03-13
Antiviral - Nucleoside Analog RT Inhibitor (NRTI)
Tx: Synergistic with AZT against HIV (difficult for HIV to become resistant to both rx, AZT-resistant HIV strains = 3TC-sensitive)
Side Effects: N/D, rash
Tenofovir
33-02-21 Antiviral Tx: Hepatitis B Side Effects: GI upset Mechanism: Adenosine monophosphate analog (Pi by cell enz to active) that inhibits reverse transcriptase domain of heptatis B DNA polymerase Pharmacology:
33-03-11
Antiviral - Nucleoside Analog RT Inhibitor (NRTI)
Tx: Combination therapy for HIV (among preferred choices, fewer side effects and better viral suppression than some AZT-based regimens)
Side Effects: Well-tolerated
Mechanism: NucleoTIDE prodrug (unlike AZT), hydrolyzed to rx-monoPi, further Pi by cell enz, inhibits RT by competing w/dATP for incorporation into DNA, causing chain termination
Ribavirin
33-02-22
Antiviral
Tx: Infants and young children with documented severe Respiratory Syncitial Virus (RSV) infxn (aerosol, but aerosolized ribavirin no longer commonly used), Hepatitis C (oral capsules given with IFN-alpha and Boceprevir)
Side Effects: Aerosol may precipitate in and clog resp equipment, pulm function deterioration, IV/oral = anemia, bone marrow suppression
Mechanism: Interferes with viral mRNA synthesis
Mono-P form inhibits inosine-5’-P dehydrogenase and thus GMP (and GTP) synthesis
Tri-P form inhibits GTP-dependent capping of viral mRNA
Pharmacology:
Recombinant Interferon-alpha (PEG-IFN)
33-02-25
Antiviral
Tx: Hepatitis B, Hepatitis C (PEG-IFN’s in combo with ribavirin and boceprevir), Condyloma acuminata (venereal warts)
Side Effects: Flu-like syndrome, Leukopenia and bone marrow suppression, Neurotoxicity and myalgia
Mechanism:
Pharmacology: Side effects = greatest limit to long-term use
Boceprevir
33-02-28
Antiviral
Tx: Most effective tx for Hepatitis C genotype in combo with PEG-IFN and ribavirin as 3-rx regimen
Side Effects:
Mechanism: Reversible inhibitor or NS3 protease (cleaves polyprotein precursor into viral replication proteins) of hep C, blocks formation of infectious virus
Zidovudine (AZT)
33-03-05
Antiviral - Nucleoside Analog RT Inhibitor (NRTI)
Tx: HIV in adults and children (difficult for HIV to become resistant to both rx, 3TC-resistant HIV strains = AZT-sensitive)
Side Effects: Bone marrow suppression (neutropenia, anemia), Avoid rx which inhibit glucuronyl transferases (inhibit glucuronidation of AZT, increasing hematologic toxicity of AZT, e.g. ASA, acetaminophen, indomethacin, probenacid), Myopathy
All NRTIs = Lactic acidosis, hepatic steatosis (fatty liver)
Mechanism: Thimidine nucleoside analog Pi by cellular kinase to AZT-triP and inhibits RT and acts as chain terminator
Pharmacology:
