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16 Cards in this Set

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Acyclovir
(a) mechanism of action
(b) spectrum/clinical applications
(c) mechanisms of resistance
(d) toxicity/notes
(a) acyclic guanosine analog activated by viral thymidine kinase ; triphosphate formed by cellular enzymes; competitive substrate for viral DNA polymerase; chain terminator
(b) HSV-1, 2, VZV
(c) loss of thymidine kinase
(d) well tolerated; occasional GI irritation, HA; IV use asoc w/seizures, delirium, nephrotoxicity
Famcyclovir/valacyclovir
(a) mechanism of action
(b) spectrum/clinical applications
(c) mechanisms of resistance
(d) toxicity/notes
(a) Famciclovir: oral prodrug for penciclovir
Valacyclovir-oral prodrug of acylcovir
Mechanism same as acyclovir
(b) HSV esp VZV
(c) loss of thymidine kinase
(d) much greater oral bioavailability than acyclovir
Gancyclovir
(a) mechanism of action
(b) spectrum/clinical applications
(c) mechanisms of resistance
(d) toxicity/notes
(a) phorphorylated by viral kinase inhibits CMV DNA polymerase; does not cause chain termination
(b) CMV (retinitis) and HSV prophylaxis
(c) mutation in CMV polymerase and/or activating kinase; lack of viral kinase
(d) diarrhea, leukopenia and anemia, renal toxicity; toxicity limits use to life threatening or vision threatening infection
Foscarnet
(a) mechanism of action
(b) spectrum/clinical applications
(c) mechanisms of resistance
(d) toxicity/notes
(a) viral DNA/RNA polymerase inhibitor; binds to pyrophosphate binding site of enzyme; does not require activation by kinase
(b) CMV retinitis and Acylcovir resistant mucocuteneous HSV in AIDS patients
(c) point mutation in polymerase gene
(d) severe; includes nephrotoxocity, anemia, electrolyte disturbances; genitourinary ulceration; seizures
Amantadine and Rimantidine
(a) mechanism of action
(b) spectrum/clinical applications
(c) mechanisms of resistance
(d) toxicity/notes
(a) blocks viral penetration/uncoating via interaction w/viral M2; also causes release of dopamine from intact nerve terminals
(b) influenza A (prophylaxis); amantadine also used in Parkinson's to stimulate dopamine release
(c) amantadine resistance due to mutation in M2 protein; 90% of all influenza A strains
(d) ataxia; increased seizures activity; dizziness and hypotension; slurred speech; Rimantadine better tolerated in elderly
Ribavirin
(a) mechanism of action
(b) spectrum/clinical applications
(c) mechanisms of resistance
(d) toxicity/notes
(a) inhibits viral RNA synthesis by altering the nucleotide pools and normal messenger RNA formation; inhibits synth of guanine nucleotides by competitively inhibiting IMP dehydrogenase
(b) influenza A and B, parainfluenza, RSV, paramyxoviruses, HCV (combined with alpha interferon)
(c) unknown
Zidovudine
(a) mechanism of action
(b) spectrum/clinical applications
(c) mechanisms of resistance
(d) toxicity/notes
(a) converted to nucleoside triphosphate which interferes w/reverse transcriptase leading to inhibition of viral replication
(b) used for HIV in combo w/at least other 2 agents
(c) mutations in RT gene
(d) bone marrow suppression; myalgia; nausea; fatigue; headache; abnormal liver fct
Inteferons
(a) mechanism of action
(b) spectrum/clinical applications
(c) mechanisms of resistance
(d) toxicity/notes
(a) class of related proteins w/antiviral, antiproliferative and immun regulating activity; induce synth of a number of antiviral proteins
(b) hep B and C; Kaposi's sarcoma; leukemias; malignant melanoma
(c) anti Ifn antibodies seen with prolonged use
(d) Flu like sx esp in 1st weel; BM suppression; profound fatigue, myalgia, wt loss, incr susceptibility to bacterial infx; depression seen in 20% of patients
Zanamivir/oseltamivir
(a) mechanism
(b) clinical use
(a) inhibit influenza neuraminidase, decreasing release of progeny virus
(b) both influenza A and B
HIV Protease inhibitors
(a) examples
(b) mechanism
(c) toxicity
(a) saquinavir, ritonavir, indinavir, nelfinavir, amprenavir
(b) inhibit maturation of new virus by blocking protease in progeny virions
(c) GI intolerance (nausea, diarrhea, hyperglycemia, lipodystrophy, thrombocytopenia (indivanir)
HIV NRTI's
(a) examples
(b) mechanism
(c) toxicity
(a) prevent incorporation of DNA copy of viral genome into host by inhibition reverse transcriptase
(b) Zidovudine, Didanosine, Zalcitabine, stavudine, lamivudine, abacavir
(c) bone marrow suppression, periphreal neuropathy, lactic acidosis, megaloblastic anemia (AXT-zidovudine)
HIV NNRT's
(a) examples
(b) mechanism
(c) toxicity
(a) nevirapine, efavirenz, delavirdine
(b) inhibit reverse transcriptase of HIV
(c) Bone marrow suppression, peripheral neuropathy, rash
When are NNRT's or NRT's used?
Combo therapy with protease inhibitors (HAART); initiated when CD4 below 500 or when viral load is high. ZDV is used during pregnancy for prophylaxis.
Fusion inhibitors for HIV
(a) examples
(b) mechanism
(c) toxicity
(a) enfuvirtide
(b) bind viral gp41 subunit and inhibits conformational change required for fusion w/CD4 cells blocking entry
(c) hypersensitivity rxns, rxns at subq injection site, incr risk of bacterial pneumonia
What disease situations are the following used? Toxicity?
(a) IFN alpha
(b) IFN beta
(c) IFN gamma
(a) chronic hep B and C; kaposi's sarcoma
(b) MS
(c) NADPH oxidase deficiency
Neutropenia major toxicity
Antibiotics to avoid in pregnancy and effects
-Sulfonamides: kernicterus
-Aminoglycosides: ototoxicity
-fluroquinolones: cartilage damage
-erythromycin: acute cholestatic heptatitis in mom
-Clarithromycin: embryotoxic
-Metronidazole: mutagenesis
-Tetracyclines: discolored teeth and inhibition of bone growth
-Ribavirin: teratogenic
-Griseofulvin: teratogenic
-Chloramphenicol: gray baby