I&i Antivirals, Hiv & Tb

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Properties of base analogs

Back 1

(typical antiviral agents)
activated in cell by phosphorylation
widely distributed
eliminated by kidney
usually non-specific & non-toxic

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2 drugs for Influenza A

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Amantidine & Rimantidine

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Amantidine & Rimantidine MOA

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Inhibition of uncoating
amines inhibit viral proton translocator
Used with L dopa in Parkinsons

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2 drugs for Influenza A & B

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Zanamivir & Oseltamivir

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Zanamivir & Oseltamivir MOA

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Neuraminidase inhibitor
Prevent viral release & spread

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Idoxuirdine MOA

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causes DNA breakage- historical drug (or topical) only
very toxic

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Acycloguanosine Use

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HSV, EBV, Shingles

Front 8

Acycloguanosine MOA

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interferes with DNA replication
(chain terminator)
relys on thymidine kinase

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Ganciclovir MOA

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competitive inhibitor of dGTP- chain terminator
lacks specificity of Acyclovir

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Treatment for CMV

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Ganciclovir

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Ribavirin MOA

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labilizes viral mRNA by reducing 5' cap formation

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Ribavirin Toxicities

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BM depression, GI, CNS, Teratogenic, mutagenic, carcinogenic

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Treatment for RSV, Hep C or Hanta

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Ribavirin
Hep C use ribavirin + IFN a

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5 (or 6) first line drugs for TB

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Isoniazid, Rifampicin, Pyrazinamide, Ethambutol, Streptomycin (ciprofloxacin)

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Isoniazid MOA

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Bacteriacidal: inhibition of mycolic acid synthesis-
forms inhibitory complex w/MB acyl carrier protein

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Isoniazid SEs

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Slow acetylators- Neuorpathy b/c loss of pyridoxine- (tx w/pyroxidine NOT benzos or barbits)

Fast acetylators- hepatotoxicity

Lupus like syndrome (like hydralazine & procainamide- gives positive ANA)

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Rifampicin MOA

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Blocks RNA synthesis
(inhibits DNA dependend RNA polymerase)

Hint 17

RRRRRifampicin

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Rifampicin SEs

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Drug Interactions!!
oral contraceptives, hormones, coumadin (& theophyline- like Cipro & Zileutin), others
(colors body fluids orange/red)

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Ethambutol MOA

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inhibits mycolic acid synthesis

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Ethambutol SEs

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inability to perceive green
optic neuritis
relatively non-toxic

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Pyrazinamide MOA

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inhibits mycolic acid synthesis- inhibits fatty acid synthetase I (FASI)

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Pryazinamide SEs

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flushing, arthralgia, hepatotoxicity (monitor enzymes)
synergistic w/isoniazide

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Classes of treatment for HIV

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NRTIs
NNRTIs
PI
Entry Inhibitor

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6 NRTIs

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Azidothymidine (zidovudine)- BM
Stavudine- P & PN
Lamivudine (3-thiacytidine)- P & PN
Dideoxyinosine- P & PN
Abacavir- allergies
Tenofovir- (SEs like PIs)

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Azidothymidine MOA

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RTI & chain terminator- cell becomes deficient in thymidine

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Azidothymidine SEs

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Severe:
BM, granulocytopenia, anemia, neurotoxic, NVHA, insomnia, myalgia
25% of patients can't tolerate

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Stavudine MOA

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RTI & chain terminator

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Stavudine SEs

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interferes w/mitochondrial DNA
contraindicated w/AZT
pancreatitis

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Lamivudine MOA

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less active & less toxic than AZT

Prevents resistance to AZT

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Lamivudine SEs

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less severe than AZT
no BM, no neuro
resistance quickly w/cross resistance to ddI, ddC & abacavir

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3TC

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Lamivudine

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d4T

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Stavudine

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Prevents resistance to AZT

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Lamivudine

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Dideoxyinosine MOA

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RTI

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Dideoxyinosine SEs

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pancreatitis & mitochondrial

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Abacavir MOA

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guanosine analog, RTI

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Abacavir SEs

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allergies, fever, rash, respiratory

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Tenofovir MOA

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RTI-

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Tenofovir SEs

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Unique- GI, glycosuria, hyperglycemia & triglyceridemia, renal, neutropenia

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3 NNRTIs

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Nevirapine
Delavirdine
efavirenz

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NNRTIs MOA

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RTI not nucleoside analog

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NNRTIs SEs

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fever, nausea, CNS, hepatotoxicity
rash to Stevens-Johnson

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Protease Inhibitors Names

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saquin-
indin-
riton-
melfin-
ampren-
lopin- avir

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PIs MOA

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prevent cleavage of HIV protein precursors

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PIs SE

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diabetes & diabetic like syndrome, cholesterol & TGs increased, fat wasting, asthenia,

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Treatment guidelines for HIV

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2 NRTIs & a PI
2 NRTIs & a NNRTI
1 NRTI & 1 NNRTI & 2 PIs

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Enfuvirtide MOA

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entry inhibitor
prevents HIV binding to CD4