Anti-virals- The AIDs Flashcards
Zidovudine
RTI
PK: oral, absorbed from GI, good CNS penetration
metabolized in liver and remainder excreted in kidney
short duration of action- 5x/day
MOA: deoxythymidine analogue - converted intracellularly to active triphosphate –> incorporated into DNA but lacks 3’OH –> inhibits viral reverse transcriptase
Uses:
- any form of HIV/AIDS
- give early in disease to decrease rate of progression of disease, prolong survivial, prevent infections (kaposi sarcoma and opportunistic infections)
- given in pregnancy to dec. risk of transmission to the baby
- High doses used in AIDs dementia
- tx psoriasis and Adult T cell leukemia
Toxicity
- Myelosuppression- anemia, neutropenia
- CNS (HA/Fatigue/insomnia)
- GI (N/V/D)
Drug interactions
- inc. risk of neutropenia with acetaminopeh
- comcomitant use with neurotoxic, nephrotoxic or bone marrow affecting drugs will inc. toxicity ( DAPSON, pentamidine, vincristin, vinblastine, interferon)
- Acyclovir: somnolence and lethargy
- Cimetidine and benzodiazepine: inhibit metabolism in liver
- probenacid: impari elimination
Lamivudine (HIV)
RTI
MOA: Cytosine analogue- inhibitor of reverse transcriptase
* monotherapy can lead to resistance - combine with ziduvuddine or other RTI
Also inhibts HBV DNA polymerase- chronic HBV tx
Tenofovir
RTI
Adenosine analogue-
HIV 1 that has become resistant to other drugs
* DOC with emtricitabine for tx in naive pts
- N/V/Ab pain and flatulence
Emtricitabine
RTI
* DOC with combined with tenofovir for naive pts
given orally once per day
MOA: cytosine analog
Uses:
HIV, HBV (if resistant to lamivudine)
SE:
- Diarrhea, rash, nausea
Didanosine
RTI
MOA: inhibits mitochondrial DNA synthesis
USES
- used in combo with zidovudine
- used when pts intolerant or resistant to zidovudine
SE:
- Pancreatitis
- peripheral neuropathy
- anemia and granulocytopenia
- hyperurecemia
- lactic acidosis and hepatotoxicity
DRUG INTERACTIONS:
- Tetracyclines, fluoroquinlones will be chelated
- drug that need acid for absorption- ketoconazole
- risk of pancreatitis with pentamidine
Stavudine
RTI - resistance not common - excreted by kidney ** do not combine with zidovudine : inhibits phosphorylation of stavudine MOA: dideoxythmidine - incorporated into DNA and inhibits reverse transcrpitatse Uses: - uses in adults with advanced HIV and cant tolerate other crap - when other therapies are CI SE: - peripheral neuropathy - HA/N - lactic acidosis may occur
Zalcitabine
RTI
- Excreted in urine, oral admin, presence of food in GI may dec. the absorption,
MOA: didoxycytidine- RTI, can also inhibit other Polymerases causing toxicity, inhibits mitochondrial DNA synthesis
TOXICITY
- peripheral neuropathy
- oral and esophageal ulcers
* dont with use other drugs that cause neuropathy
* amphotericin B, foscarnet, and aminoglycosides dec. clearance of zalcitabine adn inc. likelihood of peripheral neuropathy
Abacavir
RTI
MOA: guanosine analogue
Toxicity
- serious hypersensitivity - malaise, skin rash etc.
- N/V/D
** do not discontinue and then restart— FATAL
Efavirenz
NNRTI DOC unless pt. is pregnant * teratogenic - avoid in pregnancy - induces CYP34A - penetrates BBB: dizziness, drowsines, insomnia, HA
Nevirapine
NNRTI DOC if pt is pregnant- prevents transmission to newborn - induces CYP3A4 - ketoconazole inhibits metabolisa - steven johnson syndrome - Hepatitis
Delavirdine
NNRTI
Absorption dec. by antacids, poor CNS penetration
Inhibits CYP3A
Teratogenic
Rilpivirine
NNRTI
NOT TERATOGENIC
Depression
dont use in pts with hepatitis co-infection- inc. liver enzymes
