C6+7 Flashcards
1
Q
Antiretroviral drugs?
A
zidovudin lamivudine tenofovir emtricitabine abacavir etravirine darunavir ritonavir lopinavir dolutegravir maraviroc
2
Q
Anti-HIV drugs modes?
A
NRTIs: nucleoside reverse transcriptase inhibitors
PI: inhibitors of HIV protease
HAART: Highly active antiretroviral therapy
involving drug combinations can slow or reverse the increases in viral RNA load that accompany progression of disease
3
Q
NRTIs examples?
A
Abacavir Emtricitabine Lamivudine Tenofovir Zidovudine
4
Q
NRTIs MOA?
A
- prodrugs converted by host cell kinases to triphosphates
- competitively inhibit binding of natural nucleotides to the dNTP-binding site of reverse transcriptase
- chain terminators via their insertion into the growing DNA
- they lack a 3′-hydroxyl group on the ribose ring –> attachment of the next nucleotide is impossible
5
Q
what about Abacavir?
A
- A guanosine analog
- good oral bioavailability
- 1/2 life: 12–24h
- in 5%: Hypersensitivity reactions (fatal)
6
Q
What about Emtricitabine?
A
- bioavailability: Good oral
- Elimination: kidney
- 1/2 life: long (dosing once-daily)
- contraindicated in pregnancy and young children and in patients with hepatic or renal dysfunction (propylene glycol in the oral solution)
7
Q
Emtricitabine Toxicity?
A
- asthenia
- GI distress
- headache
- hyperpigmentation of the palms and/or the soles.
8
Q
What about Lamivudine ?
A
- bioavailability: 80% by the oral route
- elimination: kidney
- also effective in hepatitis B infections
- Dosage adjustment is needed in patients with renal insufficiency
9
Q
What about Tenofovir?
A
- it is a nucleotide
- competitively inhibit reverse transcriptase and cause chain termination after incorporation into DNA.
- also has activity against HBV
10
Q
Tenofovir Pharmacokinetix?
A
- bioavailability: 25–40% Oral
- 1/2 life: > 60h
- Elimination: kidney
- may impede the renal elimination of acyclovir and ganciclovir
11
Q
Tenofovir Toxicity?
A
- include GI distress
- asthenia
- headache
12
Q
Zidovudine Pharmacokinetix?
A
- bioavailability: active orally
- distribution: most tissues (alsoCNS)
- Elimination: both hepatic metabolism to glucuronides and renal excretion
- Dosage reduction is necessary in uremic patients and cirrhosis
13
Q
Zidovudine Toxicity?
A
- bone marrow suppression
(anemia & neutropenia –> may require transfusions) - GI distress
- thrombocytopenia
- headaches
- myalgia
- acute cholestatic hepatitis
- Drugs that increase plasma levels of zidovudine:
- azoles antifungals and protease inhibitors
- Drugs that increase clearance of zidovudine:
- Rifampin
14
Q
NNRTIs Example?
A
Etravirine
15
Q
NNRTIs MOA?
A
- bind to a site on reverse transcriptase
- do not require phosphorylation to be active and do not compete with nucleoside triphosphates