Pharmacology Exam 1

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Retroviruses
- RNA as thier genetic material
- enveloped
HIV replication requires

chemokine receptor on Tcells and macrophages
HIV binds to this receptor
- CCR5 co-receptor
- chemokine receptor
HIV RT has ______ fidelity _____ mutation rate.
- low fidelity
- high mutation rate
Problems encountered with anti-HIV therapy
- virus hides in deep tissues
- virus hides in brain
- virus integrates into cellular genome
- can cause mutation in target genes unlike DNA virus
Six classes of antiretroviral agents
- Nucleoside/Nucleotide RT inhibitor
- Non-nucleoside/tide RT inhibitor
- Protease inhibitor
- fusion inhibitor
- integrase inhibitor
- CCR5 antagonist
Nucleoside/tide RT inhibitors (8 DRUGS)
- Abacavir
- Didanosine
- Emtricitabine
- Lamivudine
- Stavudine
- Tenefovir
- Zalcitabine
- Zidovudine
Nucleoside/tide RT inhibitors MoA
- require intracellular activation (phosphorylation)
- competitive inhibition of HIV RT
- termination of DNA elongation
Abacavir
- NRTI
- guanosine analog
- good OB, short HL
- skin rashes in 50%
Didanosine
- NRTI
- deoxyadenosine analog
- 30% OB
increases Didanosine serum levels
- ganciclovir
- tenofovir
decreases serum levels of Didanosine
- tipranavir
- atazanavir
Side effects of Didanovir
- pancreatitis
- peripheral neuropathy
Emtricitabine
- fluorinated analog of Lamivudine
- NRTI
- 93% OB 39hr HL
Lamivudine
- cytosine analog
- NRTI
- active against AZT resistant strains
- 80% OB 10-15 hr HL
- 20% CSF
Problems with low dose ARV therapy
- creates resistance
- some are used in low doses to treat HBV and these patients could also have HIV
Stavudine
- Thymidine analog
- NRTI
- OB 86% not dependant on food
- 3.5 hr HL
- 55% CSF
Side effects of Stavudine
- dyslipidemia (buffalo hump)
- insulin resistance
- peripheral neuropathy
Drug Drug interaction with stavudine

isoniazid
Tenofovir
- NRTI
- adenosine analog
- increased OB after fatty meal
- 60hr intracellular HL
indications for Tenofovir

used in place of stavudine in cases of dyslipidemia
Zalcitabine
- cytosine analog
- NRTI
- 80% OB on empty stomach
- 10hr intracellular HL
- peripheral neuropathy 10-20%
Zidovudine
- Deoxythymidine analog
- NRTI
- used in pregnancy
- 3-7 hr HL
- 60% CSF
- dyslipidemia and insulin resistance
Non-nucleoside RT inhibitors
- directly interact with RT inducing a conf. change
- specific for HIV 1 RT
- must be used in combo to avoid resistance
- no-cross resistance with NRTIs or PIs
NNRTIs (3 drugs)
- Delavirdine
- Efavirnez
- Nevirapine
Action of NNRTIs
- no phosphorylation required
- CYP450 interactions
- Allosteric inhibition of RT
Nevirapine
- NNRTI
- highly lipophilic
- not food dependant 90% OB
- 60% protein bound
Drug interactions with Nevirapine
- moderate induction of CYP3A4
- Rifampin
- Rifabutin
- Cimetidine or macrolides increase concentrations
Side effects with Nevirapine
- 17% skin rash
- epidermal necrolysis
- hepatic toxicity
Delaviridine
- NNRTI
- 98% protein bound
- 18% skin rash
- inhibits CYP450
Efavirnez
- NNRTI
- 99% protein bound
- increased LFT
- Congenital abnormalities
- inhibits CYP450
Protease inhibitors
- acts on late stages of HIV replication
- prevents new waves of infection
- substrate and inhibitor of CYP3A4
- only ARV to act after viral integration into host genome
PI strongest inhbitor of CYP3A4

ritonavir
weakest PI that inhibits CYP3A4

saquinavir
PIs that induce CYP
- amprenavir
- ritanovir
Only ARV to act after viral integration into the host genome

PIs
Indinavir
- PI 10x more potent for HIV1 vs 2
- must be taken on an empty stomach
- highest [CSF] among PIs
Common side effects of indinavir

blood in urine due to crystalluria and nephrolitiasis
Protese Inhibitors (6 drugs)
- saquinavir
- ritonavir
- lopinavir/ritonavir
- nelfinavir
- amprenavir
- fosamprenavir
Lopinavir/ritonavir combo
- ritonavir inhibits metabolism of lopinavir
- increased absorption with high fat meals
Nelfinavir
- PI
- increased absorption with high fat meal
Amprenavir

decreased absorption with high fat meal
Fosamprenavir

prodrug for amprenavir with improved OB
2 new PIs
- Darunavir
- Atazanavir
- dosed once daily
- used in combo with ritonavir
- recommended for ARV naive pt
Atazanacir should not be used with

PPIs
Fusion/Entry inhibitors
- bind GP41 of viral envelope preventing conf change
- no cross resistance
- administered by injection
- high cost reserved for failed treatments
- Enfuvirtide
Maraviroc
- CCR5 inhibitor
- hepatotoxicity
- cardiovascular risk
Raltegravir

integrase inhibitor
Raltegravir drug interactions through UGT1A1
- Rifampin
- Efavirenz
- Tipranavir
- Ritonavir
- Atazanavir
NRTI recommended in pregnancy
- Zidovudine
- lamivudine
NNRTIs recommended in pregnancy

Nevirapine
PIs recommended in pregnancy
- Nelfinavir
- Saquinavir
Alternate NRTIs that may be used in pregnancy
- Didanosine
- Emtricitabine
- Abacavir
- Stavudine
Alternate PIs that may be used in pregnancy
- Indinavir
- Lopinavir/Ritonavir
- Ritonavir
HAART means taking

a combination of 3 or more ARVs from at least 2 classes
HAART treatment is modified according to
- CD4+ Tcell count
- Viral load
- tolerance
Drugs under investigation for prophylaxis

tenofovir with or without emtricitabine

Author

Rx2013

61318

Card Set

Pharmacology Exam 1

Description

Treatment of AIDS

Updated

2011-01-22T20:38:28Z

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