Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology - Midterm 2 > Antiretrovirals > Flashcards

Antiretrovirals Flashcards

1
Q

When should you start HIV treatment?

A

when CD4+ count drops below 500; or in pregnant women, patient with AIDS-defining illness, HBV-HIV co-infection, or nephropathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

MOA of Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

A

Analogs of native ribosides; lack 3’OH group –> chain termination (act as reversible competitive inhibitors of RT)

Require phosphorylation by cellular enzymes –> incorporated into DNA by RT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which viruses are NRTIs active against?

A

HIV-1 and HIV-2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Most common resistance mechanisms of NRTIs

A

Mutation at viral codon 184

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Resistance to which drug restores sensitivity to Zidovudine and Tenofovir?

A

Lamivudine (Nucleoside/Nucleotide analog used against Hepatic infections)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which NRTI is especially associated with myelosuppression?

A

Zidovudine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which NRTI increases levels of Didanosine? (Drug Interaction)

A

Tenofovir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

AE of NRTIs

A

inhibition of mitochondrial DNA polymerase ==> peripheral neuropathy, lipoatrophy, myopathy, and lactic acidosis

Pancreatitis, Cardiomyopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which NRTIs are particularly associated with insulin resistance and dyslipidemia?

A

Zidovudine and Stavudine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What must be monitored while taking NRTIs?

A

serum creatinine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

True or False: NRTIs are metabolized by CYP450 enzymes.

A

False

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Contraindications of Zidovudine

A

Co-administration with Probenicid, Acetaminophen, Lorazepam, Indomethacin, and Cimetidine;

Since Stavudine and Ribavirin are activated by same pathways as Zidovudine, might reduce active levels of Zidovudine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

AE of Zidovudine

A

Bone marrow suppression, insomnia, insulin-resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Thymidine analog (for HIV treatment) that crosses BBB

A

Zidovudine; doses must be adjusted in patients with cirrhosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Thymidine analog (for HIV treatment) whose dosage must be adjusted in renal insufficiency

A

Stavudine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

MOA of Stavudine

A

Strongly inhibits beta and gamma DNA polymerases; has high affinity for mitochondrial DNA polymerase, which can lead to toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

PK/PD of Stavudine and Zidovudine

A

Oral administration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

AE of Stavudine

A

Peripheral neuropathy, lactic acidosis, insulin-resistance, neuromuscular weakness, hyperlipidemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Adenosine analog (for HIV treatment) that crosses the BBB and penetrates the CSF

A

Didanosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Acid labile Antiretroviral best taken with antacid or while fasting

A

Didanosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

AE of Didanosine

A

Pancreatitis in alcoholics and patients with hypertriglyceridemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which 2 NRTIs have a high affinity for mitochondrial DNA polymerase?

A

Didanosine and Stavudine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

NRTI; Adenosine analog preferred in current regimens (for HIV treatment)

A

Tenofovir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Fixed dose combinations of Tenofovir

A

Tenofovir + Emtricitabine & Tenofovir + Emtricitabine + Efavirenz

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Tenofovir drug interactions

A

Increases Didanosine concentration ; decreases Atazanavir concentration (give Ritonavir as booster)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

NRTIs

A

Tenofovir, Stavudine, Didanosine, Zidovudine, Lamivudine, Emticitabine, Abacavir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

NRTI taken with food to increase oral bioavailability

A

Tenofovir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Cytosine analog (for HIV treatment) that does not affect mitochondrial synthesis or bone marrow

A

Lamivudine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

AE of Lamivudine

A

Headache, dry mouth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Cytosine analog; preferred NRTI used in current regimens

A

Emtricitabine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

AE of Emtricitabine

A

Hyperpigmentation of palms and soles (especially in dark skinned individuals)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Guanosine analog that is an NRTI

A

Abacavir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

AE of Abacavir

A

Hypersensitivity Rxns; should not rechallenged sensitized individuals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Non-competitive Inhibitors of HIV-1 Reverse Tramscriptase

A

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

MOA of NNRTIs

A

Inhibit RNA and DNA-dependent DNA Polymerase; bind at same allosteric site (NNRTI pocket). DO NOT REQUIRE PHOSPHORYLATION by cellular enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

CYP3A4 substrates that act as inhibitors, inducers, or both

A

NNRTIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

True or False: NNRTIs have cross resistance with NRTIs.

A

False; they have different binding sites.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Common AE of NNRTIs

A

Steven-Johnson syndrome (rash), hypersensitivity rxns

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Dosing for Emtricitabine

A

Once a day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

NNRTIs extensively metabolized to inactive products

A

Rilvipirine and Efavirenz

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

AE of Rilvipirine

A

Insomnia, depression, increased liver enzymes, rash

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

PK/PD of Rilvipirine

A

Oral administration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

NNRTI that induces CYP3A4; metabolized by CYP3A4 and CYP2D6

A

Nevirapine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

AE of Nevirapine

A

Severe hepatotoxicity, Steven Johnson syndrome (titrate at half dose for 14 days to reduce risk)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Contraindications of Nevirapine

A

Women with CD4 > 250 and Men with CD4 > 400

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Drug interactions of Nevirapine

A

Increases metabolism of Protease Inhibitors, oral contraceptives, Ketoconazole, Methadone, Metronidazole, Quinidine, Theophylline, and Warfarin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Oral NNRTI with long half-life

A

Efavirenz –> once daily dosing

48
Q

NRTI that is potent CYP inducer and results in reduced viral load and increased CD4 count

A

Efavirenz

49
Q

AE of Efavirenz

A

Vivid dreams, possible suicidality, rash, increased TGs, HDL, and cholesterol

50
Q

Contraindications of Efavirenz

A

Pregnancy (Category D) –> use after 1st trimester

51
Q

Protease Inhibitors (for HIV treatment)

A

Ritonavir, Atazanavir, Indinavir, Nelfinavir, Lopinavir, Darunavir

52
Q

MOA of Protease Inhibitors

A

Reversibly inhibit aspartyl protease that cleaves polyprotein into Integrase, Reverse Transcriptase, and Protease

Prevent virus maturation, leading to production of non-infectious visions

53
Q

Which viruses are Protease Inhibitors active against?

A

HIV-1 and HIV-2

54
Q

True or False: Protease Inhibitors require intracellular activation

A

False

55
Q

PK/PD of Protease Inhibitors

A

Poor oral bioavailability affected by fatty foods;
Substrates for CYP3A4 and P-glycoprotein pump;
Bound to plasma proteins (alpha 1 acid glycoprotein, which is increased after trauma/surgery)

56
Q

AE of Protease Inhibitors

A

Paresthesias, disturb lipid metabolism, fat redistribution and accumulation–> buffalo hump and cushingoid appearance

57
Q

Contraindications of Protease Inhibitors

A

Rifampin and St. John’s Wort

58
Q

Drug Interactions of Protease Inhibitors

A

Inhibitors and Substrates for CYP isoforms; Rhabomyolysis with statins, excessive sedation with Midazolam and Triazolam, Respiratory depression with Fentanyl;
Adjust doses of Warfarin, Sildenafil, and Phenytoin

59
Q

Resistance mechanisms against Protease Inhibitors

A

Stepwise accumulation of mutations in protease gene

60
Q

PK Enhancers

A

Ritonavir and Cobicistat

61
Q

MOA of PK Enhancers

A

Inhibit CYP3A4 to increase Antiretroviral concentration –> lower and less frequent dosing; improve tolerability of Antiretrovirals

62
Q

How is Ritonavir administered?

A

In combination with Protease Inhibitors except Nelfavinir; never used alone

63
Q

How is Cobicistat administered?

A

In combination with the Integrase Strand Transfer Inhibitor (INSTI) Eltegravir; also in combination with Atazanavir and Darunavir

64
Q

Protease Inhibitor contraindicated in patients with a Sulfa-allergy

A

Darunavir

65
Q

PK of Atazanavir

A

Well absorbed with food; structurally unrelated to other Protease Inhibitors; metabolized and inhibits CYP3A4

66
Q

True or False: Atazanavir can be co-administered with H2- blockers and antacids.

A

False; Atazanavir must be administered more than 12 hours apart from H2-blockers and antacids

67
Q

AE of Atazanavir

A

PR interval prolongation, rash, nephrolithiasis, hyperbilirubinemia

68
Q

Clincal application of Atazanavir`

A

Given with Ritonavir

69
Q

Clinical application of Darunavir

A

Inhibits HIV protease resistant to other Protease Inhibitors

70
Q

PK of Darunavir

A

Well absorbed with food; metabolized and inhibits CYP3A4

71
Q

Drug interactions of Atazanvir

A

Inhibits PPIs

72
Q

Clinical Application of Indinavir (same as Atazanavir)

A

Given with Ritonavir

73
Q

PK of Indinavir

A

Absorption decreased when taken with food, especially fatty meals

74
Q

Contraindications of Indinavir

A

Reduce dose in hepatic insufficiency

75
Q

AE of Indinavir

A

Blurred vision, Nephrolithiasis, hyperbilirubinemia, rash

76
Q

One of preferred Protease Inhibitors; given with Ritonavir

A

Lopinavir

77
Q

PK of Lopinavir

A

Poor intrinsic bioavailability

78
Q

Contraindications of Lopinavir

A

Enzyme inducers such as St. John’s Wort; avoid Disulfiram and Metronidazole (oral solution contains alcohol)

79
Q

AE of Lopinavir

A

GI effects

80
Q

Protease Inhibitor that cannot be boosted by Ritonavir

A

Nelfinavir

81
Q

PK of Nelfinavir

A

Metabolized by several CYPs; oral bioavailability increased by fatty meals

82
Q

Protease Inhibitor whose metabolite has equal antiretroviral activity to parent compound

A

Nelfinavir

83
Q

Metabolite of Nelfinavir

A

CYP2C19

84
Q

Contraindications of Nelfinavir

A

Numerous!

85
Q

AE of Nelfinavir

A

Diarrhea (controlled by Loperamide), nausea, flatulence

86
Q

Antiretroviral that acts as Fusion Inhibitor

A

Enfuviritide (T-20)

87
Q

Activity of Enfuviritide

A

HIV-1

88
Q

MOA of Enfuviritide

A

Structurally similar to gp41; binds gp41 on viral envelope to prevent virion fusion with cell membrane

89
Q

AE of Enfuviritide

A

Injection-related (discontinue), hypersensitivity rxns, and eosinophilia; no drug interactions with other Antiretrovirals

90
Q

PK of Enfuviritide

A

Parenteral administration only

91
Q

Antiretroviral that acts as Entry Inhibitor

A

Maraviroc

92
Q

MOA of Maraviroc

A

Binds selectively and specifically to CCR5 co-receptor, blocking HIV entry

93
Q

PK of Maraviroc

A

Metabolized by CYP3A4 –> reduce dose when given with Protease Inhibitors

94
Q

AE of Maraviroc

A

Well-tolerated; risk of hepatotoxicity

95
Q

True or False: Enfuviritide is approved for treatment-experienced adults with evidence of HIV replication

A

True

96
Q

Antiretroviral class with good side effect profile and favorable effects on lipid metabolism

A

Integrase Strand Transfer Inhibitors (INSTIs)

97
Q

True or False: INSTIs are approved for treatment-experienced and treatment-naive patients with evidence of viral replication

A

True

98
Q

MOA of INSTIs

A

Bind Integrase (in HIV-1 and HIV-2) and inhibit last step in integration of viral DNA in to host DNA

99
Q

AE of INSTIs

A

Generally well tolerated (rash, nausea, headache, insomnia, diarrhea) or increases creatinine phosphokinases

100
Q

INSTIs

A

Dolutegravir, Elvitegravir, Raltegravir

101
Q

PK of Dolutegravir

A

Primarily eliminated by glucuronidation by UGT1A1 and some contribution from CYP3A4

102
Q

AE of Dolutegravir

A

Well tolerated; discontinue if organ dysfxn occurs

103
Q

Why do drug interactions occur with Dolutegravir?

A

Due to CYP3A4 interactions

104
Q

PK of Elvitegravir

A

Primarily metabolized by CYP3A and may require enhancing via Cobicistat

105
Q

Protease Inhibitor and PK Enhancer

A

Ritonavir

106
Q

Why do drug interactions occur with Elvitegravir?

A

Due to CYP interactions

107
Q

PK of Raltegravir

A

Primarily eliminated by glucuronidation by UGT1A1 enzyme (like Doltegravir)

108
Q

AE of Raltegravir

A

Well tolerated; can cause increases in creatinine phosphokinases

109
Q

Drug interactions of Raltegravir

A

Rifampin, Tipranavir, and Efavirenz may decrease Raltegravir concentration; PPIs may increase Raltegravir concentration

110
Q

Current Recommendations for Treatment-naive patients

A

2NRTIs + INSTI or 2NRTIs + Protease Inhibitor

111
Q

INSTI-based regimens for Treatment-naive patients

A

Raltegravir or Dolutegravir + Tenofovir + Emtricitabine

112
Q

Protease-based regimen for Treatment-naive patients

A

Ritonavir-boosted Darunavir + Tenofovir + Emtricitabine

113
Q

Treatment recommended for Infant born to HIV infected mother

A

Zidovudine, immediately after birth for 6 weeks

114
Q

Post-exposure prophylaxis for HIV

A

Raltegravir + Tenofovir + Emtricitabine; give for 28 days and stop if source is found to HIV negative

115
Q

Prophylactic vaccines recommended for HIV patients

A

S. pneumoniae, HAV, HBV, Influenza

116
Q

Contraindicated vaccines in patients with CD4 count < 200

A

MMR, Varicella, and Zoster

Pharmacology - Midterm 2 (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions