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HIV Drugs Flashcards

1
Q

What are the 4 categories of HIV drugs?

A

Protease inhibitors
NRTIs
NNRTIs
Other drugs

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2
Q

Protinavir, Ritonavir, Indinavir

A

Protease Inhibitors

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3
Q

Protease inhibitors work by

A

inhibiting HIV protease blocks polypeptide cleavage into reverse transcriptase, protease, integrase and structural proteins
Virus particles will bud off cell but be noninfectious

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4
Q

What does HIV protease do?

A

Product of pol gene

Cleaves polypeptides into smaller, functional units

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5
Q

gag forms

A

p24 (capsid)

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6
Q

pol forms

A

reverse transcriptase, integrase, protease

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7
Q

env forms

A

GP160: gp120+gp41 (envelope)

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8
Q

Protease Inhibitor S/E

A

N/D
Hyperlipidemia, Hyperglycemis (Insulin Resistance)
-Higher rate of CVD among HIV pts
-Fat redistribution

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9
Q

Indinavir

A

Protease Inhibitor

S/E: Kidney stones (hydration important)

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10
Q

Ritonavir

A

Inhibits cytochrome p450 system
Added as a booster to other protease inhibitors to avoid S/E
Example: Ritonavir & Lopinavir

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11
Q

How does reverse transcriptase synthesize a strand of DNA from RNA

A

It picks up triphosphorylated nucleotides (CGAT) to synthesize DNA from RNA

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12
Q

How do NRTIs inhibit reverse transcriptase?

A

They mimic one of the nucleosides (CGAT) but lack -OH group on 3’ carbon. This inhibits reverse transcriptase and terminates DNA chain.

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13
Q

Zidovudine (AZT), Lamivudine, Tenofovir, Didanosine

A

NRTIs

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14
Q

Which was the first HIV drug on the market?

A

Zidovudine (AZT) NRTIs

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15
Q

What nucleotide does Zidovudine (AZT) mimic?

A

Thymidine

  • Same base and ribose sugar
  • Zidovudine is missing -OH group on 3’ carbon of ribose sugar
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16
Q

What must NRTIs undergo to be incorporated into a DNA strand?

A

triphosphorylation by kinases

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17
Q

Which NRTI mimics a nucleotide instead of a nucleoside?

A

Tenofovir (has phosphate group)

-undergoes diphosphorylation instead of triphosphorylation

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18
Q

Nucleoside NRTIs

A

Zidovudine (AZT) and Lamivudine

-No phosphate group attached

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19
Q

NRTIs: important S/E

A

Mitochondrial Toxicity

  • All mitochondria have their own DNA
  • DNA polymerase gamma synthesizes mitochondrial DNA
  • NRTIs can inhibit these
20
Q

Mitochondrial Toxicity Sx

A

Peripheral neuropathy (pain, paresthesias)
Myopathy
Pancreatitis
Lactic Acidosis

21
Q

Mitochondria is responsible for

A

Oxidative phosphorylation

22
Q

How does lactic acidosis occur?

A

Oxidative phosphorylation inhibited so anaerobic metabolism

Severe, life-threatening cases of lactic acidosis w/ NRTIs

23
Q

Zidovudine (AZT) S/E

A

Bone marrow suppression
Zidovudine (AZT) can be inserted into DNA strands in bone marrow
Administer G-CSF or Epo

24
Q

Which NRTI is administered to pregnant women

A

Zidovudine (AZT)

25
Q

Lamivudine is also called

26
Q

Abacavir S/E

A

NRTI

  • 5% pts get hypersensitivity rxn (fever, rash, resp. distress, GI upset)
  • mistaken for opportunistic infection
27
Q

Abacavir mimics which nucleoside?

28
Q

Which NRTI is the least toxic and can also be used for Hep B?

A

Lamivudine (3TC)

-Hep B also uses reverse transcriptase

29
Q

Lamivudine (3TC) mimics which nucleoside?

30
Q

Tenofovir S/E that causes limitation

A

Severe GI upset

31
Q

Tenofovir mimics which nucleoside?

32
Q

What special S/E does Tenofovir have?

A

Polyuria and muscle weakness indicate Fanconi Syndrome

  • Loss of proximal tubule function
  • proteinuria, urinary phosphate wasting, glucosuria
  • metabolic acidosis, hypophosphatemia, hypokalemia
33
Q

Nevirapine, Efavirenz, Delavirdine

34
Q

How do NNRTIs work?

A

Bind to reverse transcriptase and modifies the protein so it can no longer function

35
Q

Do NNRTIs require phosphorylation?

36
Q

Can NNRTIs cause bone marrow suppression?

A

No. Only inhibits reverse transcriptase. Do not alter other DNA synthesis enzymes.

37
Q

Why are NNRTIs not effective for HIV-2?

A

It has a different reverse transcriptase which cannot be inhibited by the drugs

38
Q

NNRTIs S/E

A 
GI upset
Skin rash (rare progression to SJS)
39
Q

NNRTIs are metabolized by what?

A

P450 system of the liver

40
Q

Why do NNRTI levels in the blood go up/down with co-administration with other drugs?

A

NNRTIs are metabolized by P450 system

41
Q

Nevirapine

A

NNRTI

Induces P450 system

42
Q

Delaviridine

A

NNRTI

Inhibits P450 system

43
Q

Efavirenz

A

NNRTI

mixed effects on P450 system

44
Q

Raltegravir

A

Integrase Inhibitor

45
Q

Enfuvirtide

A

Binds to gp41

Inhibits fusion/entry into cells

46
Q

Maraviroc

A

Blocks CCR5 receptor on macrophages

ID Review (23 decks)

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