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Antimicrobials > Anti-viral drugs > Flashcards

Anti-viral drugs Flashcards

1
Q

What does a HIV antiretroviral regimen generally comprise of?

A

**2 nucleoside reverse transcriptase inhibitors and either a(n)
**integrase strand transfer inhibitor OR
protease inhibitor OR
non-nucleoside reverse transcriptase inhibitor.

**Newer regimen includes Dolutegravir (ISTI) and Lamivudine (NRTI)

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2
Q

When can lamivudine & dolutegravir be used?

A

most HIV tx naive pts

except those w 1) hep B/ 2) initiating ART before testing for RT genotype/HBV testing are out/ 3) RNA titres > 500,000 copies/mL

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3
Q

Name the nucleoside reverse transcriptase inhibitors (NRTIs) and state which riboside’s analogue they each are

A
  1. Emtricitabine - cytosine
  2. Lamivudine - cytosine
  3. Abacavir - guanosine
  4. Tenofovir - adenosine
  5. Zidovudine - thymidine
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4
Q

What is the mechanism of action of nucleoside reverse transcriptase inhibitors?

A

NRTIs are analogs of native ribosides.
Upon cell entry, they are phosphorylated to the corresponding triphosphate analog, which is *preferentially incorporated into the viral DNA by reverse transcriptases. Because the 3′-OH group is not present, a 3′,5′-phosphodiester bond between an incoming nucleoside triphosphate and the growing DNA chain cannot be formed, and DNA chain elongation is terminated.

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5
Q

Which 2 NRTIs should not be co-administered?

A

Emtricitabine and lamivudine as they are both cytosine analogues

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6
Q

Which NRTIs can also be used in the management of Hepatitis B?

A
  1. Emtricitabine
  2. Tenofovir
  3. Lamivudine
    (An ART regimen for patients with both HIV and HBV should include (TAF or TDF) plus (3TC or FTC))
  • if discontinued - severe acute exacerbation of hepatitis
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7
Q

How are most NRTI cleared?

A 
Renal clearance
except Zidovudine (thymidine) - hepatic clearance
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8
Q

How can all NRTI usually be taken?

A

Oral

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9
Q

What are the 2 types of Tenofovir (NRTI)?

A

Tenofovir alafenamide

Tenofovir disoproxil fumarate

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10
Q

Which is the tenofovir preferred?

A

Tenofovir alafenamide has more favorable effects on renal and bone markers

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11
Q

Which NRTI can only be used in HLA-B*5701–negative individuals?

A

Abacavir - guanosine

A test that detects the presence of HLA-B5701. HLA-B5701 is a genetic variation that is linked to hypersensitivity to the antiretroviral (ARV) drug abacavir. A person who tests positive for HLA-B*5701 should not use abacavir or any other abacavir-containing medicine.

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12
Q

Name 2 examples of long-term toxicities associated with HIV antiretroviral treatment

A
  1. metabolic syndrome

2. lipodystrophy syndrome

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13
Q

What is the mechanism of action of integrase inhibitors?

A

The inhibitor binds and inhibits the catalytic site of the HIV integrase, which terminates integration of HIV DNA into the host genome.

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14
Q

Name 3 examples of integrase inhibitors

A
  1. Dolutegravir
  2. Raltegravir
  3. Elvitegravir
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15
Q

What should not be taken tgt with integrase inhibitors?

A

Oral bioavailability affected by
Polyvalent cations
avoid antacids 2 hours before or 6 hours after

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16
Q

What is taken tgt with Elvitegravir (ISTI)?

A

Cobicistat - PK enhancer to inhibit CYP450

*usually avoid elvitegravir as+ cobicistat increase risk DDI

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17
Q

Name one adverse effects of integrase inhibitor

A

weight gain

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18
Q

Can integrase inhibitor be used in pregnancy?

A

DTG preferred throughout pregnancy
Alternative ART if trying to conceive

All pregnant pt take at least 400mcg folic acid daily

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19
Q

What is the mechanism of action of protease inhibitors?

A

Protease inhibitors bind to the site where polyprotein cutting occurs, and prevent the viral enzyme protease from releasing the individual core proteins.

*resistance less common as higher genetic barrier (req stepwise mutation)

20
Q

Name 2 examples of protease inhibitors

A
  1. Darunavir

2. Lopinavir

21
Q

What is the mechanism of action via which the pharmacokinetic enhancer such as ritonavir works?

A

Low doses of ritonavir used have no significant anti-protease activity, but sufficient CYP450- inhibitory activity that interferes with the metabolism of protease inhibitors.

  • note that ritnoavir is a str analogue of cobicistat but has additional AR effect (ritonavir booster better for HIV-2)
22
Q

Name at least 3 adverse effects associated with protease inhibitors

A
  1. GI disturbances: Nausea, vomiting, and diarrhea.
  2. Hyperglycaemia
  3. Hyperlipidaemia
  4. Hepatic injury
  5. Lipodystrophy
23
Q

Drug-drug interactions are a common problem associated with which class of HIV anti-viral drugs?

A 
Protease inhibitors
(Drug interactions are a common problem for all protease inhibitors as they are not only *substrates but also potent *inhibitors of CYP450 isoenzymes.)

CYP450 inhibitors like macrolides, azoles, rifampicin, isoniazid, fluoroquinolones(?)

24
Q

Drawbacks of HIV protease inhibitors?

A
  1. poor pt compliance as high no of pills

2. drug resistance if used alone - used w 2 RTI

25
Q

Name the NNRTI non-nucleoside reverse transcriptase inhibitor.

A

Efavirenz

26
Q

What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors (NNRTI)?

A

NNRTIs bind *HIV-1 reverse transcriptase at an allosteric hydrophobic site
to induce a conformational change resulting in enzyme inhibition.

27
Q

Name one adverse effect of efavirenz (NNRTI).

A

CNS associated effects eg vivid dreams, headache, dizziness

28
Q

Both NRTI & ISTI & PI work against?

A

HIV-1 (more common) & HIV-2

except NNRTI only HIV-1

29
Q

Which drugs cannot be used in HIV-2 infections?

A

NNRTI (efavirenz)– as high rates of resistance

Enfuvirtide

30
Q

Name the 2 entry inhibitors.

A

Enfuvirtide

Maraviroc

31
Q

All of the ART drugs are given orally except ____

A

Enfurbvitide (Entry inhibitor)– subcutaneous injection

can have injection related AR

32
Q

How does the entry inhibitor enfuvirtide work?

A

Enfuvirtide is a polypeptide that binds to HIV fusion protein gp41, preventing the conformational change, and interfering with HIV-1 entry by inhibiting the fusion of viral and cellular membranes.

33
Q

What is the mechanism of action of maraviroc?

A

Maraviroc blocks the binding of the HIV outer envelope protein gp120 to the CCR5 chemokine receptor

  • only effective in HIV preferentially expressing CCR5 over CXCR4 coreceptor
34
Q

How may HIV acquire resistance to maraviroc?

A

They may preferentially express CXCR4 co-receptor, which would then limit the ability of maraviroc to block HIV entry.

35
Q

Who is pre-exposure prophylaxis used for?

A

It is useful when people are at a high risk of getting infected with HIV. (e.g. sex workers)

36
Q

Name an anti-viral combination that is used as PrEP.

A

Tenofovir disoproxil fumarate and emtricitabine (Truvada®)

37
Q

How long after the last possible exposure to HIV should an individual taking PrEP continue the medication before he/she stops?

A

He/she should continue for at least 4 weeks after the last significant exposure.

38
Q

How soon after an exposure to HIV should an individual initiate Post-Exposure Prophylaxis?

A

He should initiate PEP within the first 72 hours.

39
Q

How long must an individual take PEP following an exposure?

A

28 days

40
Q

Is PEP and PrEP treatment regimen the same?

A

No. PEP treatment is similar to the treatment used for an established HIV infection. It will use the recommended 3 anti retrovirals regimen for 28 days.

PrEP is a combination of Emtricitabine and Tenofovir taken daily

41
Q

Name a drug that is used in the management of conditions related to Herpes simplex virus type 1 and 2 and TYPE 3: varicella-zoster virus such as cold sores, oral and genital herpes, and chicken pox.

A

Acyclovir

Valacyclovir - prodrug of acyclovir but greater oral bioavailability hence less frequent dose

42
Q

What is the mechanism of action of acyclovir?

A

Acyclovir is a nucleoside analogue that is phosphorylated by viral thymidine kinase to acyclovir monophosphate, and host cell enzymes to acyclovir triphosphate form. It

  1. Competitively inhibits viral DNA polymerase
  2. Incorporates into and terminates the growing viral DNA chain, and
  3. Inactivates the viral DNA polymerase.

(More effective against HSV than VZV as HSV more efficient thymidine kinase)

43
Q

Name one other use of acyclovir

A

prophylaxis for seropositive pt before bone marrow transplant

44
Q

Which antiviral has a better oral bioavailability, acyclovir or valacyclovir?

A

Valacyclovir

45
Q

Which anti-viral is commonly used as a prophylaxis in immunocompromised patients against cytomegaloviral infections (opportunistic infections)?

A

Ganciclovir (pro drug- oral)
Valganciclovir

*

46
Q

What is the mechanism of action of ganciclovir?

A

It is monophosphorylated intracellularly by viral thymidine kinase and viral phosphotransferase during HSV and CMV infections respectively before being phosphorylated to diphosphate and triphosphates by cellular enzymes.

The triphosphate is a competitive inhibitor of the native deoxyguanosine triphosphate for incorporation into DNA and preferentially inhibits viral rather than host cellular DNA polymerases. Incorporation into viral DNA causes termination of DNA chain elongation.

*cmv can become resistance by phsophotransferase mutation

Antimicrobials (11 decks)

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