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Pharm 2-EXAM #2 > Antiretrovirals > Flashcards

Antiretrovirals Flashcards

1
Q

Which stage of HIV is contagious?

A

Stage 1

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2
Q

What happens in the acute HIV infection stage 1?

A

Days to weeks

Fever, chills, rash, nigh sweats, muscle aches, fatigue, swollen nodes, mouth ulcers

Large amount of HIV present

Antigen/antibody test or nucleic acid test (NAT)

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3
Q

Chronic HIV infection stage 2 is

A

Asymptomatic/clinical latency

Low level reproduction

Transmission possible

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4
Q

What happens at the end of stage 2

A

Viral load (amount of HIV in blood) increases

CD4 cell count decreases

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5
Q

When is AIDS diagnosed?

A

By CD4 cell count <200 or by opportunistic infection

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6
Q

Opportunistic infection characteristics

A

Less common with effective HIV tx

Candidasis

Pneumonias

Encephalopathy

Kaposi sarcoma

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7
Q

What are the types of HIV?

A

HIV-1
HIV-2

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8
Q

What are the characteristics of HIV-1?

A

More fatal

Progressess more rapidly towards AIDS

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9
Q

What are the characteristics of HIV-2?

A

Uncommon

Less infectious

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10
Q

What are the 6 stages of HIV replication?

A
  1. Entry
  2. Reverse Transcription
  3. Integration
  4. Replication
  5. Assembly
  6. Budding & maturation
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11
Q

Which drugs effect stage 1 of replication, Entry?

A

Maraviroc

Enfuvirtide

Fostemsavir

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12
Q

What happens in the Entry stage of replication?

A

Binds CD4 receptors

Cell membrane fusion

Genetic material & enzyme enter

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13
Q

Stage 2 of HIV replication, reverse transcription involves

A

Reverse Transcriptase enzyme, which converts HIV RNA to DNA

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14
Q

Which drugs interfere with stage 2 reverse transcription?

A

Nucleoside reverse transcriptase inhibitors & non-nucleoside RTIs

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15
Q

Stage 3 of HIV replication, Integration involves

A

Enzyme & integrase inserts HIV DNA into CD4 DNA

Cell now infected for remainder of life

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16
Q

Stage 3 of HIV replication, Integration involves is effected by which medications?

A

Integrase strand transfer inhibitors

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17
Q

Stage 4 of HIV replication, replication, involves

A

Host CD4 cell used to create new viral RNA

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18
Q

Can antiretrovirals inhibit stage 4, replication?

A

NO

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19
Q

Stage 5, Assembly is

A

New viral proteins & enzymes assemble into immature & non -infectious HIV particle “ bud”

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20
Q

Can antiretrovirals inhibit stage 5, assembly?

A

NO

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21
Q

Stage 6, budding & maturation is

A

Virus bud in released from host CD4

Enzyme & protease makes mature infectious viral particle

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22
Q

What drug interferes with stage 6, budding & maturation

A

Protease inhibitors

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23
Q

What is a CCR5 antagonists drug?

A

Maraviroc

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24
Q

Characteristics of Maraviroc

A

Not used for initial tx

May be used for drug resistant virus

Risk for hepatotoxicity & orthostatic HOTN

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25
Q

MOA of Maraviroc

A

HIV enters via CD4 receptor in conjunction with a co-receptor

Blocks entry of R5 viruses into CD4

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26
Q

Entry inhibitors are classified as _____ or _____

A

Fusion Inhibitors or Attachment inhibitors

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27
Q

How do fusion inhibitors work & what is the drug?

A

Prevent viral fusion (glycoprotein binding)

Enfuvirtide

28
Q

Hoe do attachment inhibitors work?

What is the drug of choice?

A

prevents attachment & entry ( glycoprotein binding)

Fostemsavir

29
Q

What is the risk associated with taking Fostemsavir, an Attachment inhibitor?

A

Nausea

Elevated Liver Enzymes

QTc prolongation

30
Q

Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors) are often used

A

As combination drugs

31
Q

What is the MOA of Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors)?

A

Metabolized by host enzymes

Active metabolite competitively binds reverse transcriptase

Inhibits DNA chain elongation (viral replication

32
Q

Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors) are active against

A

HIV 1 & 2

HBV

33
Q

What drugs are considered to be Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors)?

A

Lamivudine

Zidovudine

Abacavir

Tenofovir

34
Q

With Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors), there is a risk for

A

Drug-resistance by the virus

35
Q

What are the adverse effects of Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors)?

A

Mitochondrial toxicity

Peripheral neuropathy

Pancreatitis

Hepatic steatosis

36
Q

What is the black box warning of Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors)?

A

Lactic acidosis syndrome

37
Q

What are the adverse reactions of Zidovudine (AZT), a Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors)?

A

N/V

Lactic Acidosis

HA

38
Q

Zidovudine (AZT), a Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors), can be used

A

In HIV management in pregnancy

In certain viral mutations

39
Q

Non-nucleoside RTIs (NNRTIs) are often administered

A

In combination with NRTIs

40
Q

Non-nucleoside RTIs (NNRTIs) are used for

A

Initial therapy & tx switch

41
Q

What is the MOA of Non-nucleoside RTIs (NNRTIs)?

A

Prevents HIV-1 reverse transcriptase from adding new nucleotides to the growing DNA chain

Different site of action than NRTIs

Reduced chain elongation & replication

42
Q

Non-nucleoside RTIs (NNRTIs) are active against

A

HIV-1

43
Q

1st generation Non-nucleoside RTIs (NNRTIs) like Efavirenz & nevirapine) are

A

Highly resistant to mutation

44
Q

The most commonly used Non-nucleoside RTIs (NNRTIs) are Efavirenz & Rilpivirine. What are their adverse effects?

A

Neurologic & psychiatric effects

Vivid dreams, confusion, dizziness, “hangover”

Irritability, anxiety, mood change, depression & increased suicidality

QTc prolongation

45
Q

What are the anesthesia considerations with NRTIs?

A

No interaction with drugs through CYP-450 system

Metronidazole-risk for peripheral neuropathy

46
Q

What are anesthesia considerations for NNRTIs?

A

CYP-450 induction of inhibition depending on drug

Opioids- reduce plasma methadone concentration by 50% (withdrawal risks)

Fentanyl & alfentanil- sub-therapeutic levels (increase dose)

47
Q

Integrase strand transfer inhibitors (INSTIs) are used as

A

Preferred 3rd agent with 2 NRTIs/NNRTIs

48
Q

What is the MOA of Integrase strand transfer inhibitors (INSTIs)?

A

Prevents b ending of viral complex to host DNA

Target the strand transfer of viral DNA integration

Inhibits activity of integrase (catalyzes integration)

49
Q

Integrase strand transfer inhibitors (INSTIs) are active against

A

HIV 1 & 2

50
Q

What drugs are considered Integrase strand transfer inhibitors (INSTIs)?

A

Raltegravir

Elvitegravir

Dolutegravir

51
Q

Risk of taking Integrase strand transfer inhibitors (INSTIs)

A

Risk of integrase resistance & cross resistance with other failed antiretrovirals

52
Q

Adverse effects of Integrase strand transfer inhibitors (INSTIs)

A

Wt gain

Insomnia

Dizziness

Rhabdomyolysis, myopathy & myositis

Depression, suicidal ideation (rare & risk in hx of mental illness)

53
Q

Protease Inhibitors are used

A

In combo with dual nucleoside therapy

Initial tx

Preferred for patients failing initial ART

54
Q

Protease Inhibitors should be administered

A

With a boosting agent like Ritonavir or Cobicistat

55
Q

What is the MOA of Protease Inhibitors?

A

Selective Bonding of viral protease

Competitive inhibition of step needed to mature new virus

Results in production of immature visions (non-infectious)

56
Q

Protease Inhibitors are active against

A

HIV 1 & 2

57
Q

Protease Inhibitors have a

A

Relatively high genetic “barrier” to resistance

58
Q

What are the adverse effects of Protease Inhibitors

A

Insulin resistance/Hyperglycemia/DM

Hyperlipidemia

Hepatotoxicity

PR prolongation

59
Q

What medications are considered to be Protease Inhibitors

A

Atazanavir

Darunavir

Lopinavir

60
Q

Most Protease Inhibitors & Elvitegravir (integrase inhibitor)

A

Combine with another agent like Ritonavir & Cobicistat, which inhibit CYP 3A4

61
Q

Boosting increases

A

Trough plasma drug concentrations, Half life & max plasma concentration, which improves potency

62
Q

What are the anesthesia considerations for Protease Inhibitors

A

They inhibit CYP 3A4

Extensive metabolism by CYP 450

63
Q

Protease Inhibitors and Benzos like Midazolam

A

Prolongs sedation & is a major respiratory depressant

64
Q

Protease Inhibitors given with Fentanyl or Alfentanil causes

A

Respiratory depression

65
Q

Protease Inhibitors given with Dexamethasone cn

A

Reduce Protease Inhibitors plasma concentration

66
Q

Protease Inhibitors given with Amio

A

Causes CV toxicity risk

67
Q

Which drugs are preferred to minimize drug interactions with Protease Inhibitors

A

Etomidate

Remifentanil

Desflurane

Atracurium

Pharm 2-EXAM #2 (5 decks)

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