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Pharm 2-EXAM #2 > Antiretrovirals > Flashcards

Antiretrovirals Flashcards

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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
MOA of Maraviroc
HIV enters via CD4 receptor in conjunction with a co-receptor Blocks entry of R5 viruses into CD4
26
Entry inhibitors are classified as _____ or _____
Fusion Inhibitors or Attachment inhibitors
27
How do fusion inhibitors work & what is the drug?
Prevent viral fusion (glycoprotein binding) Enfuvirtide
28
Hoe do attachment inhibitors work? What is the drug of choice?
prevents attachment & entry ( glycoprotein binding) Fostemsavir
29
What is the risk associated with taking Fostemsavir, an Attachment inhibitor?
Nausea Elevated Liver Enzymes QTc prolongation
30
Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors) are often used
As combination drugs
31
What is the MOA of Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors)?
Metabolized by host enzymes Active metabolite competitively binds reverse transcriptase Inhibits DNA chain elongation (viral replication
32
Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors) are active against
HIV 1 & 2 HBV
33
What drugs are considered to be Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors)?
Lamivudine Zidovudine Abacavir Tenofovir
34
With Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors), there is a risk for
Drug-resistance by the virus
35
What are the adverse effects of Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors)?
Mitochondrial toxicity Peripheral neuropathy Pancreatitis Hepatic steatosis
36
What is the black box warning of Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors)?
Lactic acidosis syndrome
37
What are the adverse reactions of Zidovudine (AZT), a Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors)?
N/V Lactic Acidosis HA
38
Zidovudine (AZT), a Nucleoside RTIS (Nucleoside Reverse Transcriptase Inhibitors), can be used
In HIV management in pregnancy In certain viral mutations
39
Non-nucleoside RTIs (NNRTIs) are often administered
In combination with NRTIs
40
Non-nucleoside RTIs (NNRTIs) are used for
Initial therapy & tx switch
41
What is the MOA of Non-nucleoside RTIs (NNRTIs)?
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
Non-nucleoside RTIs (NNRTIs) are active against
HIV-1
43
1st generation Non-nucleoside RTIs (NNRTIs) like Efavirenz & nevirapine) are
Highly resistant to mutation
44
The most commonly used Non-nucleoside RTIs (NNRTIs) are Efavirenz & Rilpivirine. What are their adverse effects?
Neurologic & psychiatric effects Vivid dreams, confusion, dizziness, "hangover" Irritability, anxiety, mood change, depression & increased suicidality QTc prolongation
45
What are the anesthesia considerations with NRTIs?
No interaction with drugs through CYP-450 system Metronidazole-risk for peripheral neuropathy
46
What are anesthesia considerations for NNRTIs?
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
Integrase strand transfer inhibitors (INSTIs) are used as
Preferred 3rd agent with 2 NRTIs/NNRTIs
48
What is the MOA of Integrase strand transfer inhibitors (INSTIs)?
Prevents b ending of viral complex to host DNA Target the strand transfer of viral DNA integration Inhibits activity of integrase (catalyzes integration)
49
Integrase strand transfer inhibitors (INSTIs) are active against
HIV 1 & 2
50
What drugs are considered Integrase strand transfer inhibitors (INSTIs)?
Raltegravir Elvitegravir Dolutegravir
51
Risk of taking Integrase strand transfer inhibitors (INSTIs)
Risk of integrase resistance & cross resistance with other failed antiretrovirals
52
Adverse effects of Integrase strand transfer inhibitors (INSTIs)
Wt gain Insomnia Dizziness Rhabdomyolysis, myopathy & myositis Depression, suicidal ideation (rare & risk in hx of mental illness)
53
Protease Inhibitors are used
In combo with dual nucleoside therapy Initial tx Preferred for patients failing initial ART
54
Protease Inhibitors should be administered
With a boosting agent like Ritonavir or Cobicistat
55
What is the MOA of Protease Inhibitors?
Selective Bonding of viral protease Competitive inhibition of step needed to mature new virus Results in production of immature visions (non-infectious)
56
Protease Inhibitors are active against
HIV 1 & 2
57
Protease Inhibitors have a
Relatively high genetic "barrier" to resistance
58
What are the adverse effects of Protease Inhibitors
Insulin resistance/Hyperglycemia/DM Hyperlipidemia Hepatotoxicity PR prolongation
59
What medications are considered to be Protease Inhibitors
Atazanavir Darunavir Lopinavir
60
Most Protease Inhibitors & Elvitegravir (integrase inhibitor)
Combine with another agent like Ritonavir & Cobicistat, which inhibit CYP 3A4
61
Boosting increases
Trough plasma drug concentrations, Half life & max plasma concentration, which improves potency
62
What are the anesthesia considerations for Protease Inhibitors
They inhibit CYP 3A4 Extensive metabolism by CYP 450
63
Protease Inhibitors and Benzos like Midazolam
Prolongs sedation & is a major respiratory depressant
64
Protease Inhibitors given with Fentanyl or Alfentanil causes
Respiratory depression
65
Protease Inhibitors given with Dexamethasone cn
Reduce Protease Inhibitors plasma concentration
66
Protease Inhibitors given with Amio
Causes CV toxicity risk
67
Which drugs are preferred to minimize drug interactions with Protease Inhibitors
Etomidate Remifentanil Desflurane Atracurium

Pharm 2-EXAM #2 (5 decks)

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