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Pathology And Pharamcology > Antiretroviral Drugs > Flashcards

Antiretroviral Drugs Flashcards

1
Q

An outer coat (the viral envelope) which consist of two layers of lipid in which are embedded proteins like?

A

the outer gp120 and the transmembrane gp41

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2
Q

Function of Gp120?

A

Gp 120 is an attachment protein

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3
Q

Function of gb41

A

Gp 41 is critical for the cell fusion process

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4
Q

HIV belongs to which family?

A

Retroviridae

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5
Q

HIV belongs to which genus ?

A

Lentivirus

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6
Q

Strandedness of HIV?
Nucleic acid composition?

A

Single stranded
RNA virus

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7
Q

The genome of HIV is ………..? and it contains …… and ….. genes?

A

9.8Kb, accessory and regulatory genes

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8
Q

There are ……… genes in the genome, and these are classified into …….., ………, and …….. genes ?

A

9 genes, structural, regulatory and accessory genes

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9
Q

The 3 Structural genes present in the HIV genome?

A

Gag, Poland Env genes

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10
Q

The 2 Regulatory genes present in the HIV genome?

A

Tat and Rev

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11
Q

The 4 Accessory genes present in the HIV genome?

A

Vpu, Vpr, Vif and Nef

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12
Q

HIV attaches itself to the T-cell via the………..by binding of the ……… molecule

A

CD4 molecules by the binding of gp120 molecule

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13
Q

A conformational change occurs in the Gp120 molecule which allows it to bind the HIV Co-receptors which are ……… or ……?

A

CCR5 or CXCR4

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14
Q

Cell fusion accompanies binding of the HIV virus to the coat cell, and this is mediated by the viral ………?

A

gp41 molecule

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15
Q

Replication cycle of the HIV takes about …… hours? and this is in……… stages?

A

Takes about 24 hours, and this is in 7 stages

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16
Q

The first three stages of the HIV replication cycle in order is …?,…..? and …..?

A

Binding, fusion and then Reverse transcription

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17
Q

The last 4 steps in the HIV replication cycle in order is ….? …….? ……? And ….? (Recall the first three in your head)

A

Integration, Replication, assembly and then budding

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18
Q

Step 1 and 2 of the HIV replication cycle occurs where?

A

On the surface of the CD4 cell

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19
Q

The 4th step (integration) of the HIV replication cycle takes place where?

A

Inside the nucleus of the CD4 cell

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20
Q

Reverse transcription, replication, assembly and budding stages of the HIV replication cycle takes place where?

A

These steps occur within the cytosol of the CD4 cell

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21
Q

What happens during the Binding stage of HIV replication?

A

Virion’s gp120 and gp41 proteins bind to cell surface receptors CD4 cell and either the CCR5 or
CXCR4 co-receptors

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22
Q

What happens during the Fusion stage of HIV replication?

A

The Viral envelope fuses with the CD4 cell membrane, there’s uncoating and release of Viral contents into the cell

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23
Q

What happens in the reverse transcription stage of HIV replication?

A

Having entered the cell, the viral RNA is transcribed into viral DNA by reverse transcriptase enzyme

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24
Q

What happens at the integration stage of HIV replication ??

A

Viral DNA is transported into the cell nucleus and is integrated into the CD4 cell DNA by HIV enzyme integrase

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25
Q

What happens during Replication stage of HIV infection?

A

Once the Viral DNA is integrated into the CD4 cell DNA, viral DNA is transcribed into messenger RNA (mRNA). mRNA is transcribed into long chains of viral enzymes and proteins which are used for the next generation of HIV

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26
Q

What happens during the Assembly stage of HIV infection???

A

New HIV proteins/enzymes and Viral RNA move to the surface of the cell and assemble into immature (noninfectious) HIV

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27
Q

What happens during the Budding and maturation stage of HIV infection???

A

Newly formed immature (noninfectious) HIV pushes itself out of the host CD4 cell.
The new HIV releases enzyme protease which * cleaves the long protein chains in the immature virus* creating several small mature (infectious) virus. Which can then go on to infect other cells

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28
Q

WHO staging of HIV disease in adults and adolescents consist of how many clinical stages?

A

Clinical Stage 1-4

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29
Q

STAGE 1 of WHO clinical staging includes what?

A

1) Asymptomatic
2) Persistent Generalized lymphadenopathy

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30
Q

STAGE 2 of WHO clinical staging includes what?

A

1) Moderate unexplained weight loss (under 10% of presumed/measured BW)
2) Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media, pharyngitis)
3) Herpes zoster
4) Angular cheilitis
5) Recurrent oral ulceration
6) Papular pruritic eruptions
7) Seborrhoeic dermatitis
8) Fungal nail infections

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31
Q

Herpes zoster, Angular cheilitis, and Recurrent oral ulceration can be seen in what WHO staging of HIV disease

A

Clinical Stage 2

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32
Q

Papular pruritic eruptions and Seborrhoeic dermatitis can be seen in what WHO clinical stage of HIV disease?

A

Clinical stage 2

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33
Q

Fungal nail infections and recurrent respiratory infections can be seen at which WHO clinical staging of HIV disease ??

A
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34
Q

Unexplained severe weight loss (over 10% of presumed or measured BW) occurs at what WHO Clinical Stages of HIV infection ??

A

Clinical stage 3

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35
Q

Unexplained anaemia, neutropenia and/or chronic thrombocytopenia occurs in what WHO clinical stage of HiV disease?? (add values to about)

A

Clinical Stage 2
Anaemia: (< 8g/dl)
neutropenia: ( < 0.5 X 10^9/1 )
Thrombocytopenia: (< 50 x 10^9 /1)

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36
Q

HIV wasting syndrome occurs in what WHO staging of HIV disease??

A

Clinical Stage 4

37
Q

Pneumocystis ………? pneumonia occurs in what WHO staging of HIV disease??

A

1) Jiroveci
2) Clinical stage 4

38
Q

1)Extrapulmonary tuberculosis….. which clinical stage??
2)Kaposi sarcoma … which clinical stage ??
3) Cytomegalovirus infection… which Clinical stage ??

A

All Clinical stage 4

39
Q

1) Pulmonary tuberculosis
2) Extrapulmonary tuberculosis
3) HIV encephalopathy
4) Unexplained persistent fever (intermittent/constant > 1 month)
5) Recurrent septicaemia (including non-typhoidal Salmonella)

A

1) clinical Stage 3
2) clinical Stage 4
3) clinical stage 4
4) clinical stage 3
5) clinical stage 4

40
Q

6) Persistent oral candidiasis
7) Disseminated mycosis
8) Symptomatic HIV -associated nephropathy or cardiomyopathy
9) Oral hairy leukoplakia
10) Invasive cervical carcinoma

A

6) clinical stage 3
7) clinical stage 4
8) clinical stage 4
9) clinical stage 3
10) clinical stage 4

41
Q

Mention 2 HIV laboratory tests and their function?

A

1) CD4 counts - measures the state of a persons immune system function
2) Viral Load - Detects the amount of virus present

42
Q

Normal CD4 count in Adults?

A

Approximately 500 - 1300 cells/mm^3

43
Q

CD4 counts help to with?

A
  1. Helps to determine the stage of HIV progression
  2. Determines the risk of opportunistic infections
  3. Historically guided decisions about ART
44
Q

In terms of Viral Load, what is the goal of ARtherapy?

A

Undetectable viral load

45
Q

High viral load means?

A

Increased risk for disease progression and HIV transmission

46
Q

Viral load is measured by

A

HIV-1 RNA PCR

47
Q

Acute Retroviral Syndrome occurs when?

A

2-6 weeks after initial infection

48
Q

About Acute Retroviral syndrome symptoms…?

A

• 2/3rd of patients experience symptoms
• Symptoms last for 2-4weeks
• first stage of infection with HIV
• symptoms are similar to Flu, influenza, mononucleosis
• Fever, Headache, Muscle aches and joint pain, Rash.

49
Q

What happens during Acute Retroviral Syndrome?

A

During this period, HIV virus is replicating rapidly and CD4 count decreases until the body’s immune response recovers CD4 cells and decreases viral load.

50
Q

Salient features of clinical latency (in the clinical progression of HIV)

A

• Virus is replicating at low levels
• CD4 cells are maintained at a healthy level
• Virus is transmittable
• This period may last for several years

51
Q

HIV clinical progression includes

A

• Acute Retroviral syndrome
• Clinical latency

52
Q

The 5 Goals of Antiretroviral Therapy (ARTs)?

A

• To improve quality of life
• To prevent vertical HIV transmission
• To restore and/or preserve immunologic function
• To Maximally and durably suppress HIV viral load
• To reduce HIV-related morbidity and prolong survival

53
Q

Basic mechanism of action of Antiretrovirals (ARVs) ?

A

They reduce the ability of HIV virus to replicate which in turn increases the body’s immune response and reduces the risk of HIV transmission

54
Q

4 Properties of an ideal ARV?

A

• Good tolerability
• No toxicities
• Complete viral suppression
• No resistance

55
Q

What is Antiretroviral therapy (ART)?

A

This is the use of antiretroviral drugs to treat HIV disease

56
Q

What is HAART?

A

Highly active antiretroviral therapy, are regimens combining several antiretroviral drugs

57
Q

What should a successful HAART regimen consist of?

A

Antiretroviral regimens should contain ** at least two**, and preferably three active drugs from multiple drug classes

58
Q

Factors to consider when selecting initial ART regimen ?

A

1) Convenience
2) The adherence potential of the patient
3) Co-morbidities
4) Potential adverse drug effects and drug interactions with other medications

59
Q

In terms of Convenience what should one consider when starting ART?

A

1) Dosing frequency,
2) Pill burden
3) Food and fluid considerations

60
Q

First Indications for the initiation of ART ?

A

ART should be initiated in all adults living with HIV regardless of WHO clinical stage and at any CD4 cell count

(Strong recommendation, medium-quality evidence)

61
Q

Second indication for the initiation of ART ?

A

ART should be initiated in all pregnant and breastfeeding women living with HIV regardless of WHO clinical stage and at any CD4 cell count and continued lifelong

62
Q

What class of ARVs work against Binding and fusion of HIV virus to CD4 cell?

A

Binding - CCR5 Antagonists
Fusion - Fusion inhibitors

63
Q

What class of ARVs work against Reverse transcription of HIV virus during the process of infection?

A

NRTI - Nucleoside/Nucleotide reverse transcriptase inhibitors
NNRTI - Non-nucleoside reverse transcriptase inhibitors

64
Q

5 examples of Nucleoside reverse transcriptase inhibitors (NRTI) ?

A

• Abacavir
• Zidovudine
• Didanosine
• Lamivudine
• Stavudine
• Emtricitabine

65
Q

An example of Nucleotide reverse transcriptase inhibitors (NRTI) ?

A

Tenofovir

66
Q

The NRTI that starts with a letter “ Z ” is called ?

A

Zidovudine

67
Q

The NRTI that starts with a letter “ E “ is called ?

A

Emtricitabine

68
Q

Two NRTIs that starts with a letter “L and S” respectively are called ?

A

Lamivudine and Stavudine

69
Q

The two NRTIs that do not have the suffix “ ine “ in their names are called

A

Abacavir and Tenofovir

70
Q

What’s the function of RNA-Dependent DNA polymerase

A

Also called Reverse transcriptase, it converts viral RNA into Pro-Viral DNA

71
Q

What’s the relationship between NRTI and Reverse transcription

A

NRTI inhibits the enzyme Reverse transcriptase therefore preventing the process from occurring.

72
Q

What’s the relationship between NRTI and the integration & replication process of HIV infection

A

NRTI inhibit the incorporation of native nucleotides and also cause the termination of chain elongation of Nascent pro-viral DNA

73
Q

• NRTs must be ………….?? to become actives.
• They Inhibit which types of HIV ?
• Many have activity against ……..?

A

• Triphosphorylated
• HIV -1 and HIV-2
• Other viruses

74
Q

• Most of the parent compounds have plasma t1/2 of ……?
• Resistance develops ………? compared with NNRTIs and PIs
• They undergo …….? to drugs with similar structures

A

• 1-10hours
• slowly
• Cross resistance

75
Q

NRTIs have minimal effect on……….? but inhibits …………? present in mitochondria

A

• Human polymerase a and b
• DNA polymerase gamma

76
Q

•……….?, ……..?, and tenofovir have low activity for ……….?

A

• Emtricitabine and Lamivudine
• DNA polymerase gamma

77
Q

…….? are the components of most antiretroviral combinations ?

A

NRTIs

78
Q

Zidovudine is a …………?

A

Thymidine analogue (3’-azido-3’ deoxythymidine)

79
Q

Zidovudine is active against ………..?.

A

HIV and HTLV I & II

80
Q

Relationship between zidovudine and lymphocytes

A

Zidovudine is has greater activity in lymphocytes than Macrophage-monocyte cell lines.
Zidovudine is more potent in activated lymphocytes than in resting lymphocytes

81
Q

Mechanism of Action of Zidovudine

A

The active form inhibits reverse transcriptase and prevents the formation of phosphodiester linkages needed for dna replication, causing chain termination

82
Q

Pharmacokinetics of Zidovudine

A
  • Subjected to first pass metabolism
  • Can be administered regardless of food.
  • Minimal protein binding
  • Crosses bbb and is detectable in breast milk, semen and fetal tissue
  • Renal excretion of glucuronide and smaller quantity of zidovudine.
83
Q

Uses of Zidovudine

A

Treatment of HIV infection
PMTCT of HIV
Post Exposure prophylaxis

84
Q

ADRs of Zidovudine in advanced disease

A

Bone marrow suppression with anemia and granulocytopenia in advanced dx and very low CD4 counts.

85
Q

ADRs of Zidovudine on chronic administration

A

Nail hyperpigmentation

86
Q

Other ADRs of Zidovudine

A
  • Fatigue, malaise, myalgia, nausea, anorexia, headache and insomnia.
  • Mitochondrial myopathy
  • Elevated creatinine kinase
  • Hepatic toxity (+/- Steatosis), lactic acidosis
87
Q

Drug interactions of Zidovudine?

A
  • Probenecid, fluconazole, atovaquone, valproic acid increase plasma conc
  • Competes with stavudine for intracellular phosphorylation.
88
Q

……….? Drug increases the plasma concentration of Zidovudine

A

Valproic acid

89
Q

Zidovudine competes with ………? Drug for intracellular ……..?

A

Stavudine for intracellular phosphorylation

Pathology And Pharamcology (7 decks)

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