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Pharmacology > Antiretrovirals > Flashcards

Antiretrovirals Flashcards

1
Q

WHO HIV clinical stage 1

A

Persistent generalised lymphadenopathy Asymptomatic

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2
Q

Unexplained persistent hepatosplenomegaly

Papular pruritic eruptions

Extensive wart virus infection

Extensive molluscum contagiosum

Fungal nail infections

A

CLINICAL STAGE 2 who hiv

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3
Q

WHO clinical stage 2 of HIV

A

Recurrent oral ulcerations

Unexplained persistent parotid enlargement

Lineal gingival erythema

Herpes zoster

Recurrent or chronic upper respiratory tract infections (otitis media, otorrhoea, sinusitis or tonsillitis)

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4
Q

Unexplainedi moderate malnutrition not adequately responding to standard therapy

Unexplained persistent diarrhoea (14 days or more) Unexplained persistent fever (above 37.5°C intermittent or constant, for longer than one month)

A

HIV WHO clinical stage 3

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5
Q

Persistent oral candidiasis (after first 6–8 weeks of life) Oral hairy leukoplakia

Acute necrotizing ulcerative gingivitis or periodontitis

A

WHO HIV Clinical stage 3

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6
Q

Lymph node tuberculosis

Pulmonary tuberculosis

Severe recurrent bacterial pneumonia

A

HIC WHO clinical stage 3

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7
Q

Describe the pneumonitis, anaemia and lung disease of WHO clinical stage 3

A

Symptomatic lymphoid interstitial pneumonitis

Chronic HIV-associated lung disease including brochiectasis

Unexplained anaemia (<8 g/dl), neutropaenia (<0.5 × 109 per litre) and or chronic thrombocytopaenia (<50 × 109 per litre)

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8
Q

Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy

Pneumocystis pneumonia

Recurrent severe bacterial infections (such as empyema, pyomyositis, bone or joint infection or meningitis but excluding pneumonia)

A

HIV WHO clinical stage 4

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9
Q

Chronic herpes simplex infection (orolabial or cutaneous of more than one month’s duration or visceral at any site)

Extrapulmonary tuberculosis

Kaposi sarcoma

A

WHO HIV clinical stage 4

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10
Q

Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs)

Central nervous system toxoplasmosis (after one month of life)

HIV encephalopathy

Cytomegalovirus infection: retinitis or cytomegalovirus infection affecting another organ, with onset at age older than one month

A

HIV WHO Clinicl stage 4

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11
Q

Extrapulmonary cryptococcosis (including meningitis)

Disseminated endemic mycosis (extrapulmonary histoplasmosis, coccidiomycosis)

Chronic cryptosporidiosis

Chronic isosporiasis

A

WHO clinical stage 4

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12
Q

Disseminated non-tuberculous mycobacterial infection

Cerebral or B-cell non-Hodgkin lymphoma

Progressive multifocal leukoencephalopathy

Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy

A

WHO HIV clinical stage 4

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13
Q

Immunological criteria for diagnosing advanced HIV in adults and children five years or older with confirmed HIV infection

A

CD4 count less than 350 per mm3 of blood in an HIV-infected adult or child

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14
Q

Immunological criteria for diagnosing advanced HIV in a child younger than five years of age with confirmed HIV infection:

A

%CD4+ <30 among those younger than 12 months %CD4+ <25 among those aged 12–35 months %CD4+ <20 among those aged 36–59 months

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15
Q

AIDS diagnosis in adults an children

A

clinical diagnosis (presumptive or definitive ) of any stage 4 condition (as defined in Annex 1) with confirmed HIV infection; OR

immunological criteria in adults and children with confirmed HIV infection and >5 years of age;

first-ever documented %CD4 count less than 200 per mm3 or %CD4+ <15; or,

among children aged 12–35 months first-ever documented CD4 of +<20; or among infants less than 12 months of age first-ever documented %CD4+ <25.

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16
Q

viral suppression

A

defined as having less than 200 copies of HIV per milliliter of blood

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17
Q

Nucleoside and nucleotide reverse transcriptase inhibitors

A

zidovudine, lamivudine, abacavir, tenofovir, emtricitabine, stavudine)

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18
Q

MOA Zidovudine

A

It inhibits the activity of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue.

t competes with the natural substrate dGTP and incorporates itself into viral DNA

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19
Q

Zidovudine adverse drug reactions

A

fatigue, headache, gastrointestinal upset, lipoatrophy, bone marrow suppression, and myopathy

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20
Q

Emtricitabine MOA

A

emtricitabine 5’-triphosphate, competes with deoxycytidine 5’-triphosphate for HIV-1 reverse transcriptase

As HIV-1 reverse transcriptase incorporates emtricitabine into forming DNA strands, new nucleotides are unable to be incorporated, leading to viral DNA chain termination.5 I

nhibition of reverse transcriptase prevents transcription of viral RNA into DNA, therefore the virus is unable to incorporate its DNA into host DNA and replicate using host cell machinery.

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21
Q

ADRs emtricitabine

A

discoloration of the skin, nails, and tongue

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22
Q

STavudine mOA

A

Stavudine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.

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23
Q

Stavudine ADRs

A

peripheral neuropathy, lactic acidosis, and facial and body lipoatrophy.[57] In addition, cases of severe neuromuscular weakness have been described

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24
Q

Lamivudine MOA

A

This nucleoside analogue is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, resulting in DNA chain termination.

25
Q

Lamivudine ADRs

A

discoloration of the skin, nails, and tongue

26
Q

Abacavir MOA

A

converted by cellular enzymes to the active metabolite carbovir triphosphate

inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.

Viral DNA growth is terminated

27
Q

Abacavir ADRs

A

Hypersensitivity reaction

Risk of cardiac disease

28
Q

Tenofovir MOA

A

inhibition of viral polymerase causing chain termination and the inhibition of viral synthesis

potent inhibitor of the viral reverse transcriptase

29
Q

Tenofovir ADRs

A

mild gastrointestinal effects (nausea, vomiting, diarrhea)

30
Q

Nevirapine MOA

A

binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities

31
Q

Non-nucleoside reverse transcriptase inhibitors

A

(nevirapine, efavirenz

32
Q

Nevirapine ADRs

A

Hypersensitivity reaction with rash and he[atotoxicity

Rash may be accompanied by fever, general malaise, fatigue, myalgias, arthralgias, blisters, oral lesions, conjunctivitis, facial edema, eosinophilia, granulocytopenia, lymphadenopathy, or renal dysfunction.

33
Q

Efavirenz moa

A

inhibits the activity of viral RNA-directed DNA polymerase (i.e., reverse transcriptase

34
Q

Efavirenz side effects

A

Cardiac QTc Interval Prolongation:

Dyslipidemia

Hepatotoxicity

Neuropsychiatric

Rash

Teratogenicity

35
Q

Protease inhibitors

A

(lopinavir, atazanavir,ritonavir)

36
Q

Lopinavir MOA

A

an inhibitor of the HIV-1 protease enzyme

the enzyme responsible for cleaving the Gag polyprotein which coordinates assembly, budding and maturation in HIV lifecycle

37
Q

Lopinavir ADRs

A

Hyperlipidaemia

Diarrhoea

Alcohol in Liquid Formulation

38
Q

atazanavir moa

A

Atazanavir selectively inhibits the virus-specific processing of viral Gag and Gag-Pol polyproteins in HIV-1 infected cells by binding to the active site of HIV-1 protease, thus preventing the formation of mature virions

39
Q

Atazanavir ADRs

A

Hyperbilirubinemia

Nephrolithiasis

Cholelithiasis

40
Q

Ritonovir MOA

A

inhibits the HIV viral proteinase enzyme that normally cleaves the structural and replicative proteins that arise from major HIV genes, such as gag and pol.

41
Q

Ritonavir ADRs

A

gastrointestinal effects, including diarrhea, nausea, vomiting, and abdominal pain. These side effects are greater with higher doses of ritonavir.

42
Q

Raltegravir MOA

A

Raltegravir inhibits HIV integrase to prevent the viral genome being incorporated into the human genome

43
Q

Raltegravir ADRs

A

Elevated Creatine Kinase

Proximal Myopathy

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

44
Q

dolutegravir MOA

A

It inhibits HIV integrase by binding to the active site and blocking the strand transfer step of retroviral DNA integration in the host cell

45
Q

When to start ART among adults (>19 years old)

A

ART should be initiated among all adults with HIV regardless of WHO clinical stage and at any CD4 cell count (strong recommendation, moderate-quality evidence).

o As a priority, ART should be initiated among all adults with severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) and adults with CD4 count ≤350 cells/mm3

46
Q

When to start ART among pregnant and breastfeeding women

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

47
Q

When to start ART among adolescents (10–19 years of age)

A

ART should be initiated among all adolescents living with HIV regardless of WHO clinical stage and at any CD4 cell count (conditional recommendation, low-quality evidence). o As a priority, ART should be initiated among all adolescents with severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) and adolescents with CD4 count ≤350 cells/mm3 (

48
Q

When to start ART among children (younger than 10 years of age)

A

ART should be initiated among all children living with HIV, regardless of WHO clinical stage or at any CD4 cell count.

o Infants diagnosed in the first year of life (strong recommendation, moderate-quality evidence). o Children living with HIV one year old to less than 10 years old (conditional recommendation, low-quality evidence).

As a priority, ART should be initiated among all children ≤2 years old or with WHO stage 3 or 4 or CD4 count ≤750 cells/mm³ or CD percentage <25% among children younger than 5 years and CD4 count ≤350 cells/mm³ among children 5 years and older.

49
Q

Factors that should be monitored when on ART

A

TB screen

WHO staging

side effects

CD 4 count

viral load

creatinine

FBC

ALT

Fasting TC TG

50
Q

Causes of treatment failure

A
  1. Drug resistance
  2. Adherence issues
51
Q

Factors contributing to development of resistance

A

Poor adherance

Insufficient drug level

Viral replication in presence of drug

resistant viru

transmission

52
Q

Howto diagnose virological failure

A

HIV RNA >1000 copies

Check VL in 2 months if still>100 copies change treatment

  • Clinical deterioration - poor growth / FTT - delay in developmental milestones - development of opportunistic infections
  • Immunological deterioration - steady decline in CD4+ count
53
Q

Failed 1st line NNRTI based regimen

Abacavir + Lamivudine + Efavirenz (or Nevirapine)

What is Recommended second line regimen?

A

Zidovudine + Lamivudine + Lopinavir/ritonavir

54
Q

Failed 1st line NNRTI based regimen

First line NNRTI-based regimen:

Stavudine + Lamivudine + Efavirenz (or Nevirapine)

what is the Recommended second line regimen:

A

Zidovudine + Lamivudine + Lopinavir/ritonavir

55
Q

Failed 1st line Protease Inhibitor (PI) based regimen

Abacavir + Lamivudine + Lopinavir/ritonavir

Stavudine + Lamivudine + Lopinavir/ritonavir Unboosted

PI-based regimen Rifampicin while on Lopinavir/ritonavi

A

*Manage as for 3rd line regimens

Should be managed by a Paediatric Infectious Disease Specialist on the basis of genotype resistance testing.

Indications for resistance testing:

• Infants = 1000 copies/ml (>=log 3) at least 8-12 weeks apart after adherence has been addressed.

Stavudine + Lamivudine + Lopinavir/ritonavir Unboosted PI-based regimen Rifampicin while on Lopinavir/ritonavi

56
Q

Resistance Testing

A

Can only be used to detect resistance to drugs currently being taken or within 4 weeks of stopping them -won’t necessarily show resistance to drugs patient was previously exposed to • Is useful to exclude drugs from a future regimen -won’t necessarily indicate which drugs will work

57
Q

Initial antiretroviral therapy regimens for the previously untreated patient

A

• TDF + emtricitabine (FTC) (or 3TC) + efavirenz (EFV)

or

• TDF + emtricitabine (FTC) (or 3TC) + dolutegravir (DTG)

or

• TDF + emtricitabine (FTC) (or 3TC) + rilpivirine (RPV) provided VL < 100 000 copies/mL.

58
Q

Recommended second-line antiretroviral therapy regimen

A

We recommend a regimen of two NRTIs and a RTV-boosted (/r) PI. Boosting of PIs involves the addition of low-dose RTV, which inhibits PI metabolism, thereby boosting PI plasma concentration and prolonging half-life. We recommend against the use of unboosted PIs

59
Q
A

Pharmacology (13 decks)

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