HIV Drugs Flashcards by Stamatia Stratoulia

What are the different types of HIV?

HIV 1 and HIV 2

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What is the difference of HIV 1 & HIV 2?

HIV 1 is world wide
HIV 2 is endemic in West Africa

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HIV mutation?

HIV mutates rapidly

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What is the probability of HIV developing resistance dependent upon?

The probability of developing resistance is directly related to total viral load

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What kind of responses does Anti-Retroviral Therapy cause?

Immunologic response
Virologic response

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What does ART do to plasma levels of HIV?

Decreases HIV plasma levels to undetectable levels.

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What are the advantages of ART/HAART?

Delay or reverse loss of immune function,
Decrease certain complications,
Preserve health,
Prolong life,
Decrease transmission

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What are the disadvantages of ART/HAART?

It is expensive
Risk of longterm side effects
Serious drug interactions
Life-long medication

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What happens if there is discontinuation of the HIV medication?

Rebound in HIV replication

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What are the goals of treatment?

Reduce HIV-associated morbidity
Prolong duration and quality of life
Preserve immunologic function
Suppress plasma HIV viral load
Prevent transmission

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What are the classifications of HIV drugs?

NRTIs
NNRTIs
PIs
INSTI
CCR5 antagonist
Fusion Inhibitors
Attachment Inhibitors
Post-attachment inhibitors

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What is the first line of treatment for HIV?

NRTIs

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What are NRTIs?

Nucleoside reverse transcriptase inhibitors;
Chemical relatives of naturally occurring nucleosides or nucleotides

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What is the MOA of NRTIs?

Suppress RT-mediated viral DNA synthesis
Suppress mitochondrial DNA polymerization

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What are the adverse effects of NRTIs?

Peripheral neuropathies
Pancreatitis
Lipoatrphy

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In order for NRTIs to be effective, what must happen to them first?

They must undergo intracellular conversion to their active forms

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What are examples of NRTIs

Zidovudine
Abacavir
Lamivudine
Tenofovir

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What is Zidovudine?

Analog of thymidine

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What is the function of Zidovudine when combined with other antiretroviral drugs?

Decrease viral load,
Increase CD4 T-cell count
Delay onset
Reduce symptom severity

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What is the MOA of Zidovudine?

Premature strand termination
Competes with natural nucleoside triphosphates for binding to the active site of reverse transcriptase
Competitive inhibition of enzyme

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What are the therapeutic uses of Zidovudine?

HIV 1
Drug of choice for preventing mother to infant transmission during labor and delivery

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What are the PK of Zidovudine?

Always combined with other antiretroviral drugs
Penetrates CNS better than most other antiretroviral drugs

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What are the adverse effects of Zidovudine?

Severe anemia
Neutropenia
Lactic acidosis with hepatic steatosis
GI disturbances
CNS reactions
Myopathy

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What are the drug interactions of Zidovudine?

Drugs that are myelosuppressive, nephrotoxic or directly toxic increase the risk of hematologic toxicity

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What is the antiviral that should NOT be taken with Zidovudine?

Ganciclovir

What is Abacavir?

An analogue of guanosine

What is the MOA of Abacavir?

Premature termination and direct inhibition of RT

What are the therapeutic effects of Abacavir?

HIV 1 infections only

What are the adverse effects of Abacavir?

Hypersensitivity reactions in patients

What kind of patients should not be given Abacavir?

Sensitized patients Can check through the genetic test (HLA-B*5701)

What is Lamivudine?

Analogue of cytidine

What are the therapeutic uses of Lamivudine?

HIV 1 Hepatitis B virus

What are the PK of Lamivudine?

Oral High bioavailability Food reduces rate of absorption Eliminated in the urine

What are the adverse effects of Lamivudine?

Best tolerated Minimal side effects Insomnia Headaches Small risk of fatal lactic acidosis

What is Tenofovir?

Analogue of adenine Nucleotide reverse transcriptase inhibitor

What is the MOA of Tenofovir?

Inhibits viral DNA synthesis Competes with natural substrate to reverse transcriptase Causes premature termination

What are the therapeutic uses of Tenofovir?

HIV 1 HBV infection

What is the difference between NRTIs and NNRTIs?

NRTIs inhibit synthesis of HIV DNA NNRTIs directly inhibit reverse transcriptase

Are NNRTIs in their active or inactive form?

Active form when administered

What are the main examples of NNRTIs?

Efavirenz Rilpivirine Nevirapine Delavirdine Etravirine Doravirine

Which is the preferred NNRTI for HIV treatment?

Efavirenz

What is the MOA of Efavirenz?

Binds directly to the centre of reverse transcriptase (RT) and inhibits it

What are the therapeutic uses of Efavirenz?

HIV 1 infection

What other drugs is Efavrenz used in combination with?

Zidovudine & Lamivudine

What are the PK of Efavirenz?

Orally taken on an empty stomach Crosses BBB Metabolised by CYP450 Excreted in urine and feaces Long half-life (40 to 55 hours)

What are the adverse effects of Efavirenz?

CNS symptoms Rash Teratogenicity Liver damage

What are the drug interactions of Efavirenz?

Ccompetes with other drugs for CYP450 Can accelerate its own metabolism and that of protease inhibitors Decreases hormonal contraceptives St. John worts can reduce levels of Efavirenz

Which drug combination with Efavirenz can increase levels of both drugs and cause toxicity?

Ritonavir

What are PIs given with to reduce viral load to undetectable levels?

NRTIs

What are some general side effects of PIs?

Fat redistribution Hyperglycemia/diabetes Reduced bone mineral density Bleeding in hemophiliacs Elevation of triglycerides and transaminases

The combination of which drugs can cause rhabdomyolysis?

PIs with simvastatin or lovastatin

What are the general PK of PIs?

Metabolised by CYP450 Induce certain CYP450 isozymes and inhibit other Resistance to one PI may mean resistance to others

What pharmacokinetic boosters are PI administered with?

Ritonavir or Cobicistat

What are the examples of PIs?

Lopinovar/Ritonavir Indinavir Atazanavir Darunavir

What name are Lopinovar and Ritonavir given under?

Kaletra

What are the therapeutic uses of Kaletra?

HIV in adults & children older than 6 months old

How is Lopinavir metabolised?

CYP450; CYP3A4

What does Ritonavir inhibit?

CYP3A4

Which levels does Kaletra increase?

Lopinovar

What is the MOA of Kaletra?

Block protease HIV remains immature and non-infectious

What are the PK of Lopinavir/ Kaletra?

Orally taken Absorption is higher with food 99% bound to blood plasma Metabolised by CYP3A4 Excreted in urine & feces

What are the adverse effects of Kaletra?

GI disturbances Cardiac effects; QT & PR prolongation Toxicity in newborns

What are the drug interactions of Kaletra?

Inhibit and induce CYP450 Disulfiram or Meronidazole

What is the therapeutic use of Indinavir?

HIV 1

What is Indinavir usually combined with?

2 NRTIs

What is the major adverse effect of Indinavir?

Nephrolithiasis

What reduces the availability of Atazanavir?

Agents that reduce acidity

Adverse effect of Atazanavir?

Nephrolithiasis

What is Darunavir?

2nd generation PI

What is the therapeutic use of Darunavir?

HIV strains that are resistant to other PIs

What is Darunavir usually given with?

Ritonavir Cobicistat

What are the adverse effects of Darunavir?

It has a sulphonamide group; careful with patients with sulfonamide allergy Signs of glucose dysregulation are NOT reported

What are examples of integrase strand transfer inhibitors?

Raltegravir Dolutegravir

What is the MOA of Raltegravir?

Prevents insertion of HIV DNA --> stops HIV replication

What is the therapeutic use of Raltegravir?

HIV 1

What is Raltegravir given with?

Tenofovir + Emtricitabine OR Lamivudine

What are the PK of Raltegravir?

Orally taken Metabolised by UGT

What are the adverse effects of Raltegravir?

Insomnia and headaches Severe hypersensitivity (RARE)

What are the drug interactions of Raltegravir?

Inhibitors of UGT can increase its levels Inducers of UGT lower its levels Antacids and polyvalent cations reduce bioavailability

What is the first line integrase inhibitor

Dolutegarvir

What are examples of HIV Fusion Inhibitors?

Enfuvirtide

What is the MOA of Enfuvirtide?

Binds to GP41 and prevents fusion

What is the PK of Enfuvirtide?

What is the therapeutic use of Enfuvirtide?

HIV1 that is resistant to other ART agents

What are the adverse effects of Enfuvirtide?

Injection site reactions Pneumonia Hypersensitivity reactions

What is an example of CCR5 antagonist?

Maraviroc

What are the uses of Maraviroc?

Indicated for combined use with other ART for patients > 16 years of age

What are the PK of Maraviroc?

Half-life of 14 to 18 hours Metabolised by CYP3A4

What are the adverse effects of Maraviroc?

Cough Dizziness Rash Fever URTI LIVER INJURY !! Cardiovascular events (rare)

What are the drug interactions of Maraviroc?

Increased by CYP3A4 inhibitors Decreased by CYP3A4 inducers

What is an example of Capsid Inhibitor?

Ienacapavir

What is the MOA of Ienacapavir?

Prevents functional disassembly of the capsid in infected cells Inhibits viral nuclear import Inhibits assembly

What are the PK of Ienacapavir?

SQ or tablet

What are the therapeutic uses of Ieancapavir?

HIV 1 with multidrug resistance

What are the side effects of Ienacapavir?

Nausea Hyperglycemia

What is an example of Attachment Inhibitors?

Fostemsavir

What is the MOA of Fostemsavir?

Binds to GP120 protein on the outer surface of HIV Prevents HIV from entering CD4 cells

What is an example of POST-attachment inhibitors?

Ibalizumab

What is Ibalizumab?

Monoclonal antibody that binds to domain 2 of CD4 immune cells

What is the MOA of Ibalizumab?

Promotes steric hindrance and prevents conformational changes that allow for HIV 1 viral entry

What are the approved regimens?

2 NRTIs + One protease inhibitor + Ritonavir/Cobicistat 2 NRTIs + NNRTI 2 NRTIs + Integrase inhibitor