Pharmacology 1: Therapeutic Approach To Infectious Diseases (HIV)

Question 1

What is the first anti-retroviral agent to be discovered?

Answer 1

Zidovudine.

Question 2

How many anti-retrovirals is the standard of care?

Answer 2

3 anti-retrovirals.

Question 3

The most important measure of ART efficacy is what?

Answer 3

Viral load.

Question 4

1- HIV enters the CD4 cells after fusion of viral ____ with ______ or _____ receptors on human cells.

Answer 4

HIV enters the CD4 cells after fusion of viral Gp41 with CCR5 or CXCR4 receptors on human cells.

Question 5

2- After entry, viral RNA is converted to DNA with the help of __________________.

Answer 5

After entry, viral RNA is converted to DNA with the help of reverse transcriptase (RNA dependent DNA polymerase).

Question 6

3- Viral DNA integrates with human DNA to form ______, with the help of enzyme _______.

Answer 6

Viral DNA integrates with human DNA to form provirus, with the help of enzyme integrase.

Question 7

4- The proviral DNA replicates and transcripts to form ____, which forms proteins via _________.

Answer 7

The proviral DNA replicates and transcripts to form RNA, which forms proteins via translation.

Question 8

5- ___________ cleaves the proteins and allows their assembly as __________.

Answer 8

Protease enzyme cleaves the proteins and allows their assembly as new virion.

Question 9

List the 4 targets of anti-retroviral drug action?

Answer 9

1- fusion/entry inhibitors.
2- reverse transcriptase inhibitors.
3- integrase inhibitors.
4- protease inhibitors.

Question 10

List the 5 classification of anti-retrovirals?

Answer 10

1- reverse transcriptase inhibitors: nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs).
2- protease inhibitors.
3- integrase inhibitors.
4- entry/fusion inhibitors.
5- CCR5 receptor antagonist.

Question 11

NRTIs are ______ - activated by what?

Answer 11

Prodrugs - activated by host cell kinases to form triphosphates.

Question 12

NRTIs _______ _____ reverse transcriptase.

Answer 12

NRTIs competitively inhibit reverse transcriptase.

Question 13

All NRTIs are excreted by _______, except _____ which is metabolized by ______ ___________.

Answer 13

All are excreted by kidneys (dose adjustment in renal failure), except abacavir which is metabolized by alcohol dehydrogenase.

Question 14

All NRTIs may cause which side effects?

Answer 14

Lactic acidosis, hepatomegaly and steatosis.

Question 15

List NRTIs?

Answer 15

• Abacavir
• Didanosine
• Emtricitabine
• Lamivudine
• Stavudine
• Tenofovir
• Zalcitabine
• Zidovudine

Question 16

Which NRTI is a nucleotide (instead of nucleoside) reverse transcriptase inhibitor?

Answer 16

Tenofovir.

Question 17

Which NRTIs need to be converted?

Answer 17

• Zalcitabine.
• Zidovudine.

Question 18

List the uses for zidovudine?

Answer 18

1-prophylaxis of needle stick injury.
2- prevention of vertical transmission.

Question 19

List the adverse effects of zidovudine?

Answer 19

BM suppression, myopathy, lipodystrophy syndrome, nail hyperpigmentation and lipoatrophy.

Question 20

Which NTRI’s oral bioavailability increases with food?

Answer 20

Tenofovir.

Question 21

What happens to didanosine’s oral bioavailability with food?

Answer 21

Reduced.

Question 22

List the adverse effects of didanosine?

Answer 22

Dose-limiting pancreatitis (max chance), hyperuricemia, optic neuritis, painful sensory peripheral neuropathy, neutropenia, diarrhea.

Question 23

List the AE of stavudine?

Answer 23

• causes dose limiting peripheral neuropathy.
• max chance of causing lactic acidosis.
• most strongly associated with lipodystrophy syndrome.
• also causes pancreatitis.

Question 24

What happens in lipodystrophy syndrome?

Answer 24

• hyperlipidemia.
• hypercholesterolemia.
• glucose intolerance, and fat redistribution,

Question 25

What are the best tolerated NRTIs?

Answer 25

Lamivudine and Emtricitabine.

Question 26

What are the advantages of Lamivudine and Emtricitabine?

Answer 26

Not associated with peripheral neuropathy or pancreatitis, also effective against Hep B.

Question 27

List the AE of abacavir?

Answer 27

Increases risk of MI, may cause severe hypersensitivity reaction > esp in patients having HLA B5701allele (testing should be done before starting abacavir).

Question 28

Max risk of pancreatitis is seen with which NRTI?

Answer 28

Didanosine.

Question 29

Max risk of peripheral neuropathy is seen with which NRTI?

Answer 29

Stavudine.

Question 30

Max risk of lipodystrophy is seen with which NRTI?

Answer 30

Stavudine.

Question 31

List NNRTIs?

Answer 31

• Delavirdine • Efavirenz • Nevirapine • Etravirine

Question 32

NNRTIs are ________ inhibitors of reverse transcriptase?

Answer 32

Non-competitive

Question 33

NNRIs are selective for which type of HIV?

Answer 33

HIV-1.

Question 34

List the disadvantages to NNRTIs?

Answer 34

- Resistance develops rapidly. - Skin rash is seen with all NNRTIs.

Question 35

List an advantage of NNRTIs?

Answer 35

Do not cause lipodystrophy.

Question 36

_____________ and ____________ are CYP450 inducers, whereas _________ is an enzyme inhibitor.

Answer 36

Nevirpine and Efavirenz are CYP450 inducers, whereas Delavirdine is an enzyme inhibitor.

Question 37

List protease inhibitors?

Answer 37

• Atazanavir • Darunavir • Fosamprenavir • Indinavir • Lopinavir • Saquinavir • Ritonavir • Nelfinavir all end with “navir”.

Question 38

How do protease inhibitors work?

Answer 38

Inhibit post-translational modification of viral proteins. PIs inhibit CYP3A4, thus inhibit metabolism of several drugs.

Question 39

List another application of Ritonavir?

Answer 39

In low doses can be used with other PIs to increase their plasma concentration > ‘Ritonavir boosting’.

Question 40

List an AE of PIs?

Answer 40

Metabolic abnormalities (including lipodystrophy syndrome) because all PIs are metabolized in the liver.

Question 41

Which PI is devoid of metabolic abnormalities?

Answer 41

Atazanavir, because it’s metabolized by alcohol dehydrogenase.

Question 42

List an entry inhibitor?

Answer 42

Efuvirtide.

Question 43

How can Enfuvirtide works?

Answer 43

Binds to Gp41 subunit of HIV envelope protein and inhibits fusion of viral and host cell membranes, prevents entry of the virus in the host cells.

Question 44

List disadvantages of Enfuvirtide?

Answer 44

Used SC and can cause injection site reactions, hypersensitivity and pneumonia. Not effective against HIV-2.

Question 45

List a CCR5 co-receptor antagonist?

Answer 45

Maraviroc.

Question 46

What is the first CCR5 co-receptor antagonist to be approved for use?

Answer 46

Maraviroc.

Question 47

What is the route of administration of Maraviroc?

Answer 47

Given orally.

Question 48

What is Maraviroc used for?

Answer 48

Only effective against CCR5-tropic virus, this type of HIV-1 virus tends to predominate early in infection.

Question 49

List integrase inhibitors?

Answer 49

• Raltegravir • Elvitegravir • Dolutegravir

Question 50

___________ is a new drug that inhibits the metabolism of ____________. It is approved as a booster for this drug.

Answer 50

Cobicistat is a new drug that inhibits the metabolism of Elvitegravir. It is approved as a booster for this drug.

Question 51

List the WHO guidelines for Anti-retroviral therapy (ART)?

Answer 51

ART should be started in all HIV patients regardless of WHO clinical stage and at any CD4 cell count.

Question 52

Which type of therapy is recommended for HIV patients?

Answer 52

Highly active anti-retroviral therapy (HAART) , it’s recommended with the primary goal of complete suppression of viral replication (viral copies < 50 copies/mL).

Question 53

What is the standard combination ART regimens?

Answer 53

standard combination ART regimens: 2 NRTI + NNRTI/Protease inhibitor (PI)/ integrase inhibitor (II).

Question 54

What is the preferred first line ART for adults?

Answer 54

Tenofovir + Lamivudine (or Emtricitabine) + Efavirenz ( 2 NRTI + 1 NNRTI/II).

Question 55

What is the second line ART for adults?

Answer 55

2 NRTI + PI.

Question 56

What is the preferred first line ART for adolescents?

Answer 56

Tenofovir + Lamivudine (or Emtricitabine) + Efavirenz Or Tenofovir + Lamivudine (or Emtricitabine) + Dolutegravir (2 NRTI + 1 NNRTI/II)

Question 57

What is the second line ART for adolescents?

Answer 57

2 NRTI + PI

Question 58

What is the preferred first line ART for children (3-10 years)?

Answer 58

Abacavir + Lamivudine + Efavirenz (2 NRTI + 1 NNRTI)

Question 59

What is the second line ART for children (3-10 years)?

Answer 59

2 NRTI + PI (or RAL(Raltegravir))

Question 60

What is the preferred first line ART for children (<3 years)?

Answer 60

Abacavir + Lamivudine + Lopnivair + Ritonavir (ritonavir boosting) (2 NRTI + 1 PI/II)

Question 61

What is the second line ART for children (<3 years)?

Answer 61

2 NRTI + RAL (Raltegravir)

Question 62

Post-exposure prophylaxis for HIV is continued for ____ days and should start within ___ hours of exposure

Answer 62

Continued for 28 days and should start within 72 hours of exposure.

Question 63

What is preferred post-exposure prophylaxis of HIV for adults and adolescents?

Answer 63

Tenofovir + Lamivudine + PI

Question 64

What is alternative post-exposure prophylaxis of HIV for adults and adolescents?

Answer 64

Raltegravir or Efavirenz are alternatives to PI. So it becomes (Tenofovir + Lamivudine + Raltegravir or Efavirenz) ( preferred is T + L + PI).

Question 65

What is preferred post-exposure prophylaxis of HIV for children <10 years?

Answer 65

Zidovudine + Lamivudine + Lopinavir.

Question 66

What is alternative post-exposure prophylaxis of HIV for children < 10 years?

Answer 66

Abacavir can be used for zidovudine. So it becomes (Zidovudine + Lamivudine + Abacavir)

Question 67

What if prophylaxis of HIV for infants?

Answer 67

Zidovudine + Nevirapine for 6 weeks.

Question 68

List anti-HIV combinations that should not be used? And why?

Answer 68

1- Zidovudine + Stavudine: pharmacological antagonism (compete for the intracellular phosphorylation). 2- Atazanavir + Indinavir: additive unconjugated hyperbilirubinemia. 3- Didanosine/Stavudine + Zalcitabine: additive peripheral neuropathy.