anti viral drugs

Question 1

what classes of drugs are there

Answer 1

1. non nucleoside reverse transcriptase inhibitors
2. nucleoside reverse transcriptase inhibitors
3. integrase inhibitor
4. protease inhibitor

Question 2

what are the drugs under nucleoside reverse transcriptase inhibitors

Answer 2

lamivudine, tenofovir, abacavir, emtricitabine, zidovudine

Question 3

what is the current standard of care for HIV treatment

Answer 3

use at least 3 drugs simultaneously for the entire duration

2- NRTI and a 3rd drug either a NNRTI, protease inhibitor or integrase inhibitor

Question 4

how does nucleoside reverse transcriptase inhibitors work

Answer 4

they are analogs of native ribosides lacking 3’OH group,

causes chain termination as they are preferentially incorporated into viral DNA by reverse transcriptase as they are phosphorylated to corresponding triphosphate analog upon cell entry

Because 3’OH group not present, a3’5 phosphodiester bond between incoming nucleoside triphosphate and growing DNA chain cannot be form

DNA chain elongation terminated

Question 5

how is nrti excreted

Answer 5

mainly renally

Question 6

What are the prenancy cat for abacavir, lamivudine, zidovudine, emtricitabine, tenofovir

Answer 6

cat c for the first 3, cat B for the last 2

Question 7

what do you not co administer with emtricitabine and why

Answer 7

lamivudine, because both are cytosine analogue, will reduce efficacy

Question 8

what do you have to do before administering abacavir

Answer 8

need to find out if the patient is negative for the HLA-B*5701 allele, need to be genotyped

Question 9

which is the least toxic antiretroviral drug

Answer 9

lamivudine

Question 10

how does integrase inhibitor work

Answer 10

binds and inhibits catalytic site of HIV integrase, terminate integration of HIV DNA into host genome, active against HIV1 and HIV 2

Question 11

how is integrase inhibitor administered

Answer 11

orally

Question 12

how is the absorption of integrase inhibitors

Answer 12

decreased absorption from gut by polyvalent cations, should be take 2hrs before or 6hrs after taking cation containing antacids or supplements

Question 13

what are the adverse effects of integrase inhibitors

Answer 13

weight gain, hypersensitivity reaction, cns effects like insomniam depression

Question 14

What is ritonavir and what does it do

Answer 14

added as a pk booster that has an inhibitory effect on cyp450 enzyme which extends shelf life of protease inhibitor

Question 15

how does protease inhibitors work

Answer 15

prevents viral protein from being cleaved into mature functional proteins

Question 16

How are protease inhibitors metabolised

Answer 16

they are substrates for CYP3A4 isoenzyme, extensive hepatic metabolism

Question 17

how are protease inhibitors eliminated

Answer 17

mostly eliminated by biliary excresion, dosage adjustment unncessary in renal impairment as very little of them are excreted unchanged in urine

Question 18

what are the main problems with protease inhibitors

Answer 18

potent inhibitors of CYP450, drugs that rely on cyp450 isoenzyme mediated metabolism may accumulate to toxic levels

Question 19

What is NNRTI not used for

Answer 19

HIV-2 as there is high rate of resistance

Question 20

What is the mechanism of action for NNRTI

Answer 20

Binds to HIV reverse transcriptase at an allosteric hydrophobic site adjacent to active site, inducing conformational change that result in enzyme inhibition

Question 21

what are the drug interaction of NNRTI

Answer 21

efavirenz induces CYP3A4, may lower concentration of CYP3A4 substrates

Question 22

What cat is NNRTI

Answer 22

cat D

Question 23

how long must prep be

Answer 23

continue prep 1 month after last possible exposure

Question 24

how long must PEP be started after recent possible exposure to PEP

Answer 24

72 hours

Question 25

what is acyclovir used for

Answer 25

HSV encephalitis and commonly used for genital herpes infection

Question 26

How is acyclovir used for

Answer 26

IV, oral, topical

Question 27

What is the mechanism of action for acyclovir

Answer 27

phosphorylated by viral thymidine kinase to acyclovir monophosphate, and host cell enzymes to acyclovir triphosphate form

it stops replication of herpes viral DNA by

1. inhibiting viral DNA polymerase
2. inactivate viral DNA polymerase
3. incorporates into and terminates viral growing DNA chain

Question 28

Does acyclovir have greater antiviral activity on HSV or VSV

Answer 28

HSV

Question 29

what are the benefits of choosing valacyclovir instead of acyclovir

Answer 29

has greater oral bioavailability and can be dosed less frequently than acyclovir

Question 30

how is acyclovir excreted

Answer 30

into urine occurs both by glomerular filtration and tubular

Question 31

What are some adverse effects of acyclovir

Answer 31

local irritation from topical application

Headache, diarrhoea, nausea, vomitting

transiet renal dysfuinction occuring in high doses or in dehydrated patients receiving drug IV

Question 32

What cat is acyclovir in pregnancy

Answer 32

cat B

Question 33

what inhibitory effect does ganciclovir have. What is it most especially effective against

Answer 33

inhibitory effect against all herpesvirus, especially effective against CMV

Question 34

What is the mechanism of action for ganciclovir

Answer 34

monophosphorylated intracellularly by viral thymidine kinase and viral phosphotransferase during HSV and CMV

Question 35

what does food do to valganciclovir

Answer 35

increases its bioavailability by 25%

Question 36

how can CMV become resistant to ganciclovir

Answer 36

1) Reduced intracellular ganciclovir phosphorylation due to mutations in viral phosphotransferase and mutation in viral DNA polymerase
Ganciclovir also less active against acyclovir resistant thymidine kinase deficient HSV strains

Question 37

how can resistance occur to acyclovir

Answer 37

Resistance can occur due to altered or deficient thymidine kinase and DNA polymerases