30 Antiviral drugs

Question 1

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - actions

Answer 1

inhibit the action of the viral reverse transcriptase of HIV viruses

Question 2

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - MOA

Answer 2

phosphorylated by host cell enzymes to give zidovudine trisphosphate which interferes with viral DNA synthesis

Question 3

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - abs/distrib/elim

Answer 3

given orally but can be given by IV infusion
CSF concentration is 65% of plasma level
the half-life of the false trisphosphate is 3h

Question 4

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - clinical use

Answer 4

HIV virus infection in combination with other agents
slows progress of the disease without curing the infection
reverse transcriptase inhibitors are also used in hepatitis B

Question 5

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - adverse effects

Answer 5

with long-term use: blood dyscrasias, GIT disturbances, myopathy, rashes, fever and a flu-like syndrome

Question 6

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - special points

Answer 6

resistance is likely to occur
to reduce this possibility, the drug is used in combination with other antiretrovirals

Question 7

30.02 REVERSE TRANSCRIPTASE INHIBITORS

Non-nucleoside agents: nevirapine, efavirenz - actions

Answer 7

inhibit the action of the viral reverse transcriptase of HIV viruses
active against HIV-1 but not HIV-2

Question 8

30.02 REVERSE TRANSCRIPTASE INHIBITORS

Non-nucleoside agents: nevirapine, efavirenz - MOA

Answer 8

bind to and denature the viral reverse transcriptase enzyme

Question 9

30.02 REVERSE TRANSCRIPTASE INHIBITORS

Non-nucleoside agents: nevirapine, efavirenz - abs/distrib/elim

Answer 9

given orally
nevirapine: good oral bioavailability, CSF concentration is 45% of plasma level, metabolised in liver
efavirenz: plasma half-life ~50h, 99% bound to plasma albumin, CSF concentration is ~1% of plasma level

Question 10

30.02 REVERSE TRANSCRIPTASE INHIBITORS

Non-nucleoside agents: nevirapine, efavirenz - clinical use

Answer 10

HIV-1 infection in combination with other antiretrovirals
can reduce mother-to-foetus transmission of the virus by ~50%

Question 11

30.02 REVERSE TRANSCRIPTASE INHIBITORS

Non-nucleoside agents: nevirapine, efavirenz - adverse effects

Answer 11

hepatotoxicity, rash, Stevens-Johnson syndrome
less common: GIT disturbances, myalgia
efavirenz can cause disturbances of sleep and dreaming, and is teratogenic

Question 12

30.03 PROTEASE INHIBITORS

Darunavir, ritanovir - actions

Answer 12

protease inhibitor

Question 13

30.03 PROTEASE INHIBITORS

Darunavir, ritanovir - MOA

Answer 13

reversibly inhibits the viral-specific protease that, during assembly and budding, cleaves precursor viral proteins to give the structural and functional proteins of the new virions
HIV infection generates Gag and Gag-Pol proteins
hepatitis C - two protease targets identified: non-structural (NS) protein 3 and NS 5A

Question 14

30.03 PROTEASE INHIBITORS

Darunavir, ritanovir - abs/distrib/elim

Answer 14

given orally
extensive first-pass metabolism

Question 15

30.03 PROTEASE INHIBITORS

Darunavir, ritanovir - clinical use

Answer 15

HIV-1 infection in combination with other antiretrovirals
can reduce mother-to-foetus transmission of the virus by ~50%
hepatitis C

Question 16

30.03 PROTEASE INHIBITORS

Darunavir, ritanovir - adverse effects

Answer 16

GIT disturbances, rhinitis, insulin resistance, lipodystrophy
CNS effects (dizziness, headaches, insomnia)
anaemia, neutropenia

Question 17

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - actions

Answer 17

interfere with viral nucleic acid synthesis

Question 18

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - MOA

Answer 18

aciclovir - converted by viral and host cell kinases to aciclovir triphosphate which selectively inhibits viral DNA polymerase
ganciclovir - converted by viral and host cell kinases to ganciclovir triphosphate which competes with guanosine triphosphate for incorporation into viral DNA, and suppresses viral DNA replication

Question 19

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - abs/distrib/elim

Answer 19

aciclovir: given orally, IV (slowly) or topically, degraded fairly rapidly within the host cell, CSF concentration is ~50% of plasma level
ganciclovir: given IV, half-life 4h but persists in host cells for 18-20h

Question 20

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - clinical use

Answer 20

herpes simplex infections (cold sores, mouth ulcers, conjunctivitis, genital infections and, more seriously, encephalitis)
herpes zoster infections (shingles, chickenpox)
ganciclovir is more active against cytomegalovirus than aciclovir, but is more toxic

Question 21

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - adverse effects

Answer 21

usually minimal
sometimes: nausea, headache
rarely: encephalitis
ganciclovir - bone marrow suppression

Question 22

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - special notes

Answer 22

ganciclovir is used by specialists for serious infections such as CMV retinitis in patients with AIDS
valaciclovir is licensed for prevention of CMV during immunosuppression following organ transplantation

Question 23

30.05 NEURAMINIDASE INHIBITORS

Oseltamivir, zanamivir - actions

Answer 23

reduces viral replication

Question 24

30.05 NEURAMINIDASE INHIBITORS

Oseltamivir, zanamivir - MOA

Answer 24

inhibits neuraminidase which is necessary for virion release

Question 25

30.05 NEURAMINIDASE INHIBITORS Oseltamivir, zanamivir - abs/distrib/elim

Answer 25

given orally - within 48h of onset of symptoms for post-exposure prophylaxis zanamivir is given intranasally

Question 26

30.05 NEURAMINIDASE INHIBITORS Oseltamivir, zanamivir - clinical use

Answer 26

prevention and treatment of infections with influenza viruses A and B

Question 27

30.05 NEURAMINIDASE INHIBITORS Oseltamivir, zanamivir - adverse effects

Answer 27

GIT disturbances, headache, dizziness, rashes very rarely: hepatitis

Question 28

30.06 BIOPHARMACEUTICAL ANTIVIRALS Immunoglobulins

Answer 28

contain antibodies against various viruses antibodies are directed against virus envelope and can ‘neutralise’ some viruses clinical use in measles, German measles, infectious hepatitis, rabies, poliomyelitis

Question 29

30.06 BIOPHARMACEUTICAL ANTIVIRALS Palivizumab

Answer 29

monoclonal antibody inhibits viral entry into host cells clinical use in respiratory syncytial virus infection in children

Question 30

30.06 BIOPHARMACEUTICAL ANTIVIRALS Interferon-α - action and MOA

Answer 30

modified recombinant DNA version of an antiviral cytokine produced by mammalian cells it stimulates the production of host enzymes that degrade both viral mRNA (thus inhibiting viral protein synthesis and halting replication) and host cell mRNA in the infected cell, thus killing it

Question 31

30.06 BIOPHARMACEUTICAL ANTIVIRALS Interferon-α - clinical use

Answer 31

interferon-α-2a used in hepatitis B and AIDs-related Kaposi sarcomas

Question 32

30.06 BIOPHARMACEUTICAL ANTIVIRALS Interferon-α - adverse effects

Answer 32

flu-like symptoms bone marrow depression alopecia thyroid, cardiovascular and hepatic dysfunction

Question 33

30.07 DRUGS USED IN HIV Abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zidovudine

Answer 33

nucleoside or nucleotide reverse transcriptase inhibitors

Question 34

30.07 DRUGS USED IN HIV Efavirenz, etravirine, nevirapine, rilpivirine

Answer 34

non-nucleoside reverse transcriptase inhibitors

Question 35

30.07 DRUGS USED IN HIV Atazanavir, daunavir, fosamprenavir, indinavir, lopinavir, ritonavir, saquinavir, tipranavir

Answer 35

protease inhibitors

Question 36

30.07 DRUGS USED IN HIV Enfuvirtide

Answer 36

inhibitor of HIV fusion with host cells

Question 37

30.07 DRUGS USED IN HIV Dolutegravir, elvitegravir, raltegravir

Answer 37

HIV integrase inhibitor

Question 38

30.07 DRUGS USED IN HIV Maraviroc

Answer 38

chemokine receptor antagonist

Question 39

30.07 DRUGS USED IN HIV Cobicistat

Answer 39

pharmacokinetic enhancer

Question 40

30.08 DRUGS USED IN HEPATITIS Hepatitis B: adefovir, entecavir, lamivudine, telbivudine, tenvofir

Answer 40

nucleoside or nucleotide analogues that inhibit reverse transcriptase multiple GI and other side effects common

Question 41

30.08 DRUGS USED IN HEPATITIS Hepatitis C: daclatasvir, ledipasvir, ombitasvir, ritonavir

Answer 41

NS 5A protease inhibitors ritonavir delays metabolism of other drugs and enhances their effects multiple side effects common ledipasvir is used as part of a fixed-dose combination with sofosbuvir

Question 42

30.08 DRUGS USED IN HEPATITIS Hepatitis C: boceprevir, paritaprevir, simeprevir, telaprevir

Answer 42

NS 3/4A protease inhibitors multiple side effects common

Question 43

30.08 DRUGS USED IN HEPATITIS Hepatitis C: dasabuvir, sofosbuvir

Answer 43

NS 5B RNA polymerase inhibitors multiple side effects common

Question 44

30.08 DRUGS USED IN HEPATITIS Hepatitis C: ribavirin

Answer 44

nucleoside analogue: uncertain mechanism also used for other viral infections multiple side effects common

Question 45

30.08 DRUGS USED IN HEPATITIS Hepatitis B and C: interferon-α, pegylated interferon-α

Answer 45

immunostimulant ‘flu-like’ side effects common