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30 Antiviral drugs Flashcards

1
Q

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - actions

A

inhibit the action of the viral reverse transcriptase of HIV viruses

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2
Q

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - MOA

A

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

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3
Q

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - abs/distrib/elim

A

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

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4
Q

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - clinical use

A

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

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5
Q

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - adverse effects

A

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

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6
Q

30.01 REVERSE TRANSCRIPTASE INHIBITORS

Zidovudine - special points

A

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

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7
Q

30.02 REVERSE TRANSCRIPTASE INHIBITORS

Non-nucleoside agents: nevirapine, efavirenz - actions

A

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

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8
Q

30.02 REVERSE TRANSCRIPTASE INHIBITORS

Non-nucleoside agents: nevirapine, efavirenz - MOA

A

bind to and denature the viral reverse transcriptase enzyme

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9
Q

30.02 REVERSE TRANSCRIPTASE INHIBITORS

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

A

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

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10
Q

30.02 REVERSE TRANSCRIPTASE INHIBITORS

Non-nucleoside agents: nevirapine, efavirenz - clinical use

A

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

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11
Q

30.02 REVERSE TRANSCRIPTASE INHIBITORS

Non-nucleoside agents: nevirapine, efavirenz - adverse effects

A

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

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12
Q

30.03 PROTEASE INHIBITORS

Darunavir, ritanovir - actions

A

protease inhibitor

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13
Q

30.03 PROTEASE INHIBITORS

Darunavir, ritanovir - MOA

A

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

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14
Q

30.03 PROTEASE INHIBITORS

Darunavir, ritanovir - abs/distrib/elim

A

given orally
extensive first-pass metabolism

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15
Q

30.03 PROTEASE INHIBITORS

Darunavir, ritanovir - clinical use

A

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

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16
Q

30.03 PROTEASE INHIBITORS

Darunavir, ritanovir - adverse effects

A

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

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17
Q

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - actions

A

interfere with viral nucleic acid synthesis

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18
Q

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - MOA

A

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

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19
Q

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - abs/distrib/elim

A

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

20
Q

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - clinical use

A

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

21
Q

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - adverse effects

A

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

22
Q

30.04 DNA POLYMERASE INHIBITORS

Aciclovir, ganciclovir - special notes

A

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

23
Q

30.05 NEURAMINIDASE INHIBITORS

Oseltamivir, zanamivir - actions

A

reduces viral replication

24
Q

30.05 NEURAMINIDASE INHIBITORS

Oseltamivir, zanamivir - MOA

A

inhibits neuraminidase which is necessary for virion release

25
Q

30.05 NEURAMINIDASE INHIBITORS

Oseltamivir, zanamivir - abs/distrib/elim

A

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

26
Q

30.05 NEURAMINIDASE INHIBITORS

Oseltamivir, zanamivir - clinical use

A

prevention and treatment of infections with influenza viruses A and B

27
Q

30.05 NEURAMINIDASE INHIBITORS

Oseltamivir, zanamivir - adverse effects

A

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

28
Q

30.06 BIOPHARMACEUTICAL ANTIVIRALS

Immunoglobulins

A

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

29
Q

30.06 BIOPHARMACEUTICAL ANTIVIRALS

Palivizumab

A

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

30
Q

30.06 BIOPHARMACEUTICAL ANTIVIRALS

Interferon-α - action and MOA

A

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

31
Q

30.06 BIOPHARMACEUTICAL ANTIVIRALS

Interferon-α - clinical use

A

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

32
Q

30.06 BIOPHARMACEUTICAL ANTIVIRALS

Interferon-α - adverse effects

A

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

33
Q

30.07 DRUGS USED IN HIV

Abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zidovudine

A

nucleoside or nucleotide reverse transcriptase inhibitors

34
Q

30.07 DRUGS USED IN HIV

Efavirenz, etravirine, nevirapine, rilpivirine

A

non-nucleoside reverse transcriptase inhibitors

35
Q

30.07 DRUGS USED IN HIV

Atazanavir, daunavir, fosamprenavir, indinavir, lopinavir, ritonavir, saquinavir, tipranavir

A

protease inhibitors

36
Q

30.07 DRUGS USED IN HIV

Enfuvirtide

A

inhibitor of HIV fusion with host cells

37
Q

30.07 DRUGS USED IN HIV

Dolutegravir, elvitegravir, raltegravir

A

HIV integrase inhibitor

38
Q

30.07 DRUGS USED IN HIV

Maraviroc

A

chemokine receptor antagonist

39
Q

30.07 DRUGS USED IN HIV

Cobicistat

A

pharmacokinetic enhancer

40
Q

30.08 DRUGS USED IN HEPATITIS

Hepatitis B: adefovir, entecavir, lamivudine, telbivudine, tenvofir

A

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

41
Q

30.08 DRUGS USED IN HEPATITIS

Hepatitis C: daclatasvir, ledipasvir, ombitasvir, ritonavir

A

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

42
Q

30.08 DRUGS USED IN HEPATITIS

Hepatitis C: boceprevir, paritaprevir, simeprevir, telaprevir

A

NS 3/4A protease inhibitors
multiple side effects common

43
Q

30.08 DRUGS USED IN HEPATITIS

Hepatitis C: dasabuvir, sofosbuvir

A

NS 5B RNA polymerase inhibitors
multiple side effects common

44
Q

30.08 DRUGS USED IN HEPATITIS

Hepatitis C: ribavirin

A

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

45
Q

30.08 DRUGS USED IN HEPATITIS

Hepatitis B and C: interferon-α, pegylated interferon-α

A

immunostimulant
‘flu-like’ side effects common

Pharmacology (34 decks)

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