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Pharmacology > Antivirals > Flashcards

Antivirals Flashcards

1
Q

What are viruses

A

They are obligate intracellular parasites that:
-can’t replicate on their own
-must attach to and enter the living host cell
-use the host cell’s metabolic machinery to replicate

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2
Q

What is a virion

A

Nucleic acid (DNA/RNA)+ capsid (protein coat) +/- envelope (composed of lipids, proteins and carbohydrates)

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3
Q

Name some DNA viruses

A

Herpes virus (chicken pox, shingles, genital herpes)
Hepadnavirus (HBV)

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4
Q

Name some RNA viruses

A

Orthomyxovirus (influenza)
Retrovirus (AIDS)
Coronavirus (COVID-19)

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5
Q

Different viral infections

A

Some are self-limiting and resolve on their own (rhinovirus: common cold)
Others can be severe and life threatening (COVID 19)

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6
Q

Action of antivirals

A

Some act intracellularly: nucleobase (purine/pyrimidine) analogs
Some are prodrugs and need to be activated via phosphorylation by viral or cellular enzymes

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7
Q

What do antivirals generally inhibit

A

Viral replication

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8
Q

Examples of Herpes Simplex virus HSV

A

HSV1: oral herpes-cold sores
HSV2: genital herpes

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9
Q

Examples of Herpes Zoster Virus HZV

A

Shingles

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10
Q

Examples of Varicella Zoster Virus VZV

A

Chicken pox

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11
Q

Antivirals that are DNA Polymerase inhibitors

A

Aciclovir
Valaciclovir
Ganciclovir
Valganciclovir
Penciclovir
Famciclovir

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12
Q

What is Aciclovir

A

Its a guanosine analogue
Its a prodrug

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13
Q

How is Aciclovir activated

A

Only in infected cells

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14
Q

MOA of Aciclovair

A
  1. Acyclovir is converted to Acyclovir Monophosphate by Viral Thymidine Kinase
  2. Acyclovir Monophosphate is converted to Acyclovir Diphosphate by Cellular Guanylate kinase
  3. Acicolvair triphosphate is converted to Aciclovair Triphosphate by Cellular Nucleoside diphosphate kinase
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15
Q

Effect of Aciclovir Triphosphate

A

It gets incorporated into the growing viral DNA
–> irreversibly inhibits viral DNA Polymerase by acting as a fake substrate for DP
–> Terminates elongation of viral DNA

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16
Q

Indications of Aciclovir

A

HSV 1&2 treatment
VZV: chicken pox
Prophylaxis of recurrent episodes >6/year of Herpes Genitalis

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17
Q

When is IV admin of Aciclovir used

A

for severe cases e.g. servere herpes infections, disseminated herpes infections, herpes simplex encephalitis

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18
Q

DIs of Aciclovir

A

Aminoglycosides: incr. risk of nephrotoxicity
Probenecid: decr. renal elimination

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19
Q

AEs of Aciclovir

A

oral: NVD
IV: nephrotoxic: reversible, Phlebitis at injection site, NV
topical: burning, stinging

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20
Q

What is Valaciclovir

A

its a prodrug (L-valine ester) of aciclovir
Has improved bioavailability (due to ester group thats been added to it)
converted to Aciclovir by cellular enzymes

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21
Q

Indications of Valaciclovir

A

HZV: shingles
Acute genital HSV
Prevention+treatment of recurrent herpes genitalis
Mucocutaneous HSV

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22
Q

Valaciclovir can also be used in

A

immunocompromised patients

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23
Q

What is Ganciclovir

A

analogue of aciclovir

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24
Q

MOA of Ganciclovir

A

inhibits viral DNA replication

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25
Q

Ganciclovir has activity against

A

Cytomegalovirus (CMV) 100x> Aciclovir
HSV and VZV=aciclovir

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26
Q

Indications of Ganciclovir

A

Prophylaxis + treatment of CMV retinitis prophylaxis in immunocompromised patients
Prevents CMV infections in oral transplant patients (valganciclovir)

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27
Q

AEs of Ganciclovir

A

Myelosuppression
Neutropenia
Thrombocytopenia

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28
Q

What is Valganciclovir

A

Analogue of Ganciclovir

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29
Q

Effect of Valganciclovir

A

has bioavailability > Ganciclovir

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30
Q

What is Penciclovir

A

topical antiviral similar to aciclovir

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31
Q

Indications of Penciclovir

A

Treatment of recurrent orolabial herpes simplex

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32
Q

MOA of Penciclovir

A

Penciclovir triphosphate inhibits herpes DNA synthesis by acting as a false substrate for viral DNA Polymerase

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33
Q

What is Famciclovir

A

Prodrug of Penciclovir thats taken orally

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34
Q

Indications of Famciclovir

A

Recurrent Genital Herpes
Recurrent Herpes Labialis

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35
Q

PK of Famciclovir
AME

A

rapidly absorbed
–> metabolised into Penciclovir
–> excreted renally as Penciclovir and its 6-deoxy precursor

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36
Q

AEs of Famciclovir

A

headache
nausea

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37
Q

Name another antiviral used for Herpes infections

A

Foscarnet

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38
Q

What is Foscarnet

A

a non-nucleoside DNA Polymerase inhibitor

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39
Q

MOA of Foscarnet

A

Direct inhibition of DNA Polymerase
–> doesn’t require phosphorylation thus its not a prodrug
–> Not incorporated into growing viral DNA

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40
Q

Foscarnet is active against

A

Herpes
Varicella
CMV
–> including those resistant to aciclovir and ganciclovir

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41
Q

Indication for Foscarnet

A

CMV

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42
Q

AE of Foscarnet

A

Nephrotoxicity

43
Q

Name the drugs that are indicated for Hep B and C

A

Interferon
Ribavirin
Entecavir
Tenofovir
Emtricitabine
Lamivudine (ARV)

44
Q

What are interferons?

A

are naturally occurring glycoproteins that modulate the response of the immune system to viruses, bacteria, cancer and other foreign substances that invade the body

45
Q

Interferons possess what

A

antiviral, immunomodulatory and antiproloferative effects

46
Q

When are Interferons produced

A

at earliest response of body to viral infections

47
Q

MOA of IFNa

A

binds to IFN R on cell membrane where it induces release of intracellular enzymes that cause degradation of viral mRNA and inhibits Protein synthesis

48
Q

Indications of IFNa

A

Chronic HBV

49
Q

What is Peginterferon

A

are modified interferons with improved PK properties such as:
reduced clearance
incr. T1/2
require reduced dosing frequency

50
Q

Indications of Peginterferon alfa

A

Chronic HCV

51
Q

Admin of IFNa

A

SC, IV, intralesionally

52
Q

Distribution of IFNa

A

in all body tissues except CNS and eye

53
Q

CIs of IFNa

A

seizures
pre-exisiting sever CVS disease
severe renal or hepatic impairment
Compromised CNS function

54
Q

DIs of IFNa

A

Alcohol & CNS depressants
–> enhanced CNS depression

55
Q

AEs of IFNa

A

Depression
Suicidal thoughts
flu-like symptoms: during 1st week thereafter resolves by itself

56
Q

Indications and Admin of Peg-alfa + Ribavirin

A

chronic HCV
SC into abdomen, thigh, foot

57
Q

What is Ribavirin

A

Guanosine analogue that requies activation into its triphosphate form

58
Q

Spectrum of Ribavirin

A

Broad spectrum antiviral that inhibits a wide range of DNA and RNA viruses

59
Q

Indications of Ribavirin

A

chronic HCV: combined with Peg-alfa
Severe respiratory syncytial virus (RSV) infection
Viral hemorrhagic fevers

60
Q

MOA of Ribavirin Monophosphate

A

inhibits Inosine Monophosphate dehydrogenase IMPDH thus it stops nucleic acid (guanosine monophosphate) synthesis–> depletes GTP (guanosine triphosphate) pool= reduction of viral protein synthesis and viral replication

61
Q

MOA of Ribavirin Triphosphate

A

inhibits viral RNA Polymerase–> stops viral RNA synthesis and viral replication
inhibits translocation of viral mRNA guanylyl transferase–> stops viral mRNA capping

62
Q

Function of Guanylyl Transferase

A

responsible for mRNA synthesis

63
Q

AEs of Ribavirin

A

flu-like symptoms
Neuropshyc
GIT

64
Q

What is Emtricitabine?

A

Its a nucleoside (cytidine) analogue that needs to be activated to the triphospahte form

65
Q

Indications of Emtricitabine

A

HBV/HIV co-infection in combination with Tenofovir

66
Q

MOA of Emtricitabine

A

competes with Cytosine Triphosphate for incorporation into developing viral DNA strand–> chain termination–> blockage if viral replication

67
Q

Overall effect of Emtricitabine

A

inhibits HBV DNA Polymerase during reverse transcriptase (when HBV Polymerase acts as HBV reverse Transcriptase)

68
Q

AEs of Emtricitabine

A

NV
Headache
rash

69
Q

What is Lamivudine?

A

Its a nucleoside (cytidine) anolgue that needs to be activated to the triphosphate form

70
Q

Indications of Lamivudine

A

HBV/HIV co-infection in combination with Tenofovir

71
Q

MOA of Lamivudine

A

competes with Cytosine Triphosphate for incorporation into developing viral DNA strand–> chain termination–> blockage of viral DNA replication

72
Q

Overall effect of Lamivudine

A

inhibits HBV reverse transcriptase

73
Q

AEs of Lamivudine

A

Peripheral neuropathy
Pancreatitis
Neutropenia

74
Q

What is Tenofovir?

A

Its a nucleotide (adenosine) analogue

75
Q

Indications of Tenofovir

A

HBV/HIV co-infection in combination with Emtricitabine or Lamivudine

76
Q

MOA of Tenofovir

A

inhibits HBV reverse transcriptase–> HBV DNA chain termination

77
Q

CIs of Tenofovir

A

Renal failure due to its nephrotoxicty

78
Q

DIs of Tenofovir

A

Nephrotoxic drugs or those competeing for active tubular secretion:
Acicovir, valaciclovir, Ganciclovir, valganciclovur–> incr. Tenofovir plasma levels

79
Q

AEs of Tenofovir

A

Nephrotoxic–> proteinuria, Fanconi syndrome may develop

80
Q

What is Entecavir?

A

Its a nucleoside (guanine) analogue that needs to be activated to the triphosphate form

81
Q

MOA of Entecavir

A

Inhibits all 3 activities of HBV Polymerase:
1. base priming
2. reverse transcription of -ive strand from Pregenomic mRNA
3. synthesis of +ive strand of HBV DNA

82
Q

Bioavailability of Entecavir is reduced by

A

food

83
Q

Indications of Entecavir

A

active and chronic HBV
*active against Lamivudine Resistant mutants

84
Q

AEs of Entecavir

A

CVS
GIT
Muscle pain or weakness
dizziness

85
Q

Causative agents of Common cold

A

Rhinoviruses
Coronavirus
Adenovirus

86
Q

Causative agents of Flu

A

Influenza virus

87
Q

Influenza viruses can change in which ways

A

Antigenic drift
Antigenic shift

88
Q

What is antigenic drift

A

minor change in virus that affects the outer proteins

89
Q

What is antigenic shift

A

major change in virus where the nucleic acids are changed

90
Q

Which are the anti-influenza drugs

A

Neuraminidase inhibitors
M2 protein inhibitors

91
Q

Which are the Neuraminidase inhibitors NAIs

A

Oseltamivir
Zanamivir

92
Q

Which are the M2 Protein inhibitors

A

Amantadine
Rimantidine

93
Q

MOA of NAIs

A

inhibit Neuraminidase enzyme thus preventing the release of progeny virions from infected cell thus preventing the spread of the virus from the body

94
Q

MOA of M2 protein inhibitors

A

bind to M2 protein (A/M2 ion channel)–> inhibiting the uncoating of viral RNA–> inhibit viral replication

95
Q

Oseltamivir is active against which influenza strains

A

Influenza A and B

96
Q

Zanamivir is active against which influenza strains

A

Influenza A and B

97
Q

Amantadine and Rimantidine is active against which influenza strains

A

Influenza A

98
Q

Clinical uses of Oseltamivir

A

Influenza A+B
H1N1 and H5N1
treatment + prophylaxis of influenza
shortens duration and severity of illness and reduces its complications

99
Q

AEs of Oseltamivir

A

NV
Diarrhea
GI irritation
insomnia

100
Q

Clinical uses of Zanamivir

A

Uncomplicated acute illness due to influenza A and B viruses

101
Q

AEs of Zanamivir

A

Cold symptoms
NV
Diarrhea

102
Q

Clinical uses of Amantadine and Rimantadine

A

Prophylaxis and treatment of Influenza A

103
Q

AEs of Amantadine and Rimantadine

A

Insomnia
Loss of appetite
dizziness
drowsiness
headache
dry mouth

Pharmacology (50 decks)

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