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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
Ganciclovir has activity against
Cytomegalovirus (CMV) 100x> Aciclovir HSV and VZV=aciclovir
26
Indications of Ganciclovir
Prophylaxis + treatment of CMV retinitis prophylaxis in immunocompromised patients Prevents CMV infections in oral transplant patients (valganciclovir)
27
AEs of Ganciclovir
Myelosuppression Neutropenia Thrombocytopenia
28
What is Valganciclovir
Analogue of Ganciclovir
29
Effect of Valganciclovir
has bioavailability > Ganciclovir
30
What is Penciclovir
topical antiviral similar to aciclovir
31
Indications of Penciclovir
Treatment of recurrent orolabial herpes simplex
32
MOA of Penciclovir
Penciclovir triphosphate inhibits herpes DNA synthesis by acting as a false substrate for viral DNA Polymerase
33
What is Famciclovir
Prodrug of Penciclovir thats taken orally
34
Indications of Famciclovir
Recurrent Genital Herpes Recurrent Herpes Labialis
35
PK of Famciclovir AME
rapidly absorbed --> metabolised into Penciclovir --> excreted renally as Penciclovir and its 6-deoxy precursor
36
AEs of Famciclovir
headache nausea
37
Name another antiviral used for Herpes infections
Foscarnet
38
What is Foscarnet
a non-nucleoside DNA Polymerase inhibitor
39
MOA of Foscarnet
Direct inhibition of DNA Polymerase --> doesn't require phosphorylation thus its not a prodrug --> Not incorporated into growing viral DNA
40
Foscarnet is active against
Herpes Varicella CMV --> including those resistant to aciclovir and ganciclovir
41
Indication for Foscarnet
CMV
42
AE of Foscarnet
Nephrotoxicity
43
Name the drugs that are indicated for Hep B and C
Interferon Ribavirin Entecavir Tenofovir Emtricitabine Lamivudine (ARV)
44
What are interferons?
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
Interferons possess what
antiviral, immunomodulatory and antiproloferative effects
46
When are Interferons produced
at earliest response of body to viral infections
47
MOA of IFNa
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
Indications of IFNa
Chronic HBV
49
What is Peginterferon
are modified interferons with improved PK properties such as: reduced clearance incr. T1/2 require reduced dosing frequency
50
Indications of Peginterferon alfa
Chronic HCV
51
Admin of IFNa
SC, IV, intralesionally
52
Distribution of IFNa
in all body tissues except CNS and eye
53
CIs of IFNa
seizures pre-exisiting sever CVS disease severe renal or hepatic impairment Compromised CNS function
54
DIs of IFNa
Alcohol & CNS depressants --> enhanced CNS depression
55
AEs of IFNa
Depression Suicidal thoughts flu-like symptoms: during 1st week thereafter resolves by itself
56
Indications and Admin of Peg-alfa + Ribavirin
chronic HCV SC into abdomen, thigh, foot
57
What is Ribavirin
Guanosine analogue that requies activation into its triphosphate form
58
Spectrum of Ribavirin
Broad spectrum antiviral that inhibits a wide range of DNA and RNA viruses
59
Indications of Ribavirin
chronic HCV: combined with Peg-alfa Severe respiratory syncytial virus (RSV) infection Viral hemorrhagic fevers
60
MOA of Ribavirin Monophosphate
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
MOA of Ribavirin Triphosphate
inhibits viral RNA Polymerase--> stops viral RNA synthesis and viral replication inhibits translocation of viral mRNA guanylyl transferase--> stops viral mRNA capping
62
Function of Guanylyl Transferase
responsible for mRNA synthesis
63
AEs of Ribavirin
flu-like symptoms Neuropshyc GIT
64
What is Emtricitabine?
Its a nucleoside (cytidine) analogue that needs to be activated to the triphospahte form
65
Indications of Emtricitabine
HBV/HIV co-infection in combination with Tenofovir
66
MOA of Emtricitabine
competes with Cytosine Triphosphate for incorporation into developing viral DNA strand--> chain termination--> blockage if viral replication
67
Overall effect of Emtricitabine
inhibits HBV DNA Polymerase during reverse transcriptase (when HBV Polymerase acts as HBV reverse Transcriptase)
68
AEs of Emtricitabine
NV Headache rash
69
What is Lamivudine?
Its a nucleoside (cytidine) anolgue that needs to be activated to the triphosphate form
70
Indications of Lamivudine
HBV/HIV co-infection in combination with Tenofovir
71
MOA of Lamivudine
competes with Cytosine Triphosphate for incorporation into developing viral DNA strand--> chain termination--> blockage of viral DNA replication
72
Overall effect of Lamivudine
inhibits HBV reverse transcriptase
73
AEs of Lamivudine
Peripheral neuropathy Pancreatitis Neutropenia
74
What is Tenofovir?
Its a nucleotide (adenosine) analogue
75
Indications of Tenofovir
HBV/HIV co-infection in combination with Emtricitabine or Lamivudine
76
MOA of Tenofovir
inhibits HBV reverse transcriptase--> HBV DNA chain termination
77
CIs of Tenofovir
Renal failure due to its nephrotoxicty
78
DIs of Tenofovir
Nephrotoxic drugs or those competeing for active tubular secretion: Acicovir, valaciclovir, Ganciclovir, valganciclovur--> incr. Tenofovir plasma levels
79
AEs of Tenofovir
Nephrotoxic--> proteinuria, Fanconi syndrome may develop
80
What is Entecavir?
Its a nucleoside (guanine) analogue that needs to be activated to the triphosphate form
81
MOA of Entecavir
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
Bioavailability of Entecavir is reduced by
food
83
Indications of Entecavir
active and chronic HBV *active against Lamivudine Resistant mutants
84
AEs of Entecavir
CVS GIT Muscle pain or weakness dizziness
85
Causative agents of Common cold
Rhinoviruses Coronavirus Adenovirus
86
Causative agents of Flu
Influenza virus
87
Influenza viruses can change in which ways
Antigenic drift Antigenic shift
88
What is antigenic drift
minor change in virus that affects the outer proteins
89
What is antigenic shift
major change in virus where the nucleic acids are changed
90
Which are the anti-influenza drugs
Neuraminidase inhibitors M2 protein inhibitors
91
Which are the Neuraminidase inhibitors NAIs
Oseltamivir Zanamivir
92
Which are the M2 Protein inhibitors
Amantadine Rimantidine
93
MOA of NAIs
inhibit Neuraminidase enzyme thus preventing the release of progeny virions from infected cell thus preventing the spread of the virus from the body
94
MOA of M2 protein inhibitors
bind to M2 protein (A/M2 ion channel)--> inhibiting the uncoating of viral RNA--> inhibit viral replication
95
Oseltamivir is active against which influenza strains
Influenza A and B
96
Zanamivir is active against which influenza strains
Influenza A and B
97
Amantadine and Rimantidine is active against which influenza strains
Influenza A
98
Clinical uses of Oseltamivir
Influenza A+B H1N1 and H5N1 treatment + prophylaxis of influenza shortens duration and severity of illness and reduces its complications
99
AEs of Oseltamivir
NV Diarrhea GI irritation insomnia
100
Clinical uses of Zanamivir
Uncomplicated acute illness due to influenza A and B viruses
101
AEs of Zanamivir
Cold symptoms NV Diarrhea
102
Clinical uses of Amantadine and Rimantadine
Prophylaxis and treatment of Influenza A
103
AEs of Amantadine and Rimantadine
Insomnia Loss of appetite dizziness drowsiness headache dry mouth

Pharmacology (50 decks)

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