EXAM #4: ANTIVIRAL DRUGS Flashcards

1
Q

What type of genome do the Herpesviruses contain?

A

dsDNA

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2
Q

What is being targeted in some way by all the drugs that treat Herpesviruses?

A

viral DNA polymerase

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3
Q

What stage of disease caused by the Herpesviruses is targeted by antiviral drugs?

A

Lytic stage i.e. productive phase of infection ONLY

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4
Q

What type of drug is Acyclovir?

A

Nucleoside analog

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5
Q

What is the MOA of Acyclovir?

A

1) Competitive inhibitor of viral DNA polymerase

2) Causes chain termination via incorportation into the viral genome

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6
Q

What is required for the activation of Acyclovir?

A

Phosphorylation by viral thymidine kinase

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7
Q

How causes resistance with Acyclovir?

A

Mutation of thymidine kinase

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8
Q

What are the clinical indications for ORAL Acyclovir?

A

1) Genital herpes (HSV-2)

2) Varicella zoster (VZV)

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9
Q

What are the clinical indications for IV Acyclovir?

A

1) Severe/ disseminated disease
2) Neonate infections
3) HSV encephalitis
4) VZV in immunocompromised patients

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10
Q

What major toxicity is associated with Acyclovir?

A

Nephrotoxicity

This is combated partly by proper hydration prior to administration

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11
Q

What is Valacyclovir?

A

Acyclovir prodrug with a Valine moiety

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12
Q

What is the utility of Valacyclovir?

A

Increased oral bioavilibility compared to Acyclovir

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13
Q

What are the clinical indications for Valacyclovir?

A

1) Genital herpes (HSV-2)
2) Varicella
3) Oral herpes (HSV-1)

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14
Q

What is unique about Foscarnet compared to Acyclovir?

A

Does NOT require phosphorylation by Thymidine Kinase

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15
Q

What are the indications for Foscarnet?

A

1) HSV and VZV infections that are RESISTANT to Acyclovir
2) CMV Retinitis
3) CMV Colitis
4) CMV Esophagitis

*Note that it is ONLY given IV

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16
Q

What is the major toxicity associated with Foscarnet?

A

1) Renal impairment/ nephrotoxicity

2) Changes in blood chemistry

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17
Q

What type of drug is Ganciclovir?

A

Acyclic guanosine analog

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18
Q

What is the MOA of Ganciclovir?

A

1) Phosphorylation by CMV viral kinase
2) Competitive inhibition of viral DNA polymerase
3) Chain termination upon incorportion

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19
Q

How does Ganciclovir compare to Acyclovir?

A

B/c it is phosphorylated by a CMV enzyme, it is much more effective in treating CMV infections

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20
Q

What is the mechanism of Ganciclovir resistance?

A

Mutation of the CMV viral kinase (UL97)

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21
Q

What are the clinical indications for Ganciclovir?

A

1) CMV-anything

2) Prevention of CMV disease in transplant recipients

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22
Q

How is Ganciclovir administered for CMV retinitis?

A

Intraocular

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23
Q

What are the major adverse effects associated with Ganciclovir?

A

1) Myelosuppression
2) CNS toxicity
3) Injection site reaction to IV

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24
Q

What is Valganciclovir?

A

Prodrug of Ganciclovir

*Higher oral bioavalibility

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25
Q

What are the clinical indications for Valganciclovir?

A

1) CMV Retinitis

2) Prophylaxis in transplant recipients

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26
Q

What type of drug is Trifluridine?

A

Fluorinated pyrimidine nucleoside

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27
Q

What is the MOA of Trifluridine?

A

1) Phosphorylation by cellular enzymes

2) Competitive inhibition of thymidine incorporation into DNA

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28
Q

What are the clinical indications for Trifluridine?

A

HSV-1 and HSV-2 induced:

  • Keratoconjunctitivitis
  • Keratitis
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29
Q

What type of virus is the Influenza virus?

A

Segmented ssRNA

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30
Q

What family does the Influenza virus belong to?

A

Orthomyxovirus

31
Q

What is the most common complication of the seasonal flu?

A

Pneumonia

32
Q

What type of drug is Oseltamivir?

A

Sialic acid analog

*Prodrug that is metabolized to active form by liver

33
Q

What is the MOA of Oseltamivir?

A

Neurominidase inhibitor

*Note that it is taken ORALLY

34
Q

What causes resistance to Oseltamivir?

A

Point mutations in hemagglutinin or neurominidase genes

35
Q

What are the clinical indications for Oseltamivir?

A

1) Influenza A or B
- Within 48 hours of symptom onset
- Kids 1+ years
2) Prophylaxis for influenza

36
Q

What is the major advese effect associated with Oseltamivir?

A

Neuropsychiatric symptoms

37
Q

What type of drug is Zanamivir?

A

Sialic acid analog

38
Q

What is the MOA of Zanamivir?

A

Neurominidase inhibitor i.e. same as Oseltamivir

*Note that it is INHALED

39
Q

How is Zanamivir administered?

A

Inhalation

40
Q

What are the clinical indications for Zanamivir?

A

Influenza A or B infection EXCEPT 7+ years old

41
Q

What is the major adverse effect associated with Zanamivir?

A

Bronchospasm and decreased pulmonary function

42
Q

When is Zanamivir contraindicated?

A

Patients with pre-existing pulmonary disease

43
Q

What class of drug is Peramivir?

A

Neuroaminidase inhibitor

*Note that it is given IV

44
Q

How is Peramivir administered?

A

IV

45
Q

What are the clinical indications for Peramivir?

A

Acute uncomplicated influenza that onset in less than 48 hours

46
Q

What are the major toxicities associated with Peramivir?

A

1) Steven Johnson’s Syndrome

2) Neuropsychiatric syndromes

47
Q

What is the MOA of Amantidine and Rimantadine?

A

Inhibition of the Influenza A M2 protein, an ion channel protein required for nucleocapsid release

48
Q

What is the mechanism of resistance to Amantidine and Rimantadine?

A

Mutations in Influenza A M2 protein

49
Q

What are the clinical indications for Amantadine and Rimantadine?

A

Influenza A (48 hour stipulation)

50
Q

What type of virus is RSV?

A

Eneveloped ssRNA virus

51
Q

What viral family does RSV fall in?

A

Paramyxovirus

52
Q

What is the difference between the disease caused by RSV in different age groups?

A

Under 1 y/o= bronchiolitis and pneumonia

Kids/adults= cold

Elderly= severe respiratory infection

53
Q

What type of drug is Ribavirin?

A

Guanosine analog

54
Q

What is the MOA of Ribavirin?

A

1) Phosphorylation by adenosine kinase

2) Interferes with GTP/ mRNA capping

55
Q

How is Ribavirin administered?

A

Aerosol for RSV

56
Q

What are the clinical indications for Ribavirin?

A

1) RSV

2) Hepatitis C (+ pegylated INF-a)

57
Q

What are the major adverse effect associated with Ribavirin?

A

Hemolytic anemia

58
Q

What are the contraindications for Ribavirin?

A

1) Pregnancy
2) Anemia
3) Ischemic vascular disease
4) Severe renal disease

59
Q

What are the major MOAs of the direct acting antivirals used to treat Hepatitis C?

A

1) Protease inhibitors (prevent cleavage of immature virions into mature)
2) RNA Polymerase Inhibitors (genome replication)
3) HCV NS5A inhibitors (virion assembly)

60
Q

What are the two DAA Protease Inhibitors?

A

1) Partaprevir

2) Simeprevir

61
Q

What is the result of protease inhibition in HCV infection?

A

Inhibits the enzyme necessary for cleavage of immature viral polypeptides into mature proteins needed for infection

62
Q

What drugs are the HCV RNA polymerase inhibitors?

A

1) Sofosbuvir

2) Desabuvir

63
Q

What drugs are the HCV NS5A inhibitors?

A

1) Ledipasvir

2) Ombitasvir

64
Q

How is Partaprevir commonly administered?

A

Orally, in combination with ombitasvir and ritonavir

65
Q

What leads to Partaprevir resistance?

A

NS3 mutations i.e. protease mutations

66
Q

How is Simeprevir commonly administered?

A

Orally in conjunction with Sofosbuvir or ribavirin + peylated INF-a

67
Q

What causes Simeprevir resistance?

A

Genetic polymorphism in NS3 that hast to be screened for prior to use of the drug

68
Q

How is Ledipasvir commonly given?

A

Orally with Sofosbuvir

69
Q

How is Ombitasvir commonly given?

A

Orally with Paritaprevir and ritonavir

70
Q

What is the MOA of Sofosbuvir?

A

Nucleotide analog prodrug

71
Q

What is the MOA of Desaburive?

A

Non-nucleoside analog that inhibits HCV RNA-RNA polymerase

72
Q

What should you avoid giving Sofosbuvir with?

A

Potent inducers of p-glycoprotein e.g. Rifampin

73
Q

How is Desaburive commonly administered?

A

Orally with Ombitasvir, Partiaprevir, and Ritonavir