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Pharmacology- Katzung (Spring 2019) > Antiviral > Flashcards

Antiviral Flashcards

1
Q

Nucleoside analogues

A 
Acyclovir
Famciclovir
Valacyclovir
Panciclovir
Ganciclovir
Valganciclovir
Cidofovir
Trifluridine
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2
Q

Nucleoside analogues - MoA

A

Prodrugs that are converted to monophosphate by virus enzymes, and then to active triphosphate metabolites by host enzymes. Competitive inhibition of viral DNA polymerase.

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3
Q

Acyclovir - Clinical use

A

HSV, VZV
Prophylaxis of CMV
Chickenpox

IV form: most effective treatment for serious herpesvirus infections, including herpetic encephalitis and severe HSV and VZV infections in immunocompromised patients

Topical form: herpes genitalis and mild mucocutaneous infections in immunocompromised patients. In cases of herpes genitalis, however, topical form is less effective than oral form

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4
Q

Acyclovir - Adverse effects

A

Well tolerated
Headache, GI disturbances, rash (General for all the nucleoside analoges)

IV: phlebitis + reversible renal dysfunction

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5
Q

Famciclovir - Clinical use

A

HSV

VZV

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6
Q

Valacyclovir - Clinical use

A

HSV, VZV

Prophylaxis of CMV , such as in bone marrow and organ transplant recipients and in persons with HIV

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7
Q

Panciclovir - Clinical use

A

Herpes labialis

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8
Q

Ganciclovir - Clincal use

A

Prevent CMV diseases, including retinitis, esophagitis, and colitis
HSV: keratitis (infection of the corneal epithelium) caused by HSV-1 and HSV-2

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9
Q

Ganciclovir - Adverse effects

A

Leukopeina, thrombocytopenia

Retinal detachment, liver and renal dysfunction

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10
Q

Ganciclovir - Interactions

A

Severe myelosupression with zidovudine

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11
Q

Valganciclovir - Clinical use

A

Prevent and treatment of less severe CMV infections, including those occurring in renal and heart transplant patients

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12
Q

Cidofovir - Clinical use

A

Prevent CMV diseases resistant to ganciclovir

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13
Q

Cidofovir - Contraindications

A

Contraindicated in patients taking other nephrotoxic drugs, such as aminoglycosides and amphotericin B.

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14
Q

Cidofovir - Adverse effects

A

Nephrotoxicity, neutropenia, metabolic acidosis.

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15
Q

Trifluridine - Clinical use

A

Ocular herpervirus infections, primarily herpetic epithelial keratitis and keratoconjuctivitis

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16
Q

Pyrophosphate derivative (HSV drug)

A

Foscarnet

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17
Q

Foscarnet - MoA

A

Blocks pyrophosphate-binding sites on viral DNA polymerase and prevents attachment of nucleotide precursor to DNA. Does not need activation by viral/host kinases.

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18
Q

Foscarnet - Clinical use

A

CMV, VZV, HSV
CMV retinitis in AIDS patients
Acyclovir-resistant HSV infections
Shingles

Combined with ganciclovir to treat infections resistant to either drug alone because of their synergistic effect on viral DNA polymerase

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19
Q

Foscarnet - Adverse effects

A

Renal impairment and acute renal failure, hematologic deficiencies, cardiac arrhythmias + heart failure, seizures, pancreatitis

Renal toxicity can be minimized by administering intravenous fluids to induce diuresis before and during treatment

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20
Q

Nucleoside reverse transcriptase inhibitors (NRTIs)

A 
Didanosine 
Lamivudine 
Stavudine
Emtricitabine 
Zidovudine (ZDV)
Abacivir (ABC)
Tenofovir
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21
Q

Nucleoside reverse transcriptase inhibitors (NRTIs) - MoA

A

Triphosphate metabolites of the drug compete with nucleoside triphosphates for incorporation into viral DNA. Cause DNA chain termination.
Inhibit host cell DNA polymerase somewhat.

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22
Q

Nucleoside reverse transcriptase inhibitors (NRTIs) - Clinical use

A

HIV

Some are active for Epstein-Barr virus and hepatitis B virus

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23
Q

Nucleoside reverse transcriptase inhibitors (NRTIs) - Special considerations

A

Included in almost all HIV treatment regimens.
Often more effective with multiple NRTIs (antimetabolites of different bases of DNA).
Cross BBB.
Careful with renal impairment

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24
Q

Nucleoside reverse transcriptase inhibitors (NRTIs) - Adverse effects

A

Lactic acidosis, hepatic steatosis, lipodystrophy

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25
Q

First line HIV drugs

A

Abacivir (ABC)
Tenofovir
Emtricitabine
Lamivudine

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26
Q

Alternative for 1st line drugs for HIV

A

Stavudine

Didanosine

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27
Q

Nucleoside reverse transcriptase inhibitors (NRTIs) - For treatment of hepatitis B

A

Lamivudine

Tenofovir

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28
Q

Which NRTI is used to treat HIV in pregnant women?

A

Zidovudine (ZDV)

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29
Q

Which NRTIs are not used together and why?

A

Zidovudine and stavudine because they appear to be antagonistic

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30
Q

Abacavir - Adverse effects

A

Hypersensitivity reactions

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31
Q

Which NRTIs cause Pancreatitis and Peripheral neuropathy

A

Didanosine and Stavudine

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32
Q

Tenofovir - Adverse effect (the most important)

A

Renal impairment

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33
Q

Zidovudine - Adverse effect (the most important)

A

Bone marrow suppression

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34
Q

Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

A

Efavirenz
Nevirapine
Delavirdine

35
Q

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - MoA

A

Direct inhibition of reverse transcriptase

36
Q

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Clinical use

37
Q

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Special considerations

A

Cross BBB
Act synergistically with NRTIs and PIs against HIV.
Never used alone for HIV

38
Q

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Contraindications

A

Contraindicated for hepatic impairment

39
Q

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Adverse effects

A

Moderately well tolerated
Rash (can progress to Stevens-Johnson syndrome)
Hepatotoxicity
Drug interactions

40
Q

Which is the most potent NNRTI?

41
Q

Efavirenz - Contraindications

A

Contraindicated during pregnancy

42
Q

Efavirenz - Adverse effects

A

Teratogenic

Neuropsychiatric reactions

43
Q

Nevirapine - Interactions

A

Induces CYP3A4 + CYP2B6: Increases metabolism of certain drugs

Increases metabolism of PIs, contraceptive steroids, other drugs

44
Q

Nevirapine - Adverse effects

A

Hepatotoxicity, rash (+Stevens-Johnson syndrome)

45
Q

Delavirdine - Special consideration

A

Usually not recommended for HIV (less potent)

46
Q

Protease inhibitors (PIs) (Most important)

A

Ritonavir
Atazanavir
Darunavir

47
Q

Protease inhibitors (PIs) - MoA

A

Bind HIV protease and inhibits proteolytic activity. Production of immature, noninfectious viral particles.

48
Q

Protease inhibitors (PIs) - Clinical use

49
Q

Protease inhibitors (PIs) - Adverse effects

A

Lipodystrophy, hyperlipidemia, insulin resistance and DM, liver dysfunction, hepatitis.

50
Q

Protease inhibitors (PIs) - Interactions

A

Inhibits metabolism of other drugs: PIs, antiarrhythmic agents, opioids, tricyclic antidepressants

Nevirapine: Increase PI metabolism.

51
Q

Which PI has the highest incidence of adverse effects?

52
Q

Which two PI is preffered for treating HIV?

A

Atazanavir

Darunavir

53
Q

Fusion and entry inhibitors

A

Maraviroc

Enfuvirtide

54
Q

Fusion and entry inhibitors - MoA

A

Inhibits fusion and entry of HIV

55
Q

Fusion and entry inhibitors - Clinical use

A

HIV by drug-resistant strains

56
Q

Maraviroc - MoA

A

Binds to CCR5 and prevents entry of HIV-1 to cells.

57
Q

Enfuvirtide - MoA

A

Binds to HIV glycoprotein 41 and block the fusion process

58
Q

Enfuvirtide - Adverse effects

A

Injection site reactions

59
Q

Integrase strand transfer inhibitors

A

Raltegravir
Dolutegravir
Elvitegravir

60
Q

Integrase strand transfer inhibitors - MoA

A

Prevents DNA strand transfer by binding integrase

61
Q

Integrase strand transfer inhibitors - Clinical use

62
Q

Neuraminidase inhibitors - MoA

A

Inhibits neuraminidase in influenza A and B, preventing release of virions from infected cells and preventing spread through the resp tract

63
Q

Neuraminidase inhibitors clinical use

A

Prophylaxis and treatment of influenzae.

Reduce complications of influenzae (otitis media, pneumonia)

64
Q

Neuraminidase inhibitors adverse effect

A

Minor respiratory and GI reactions

65
Q

Zanamivir contraindication

A

Patients with airway disease

66
Q

Adamantanes - MoA

A

Block M2 proton channel, prevents acidification of influenza A, and fusion of viral membranes.

Amantadine also increase release of dopamine

67
Q

Adamantenes

A

Amantadine

Rimantadine

68
Q

Adamantanes - Clinical use

A

Prevention and treatment of influenza A

69
Q

Amantadine - Clinical use

A

Parkinson disease

70
Q

Drugs for hepatitis and other viral infections

A

Ribavirin
Nucleoside and nucleotide analogues
Interferon alfa
Sofosbuvir and Valpatasavir

71
Q

Ribavirin - MoA

A

Inhibits guanine triphosphate and viral nucleic acid synthesis.

72
Q

Ribavirin - Clinical use

A 
Severe RSV infection + chronic hepatitis
Hepatitis A and C
HSV
Influenza A
Mumps virus
Adenovirus
Colorado tick fever virus
Crimean-Congo hemorrhagic fever virus
Hantaan virus
Respiratory syncytial virus
Rift valley fever virus
Yellow fever virus.
73
Q

Ribavirin - Contraindication

A

Contraindicated: pregnancy + lactating women, ZDV treatment, Teratogenic

74
Q

Ribavirin - Adverse effects

A

Adm inhalation: serious pulmonary and cardiovascular effects (apnea, pneumothorax, worsening resp status, cardiac arrest)

Oral adm: hemolytic anemia (worsen cardiac disease, MI)

75
Q

Ribavirin - Interactions

A

Antagonize ZDV

76
Q

Inteferon alfa - MoA

A

Bind to cell surface receptors and enhance host cell protective defenses (gene transcription, inhibit protein synthesis, degradation of viral RNA, activation of cytotoxic T cells + NK cells)

77
Q

Interferon alfa - Clinical use

A 
Hepatitis B and C
Papillomaviruses 
Genital warts
Hairy cell leukemia
Chronic myelocytic leukemia
Kaposi sarcoma
Renal carcinoma
Malignant melanoma
Multiple myeloma
Neoplastic diseases
78
Q

Interferon alfa - Adverse effects

A 
Hematologic toxicity
Cardiac arrhythmias
Changed BP
CNS dysfunction
GI distress
79
Q

Sofosbuvir and valpatasavir - MoA

A

Inhibits HCV RNA-directed RNA polymerase

80
Q

Sofosbuvir and valpatasavir - Clinical use

A

Hepatitis C

81
Q

Palivizumab - MoA

A

Inactivates the fusion protein of RSV, inhibits viral entry into target cells

82
Q

Palivizumab - Clinical use

A

Prevent and treat RSV infection in infants and children under 2 years that are at increased risk of severe disease.

83
Q

Drugs for influenza - Administration

A

All oral

Nasal spray: Zanamivir

84
Q

Hepatitis and other viral drugs - Administration

A

All oral
Subcutaneous: Interferon alfa
Ribavirin: Oral + inhalation, IV

Pharmacology- Katzung (Spring 2019) (52 decks)

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