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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
First line HIV drugs
Abacivir (ABC) Tenofovir Emtricitabine Lamivudine
26
Alternative for 1st line drugs for HIV
Stavudine | Didanosine
27
Nucleoside reverse transcriptase inhibitors (NRTIs) - For treatment of hepatitis B
Lamivudine | Tenofovir
28
Which NRTI is used to treat HIV in pregnant women?
Zidovudine (ZDV)
29
Which NRTIs are not used together and why?
Zidovudine and stavudine because they appear to be antagonistic
30
Abacavir - Adverse effects
Hypersensitivity reactions
31
Which NRTIs cause Pancreatitis and Peripheral neuropathy
Didanosine and Stavudine
32
Tenofovir - Adverse effect (the most important)
Renal impairment
33
Zidovudine - Adverse effect (the most important)
Bone marrow suppression
34
Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz Nevirapine Delavirdine
35
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - MoA
Direct inhibition of reverse transcriptase
36
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Clinical use
HIV
37
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Special considerations
Cross BBB Act synergistically with NRTIs and PIs against HIV. Never used alone for HIV
38
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Contraindications
Contraindicated for hepatic impairment
39
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Adverse effects
Moderately well tolerated Rash (can progress to Stevens-Johnson syndrome) Hepatotoxicity Drug interactions
40
Which is the most potent NNRTI?
Efavirenz
41
Efavirenz - Contraindications
Contraindicated during pregnancy
42
Efavirenz - Adverse effects
Teratogenic | Neuropsychiatric reactions
43
Nevirapine - Interactions
Induces CYP3A4 + CYP2B6: Increases metabolism of certain drugs Increases metabolism of PIs, contraceptive steroids, other drugs
44
Nevirapine - Adverse effects
Hepatotoxicity, rash (+Stevens-Johnson syndrome)
45
Delavirdine - Special consideration
Usually not recommended for HIV (less potent)
46
Protease inhibitors (PIs) (Most important)
Ritonavir Atazanavir Darunavir
47
Protease inhibitors (PIs) - MoA
Bind HIV protease and inhibits proteolytic activity. Production of immature, noninfectious viral particles.
48
Protease inhibitors (PIs) - Clinical use
HIV
49
Protease inhibitors (PIs) - Adverse effects
Lipodystrophy, hyperlipidemia, insulin resistance and DM, liver dysfunction, hepatitis.
50
Protease inhibitors (PIs) - Interactions
Inhibits metabolism of other drugs: PIs, antiarrhythmic agents, opioids, tricyclic antidepressants Nevirapine: Increase PI metabolism.
51
Which PI has the highest incidence of adverse effects?
Ritonavir
52
Which two PI is preffered for treating HIV?
Atazanavir | Darunavir
53
Fusion and entry inhibitors
Maraviroc | Enfuvirtide
54
Fusion and entry inhibitors - MoA
Inhibits fusion and entry of HIV
55
Fusion and entry inhibitors - Clinical use
HIV by drug-resistant strains
56
Maraviroc - MoA
Binds to CCR5 and prevents entry of HIV-1 to cells.
57
Enfuvirtide - MoA
Binds to HIV glycoprotein 41 and block the fusion process
58
Enfuvirtide - Adverse effects
Injection site reactions
59
Integrase strand transfer inhibitors
Raltegravir Dolutegravir Elvitegravir
60
Integrase strand transfer inhibitors - MoA
Prevents DNA strand transfer by binding integrase
61
Integrase strand transfer inhibitors - Clinical use
HIV
62
Neuraminidase inhibitors - MoA
Inhibits neuraminidase in influenza A and B, preventing release of virions from infected cells and preventing spread through the resp tract
63
Neuraminidase inhibitors clinical use
Prophylaxis and treatment of influenzae. | Reduce complications of influenzae (otitis media, pneumonia)
64
Neuraminidase inhibitors adverse effect
Minor respiratory and GI reactions
65
Zanamivir contraindication
Patients with airway disease
66
Adamantanes - MoA
Block M2 proton channel, prevents acidification of influenza A, and fusion of viral membranes. Amantadine also increase release of dopamine
67
Adamantenes
Amantadine | Rimantadine
68
Adamantanes - Clinical use
Prevention and treatment of influenza A
69
Amantadine - Clinical use
Parkinson disease
70
Drugs for hepatitis and other viral infections
Ribavirin Nucleoside and nucleotide analogues Interferon alfa Sofosbuvir and Valpatasavir
71
Ribavirin - MoA
Inhibits guanine triphosphate and viral nucleic acid synthesis.
72
Ribavirin - Clinical use
``` 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
Ribavirin - Contraindication
Contraindicated: pregnancy + lactating women, ZDV treatment, Teratogenic
74
Ribavirin - Adverse effects
Adm inhalation: serious pulmonary and cardiovascular effects (apnea, pneumothorax, worsening resp status, cardiac arrest) Oral adm: hemolytic anemia (worsen cardiac disease, MI)
75
Ribavirin - Interactions
Antagonize ZDV
76
Inteferon alfa - MoA
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
Interferon alfa - Clinical use
``` Hepatitis B and C Papillomaviruses Genital warts Hairy cell leukemia Chronic myelocytic leukemia Kaposi sarcoma Renal carcinoma Malignant melanoma Multiple myeloma Neoplastic diseases ```
78
Interferon alfa - Adverse effects
``` Hematologic toxicity Cardiac arrhythmias Changed BP CNS dysfunction GI distress ```
79
Sofosbuvir and valpatasavir - MoA
Inhibits HCV RNA-directed RNA polymerase
80
Sofosbuvir and valpatasavir - Clinical use
Hepatitis C
81
Palivizumab - MoA
Inactivates the fusion protein of RSV, inhibits viral entry into target cells
82
Palivizumab - Clinical use
Prevent and treat RSV infection in infants and children under 2 years that are at increased risk of severe disease.
83
Drugs for influenza - Administration
All oral | Nasal spray: Zanamivir
84
Hepatitis and other viral drugs - Administration
All oral Subcutaneous: Interferon alfa Ribavirin: Oral + inhalation, IV

Pharmacology- Katzung (Spring 2019) (52 decks)

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