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Thera VIII > 12 Treatment of Viral Infections Cupo > Flashcards

12 Treatment of Viral Infections Cupo Flashcards

1
Q

In anti-viral therapy, what is the MOA of Direct Inactivation of Virus (Virucides)?

A

Cryotherapy or podophyllin in HPV. Destroys host/virus simultaneously. Limitation –> only for mucocutaneous lesions

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2
Q

What is Acyclovir (Zovirax)?

A

Synthetic, purine nucleoside analog

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3
Q

What is the spectrum of Acyclovir activity?

A

HSV-1, HSV-2, VZV, EBV, CMV. Potency 10 fold more potent vs HSV-1 and HSV-2 than VZV; even less active against CMV

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4
Q

What are the therapeutic uses of Acyclovir?

A

Genital Herpes Simplex I or II (5mg/kg/Q8h IV). Herpes (varicella) zoster (10mg/kg/Q8h IV). Mucocutaneous herpes relapse in immunocompromised. Disseminated or visceral HSV infection (i.e., Hepatitis, Gastritis, and Enteritis). CMV prophylaxis

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5
Q

What is the elimination of Acyclovir?

A

Renal excretion via GF and tubular secretion

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6
Q

What are the ADRs associated with Acyclovir?

A

GI (N/V/D). CNS (HA, dizziness, fatigue, altered sensorium, tremor, seizures). Skin rash. Crystalluria (risk factors: increased SCr, other toxins, dehydration)

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7
Q

What are the DDIs with Acyclovir?

A

Probenecid (increased T1/2, and acyclovir concentration). Other nephrotoxins (cyclosporine, tacrolimus)

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8
Q

What is Valacyclovir (Valtrex)?

A

Amino acid ester prodrug of Acyclovir. Developed to achieve therapeutic concentrations of Acyclovir at target sites to treat moderately susceptible strains (i.e., VZV, CMV)

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9
Q

What is Valacyclovirs spectrum of activity?

A

HSV-1, HSV-2, VZV, EBV, and CMV

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10
Q

What are the ADRs associated with Valacyclovir?

A

GI (N/V/D, constipation, abdominal pain, anorexia, dyspepsia). CNS (HA), eye pain, photophobia, tremors, dizziness. Increased LFTs

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11
Q

What are the DDIs with Valacyclovir?

A

Probenecid

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12
Q

What is Famciclovir (Famvir)?

A

Synthetic acyclic guanine derivative. A prodrug of Penciclovir

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13
Q

What is Famciclovirs spectrum of activity?

A

HSV-1, HSV-2, VZV, EBV

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14
Q

What are the ADRs associated with Famciclovir?

A

N/V/D, abdominal pain. HA. Fatigue. Dizziness

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15
Q

What are the DDIs with Famciclovir?

A

Probenecid

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16
Q

What is HSV-1?

A

More frequently associated with non-genital lesions (i.e., oral cavity, facial area)

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17
Q

What is HSV-2?

A

Usually genital lesions

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18
Q

What are some unique HSV properties?

A

Can invade and replicate in CNS. Ability to establish a latent infection

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19
Q

What is the Primary Infection of Genital Herpes?

A

HSV-2. Initial manifestation up to 3 weeks. Systemic complication: paresthesias, swelling, dysuria, inguinal adenopathy. More severe 1st episode, more likely to recur

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20
Q

How is Valacyclovir dosed for first genital herpes episode?

A

1,000mg BID x10 days

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21
Q

How is Valacyclovir dosed for recurrent genital herpes (episodic)?

A

500mg TID x3-5 days. OR. 1,000mg QD x5 days

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22
Q

How is Valacyclovir dosed for recurrent genital herpes (suppressive)?

A

500mg QD. OR. 1,000mg QD

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23
Q

How is Acyclovir dosed for first genital herpes episode?

A

400mg TID or 200mg 5x/day for 10 days

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24
Q

How is Acyclovir dosed for recurrent genital herpes (episodic)?

A

400mg TID x5 days. OR. 800mg BID x5 days. OR. 200mg 5x/day for 5 days

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25
Q

How is Acyclovir dosed for recurrent genital herpes (suppressive)?

A

400mg BID

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26
Q

How is Famciclovir dosed for first genital herpes episode?

A

250mg TID x10 days

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27
Q

How is Famciclovir dosed for recurrent genital herpes (episodic)?

A

125mg BID x5 days

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28
Q

How is Famciclovir dosed for recurrent genital herpes (suppressive)?

A

250mg BID up to 1 year

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29
Q

What is HSV Encephalitis?

A

Usual etiology: HSV-1. Most common, sporadic viral infection in CNS. High mortality (up to 70%) without prompt Rx

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30
Q

What are the presenting signs of HSV Encephalitis?

A

Acute onset fever, HA, loss of consciousness, seizures

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31
Q

What is the diagnosis of HSV Encephalitis like?

A

Difficult. LP to check CSF for pleocytosis, increased protein. Also, antibody + for HSV-1, PCR for HSV-DNA

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32
Q

What is the treatment for HSV Encephalitis?

A

Acyclovir 10mg/kg IV Q8h x14-21 days

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33
Q

What is Varicella Zoster Virus (Shingles)?

A

Reactivation of latent VZV in posterior root or cranial sensory nerve ganglia. Incidence and severity age-dependent. Immunosuppression induces episode. Present with lesions, intense pain +/- fever. 3 major sequelae

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34
Q

What is the anti-viral dosing in VZV?

A

Acyclovir: 800mg 5x/day for 7-10 days. Famciclovir: 500mg Q8h x7 days. Valacyclovir: 1g PO Q8h x7 days

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35
Q

What is the CDC recommendation for the VZV vaccine?

A

Single dose, age > 60 years. All patients, despite prior shingles episodes. It decreases singles occurrence by 50% overall. Live, attenuated VZV

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36
Q

When is the VZV vaccine contraindicated?

A

Immunodeficiency, defer in those w/ active TB, childbearing age, pregnancy, children

37
Q

What is Cytomegalovirus (CMV)?

A

Ubiquitous herpes virus. Infection early in life (~40-50% seroconversion by age 35). Latent and benign in immunocompetent. Risk factors for infection: Solid organ transplant, AIDS

38
Q

What are the anti-viral agents used for CMV?

A

Ganciclovir. Foscarnet. Cidofovir

39
Q

How is Ganciclovir dosed for CMV?

A

5mg/kg/Q12h IV x14 days, then 2.5-5mg/kg/day as maintenance

40
Q

How is Foscarnet dosed for CMV?

A

60mg/kg/Q8h IV for 14-21 days, then 90-120mg/kg IV QD as maintenance

41
Q

What is the Immune-Based therapy for CMV?

A

Immunoglobulin 500-1000mg/kg for 2-7 days IV. CMV-Immunoglobulin (Ctyogam) 200mg/kg IV

42
Q

What is done for the diagnosis of CMV?

A

Culture: Detect replicating CMV in fluids. Antiviral titers: serology. PCR: quantification of CMV viral load. Gold standard: biopsy and histopathologic detection of CMV inclusion bodies in tissue

43
Q

What are the characteristics of CMV Post-Transplant?

A

Most important viral pathogen affecting transplant recipient. Usually, appears 1-4 months post-transplant. Risk factor: immunosuppression secondary to anti-rejection regimen

44
Q

What is the time course for Post-Transplant infection?

A

Most opportunistic infections occur when the intensity of immunosuppression is highest. Time course divided into three groups: 1) Time zero to one month, 2) one to six months, 3) > 6 months

45
Q

What are the risk factors for CMV?

A

Donor/recipient serology (D-/R- < D-/R+ or D+/R+ < D+/R-). Net level of immunosuppression (cyclosporine, tacrolimus &laquo_space;azathioprine, mycophenolate mofetil &laquo_space;OKT3). Type of transplant (liver/lung > heart > kidney)

46
Q

What are the clinical manifestations of CMV disease in solid organ transplant?

A

Flu-like syndrome. Indirect effects - graft rejection, immunosuppression (bacterial, fungal infection), decreased patient survival. Target organ infections (liver (hepatitis), lung (interstitial pneumonitis)). Other infections (gastritis, esophagitis, retinitis)

47
Q

What is used in the treatment of CMV disease?

A

First line: Ganciclovir. Second line: Foscarnet

48
Q

How is Ganciclovir dosed in CMV?

A

5mg/kg IVPB Q12h x14-21 days. Dosage adjustment for renal insufficiency. Stringent CBC monitoring

49
Q

How is Foscarnet dosed in CMV?

A

60mg/kg IVPB Q8h

50
Q

What is the recommended prophylaxis time for CMV?

A

Prophylaxis for at least 12-14 weeks

51
Q

What is the MOA of Ganciclovir?

A

A synthetic guanine derivative. Ganciclovir –> ganciclovir-triphosphate –> inhibition of DNA polymerase –> ultimately, inhibits incorporation into elongating viral DNA chain

52
Q

What is Ganciclovirs spectrum of activity?

A

CMV!!! HSV-1, HSV-2, VZV, EBV. First line for CMV only, given unfavorable safety profile

53
Q

What is the elimination of Ganciclovir like?

A

Renal excretion of up to 90% of drug via glomerular filtration and tubular secretion

54
Q

What are the ADRs associated with Gancloclovir?

A

Granulocytopenia, Thrombocytopenia!!! N/V/D. Anemia. Rash. HA, confusion. Increased LFTs

55
Q

What are the DDIs with Ganciclovir?

A

Cytotoxic drugs (concomitant bone marrow suppression). Probenecid (AUC increased by > 50%)

56
Q

What is the metabolism and elimination of Ganciclovir like?

A

Rapid hydrolysis of GCV. Intestinal and hepatic esterases represent a high-capacity system. No other metabolites detected. GCV drug interactions applicable to Val-GCV. Renal impairment requires dose adjustment

57
Q

What is the Valganciclovir dose for CrCl > 60?

A

900mg QD

58
Q

What is the Valganciclovir dose for CrCl 40-60?

A

450mg QD

59
Q

What is the Valganciclovir dose for CrCl 25-40?

A

450mg every 2 days

60
Q

What is the Valganciclovir dose for CrCl 10-25?

A

450mg 2x/week

61
Q

What is the Valganciclovir dose for CrCl < 10?

A

Change to IV Ganciclovir 0.625mg/kg 3x/week after dialysis

62
Q

What is Foscarnet (Foscavir)?

A

A pyrophosphate analog. MOA: Selective inhibition at pyrophosphate binding site on virus-specific DNA polymerase

63
Q

What is the spectrum of activity for Foscarnet?

A

CMV, HSV-1, HSV-2, VZV, EBV

64
Q

What is the elimination of Foscarnet like?

A

Up to 80-90% excreted in the urine unchanged via glomerular filtration and tubular secretion

65
Q

What are the ADRs associated with Foscarnet?

A

Nephrotoxicity (major limiting factor). Fever, N/V/D. Anemia. HA (very common). Seizures. Hypokalemia, hypocalcemia, hypomagnesemia. Increased LFTs

66
Q

What are the risk factors for Nephrotoxicity when using Foscarnet?

A

High doses. Rapid infusion. Dehydration. Pre-existing renal insufficiency. Concommitant nephrotoxic agents

67
Q

What are the indications for Foscarnet use?

A

CMV in immunocompromised patients (2nd line), treatment of Acyclovir-resistant mucocutaneous HSV. Optimal therapeutic role: Secondary agent in the treatment of CMV disease d/t its unfavorable ADRs

68
Q

What is the dosing of Foscarnet like?

A

60mg/kg IV Q8h x2-3 weeks; followed by chronic maintenance of 90-120mg/kg/day for CMV retinitis. 40mg/kg IV 8-12h for HSV mucocutaneous lesions. Dosage adjustment for mild-moderate renal insufficiency

69
Q

What is the MOA of Cidofovir?

A

Intracellular phosphorylation to di-phosphate –> mimics natural deoxycytidine (dCTP) –> binds DNA polymerase –> inhibits viral replication. IV only

70
Q

What are the ADRs associated with Cidofovir?

A

Nephrotoxic (prehydrate, probenecid, slow infusion). Uveitis, rash, neutropenia, GI

71
Q

What is CMV resistance like?

A

Overall rates 4-9%; up to 15-25% in D+/R- lung transplants

72
Q

What is Mortality from influenza due to?

A

Underlying disease decompensation. Bacterial superinfection. Direct progression of viral disease

73
Q

What are the risk factors for Influenza Complications?

A

Age > 50 years. Residence in nursing home/chronic care facilities. Chronic pulmonary disease (e.g. asthma, COPD). Chronic cardiovascular disease. Chronic metabolic disease, renal dysfunction, hemoglobinopathy. Immunosuppression. Long-term ASA therapy (ages 6 months - 18 years). Second or third trimester pregnancy. Children

74
Q

What is the time to administer the Influenza Vaccine?

A

4 weeks prior to predicted onset of flu season. Usually, mid-October through November

75
Q

What are the contraindications to the Influenza Vaccine?

A

In patients with allergy to eggs or any vaccine component

76
Q

What is the Influenza Vaccine like in the elderly?

A

Produces lower HA-inhibition antibody titers. May not eliminate URTI susceptibility. May reduce LRTI morbidity/mortality

77
Q

What is Amantadine (Symmetrel)?

A

Influenza A Virus medication. Used for prevention and treatment of respiratory tract illness d/t A. Not effective, lots of resistance

78
Q

What is Rimantadine (Flumadine)?

A

Influenza A medication. Used for the prevention of s/sx of respiratory infection; for treatment administration w/in 24-48h of sx onset and continue for 7-10 days. Not effective, high resistance

79
Q

What is Oseltamivir (TamiFlu)?

A

Used for Influenza A and B. MOA: selective inhibitor of Influenza A, B neuraminidase. Dose adjust for CrCl < 30

80
Q

How is TamiFlu dosed for treatment of Influenza A or B?

A

75mg BID x5 days

81
Q

How is TamiFlu dosed for prophylaxis of Influenza A or B?

A

75mg QD x6 weeks

82
Q

What are the ADRs associated with Oseltamivir?

A

GI (N/V). CNS (dizziness, HA, fatigue, vertigo). No cardiac effects; alterations to lab tests

83
Q

What are the drug interactions with Oseltamivir (TamiFlu)?

A

Probenecid (d/t decreased tubular secretion)

84
Q

What is Zanamivir (Relenza)?

A

Inhibitor of Influenza A and B neuraminidase. Supplied as a Rotadisk for oral inhalation. NOT used for prophylaxis

85
Q

How is Zanamivir dosed for treatment of influenza A or B?

A

10mg (2 inhalations) by mouth BID x5 days

86
Q

What are the ADRs associated with Zanamivir?

A

Respiratory/Relative contraindications - bronchospasm. GI. Hepatic (transient increase in liver enzymes)

87
Q

When is prophylaxis of Influenza used?

A

When vaccination occurred after outbreak. When antibody response to vaccine may be poor. When vaccine contraindicated

88
Q

What is viral resistance like for Influenza?

A

Caused by point mutations in viral M2 protein gene. Associated with therapeutic use of amantadine and rimantadine. Causes disease comparable to “wild” virus. Can be transmitted within households

89
Q

What is Oseltamivir and Zanamavir’s place in therapy?

A

Overall decrease in symptom duration by 1 day. May consider in high risk groups (elderly, pre-existing cardiac or pulmonary disease, renal failure)

Thera VIII (24 decks)

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