Flashcards in 12 Treatment of Viral Infections Cupo Deck (89):
In anti-viral therapy, what is the MOA of Direct Inactivation of Virus (Virucides)?
Cryotherapy or podophyllin in HPV. Destroys host/virus simultaneously. Limitation --> only for mucocutaneous lesions
What is Acyclovir (Zovirax)?
Synthetic, purine nucleoside analog
What is the spectrum of Acyclovir activity?
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
What are the therapeutic uses of Acyclovir?
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
What is the elimination of Acyclovir?
Renal excretion via GF and tubular secretion
What are the ADRs associated with Acyclovir?
GI (N/V/D). CNS (HA, dizziness, fatigue, altered sensorium, tremor, seizures). Skin rash. Crystalluria (risk factors: increased SCr, other toxins, dehydration)
What are the DDIs with Acyclovir?
Probenecid (increased T1/2, and acyclovir concentration). Other nephrotoxins (cyclosporine, tacrolimus)
What is Valacyclovir (Valtrex)?
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)
What is Valacyclovirs spectrum of activity?
HSV-1, HSV-2, VZV, EBV, and CMV
What are the ADRs associated with Valacyclovir?
GI (N/V/D, constipation, abdominal pain, anorexia, dyspepsia). CNS (HA), eye pain, photophobia, tremors, dizziness. Increased LFTs
What are the DDIs with Valacyclovir?
What is Famciclovir (Famvir)?
Synthetic acyclic guanine derivative. A prodrug of Penciclovir
What is Famciclovirs spectrum of activity?
HSV-1, HSV-2, VZV, EBV
What are the ADRs associated with Famciclovir?
N/V/D, abdominal pain. HA. Fatigue. Dizziness
What are the DDIs with Famciclovir?
What is HSV-1?
More frequently associated with non-genital lesions (i.e., oral cavity, facial area)
What is HSV-2?
Usually genital lesions
What are some unique HSV properties?
Can invade and replicate in CNS. Ability to establish a latent infection
What is the Primary Infection of Genital Herpes?
HSV-2. Initial manifestation up to 3 weeks. Systemic complication: paresthesias, swelling, dysuria, inguinal adenopathy. More severe 1st episode, more likely to recur
How is Valacyclovir dosed for first genital herpes episode?
1,000mg BID x10 days
How is Valacyclovir dosed for recurrent genital herpes (episodic)?
500mg TID x3-5 days. OR. 1,000mg QD x5 days
How is Valacyclovir dosed for recurrent genital herpes (suppressive)?
500mg QD. OR. 1,000mg QD
How is Acyclovir dosed for first genital herpes episode?
400mg TID or 200mg 5x/day for 10 days
How is Acyclovir dosed for recurrent genital herpes (episodic)?
400mg TID x5 days. OR. 800mg BID x5 days. OR. 200mg 5x/day for 5 days
How is Acyclovir dosed for recurrent genital herpes (suppressive)?
How is Famciclovir dosed for first genital herpes episode?
250mg TID x10 days
How is Famciclovir dosed for recurrent genital herpes (episodic)?
125mg BID x5 days
How is Famciclovir dosed for recurrent genital herpes (suppressive)?
250mg BID up to 1 year
What is HSV Encephalitis?
Usual etiology: HSV-1. Most common, sporadic viral infection in CNS. High mortality (up to 70%) without prompt Rx
What are the presenting signs of HSV Encephalitis?
Acute onset fever, HA, loss of consciousness, seizures
What is the diagnosis of HSV Encephalitis like?
Difficult. LP to check CSF for pleocytosis, increased protein. Also, antibody + for HSV-1, PCR for HSV-DNA
What is the treatment for HSV Encephalitis?
Acyclovir 10mg/kg IV Q8h x14-21 days
What is Varicella Zoster Virus (Shingles)?
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
What is the anti-viral dosing in VZV?
Acyclovir: 800mg 5x/day for 7-10 days. Famciclovir: 500mg Q8h x7 days. Valacyclovir: 1g PO Q8h x7 days
What is the CDC recommendation for the VZV vaccine?
Single dose, age > 60 years. All patients, despite prior shingles episodes. It decreases singles occurrence by 50% overall. Live, attenuated VZV
When is the VZV vaccine contraindicated?
Immunodeficiency, defer in those w/ active TB, childbearing age, pregnancy, children
What is Cytomegalovirus (CMV)?
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
What are the anti-viral agents used for CMV?
Ganciclovir. Foscarnet. Cidofovir
How is Ganciclovir dosed for CMV?
5mg/kg/Q12h IV x14 days, then 2.5-5mg/kg/day as maintenance
How is Foscarnet dosed for CMV?
60mg/kg/Q8h IV for 14-21 days, then 90-120mg/kg IV QD as maintenance
What is the Immune-Based therapy for CMV?
Immunoglobulin 500-1000mg/kg for 2-7 days IV. CMV-Immunoglobulin (Ctyogam) 200mg/kg IV
What is done for the diagnosis of CMV?
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
What are the characteristics of CMV Post-Transplant?
Most important viral pathogen affecting transplant recipient. Usually, appears 1-4 months post-transplant. Risk factor: immunosuppression secondary to anti-rejection regimen
What is the time course for Post-Transplant infection?
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
What are the risk factors for CMV?
Donor/recipient serology (D-/R- < D-/R+ or D+/R+ < D+/R-). Net level of immunosuppression (cyclosporine, tacrolimus << azathioprine, mycophenolate mofetil << OKT3). Type of transplant (liver/lung > heart > kidney)
What are the clinical manifestations of CMV disease in solid organ transplant?
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)
What is used in the treatment of CMV disease?
First line: Ganciclovir. Second line: Foscarnet
How is Ganciclovir dosed in CMV?
5mg/kg IVPB Q12h x14-21 days. Dosage adjustment for renal insufficiency. Stringent CBC monitoring
How is Foscarnet dosed in CMV?
60mg/kg IVPB Q8h
What is the recommended prophylaxis time for CMV?
Prophylaxis for at least 12-14 weeks
What is the MOA of Ganciclovir?
A synthetic guanine derivative. Ganciclovir --> ganciclovir-triphosphate --> inhibition of DNA polymerase --> ultimately, inhibits incorporation into elongating viral DNA chain
What is Ganciclovirs spectrum of activity?
CMV!!! HSV-1, HSV-2, VZV, EBV. First line for CMV only, given unfavorable safety profile
What is the elimination of Ganciclovir like?
Renal excretion of up to 90% of drug via glomerular filtration and tubular secretion
What are the ADRs associated with Gancloclovir?
Granulocytopenia, Thrombocytopenia!!! N/V/D. Anemia. Rash. HA, confusion. Increased LFTs
What are the DDIs with Ganciclovir?
Cytotoxic drugs (concomitant bone marrow suppression). Probenecid (AUC increased by > 50%)
What is the metabolism and elimination of Ganciclovir like?
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
What is the Valganciclovir dose for CrCl > 60?
What is the Valganciclovir dose for CrCl 40-60?
What is the Valganciclovir dose for CrCl 25-40?
450mg every 2 days
What is the Valganciclovir dose for CrCl 10-25?
What is the Valganciclovir dose for CrCl < 10?
Change to IV Ganciclovir 0.625mg/kg 3x/week after dialysis
What is Foscarnet (Foscavir)?
A pyrophosphate analog. MOA: Selective inhibition at pyrophosphate binding site on virus-specific DNA polymerase
What is the spectrum of activity for Foscarnet?
CMV, HSV-1, HSV-2, VZV, EBV
What is the elimination of Foscarnet like?
Up to 80-90% excreted in the urine unchanged via glomerular filtration and tubular secretion
What are the ADRs associated with Foscarnet?
Nephrotoxicity (major limiting factor). Fever, N/V/D. Anemia. HA (very common). Seizures. Hypokalemia, hypocalcemia, hypomagnesemia. Increased LFTs
What are the risk factors for Nephrotoxicity when using Foscarnet?
High doses. Rapid infusion. Dehydration. Pre-existing renal insufficiency. Concommitant nephrotoxic agents
What are the indications for Foscarnet use?
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
What is the dosing of Foscarnet like?
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
What is the MOA of Cidofovir?
Intracellular phosphorylation to di-phosphate --> mimics natural deoxycytidine (dCTP) --> binds DNA polymerase --> inhibits viral replication. IV only
What are the ADRs associated with Cidofovir?
Nephrotoxic (prehydrate, probenecid, slow infusion). Uveitis, rash, neutropenia, GI
What is CMV resistance like?
Overall rates 4-9%; up to 15-25% in D+/R- lung transplants
What is Mortality from influenza due to?
Underlying disease decompensation. Bacterial superinfection. Direct progression of viral disease
What are the risk factors for Influenza Complications?
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
What is the time to administer the Influenza Vaccine?
4 weeks prior to predicted onset of flu season. Usually, mid-October through November
What are the contraindications to the Influenza Vaccine?
In patients with allergy to eggs or any vaccine component
What is the Influenza Vaccine like in the elderly?
Produces lower HA-inhibition antibody titers. May not eliminate URTI susceptibility. May reduce LRTI morbidity/mortality
What is Amantadine (Symmetrel)?
Influenza A Virus medication. Used for prevention and treatment of respiratory tract illness d/t A. Not effective, lots of resistance
What is Rimantadine (Flumadine)?
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
What is Oseltamivir (TamiFlu)?
Used for Influenza A and B. MOA: selective inhibitor of Influenza A, B neuraminidase. Dose adjust for CrCl < 30
How is TamiFlu dosed for treatment of Influenza A or B?
75mg BID x5 days
How is TamiFlu dosed for prophylaxis of Influenza A or B?
75mg QD x6 weeks
What are the ADRs associated with Oseltamivir?
GI (N/V). CNS (dizziness, HA, fatigue, vertigo). No cardiac effects; alterations to lab tests
What are the drug interactions with Oseltamivir (TamiFlu)?
Probenecid (d/t decreased tubular secretion)
What is Zanamivir (Relenza)?
Inhibitor of Influenza A and B neuraminidase. Supplied as a Rotadisk for oral inhalation. NOT used for prophylaxis
How is Zanamivir dosed for treatment of influenza A or B?
10mg (2 inhalations) by mouth BID x5 days
What are the ADRs associated with Zanamivir?
Respiratory/Relative contraindications - bronchospasm. GI. Hepatic (transient increase in liver enzymes)
When is prophylaxis of Influenza used?
When vaccination occurred after outbreak. When antibody response to vaccine may be poor. When vaccine contraindicated
What is viral resistance like for Influenza?
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