ANTI-VIRAL AGENTS Sarrah Mitchell Sarrah Mitchell

Introduction Viruses cause a variety of conditions, ranging from warts, to the common cold and flu, to diseases such as chickenpox and measles. Viruses are intracellular parasites with no metabolic machinery of their own; they lack both a cell wall and a cell membrane. To replicate, viruses must attach to and enter a living host cell – animal, plant, or bacterium – and use its metabolic process. Viral replication requires DNA or RNA synthesis. All viruses require cells to replicate. Most antiviral drugs must penetrate cells that are already infected to produce a therapeutic antiviral response. Few drugs are sufficiently selective to prevent viral replication without injury to the host. Optimal antiviral effectiveness requires a competent host immune system that can eliminate and effectively halt virus replication.

Agents used to treat Influenza and Respiratory Viruses  Influenza A and respiratory viruses invade respiratory tract and cause the signs and symptoms of the flu amantadine (Symmetrel), oseltamivir (Tamiflu), ribavirin (Virazole), rimantadine (Flumadine) are some of the agents used for Influenza A and respiratory viruses

MECHANISM OF ACTION  Unknown  The belief is these agents prevent shedding of the viral protein coat and entry of the virus into cells thereby preventing viral replication, causing viral death.

INDICATIONS FOR USE  amantadine (Symmetrel): Treat and prevent respiratory virus infection  oseltamivir (Tamiflu): Treat and prevent uncomplicated influenza for patient who is symptomatic less that 2 days  ribavirin (Virazole): Treat influenza A, respiratory synctial virus (RSV) and herpes virus infections as well as treat children with RSV  rimantadine (Flumadine): Prophylaxis and treat illness caused by influenza A virus in adults; prophylaxis against influenza A virus in children

CONTRAINDICATIONS/ ADVERSE EFFECTS  Pregnant and lactating women should not use these drugs unless the benefit clearly outweighs the potential risk  Patients with hepatic dysfunction are at increased risk for toxicity and worsening hepatic problems ADVERSE EFFECTS : Light-headedness, dizziness, insomnia, nausea, dyspnea, orthostatic hypotension, depression

DRUG-DRUG INTERACTIONS  May experience atropine like effects if amantadine and rimantadine are taken with anticholinergic drugs  Loss of effectiveness of aspirin and acetaminophen when taken with rimantadine  Levels of ribavirin may be reduced when taken with antacids  ribavirin should be avoided if patient is also taking nucleoside reverse transcriptase inhibitor.

ROUTES AND DOSAGE RANGES amantadine (Symmetrel) – Adult: 200mg po BID, Pediatric (9- 12yrs): 100mg po BID, Pediatric (1-9yrs): 2-4mg/lb po daily oseltamivir (Tamiflu) – Adult: 75mg po BID x 5days (Treatment); 75mg po daily x 7days (Prevention), Pediatric (1-12yrs): 30-75mg po BID x 5days (Treatment); 30-75mg po daily x 7days (Prevention) ribavirin (Virazole) – Pediatric: 20mg/mL in the reservoir for aerosol treatment over 12-18h each day x 3-7days rimantadine (Flumadine) – Adult: 100mg po BID, Pediatric (≥10yrs): 5mg/kg po daily

NURSING IMPLICATIONS ASSESSMENT  Assess for contraindications or cautions: known history of allergy to antivirals to avoid hypersensitivity reactions; history of liver or renal dysfunction and current status related to pregnancy or lactation.  Physical assessment to get baseline for evaluating effectiveness and adverse effects of drugs.  Assess orientation and reflexes to evaluate CNS effects of drugs.  Assess VS, signs and symptoms of viral infection, urinary output and renal and hepatic function tests.

NURSING DIAGNOSIS  Acute Pain related to GI, CNS, or GU effects of the drug  Disturbed Sensory Perception (Kinesthetic) related to CNS effects of the drug  Deficient Knowledge related to drug therapy

IMPLEMENTATION  Start the drug regimen as soon after exposure to the virus as possible to enhance effectiveness and decrease risk of complications  Administer influenza A vaccine before the flu season begins to decrease the risk of contracting the flu and reduce complications  Administer full course of drug for beneficial effects

EVALUATION  Monitor patient response to the drug  Monitor for adverse effects  Determine the effectiveness of the teaching plan  Monitor the effectiveness of comfort and safety measures and compliance with the regimen

Question # 1 WHEN IS IT BEST FOR THE FLU VACCINE TO BE GIVEN TO PATIENTS?

AGENTS FOR HERPES AND CYTOMEGALOVIRUS  Herpes shows symptoms such as cold sores, shingles and genital infections. Cytomegalovirus (CMV) affects the eye, respiratory tract and liver. Antiviral drugs used to treat these infections include acyclovir (Zovirax), famciclovir (Famvir), foscarnet (Foscavir), valacyclovir (Valtrex)

MECHANISM OF ACTION  Inhibit viral DNA replication  Prevents replication of the virus by forming shorter, non effective DNA chains

INDICATIONS FOR USE  acyclovir (Zovirax): Treatment of herpes virus infection  famciclovir (Famvir): Treatment of herpes virus infections such as herpes zoster or shingles and for recurrent episodes of genital herpes  foscarnet (Foscavir): Treatment of CMV and acyclovir resistant herpes simplex infections in immunocompromised patients  valacyclovir (Valtrex): Treatment of herpes zoster and recurrent genital herpes; cold sores

CONTRAINDICATIONS/ ADVERSE EFFECTS/DRUG- DRUG INTERACTION  Pregnant and lactating women should not use these drugs unless the benefit clearly outweighs the potential risk  Avoid use in patients with known allergies to antiviral agents, patients with renal disease or patients with severe CNS disorders ADVERSE EFFECTS : Nausea and vomiting, headache, depression, paresthesia, neuropathy, rash and hair loss. Burning at IV injection sites, renal failure or toxicity. DRUG-DRUG INTERACTION: When used with aminoglycoside antibiotics risk of nephrotoxicity increases. Risk of drowsiness when used with zidovudine.

ROUTES AND DOSAGE RANGES  acyclovir (Zovirax) – Adult: 5-10mg/kg q8h IV, IM or SC, or 200mg/day q4h x 10days and then 400mg po BID x 12months. Pediatric: mg/m² q8h IV, IM or SC x7- 10days or 20mg/kg po QID x 5days  famciclovir (Famvir) – Herpes Zoster: 500mg po q8h x 7days. Genital Herpes: 125mg po BID x 5days  foscarnet (Foscavir) – Adult: 40-60mg/kg q8-12h IV given as a 2hr infusion  valacyclovir (Valtrex) – Herpes Zoster: 1g po TID x 7days. Genital Herpes: 500mg po BID x 5days

NURSING IMPLICATIONS ASSESSMENT  Assess patient for any allergies to antivirals, renal dysfunction or severe CNS disorders  Perform physical assessment to obtain baseline  Assess orientation and reflexes to monitor CNS baseline  Evaluate renal function tests

NURSING DIAGNOSIS  Acute Pain related to GI, CNS, or local effects of the drug  Disturbed Sensory Perception (Kinesthetic) related to CNS effects of the drug  Deficient Knowledge related to drug therapy

IMPLEMENTATION  Start the drug regimen as soon after diagnosis to improve effectiveness  Ensure good hydration  Monitor renal function tests periodically during treatment  Educate patient: most importantly to avoid sexual intercourse if genital herpes is being treated, avoid driving and hazardous task of drowsiness or dizziness occurs  Administer full course of drug for beneficial effects  Warn patient of GI upset, nausea and vomiting

EVALUATION  Monitor patient response to the drug (alleviation of symptoms associated with herpes and CMV)  Monitor for adverse effects  Determine the effectiveness of the teaching plan  Monitor the effectiveness of comfort and safety measures and compliance with the regimen

QUESTION # 2 WHAT IS THE MOST IMPORTANT TEACHING FOR A PATIENT WITH THE HERPES VIRUS?WHAT IS THE MOST IMPORTANT TEACHING FOR A PATIENT WITH THE HERPES VIRUS?

AGENTS FOR HIV AND AIDS  A combination of different antiviral drugs is used to attack the virus which causes HIV and AIDS. Theses drugs are also known as antiretroviral agents. They fall into one of these groups: nonnucleoside and nucleoside reverse transcriptase inhibitors, the protease inhibitors, the fusion inhibitors, CCR5 coreceptor antagonists and integrase inhibitors.

Nonnucleoside Reverse Transcriptase Inhibitors delavirdine (Rescriptor) MECHANISM OF ACTION: Bind directly to HIV reverse transcriptase. Prevent the transfer of information that allow the virus to carry on formation of viral DNA. INDICATION FOR USE: Treatment of HIV infection, usually in combination with other antiviral agents. CONTRAINDICATIONS: Pregnant women and patients with hypersensitivity. ADVERSE EFFECTS: Constipation, nausea, diarrhea, rash associated with fever, oral lesions, muscle or joint pain.

Nonnucleoside Reverse Transcriptase Inhibitors cont. delavirdine (Rescriptor) DRUG INTERACTIONS: Antacids and didanosine decrease absorption. When given concurrently, delavirdine increases serum level of dapsone, quinidine, warfarin, CCBs and antidysrhythmics. ROUTES AND DOSAGE RANGES: Adult – 400mg po TID

Nucleoside Reverse Transcriptase Inhibitors zidovudine [AZT] (Retrovir, Aztec) MECHANISM OF ACTION: Interfere with viral RNA-directed DNA polymerase, thereby impeding replication of retroviruses, such as HIV. INDICATION FOR USE: Treatment of symptomatic HIV in adults and children as part of combination therapy; prevention of maternal transmission of HIV CONTRAINDICATIONS: Hypersensitivity and lactating women ADVERSE EFFECTS: Seizures, headache, anemia, severe bone marrow suppression

Nucleoside Reverse Transcriptase Inhibitors cont. zidovudine [AZT] (Retrovir, Aztec) DRUG INTERACTIONS: AZT toxicity increased when taken with aspirin, dapsone, indomethacin and interferon. Increased bone marrow suppression with antineoplastics, radiation therapy or ganciclovir. ROUTES AND DOSAGE RANGES: Adult – 100mg po q4h; Pediatric (6wk-12yrs) – mg/m² po q6h; Maternal 100mg po 5x daily from 14 wk gestation until start of labor

Protease Inhibitors nelfinavir (Viracept) MECHANISM OF ACTION: Interfere with the multiplication of virus and slow the progression of the disease INDICATION FOR USE: Combination therapy for the treatment of adults and children with HIV CONTRAINDICATIONS: Hypersensitivity and lactating women ADVERSE EFFECTS: Seizures, GI effects like diarrhea, nausea and vomiting, changes in liver function

Protease Inhibitors cont. nelfinavir (Viracept) DRUG INTERACTIONS: Severe toxic and life threatening arrhythmias may occur if combined with rifampin, triazolam or midazolam. ROUTES AND DOSAGE RANGES: Adult – 750mg po TID; Pediatric (2-13yrs) – 20-30mg/kg per dose po TID

Integrase Inhibitors raltegravir (Isentress) MECHANISM OF ACTION: Inhibits activity of enzyme, integrase, needed for viral replication. INDICATION FOR USE: Part of combination therapy for the treatment of HIV CONTRAINDICATIONS: Hypersensitivity and lactation ADVERSE EFFECTS: Headache, dizziness, anemia, fever, diarrhea

Integrase Inhibitors cont. raltegravir (Isentress) DRUG INTERACTIONS: If taken with rifampin may decrease serum levels of raltegravir. Should not be taken with St. Johns wort. ROUTES AND DOSAGE RANGES: Adult – 400mg po BID

NURSING IMPLICATIONS ASSESSMENT  Assess for contraindications and cautions to use of drugs, history to allergies, renal dysfunction, pregnancy or lactation  Assess temperature to monitor for infections  Check CBC results to monitor bone marrow activity and T cell number  Perform physical assessment  Assess orientation and reflexes

NURSING DIAGNOSIS  Imbalanced Nutrition: Less than body requirements related to GI effects of drugs  Risk for injury related to CNS effects of drugs  Deficient Knowledge related to drug therapy

IMPLEMENTATION  Monitor renal and hepatic function before and periodically during therapy  Ensure patient completes course of drug regimen  Administer drug around the clock  Monitor nutritional status if GI effects are severe  Provide safety precautions  Educate patient about the drugs prescribed as well as side effects of drugs and precautions to be taken while taking drugs

EVALUATION  Monitor patient response to the drug  Monitor for adverse effects  Evaluate effectiveness of teaching plan  Monitor effectiveness of comfort and safety measures as well as compliance with regimen

Question # 3 WHY SHOULD NNRTIs NOT BE GIVEN WITH ANTACIDS?WHY SHOULD NNRTIs NOT BE GIVEN WITH ANTACIDS?

REFERENCES  Deglin, J. H., & Vallerand, A. H. (2009). Davis’ Drug Guide for Nurses (11th, ed.). Philadelphia, Pa: F.A. Davis Company.  Karch, A. M. (2011). Focus on nursing pharmacology (5th ed.). Philadelphia PA: Wolters Kluwer Health/Lippincott Williams & Wilkins.  McCuistion, L. E., & Gutierrez, K. J. (2007). Saunders Nursing Survival Guide: Pharmacology (2nd ed.). St. Louis, MO: Saunders.