Pharmacology Chapter 10
c
1. In assessing a patient, a viral cause might be suspected if the patient was diagnosed with a. tuberculosis. b. leprosy. c. the common cold. d. gonorrhea.
c
5. Which of the following would be an important teaching point for the patient receiving an agent to treat herpes virus or CMV? a. Stop taking the drug as soon as the lesions have disappeared. b. Sexual intercourse is fine—as long as you are taking the drug, you are not contagious. c. Drink plenty of fluids to decrease the drug's toxic effects on the kidneys. d. There are few if any associated GI adverse effects.
Yellow sclera and hepatomegaly
A female HIV-positive patient with a high CD4 count has been taking nevirapine (Viramune) for 9 weeks. What clinical manifestations indicate to the nurse that the patient is having complications from this medication?
Inhaled
A neonatal intensive care unit nurse is caring for an infant diagnosed with respiratory syncytial virus. What route of delivery will the nurse use when ribavirin is administered to this infant?
Injecting drug user
A school nurse is talking with a health class of freshman high school students about human immunodeficiency virus (HIV). What patient would the nurse tell the students is at the greatest risk of contracting HIV?
Hepatitis B is transmitted through sexual contact. Hepatitis B is transmitted through blood-to-blood contact. Hepatitis B is transmitted from the mother to her unborn baby.
A school nurse is teaching a health class to a group of high school students. The nurse is preparing a lecture on hepatitis B and knows to include what information about the transmission of hepatitis B in the lecture? (Mark all that apply.)
acyclovir cidofovir famciclovir foscarnet ganciclovir valacyclovir valganciclovir
AGENTS FOR HERPES VIRUS AND CYTOMEGALOVIRUS
amantadine oseltamivir peramivir ribavirin
AGENTS FOR INFLUENZA A AND RESPIRATORY VIRUSES
collection of less serious opportunistic infections with HIV infection; the decrease in the number of helper T cells is less severe than in fully developed AIDS
AIDS-related complex (ARC)
Agents for Influenza A and Respiratory Viruses
Agents for influenza A and respiratory viruses include amantadine (generic), oseltamivir (Tamiflu), peramivir (Rapivab), ribavirin (Virazole), rimantadine (Flumadine), and zanamivir (Relenza).
Adverse Effects
As with the other antivirals, patients taking these drugs often experience GI effects, including nausea, vomiting, diarrhea, anorexia, and changes in liver function. Elevated cholesterol and triglyceride levels may occur. There is often a redistribution of fat to a buffalo hump with thinning of arms and legs. Rashes, pruritus, and the potentially fatal Stevens-Johnson syndrome have also occurred.
True
Children younger than the age of 12 years should not receive indinavir.
Monitoring renal function two or three times weekly during induction
How is the risk of renal impairment best minimized when foscarnet is administered?
CCR5 Coreceptor Antagonist
In 2007, another new class of drugs was introduced for the treatment of HIV. Maraviroc (Selzentry) is a CCR5 coreceptor antagonist
Integrase Inhibitors
In late 2007, another class of drugs—integrase inhibitors—was introduced to treat HIV infection. There are now two drugs in this class, dolutegravir (Tivicay) and raltegravir (Isentress)
Therapeutic Actions and Indications
Protease is essential for the maturation of an infectious virus; without it an HIV particle is immature and noninfective, unable to fuse with and inject itself into a cell. All of these drugs are used as part of combination therapy for the treatment of HIV infection
Therapeutic Actions and Indications
Research has shown that they are very effective in immunocompromised individuals, such as patients with AIDS, those taking immunosuppressants, elderly patients, and those with multiple infections
Locally Active Antiviral Agents
Some antiviral agents are given locally to treat local viral infections. These agents include docosanol (Abreva), ganciclovir (Zirgan), imiquimod (Aldara), penciclovir (Denavir), and trifluridine (Viroptic).
Adverse Effects
The adverse effects most commonly experienced with these drugs are GI related—dry mouth, constipation or diarrhea, nausea, abdominal pain, and dyspepsia. Dizziness, blurred vision, and headache have also been reported. A flu-like syndrome of fever, muscle aches and pains, fatigue, and loss of appetite often occurs with the anti-HIV drugs, but these signs and symptoms may also be related to the underlying disease.
Adverse Effects
The adverse effects most frequently seen with these drugs are headache, dizziness, nausea, diarrhea, and elevated liver enzymes. Severe hepatomegaly with steatosis, sometimes fatal, has been reported with adefovir and telbivudine use. Lactic acidosis and renal impairment have been reported with entecavir and adefovir. A potential risk for hepatitis B exacerbation could occur when the drugs are stopped. Therefore, teach patients the importance of not running out of their drugs and use extreme caution when discontinuing these drugs.
"This is a topical medication that is not absorbed into the body so adverse effects are limited to burning, stinging, or discomfort at the site."
The client is prescribed docosanol to treat a cold sore on the lip. The client tells the nurse, "I've read some bad things online about the side effects. Is it safe to use?" What is the nurse's best response?
Adverse Effects
The most common adverse effects are fatigue, nausea, diarrhea, and rash. Severe skin reactions can occur.
Each medication is only effective against a small number of specific viral infections.
There are many antiviral medications on the market. What is the clinical reason for this?
Contraindications and Cautions
There are no adequate studies of nonnucleoside reverse transcriptase inhibitors in pregnancy, so use should be limited to situations in which the benefits clearly outweigh any risks. It is suggested that women should not breastfeed if they are infected with HIV. Safety for the use of delavirdine in children has not been established.
Therapeutic Actions and Indications
These antiviral agents act on viruses by interfering with normal viral replication and metabolic processes. They are indicated for specific, local viral infections
Become vaccinated against prevalent virus infections.
To prevent viral infections, what precaution should the general public take?
DNA virus that accounts for many respiratory, ophthalmic, and liver infections
cytomegalovirus (CMV)
a drug that prevents the fusion of the HIV-1 virus with the human cellular membrane, preventing it from entering the cell
fusion inhibitor
human lymphocyte that helps to initiate immune reactions in response to tissue invasion
helper T cell
a serious to potentially fatal viral infection of the liver, transmitted by body fluids
hepatitis B
RNA virus that invades tissues of the respiratory tract, causing the signs and symptoms of the common cold or "flu"
influenza A
a drug that inhibits the activity of the virus-specific enzyme integrase, an encoded enzyme needed for viral replication; blocking this enzyme prevents the formation of the HIV-1 provirus
integrase inhibitor
tissue hormone that is released in response to viral invasion; blocks viral replication
interferon
drugs that bind to sites on the reverse transcriptase within the cell cytoplasm, preventing RNA- and DNA-dependent DNA polymerase activities needed to carry out viral DNA synthesis; prevents the transfer of information that allows the virus to replicate and survive
nonnucleoside reverse transcriptase inhibitors
Zidovudine
oral-onset=varies-peak=30-90 minutes IV-onset=rapid-peak=end of infusion
drugs that block the activity of the enzyme protease in HIV; protease is essential for the maturation of infectious virus, and its absence leads to the formation of an immature and noninfective HIV particle
protease inhibitors
Enfuvirtide
subcutaneous-slow-4 to 8 hrs
a,e,f
2. Appropriate nursing diagnoses related to drug therapy for a patient receiving combination antiviral therapy for the treatment of HIV infection would include the following: a. Disturbed sensory perception (kinesthetic) related to the CNS effects of the drugs b. Imbalanced nutrition: More than body requirements related to appetite stimulation c. Heart failure related to cardiac effects of the drugs d. Adrenal insufficiency related to endocrine effects of the drugs e. Acute pain related to GI, CNS, or dermatological effects of the drugs f. Deficient knowledge regarding drug therapy
b
2. Virus infections have proved difficult to treat because they a. have a protein coat. b. inject themselves into human cells to survive and to reproduce. c. are bits of RNA or DNA. d. easily resist drug therapy.
d
4. Herpes viruses cause a broad range of conditions but have not been identified as the causative agent in a. cold sores. b. shingles. c. genital infections. d. leprosy.
Nurses who are pregnant or who may be pregnant should not administer the drug.
A 3-month-old infant has been diagnosed with respiratory syncytial virus (RSV) and will begin treatment with inhaled ribavirin. Which of the following measures should be taken in the care of this patient and administration of ribavirin?
The client's CD4 count
A 42-year-old client, diagnosed with human immunodeficiency virus (HIV), has been receiving antiretroviral therapy for several years. Recently, raltegravir was added to the drug regimen. When assessing the success of this addition to the treatment, the nurse should prioritize which laboratory value?
The client will experience fewer recurrences.
A 45-year-old client is prescribed acyclovir for the treatment of genital herpes. Which is an expected outcome for this client?
Increased CD4+ cell counts
A 58-year-old with HIV is starting treatment with Combivir. He currently has a CD4+ cell count of less than 200 cells/mL and a viral load greater than 45,000 copies/mL. The nurse treating the client knows that what is a sign of effective drug therapy?
Peripheral neuropathy
A HIV-positive patient is being treated with didanosine as part of the antiretroviral therapy. Which of the following symptoms should the nurse monitor for and immediately report to the care provider?
2 days.
A client comes to the health care facility reporting flulike symptoms. After a thorough assessment, the client is diagnosed with influenza and is to receive oseltamivir. The nurse understands that this drug has been prescribed because the client been symptomatic for less than:
Discontinue the therapy.
A client has been treated with abacavir for the past 6 weeks. The client contacts the physician's office with reports of diarrhea, abdominal pain, sore throat, cough, and shortness of breath. Which is the appropriate action to take for this situation?
They have synergistic antiviral effects.
A client is administered a nucleotide reverse transcriptase inhibitor in combination with a nonnucleotide reverse transcriptase inhibitor. What is the rationale when administering these medications together?
Intravenous
A client is diagnosed with cytomegalovirus infection and is to receive foscarnet. The nurse would expect to administer this drug by which route?
Antiviral effects may be reduced.
A client is receiving a nonnucleoside reverse transcriptase inhibitor. Why should the nurse caution the client to avoid the concurrent use of St. John's wort?
Dry mouth and dyspepsia
A client is receiving nevirapine as part of a treatment for HIV infection. The nurse would instruct the client about which adverse effects as most commonly experienced?
"It's possible you might have changes in body fat distribution."
A client is receiving tenofovir as part of a therapy regimen for HIV infection. The nurse should provide what teaching related to what the client may experience?
Provide for frequent rest periods.
A client who is hospitalized and receiving antiretroviral therapy has a nursing diagnosis of Risk for Injury related to weakness and dizziness. Which would be most appropriate for the nurse to do?
Liver function
A client with HIV has had a CCR5 co-receptor antagonist added to the antiretroviral regimen. What assessment should the nurse prioritize?
The client has hepatitis C and a history of heavy alcohol use.
A client's health care provider is considering the addition of efavirenz to the client's drug regimen for the treatment of recently diagnosed HIV. Which aspects of the client's medical history should prompt the nurse to question the use of this drug?
Platelet count 118,000/mm3 (low)
A client, undergoing treatment for cytomegalovirus, received an initial dose of IV ganciclovir 3 days ago. When reviewing this client's most recent blood work, what abnormality should the nurse recognize as a possible adverse effect of this drug?
Fusion Inhibitor
A newer class of drug is the fusion inhibitor (see Table 10.3). This agent acts at a different site than do other HIV antivirals. The fusion inhibitor prevents the fusion of the virus with the human cellular membrane, which prevents the HIV-1 virus from entering the cell. Enfuvirtide (Fuzeon) is used in combination with other antiretroviral agents to treat adults and children older than 6 years who have evidence of HIV-1 replication despite ongoing antiretroviral therapy.
Alcohol use
A nurse is assessing a 66-year-old man who is HIV-positive. The patient has been prescribed didanosine (Videx). It would be most important to question the patient about which of the following?
if the client has a CD4 T-cell count less than 350 cells/mm3
A nurse is caring for a client diagnosed with HIV. The client wants to know when they will be started on medication for their disease. What would be the nurse's best response?
"Wear gloves when applying the ointment."
A nurse is teaching a client with herpes zoster to apply acyclovir ointment. What guidance should the nurse include in the instructions?
Refraining from use of St. John's wort, which can cause decreased effectiveness of saquinavir
A patient being treated for HIV with saquinavir informs the nurse they he has been "suffering from depression" and taking St. John's wort to help. What is important for the nurse to discuss with this patient?
Aminoglycoside
A patient comes to the clinic with a herpes outbreak. The nurse notes from the patient's chart that the patient is just beginning a course of antibiotics prescribed by another physician in the clinic. What classification of antibiotic should not be taken with a medication used to treat herpes?
Combination antiretroviral therapy
A patient diagnosed with acute primary HIV infection is in the clinic. What treatment should be initiated for this patient?
Liver function testing and HIV testing
A patient with chronic hepatitis B (HBV) infection is scheduled to begin a new treatment regimen that will include adefovir dipivoxil. What assessments should be prioritized before the initiation of this drug treatment?
Contraindications and Cautions
Because of its renal clearance, amantadine must be used at reduced doses and with caution in patients who have any renal impairment to avoid altered metabolism and excretion of the drug. Because it is embryotoxic in animals and crosses into breast milk, amantadine should be used during pregnancy and lactation only if the benefits clearly outweigh the risks to the fetus or neonate. Patients with renal dysfunction who are taking oseltamivir require reduced doses and close monitoring to avoid altered metabolism and excretion of the drug. Oseltamivir should be used during pregnancy and lactation only if the benefits clearly outweigh the risks to the fetus or neonate because there are no adequate studies in pregnancy and lactation. Women of childbearing age should be advised to use barrier contraceptives if they are taking ribavirin. The drug has been associated with serious fetal effects. Rimantadine and peramivir are embryotoxic in animals and should be used during pregnancy only if the benefits clearly outweigh the risks. These drugs should not be used by nursing mothers because they cross into breast milk and can cause toxic reactions in the neonate. Use in children should be limited to prevention of influenza A infections. Because of the renal excretion, zanamivir must be used cautiously in patients with any renal impairment. It should be used during pregnancy and lactation only if the benefits clearly outweigh the risks to the fetus or neonate.
Adverse Effects
Because these drugs are not absorbed systemically, the adverse effects most commonly reported are local burning, stinging, and discomfort. These effects usually occur at the time of administration and pass with time.
a drug that blocks the receptor site on the T cell membrane that the HIV virus needs to interact with in order to enter the cell.
CCR5 coreceptor antagonist
Nonnucleoside Reverse Transcriptase Inhibitors delavirdine efavirenz etravirine nevirapine rilpivirine Nucleoside Reverse Transcriptase Inhibitors abacavir didanosine emtricitabine lamivudine stavudine tenofovir zidovudine Protease Inhibitors atazanavir darunavir fosamprenavir indinavir lopinavir nelfinavir ritonavir saquinavir tipranavir Fusion Inhibitor enfuvirtide CCR5 Coreceptor Antagonist maraviroc Integrase Inhibitor dolutegravir raltegravir
AGENTS FOR HIV AND AIDS
adefovir entecavir telbivudine
ANTI-HEPATITIS B AGENTS
daclatasvir simeprevir sofosbuvir
ANTI-HEPATITIS C AGENTS
Pharmacokinetics
Abacavir is an oral drug that is rapidly absorbed from the GI tract. It is metabolized in the liver and excreted in feces and urine with a half-life of 1 to 2 hours. Didanosine is rapidly destroyed in an acid environment and therefore must be taken in a buffered form. It reaches peak levels in 15 to 75 minutes. Didanosine undergoes intracellular metabolism with a half-life of 8 to 24 hours. It is excreted in the urine. Emtricitabine has the advantage of being a one-capsule-a-day therapy. Emtricitabine has a rapid onset and peaks in 1 to 2 hours. It has a half-life of 10 hours, and after being metabolized in the liver is excreted in the urine and feces. Dose needs to be reduced in patients with renal impairment. It has been associated with severe and even fatal hepatomegaly with steatosis, a fatty degeneration of the liver. Lamivudine is rapidly absorbed from the GI tract and is excreted primarily unchanged in the urine. It peaks within 4 hours and has a half-life of 5 to 7 hours. Because excretion depends on renal function, dose reduction is recommended in the presence of renal impairment. The drug is available as an oral solution, Epivir-HBV; it is also recommended for the treatment of chronic hepatitis B. Stavudine is rapidly absorbed from the GI tract, reaching peak levels in 1 hour. Most of the drug is excreted unchanged in the urine, making it important to reduce dose and monitor patients carefully in the presence of renal dysfunction. It can be used for adults and children and is only available in an extended release form, allowing for once-a-day dosing. Tenofovir is a newer drug that affects the virus at a slightly different point in replication—a nucleotide that becomes a nucleoside. It is used only in combination with other antiretroviral agents. It is rapidly absorbed from the GI tract, reaching peak levels in 45 to 75 minutes. Its metabolism is not known, but it is excreted in the urine. Zidovudine was one of the first drugs found to be effective in the treatment of AIDS. It is rapidly absorbed from the GI tract, with peak levels occurring within 30 to 75 minutes. Zidovudine is metabolized in the liver and excreted in the urine, with a half-life of 1 hour.
children
Acyclovir is the drug of choice for children with herpes virus or CMV infections. Children are very sensitive to the effects of most antiviral drugs, and more severe reactions can be expected when these drugs are used in children. Many of these drugs do not have proven safety and efficacy in children, and extreme caution should be used. Most of the drugs for prevention and treatment of influenza virus infections can be used, in smaller doses, for children. The drugs used in the treatment of AIDS are frequently used in children, many now have recommended pediatric dosing but others may be used without the evidence of safety because of the seriousness of the disease. Dose should be lowered according to body weight, and children must be monitored very closely for adverse effects on kidneys, bone marrow, and liver.
adults
Adults need to know that these drugs are specific for the treatment of viral infections. The use of antibiotics to treat such infections can lead to the development of resistant strains and superinfections that can cause more problems. Patients with HIV infection who are taking antiviral medications need to be taught that these drugs do not cure the disease, that opportunistic infections can still occur, and that precautions to prevent transmission of the disease need to be taken. Pregnant women, for the most part, should not use these drugs unless the benefit clearly outweighs the potential risk to the fetus or neonate. Women of childbearing age should be advised to use barrier contraceptives if they take any of these drugs. Zidovudine has been safely used in pregnant women. The Centers for Disease Control and Prevention advises that women with HIV infection should not breastfeed to protect the neonate from the virus.
Therapeutic Actions and Indications
All three of these antiviral drugs are indicated for the treatment of adults with chronic hepatitis B who have evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases or histologically active disease. The drugs inhibit reverse transcriptase in the hepatitis B virus and cause DNA chain termination, leading to blocked viral replication and decreased viral load
Pharmacokinetics
Amantadine is slowly absorbed from the gastrointestinal (GI) tract, reaching peak levels in 4 hours. Excretion occurs unchanged through the urine, with a half-life of 15 hours. Oseltamivir is readily absorbed from the GI tract, extensively metabolized in the urine, and excreted in the urine with a half-life of 6 to 10 hours. Peramivir is given intravenously (IV) as a single dose, reaches peak levels at the end of the infusion, and has a half-life of 20 hours. Ribavirin, an inhaled drug when used for this purpose, is slowly absorbed through the respiratory tract. It is metabolized at the cellular level and is excreted in the feces and urine with a half-life of 9.5 hours. It is teratogenic and has a high-risk pregnancy rating. Rimantadine is absorbed from the GI tract with peak levels achieved in 6 hours. This drug is extensively metabolized in the liver and excreted in the urine. Zanamivir must be delivered by a Diskhaler device, which comes with every prescription of zanamivir. It is absorbed through the respiratory tract and excreted unchanged in the urine with a half-life of 2.5 to 5.1 hours.
The patient has lipodystrophy from the efavirenz.
An HIV-positive patient is taking efavirenz and tells the nurse that she now has fat on the upper back and neck but is losing fat in the extremities and face. What does the nurse determine is causing this patient's symptoms?
"It's a relief to know that this drug will stop me from spreading the infection."
An adult client is being treated for genital herpes with acyclovir. Which client statement indicates a need for further health education?
Shingles
An elderly female client is admitted to the medical floor with pustules on her body that travel along the nerve route in her legs and arms. The health care provider prescribes the drug acyclovir (Zovirax). What disease is this client demonstrating?
Facilitating exit from an infected host cell.
Antiretroviral drugs have different mechanisms of action. Which action below is not a common antiretroviral mechanism?
Pharmacokinetics
Delavirdine is rapidly absorbed from the GI tract, with peak levels occurring within 1 hour. Delavirdine is extensively metabolized by the cytochrome P-450 system in the liver and is excreted through the urine. Efavirenz is absorbed rapidly from the GI tract, reaching peak levels in 3 to 5 hours. Efavirenz is metabolized in the liver by the cytochrome P-450 system and is excreted in the urine and feces with a half-life of 52 to 76 hours. Etravirine is rapidly absorbed from the GI tract, reaching peak levels in 2.5 to 4 hours. Etravirine is metabolized in the liver by the cytochrome P-450 system and is excreted in feces and urine with a half-life of 21 to 61 hours. Nevirapine is recommended for use in adults and children older than 2 months. After rapid GI absorption with a peak effect occurring at 4 hours, nevirapine is metabolized by the cytochrome P-450 system in the liver. Excretion is through the urine with a half-life of 45 hours. Box 10.4 provides information about the emergence of resistance to certain reverse transcriptase inhibitor combinations. Rilpivirine (Edurant) is the newest drug in this class. It is rapidly absorbed from the GI tract, reaching peak levels in 4 to 5 hours. It is metabolized in the liver and excreted in feces and urine with a half-life of 50 hours.
Contraindications and Cautions
Drugs indicated for the treatment of herpes and CMV are highly toxic and should not be used during pregnancy or lactation to prevent adverse effects on the fetus or infant; use only if the benefits clearly outweigh the potential risks to the fetus or infant. Avoid use in patients with known allergies to antiviral agents to prevent serious hypersensitivity reactions; in patients with renal disease, which could interfere with excretion of the drug; or in patients with severe CNS disorders because the drug can affect the CNS, causing headache, neuropathy, paresthesias, confusion, and hallucinations. Cidofovir has been proven to be embryotoxic in animals. Use cidofovir with caution in children with AIDS because of the potential carcinogenic effects and effects on fertility. If no other treatment option is available, monitor the child very closely. For famciclovir, safety of use in children younger than 18 years of age has not been established. Foscarnet has been shown to affect bone development and growth. Foscarnet, as well as ganciclovir and valganciclovir, should not be used in children unless the benefit clearly outweighs the risk and the child is monitored very closely.
Clinically Significant Drug-Drug Interactions
Fosamprenavir should not be used in patients who are receiving ritonavir if they have used protease inhibitors to treat their disease because of a risk of serious adverse effects. If nelfinavir is combined with pimozide, rifampin, triazolam, or midazolam, severe toxic effects and life-threatening arrhythmias may occur. Such combinations should be avoided. Indinavir and nevirapine interact to cause severe toxicity. If these two drugs are given in combination, the doses should be adjusted and the patient should be monitored closely. Tipranavir, darunavir, and fosamprenavir have been shown to interact with many other drugs. Before administering these drugs, it is important to check a drug guide to assess for potential interactions with other drugs being given. Many potentially serious toxic effects can occur when ritonavir is taken with nonsedating antihistamines, sedatives/hypnotics, or antiarrhythmics because of the activity of ritonavir in the liver. Patients with hepatic dysfunction are at increased risk for serious effects when taking ritonavir and require a reduced dose and close monitoring.
Clinically Important Drug-Drug Interactions
Life-threatening effects can occur if delavirdine is combined with antiarrhythmics, clarithromycin, dapsone, antituberculosis drugs, calcium channel blockers, warfarin, quinidine, indinavir, saquinavir, or dapsone. These combinations should be avoided if at all possible. There is a risk of serious adverse effects if efavirenz is combined with midazolam, rifabutin, triazolam, or ergot derivatives; these combinations should be avoided. There may be a lack of effectiveness if nevirapine is combined with hormonal contraceptives or protease inhibitors. St. John's wort should not be used with these drugs; a decrease in antiviral effects can occur.
Contraindications and Cautions
Locally active antiviral drugs are not absorbed systemically, but caution must be used in patients with known allergic reactions to any topical drugs.
Anti-Hepatitis C Agents
Simeprevir (Olysio), sofosbuvir (Sovaldi), and daclatasvir (Daklinza) as well as a number of drugs only available in a combination product are approved for treating hepatitis C. Most liver transplants performed in the United States are due to progressive liver disease caused by hepatitis C virus (HCV) infection. After initial infection with HCV, most people develop chronic hepatitis C. Some will develop cirrhosis of the liver over many years. People can get HCV in a number of ways including exposure to blood that is infected with the virus, being born to a mother with HCV, sharing a needle, having sex with an infected person, sharing personal items such as a razor or toothbrush with someone who is infected with the virus, or from unsterilized tattoo or piercing tools.
Clinically Significant Drug-Drug Interactions
Tenofovir can cause large increases in the serum level of didanosine. If both of these drugs are given, tenofovir should be given 2 hours before or 1 hour after didanosine. Lamivudine and zalcitabine inhibit the effects of each other and should not be used together. Severe toxicity can occur if abacavir is combined with alcohol; this combination should be avoided. Didanosine can cause decreased effects of several antibiotics and antifungals; any antibiotic or antifungal started with didanosine should be evaluated carefully. There is an increased risk of potentially fatal pancreatitis if stavudine is combined with didanosine and increased risk of severe hepatomegaly if it is combined with other nonnucleoside antivirals; these combinations are often used, and the patient needs to be monitored very closely. There have been reports of severe drowsiness and lethargy if zidovudine is combined with cyclosporine; warn the patient to take appropriate safety precautions.
Adverse Effects
The adverse effects most commonly associated with these antivirals include nausea and vomiting, headache, depression, paresthesias, neuropathy, rash, and hair loss (Fig. 10.4). Rash, inflammation, and burning often occur at sites of IV injection and topical application. Renal dysfunction and renal failure also have been reported. Cidofovir is associated with severe renal toxicity and granulocytopenia. Ganciclovir and valganciclovir have been associated with bone marrow suppression. Foscarnet has been associated with seizures, especially in patients with electrolyte imbalance.
Nucleoside Reverse Transcriptase Inhibitors
The nucleoside reverse transcriptase inhibitors (NRTIs) (see Table 10.3) were the first class of drugs developed to treat HIV infections. These are drugs that compete with the naturally occurring nucleosides within a human cell that the virus would need to develop. The NRTIs include the following agents: abacavir (Ziagen), didanosine (Videx), emtricitabine (Emtriva), lamivudine (Epivir), stavudine (Zerit), tenofovir (Viread), and zidovudine (Retrovir).
the client's weight.
The nurse is caring for a 3-year-old with HIV. The nurse knows that, when administering antiviral drug therapy in young children with HIV, dosage calculations are typically based on:
The need to adhere rigidly to the prescribed drug schedule
The nurse is providing health education to a client who has recently been diagnosed with HIV and will soon begin antiretroviral therapy. What teaching point should the nurse prioritize?
"This medication will maintain the symptoms and cure my disease."
The nurse is reviewing the medication instruction for the client taking acyclovir. Which statement by the client would indicate the need for additional teaching?
"I should expect some nausea and vomiting."
The nurse is teaching a male client with HIV about his new antiviral drug regimen. Which client statement would suggest that the teaching plan was effective?
"Antivirals are the cure for viral infections."
The nursing instructor has been teaching about antivirals, actions and effects. The instructor realizes that a student needs further instruction when the student makes which statement?
Understanding medication therapy
The nursing instructor is discussing HIV/AIDS with the junior nursing class. The instructor tells the students that it is important to understand how HIV-1 integrates itself into a person's immune system and how immunity plays a role in the course of HIV disease. What else is this knowledge essential for?
Viruses are tiny and replicate inside cells.
The nursing student asks the instructor why it is more difficult to develop antiviral drugs than anti-infectives. The nursing instructor's best reply would be which?
Protease Inhibitors
The protease inhibitors block protease activity within the HIV virus. The protease inhibitors that are available for use include atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva), indinavir (Crixivan), lopinavir/ritonavir (Kaletra), nelfinavir (Viracept), ritonavir (Norvir), saquinavir (Invirase), and tipranavir (Aptivus).
Clinically Important Drug-Drug Interactions
The risk of nephrotoxicity increases when agents indicated for the treatment of herpes and CMV are used in combination with other nephrotoxic drugs, such as the aminoglycoside antibiotics. The risk of drowsiness also rises when these antiviral agents are taken with zidovudine, an antiretroviral agent.
Reverse transcriptase is used to turn the RNA of the virus into DNA.
The student nurse has learned that HIV is a retrovirus. Reverse transcriptase is the enzyme it contains. The student understands this enzyme when making which statement?
Pharmacokinetics
These are oral drugs that are readily absorbed from the GI tract, metabolized in the liver, and excreted in the urine. Half-lives range from 4 to 10 hours. These drugs must also be taken with peginterferon and ribavirin; daclatasvir is taken with sofosbuvir with or without ribavirin.
Contraindications and Cautions
These drugs are contraindicated with any known allergy to the drugs to prevent hypersensitivity reactions and with lactation and pregnancy because these drugs must be given with ribavirin which has known toxicity to the infant. Use caution when administering these drugs to patients with severe liver disease because of increased toxicity with these drugs. Safety has not been established for use in patients who also have hepatitis B and/or HIV infections because exacerbations of these diseases might occur. The financial burden of these drugs caused a lot of problems when they were introduced
Contraindications and Cautions
These drugs are contraindicated with any known allergy to the drugs to prevent hypersensitivity reactions and with lactation because of potential toxicity to the infant. Use caution when administering these drugs to patients with renal impairment and severe liver disease because of increased toxicity with these drugs and those who are pregnant because the effects on the fetus are not known.
Pharmacokinetics
These drugs are rapidly absorbed from the GI tract, with peak effects occurring in 0.5 to 1.5 hours (entecavir), 0.5 to 4 hours (adefovir), and 1 to 4 hours (telbivudine). Entecavir and adefovir are metabolized in the liver and excreted in the urine. Telbivudine is excreted unchanged in the urine. Adefovir has a half-life of 7.5 hours; entecavir has a half-life of 128 to 149 hours; and telbivudine has a half-life of 40 to 49 hours. It is not known whether any of these drugs crosses the placenta or enters breast milk.
Clinically Important Drug Interactions
Toxic effects or loss of therapeutic effect could occur if combined with other protease inhibitors or other antivirals. If combining any of these, check a drug reference to make sure dosage is adjusted as needed. St. John's wort should be avoided as it leads to loss of effectiveness.
Adverse Effects
Use of these antiviral agents is frequently associated with various adverse effects that may be related to possible effects on dopamine levels in the brain. These adverse effects include light-headedness, dizziness, and insomnia; nausea; orthostatic hypotension; and urinary retention. Peramivir has been associated with serious skin reactions, including Stevens-Johnson syndrome and erythema multiforme.
Inhibiting the activity of a virus specific encoded enzyme needed for viral replication
When describing the action of an integrase inhibitor, the nurse understands that this class of drug acts by which mechanism?
Take drug therapy as prescribed. Transmission can occur while on medication. Advise the patient about the adverse effect of granulocytopenia.
When focusing on the lifestyle of the patient with HIV, what are important teaching considerations? (Select all that apply.)
Take drug therapy as prescribed. Transmission can occur while on medication. Advise the patient about the adverse effect of granulocytopenia. page 143
When focusing on the lifestyle of the patient with HIV, what are important teaching considerations? (Select all that apply.)
RSV
When providing care to a client with a viral infection, the nurse knows that ribavirin (Virazole) for inhalation is used to treat which virus?
Antivirals do not eliminate existing viruses from tissues.
Which statement regarding antiviral medications is true?
Nucleoside reverse transcriptase inhibitors
Which was the first class of drugs developed to treat HIV infections?
viral RNA into viral DNA.
While providing care to a client with HIV infection, the nurse knows that reverse transcriptase is an enzyme that retroviruses use to affect RNA and DNA to turn:
a usually mild viral infection of the liver that can progress to chronic inflammation; most often seen hepatitis after blood transfusions
hepatitis C
Clinically Important Drug-Drug Interactions
here is an increased risk of renal toxicity if these drugs are taken with other nephrotoxic drugs. If such a combination is used, monitor the patient closely. An evaluation of risks versus benefits may be necessary if renal function begins to deteriorate.
DNA virus that accounts for many diseases, including shingles, cold sores, genital herpes, and encephalitis
herpes
drugs that prevent the growth of the viral DNA chain, preventing it from inserting into the host DNA, so viral replication cannot occur
nucleoside reverse transcriptase inhibitors
Nevirapine
oral-rapid onset-peak 4 hrs
Adefovir
oral-rapid-0.6-4 duration unknown
Raltegravir
oral-rapid-3 hrs
Simeprevir
oral-rapid-4 to 6 hrs duration unknown
Rimantadine
oral-slow onset-peak 6 hrs
Maraviroc
oral-slow-0.5-4 hrs
Fosamprenavir
oral-varies-1.5-4
b
8. Locally active antiviral agents can be used to treat a. HIV infection. b. warts. c. RSV. d. CMV systemic infections.
Immunocompromised
A 21-year-old woman diagnosed with HIV/AIDS 4 years ago now presents with cytomegalovirus (CMV). The nurse explains to the woman that this infection is caused by a common organism that normally does not cause infection in someone who is not what?
"Zidovudine slows the progression of the disease but does not cure it."
A 23-year-old client is prescribed zidovudine for treatment of human immunodeficiency virus (HIV). Which statement indicates that the client has understood the client teaching regarding the action of this medication?
retrovirus that attacks helper T cells, leading to a decrease in immune function and AIDS or ARC
human immunodeficiency virus (HIV)
Nelfinavir
A client with a diagnosis of HIV has impaired renal function due to a concurrent diagnosis of diabetic nephropathy. What medication is most appropriate to treat this client's HIV?
HIV
A client with active AIDS is infected with a retrovirus. This virus is better known as which?
a
7. Nursing interventions for the patient receiving antiviral drugs for the treatment of HIV probably would include a. monitoring renal and hepatic function periodically during therapy. b. administering the drugs just once a day to increase drug effectiveness. c. encouraging the patient to avoid eating if GI upset is severe. d. stopping the drugs and notifying the prescriber if severe rash occurs.
a,d,e,f
1. When explaining to a client the reasoning behind using combination therapy in the treatment of HIV, the nurse would include which of the following points? a. The virus can remain dormant within the T cell for a very long time; it can mutate while in the T cell. b. Adverse effects of many of the drugs used to treat this virus include immunosuppression, so the disease could become worse. c. The drugs are cheaper if used in combination. d. The virus slowly mutates with each generation. e. Attacking the virus at many points in its life cycle has been shown to be most effective. f. Research has shown that using only one type of drug that targeted only one point in the virus life cycle led to more mutations and more difficulty in controlling the disease.
c
3. Naturally occurring substances that are released in the body in response to viral invasion are called a. antibodies. b. immunoglobulins. c. interferons. d. interleukins.
b
6. HIV selectively enters which of the following cells? a. B clones b. Helper T cells c. Suppressor T cells d. Cytotoxic T cells
Pharmacokinetics
Atazanavir is rapidly absorbed from the GI tract and can be taken with food. After metabolism in the liver, it is excreted in the urine and feces with a half-life of 6.5 to 7.9 hours. It is not recommended for patients with severe hepatic impairment; for those with moderate hepatic impairment, the dose should be reduced. Darunavir is well absorbed from the GI tract, reaching peak levels in 2.5 to 4 hours. It is metabolized in the liver and excreted in the urine and feces with a half-life of 15 hours. It is not recommended for patients with severe hepatic impairment. Fosamprenavir is rapidly absorbed after oral administration, reaching peak levels in 1.5 to 4 hours. It is metabolized in the liver and excreted in the urine and feces. Indinavir is rapidly absorbed from the GI tract, reaching peak levels in 0.8 hour. Indinavir is metabolized in the liver by the cytochrome P-450 system. It is excreted in the urine with a half-life of 1.8 hours. Patients with hepatic or renal impairment are at risk for increased toxic effects, necessitating a reduction in dose. Lopinavir is used as a fixed combination drug that combines lopinavir and ritonavir. The ritonavir inhibits the metabolism of lopinavir, leading to increased lopinavir serum levels and effectiveness. (Box 10.5 reviews the dose calculation with lopinavir.) It is readily absorbed from the GI tract, reaching peak levels in 3 to 4 hours, and undergoes extensive hepatic metabolism by the cytochrome P-450 system. Lopinavir is excreted in urine and feces.
False
Locally active antiviral agents can be applied to open lesions.
Anti-Hepatitis B Agents
Hepatitis B is a serious to potentially fatal viral infection of the liver. The hepatitis B virus can be spread by blood or blood products, sexual contact, or contaminated needles or instruments. Healthcare workers are at especially high risk for contracting hepatitis B due to needle sticks. Hepatitis B has a higher mortality than other types of hepatitis. Individuals infected may also develop a chronic condition or become a carrier. In the past, hepatitis B was treated with interferons (see Chapter 17). In 2004 and 2005, adefovir (Hepsera) and entecavir (Baraclude) were the first drugs approved specifically for treating chronic hepatitis B. In 2006, another NRTI, telbivudine (Tyzeka), was found to be very effective in preventing viral replication in active hepatitis B patients
Agents for Herpes and Cytomegalovirus
Herpes viruses account for a broad range of conditions, including cold sores, encephalitis, shingles, and genital infections. Cytomegalovirus (CMV), although slightly different from the herpes virus, can affect the eye, respiratory tract, and liver and reacts to many of the same drugs. Antiviral drugs used to combat these infections include acyclovir (Sitavig, Zovirax), cidofovir (generic), famciclovir (generic), foscarnet (Foscavir), ganciclovir (Cytovene), valacyclovir (Valtrex), and valganciclovir (Valcyte)
Therapeutic Actions and Indications
NRTIs compete with the naturally occurring nucleosides within the cell that the virus would use to build the DNA chain. These nucleosides, however, lack a substance needed to extend the DNA chain. As a result, the DNA chain cannot lengthen and cannot insert itself into the host DNA. Thus, the virus cannot reproduce. They are used as part of combination therapy for the treatment of HIV infection.
Pharmacokinetics
Most of the agents for herpes and CMV are readily absorbed and excreted through the kidney. Although cidofovir has been proven to be embryotoxic in animals, no adequate studies have been completed for the other agents. Acyclovir, which can be given orally or buccally, parenterally or applied topically, reaches peak levels within 1 hour and has a half-life of 2.5 to 5 hours. It is excreted unchanged in the urine. It crosses into breast milk, which exposes the neonate to high levels of the drug. Cidofovir, which is given by IV infusion, reaches peak levels at the end of the infusion and in studies was cleared from the system within 15 minutes after the infusion. It is excreted unchanged in the urine and must be given with probenecid to decrease nephrotoxicity by slowing the renal clearance of the drug. The dose must be decreased according to renal function and creatinine clearance; renal function tests must be done before each dose and the dose planned accordingly. Famciclovir, an oral drug, is well absorbed from the GI tract, reaching peak levels in 2 to 3 hours. Famciclovir is metabolized in the liver and excreted in the urine and feces. It has a half-life of 2 hours and is known to cross the placenta. Foscarnet is available in IV form only. It reaches peak levels at the end of the infusion and has a half-life of 4 hours. About 90% of foscarnet is excreted unchanged in the urine, making it highly toxic to the kidneys. Use caution and at reduced dose in patients with renal impairment. Ganciclovir is available in IV and oral forms. It has a slow onset and reaches peak levels at 1 hour if given IV and 2 to 4 hours if given orally. This drug is primarily excreted unchanged in the feces with some urinary excretion, with a half-life of 2 to 4 hours. Valacyclovir is a prodrug, an agent that is converted by the body into a drug. Valacyclovir is rapidly absorbed from the GI tract and metabolized in the liver to acyclovir. Excretion occurs through the urine, so caution should be used in patients with renal impairment. Valganciclovir is also an oral prodrug (i.e., it is immediately converted to ganciclovir once it is in the body). It is rapidly absorbed and reaches peak levels in 3 hours. It is primarily excreted unchanged in the feces with some urinary excretion, with a half-life of 2.5 to 3 hours.
Contraindications and Cautions
Of the nucleosides, zidovudine is the only agent that has been proven to be safe when used during pregnancy. Of the other agents, there have been no adequate studies in pregnancy, so use should be limited to situations in which the benefits clearly outweigh any risks. Women infected with HIV are urged not to breastfeed. Tenofovir, zidovudine, and emtricitabine should be used with caution in the presence of hepatic dysfunction or severe renal impairment because of their effects on the liver and kidneys. Zidovudine should also be used with caution with any bone marrow suppression because it could aggravate the suppression.
Clinically Important Drug-Drug Interactions
Patients who receive amantadine or rimantadine may experience increased atropine-like effects if either of these drugs is given with an anticholinergic drug. Patients taking rimantadine may also experience a loss of effectiveness of aspirin and acetaminophen if these are also being used. Ribavirin levels may be reduced if it is given with antacids. The use of ribavirin should be avoided if the patient is also receiving a nucleoside reverse transcriptase inhibitor (NRTI). This combination should be avoided. Live attenuated nasal influenza vaccine should not be used within 2 weeks before or 48 hours after peramivir to avoid adverse reactions.
Therapeutic Effects and Indications
The new drugs approved for treating this disease are protease inhibitors. They can be used in combination with ribavirin or ribavirin and peginterferon or other hepatitis C drugs to treat chronic hepatitis C in patients with compromised liver function.
Adverse Effects
Serious-to-fatal hypersensitivity reactions have occurred with abacavir, and it must be stopped immediately at any sign of a hypersensitivity reaction (fever, chills, rash, fatigue, GI upset, flu-like symptoms). Serious pancreatitis, hepatomegaly, and neurological problems have been reported with didanosine, which is why its use is limited to the treatment of advanced infections. Emtricitabine has been associated with severe and even fatal hepatomegaly with steatosis. Severe hepatomegaly with steatosis has been reported with tenofovir, so it must be used with extreme caution in any patient with hepatic impairment or lactic acidosis. Patients also need to be alerted that the drug may cause changes in body fat distribution, with loss of fat from arms, legs, and face and deposition of fat on the trunk, neck, and breasts. Severe bone marrow suppression has occurred with zidovudine.
Therapeutic Actions and Indications
The nonnucleoside reverse transcriptase inhibitors bind directly to HIV reverse transcriptase, blocking both RNA- and DNA-dependent DNA polymerase activities. They prevent the transfer of information that would allow the virus to carry on the formation of viral DNA. As a result, the virus is unable to take over the cell and reproduce. These antiviral agents are indicated for the treatment of patients with documented AIDS or ARC who have decreased numbers of helper T cells and evidence of increased opportunistic infections in combination with other antiviral drugs
Nonnucleoside Reverse Transcriptase Inhibitors
The nonnucleoside reverse transcriptase inhibitors have direct effects on the HIV virus activities within the cell. The nonnucleoside reverse transcriptase inhibitors available include delavirdine (Rescriptor), efavirenz (Sustiva), etravirine (Intelence), nevirapine (Viramune), and rilpivirine (Edurant).
Ribavirin
The nurse is caring for a child with respiratory syncytial virus (RSV). Which drug should the nurse expect the pediatrician to order?
Ribavirin
The nurse knows that pregnant caregivers should not inhale which medication while administering the medication to clients?
A direct way of measuring drug resistance and how much of a drug is necessary to stop HIV from replicating
What would the nurse identify as the primary purpose of performing phenotype testing for a patient infected with HIV?
Regularly rotate the subcutaneous injection sites that are used.
When administering the fusion protein inhibitor enfuvirtide, the nurse should include which technique to assure the medication's continued effectiveness?
his body has not produced antibodies to the AIDS virus
When assisting the patient to interpret a negative HIV test result, the nurse informs the patient that the results mean
particle of DNA or RNA surrounded by a protein coat that survives by invading a cell to alter its functioning
virus
Agents for HIV and AIDS
Human immunodeficiency virus (HIV) attacks the helper T cells (CD4 [cluster of differentiation 4] cells) within the immune system. This virus (an RNA strand) reacts with a receptor site on the CD4 cell, fuses with the membrane, and then enters the helper T cell, where it uses reverse transcriptase to copy the RNA and produce a double-stranded viral DNA. The virus uses various nucleosides found in the cell to synthesize this DNA strand. The DNA enters the host cell nucleus and slides into the chromosomal DNA to change the cell's processes to ones that produce new viruses. This changes the cell into a virus-producing cell. As a result, the cell loses its ability to perform normal immune functions. The newly produced viruses mature through the action of various proteases and then are released from the cell. Upon release, they find a new cell to invade, and the process begins again. Eventually, as more and more viruses are released and invade more CD4 cells, the immune system loses an important mechanism responsible for propelling the immune reaction into full force when the body is invaded. Loss of helper T cell function causes acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC), diseases that are characterized by the emergence of a variety of opportunistic infections and cancers that occur when the immune system is depressed and unable to function properly. The HIV mutates over time, presenting a slightly different configuration with each new generation. Treatment of AIDS and ARC has been difficult for two reasons: (1) the length of time the virus can remain dormant within the T cells (i.e., months to years) and (2) the adverse effects of many potent drugs, which may include further depression of the immune system. A combination of at least three different antiviral drugs is used to attack the virus at various points in its life cycle to achieve maximum effectiveness with the least amount of toxicity. The types of antiviral agents that are used to treat HIV infections are the nonnucleoside reverse transcriptase inhibitors, the nucleoside reverse transcriptase inhibitors (NRTIs), the protease inhibitors, and three newer classes of drugs—the fusion inhibitors, CCR5 (C-C chemokine receptor type 5) coreceptor antagonists, and integrase inhibitors (Table 10.3). Collectively, these drugs are known as antiretroviral agents. The HIV virus poses a serious health risk. The patient and the family of the patient diagnosed with HIV infection will need tremendous support and teaching to cope with the disease and its treatment. See Box 10.3 for public education information regarding AIDS.
Patients with renal impairment
In which of the following patients is the use of cidofovir contraindicated?
Docosanol ganciclovir imiquimod penciclovir trifluridine
LOCALLY ACTIVE ANTIVIRAL AGENTS
Contraindications and Cautions
Of the protease inhibitors listed, saquinavir is the only agent that has not been shown to be teratogenic; however, its use during pregnancy should be limited. Saquinavir crosses into breast milk, and women are advised not to breastfeed while taking this drug. For the other agents, there are no adequate studies in pregnancy, so use should be limited to situations in which the benefits clearly outweigh any risks. It is suggested that women should not breastfeed if they are infected with HIV. Patients with mild to moderate hepatic dysfunction should receive a lower dose of fosamprenavir, and patients with severe hepatic dysfunction should not receive this drug or darunavir because of their toxic effects on the liver. Patients receiving tipranavir must have liver function monitored regularly because of the possibility of potentially fatal liver dysfunction. Saquinavir must also be used cautiously in the presence of hepatic dysfunction. Patients receiving darunavir may also be at risk for developing diabetes mellitus or hyperglycemia and may require dosage adjustments if being treated with antidiabetic drugs. Darunavir is also associated with mild to severe dermatologic reactions including Stevens-Johnson syndrome, and the drug should be stopped if a severe reaction develops. The safety of indinavir for use in children younger than 12 years has not been established. Darunavir should not be used in children younger than 3 years of age because of the potential for toxic effects.
Older Adults
Older patients may be more susceptible to the adverse effects associated with these drugs; they should be monitored closely. Patients with hepatic dysfunction are at increased risk for worsening hepatic problems and toxic effects of those drugs that are metabolized in the liver. Drugs that are excreted unchanged in the urine can be especially toxic to patients who have renal dysfunction. If hepatic or renal dysfunction is expected (extreme age, alcohol abuse, use of other hepatotoxic or nephrotoxic drugs), the dose may need to be lowered and the patient should be monitored more frequently.