Categories
Chemotherapeutic Agents Nursing Pharmacology

Antiviral Agents

Antiviral Agents

Viruses That Respond to Antiviral Therapy

  • Influenza A and some respiratory viruses
  • Herpes viruses
  • Cytomegalovirus (CMV)
  • Human immunodeficiency virus (HIV) that causes acquired immune deficiency syndrome (AIDS)
  • Some viruses that cause warts and certain eye infections

Antivirals Across the Lifespan

Antivirals Across the Lifespan
Antivirals Across the Lifespan

Characteristics of Common Viruses

  • Viral replication
    • A virus cannot replicate on its own
      • It must attach to and enter a host cell
      • It then uses the host cell’s energy to synthesize protein, DNA, and RNA
  • Viruses are difficult to kill because they live inside our cells
    • Any drug that kills a virus may also kill our cells

Stages of Virus Replication

Stages of Virus Replication
Stages of Virus Replication

Characteristics of Antiviral Drugs

  • Able to enter the cells infected with virus
  • Interfere with viral nucleic acid synthesis and/or regulation
  • Some agents interfere with the ability of the virus to bind to cells
  • Some agents stimulate the body’s immune system

Common Respiratory Viruses

  • Influenza A
  • Influenza B
  • Respiratory syncytial virus

Signs & Symptoms of Respiratory Viruses

  • Cough
  • Fever
  • Inflammation of the nasal mucosa
  • Inflammation of the mucosa of the respiratory tract

Signs and Symptoms of Herpes Virus

  • Painful vesicles that often occur in clusters on skin, cornea, or mucous membranes
  • Usual course of primary disease is 2 weeks
  • Duration of recurrences varies

Signs and Symptoms of CMV

  • May be asymptomatic
  • Fatigue
  • Nausea
  • Jaundice
  • If contracted during pregnancy, can result in stillbirth, brain damage, or birth defects

Signs and Symptoms of HIV/AIDS

  • Attach helper T cells
  • Acute infection: fever, rash, and myalgia
  • Asymptomatic infection: follows acute infection; duration varies
  • Persistent generalized lymphadenopathy: adenopathy persists more than 3 months
  • Constitutional symptoms: fever lasting more than a month, involuntary weight loss, chronic fatigue
  • Neurologic disease: dementia
  • Secondary infections: pneumocystis carinii and disseminated herpes simplex

Influenza A & Respiratory Viruses

  • Action: prevent shedding of the viral protein coat
  • Pharmacokinetics: administered orally and excreted unchanged in the urine
  • Contraindications: allergy, pregnancy, and lactation
  • Adverse reactions: dizziness, insomnia, nausea, orthostatic hypotension
  • Drug-to-drug interactions: anticholinergic agents

Herpes & Cytomegalovirus

  • Action: inhibit viral DNA replication by competing with viral substrates to form shorter, noneffective DNA chains
  • Pharmacokinetics: administered orally, IV, or topically; excreted unchanged in the urine
  • Contraindications: pregnancy and lactation
  • Adverse reactions: nausea, vomiting, headache, rash, and hair loss
  • Drug-to drug-interactions: nephrotoxic drugs and zidovudine

Drugs Used to Treat HIV/AIDS

  • Reverse transcriptase inhibitors
  • Protease inhibitors
  • Nucleosides
  • Fusion inhibitors

Reverse Transcriptase Inhibitors

  • Action: bind directly to HIV reverse transcriptase, blocking both RNA- and DNA-dependent DNA polymerase activities
  • Pharmacokinetics: given orally, metabolized in the liver, and excreted in the urine
  • Contraindications: pregnancy and lactation
  • Adverse reactions: headache, nausea, vomiting, rash, chills, fever, and diarrhea

Protease Inhibitors

  • Action: block protease activity within the HIV virus
  • Pharmacokinetics: agents are teratogenic except for saquinavir
  • Contraindications: pregnancy and lactation

Nucleosides

  • Action: interfere with HIV replication by inhibiting cell protein synthesis
  • Pharmacokinetics: given orally or IV, metabolized in the liver, and excreted in the urine
  • Adverse reactions: HA, insomnia, dizziness, nausea, diarrhea, fever, and rash

Fusion Inhibitors

  • Action: prevent the fusion of the virus with the human cellular membrane
  • Pharmacokinetics: given sub-q, metabolized in the liver, recycled in the tissues, and not excreted
  • Contraindication: no true contraindication
  • Adverse reactions: HA, dizziness, myalgia, nausea, vomiting, and diarrhea
  • Drug-to-drug interactions: pimozide, rifampin, triazolam, midazolam, and oral contraceptives

Locally Active Antiviral Agents

  • Action: act on viruses by interfering with normal viral replication and metabolic processes
  • Pharmacokinetics: not absorbed systemically
  • Contraindication: allergy to the drug
  • Adverse reactions: local burning, stinging, and discomfort

Prototype of Respiratory Antiviral Agents

Rimantadine
Rimantadine

Prototype of Herpes and Cytomegalovirus Agents

Acyclovir
Acyclovir

Prototype of HIV/AIDS Antiviral Agents

Nevirapine
Nevirapine

 

Zidovidine
Zidovidine

Nursing Considerations for Respiratory Antiviral Therapy

  • Assessment (history and physical exam)
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations for Herpes Virus and Cytomegalovirus

  • Assessment (history and physical exam)
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations for HIV/AIDS Antiviral Therapy

  • Assessment (history and physical exam)
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations for Locally Active Antiviral Agents

  • Assessment (history and physical exam)
  • Nursing diagnosis
  • Implementation
  • Evaluation
Categories
Medical Surgical

Acquired Immunodeficiency Syndrome (HIV infection)

Acquired immunodeficiency syndrome (AIDS) is defined as the most severe form of a continuum of illnesses associated with human immunodeficiency virus (HIV) infection. HIV belongs to a group of viruses known as retroviruses. These viruses carry their genetic material in the form of ribonucleic acid (RNA) rather than deoxyribonucleic acid (DNA). Infection with HIV occurs when it enters the host CD4 (T) cell and cause this cell to replicate viral RNA and viral proteins, which in turn invade other CD4 cells.

The stage of HIV disease is based on clinical history, physical examination, laboratory evidence of immune dysfunction, signs and symptoms, and infections and malignancies. The stage of primary infection is acute and spans the time from infection to antibody development. Four categories of infected states have been denoted:

  • Primary Infection (A dramatic drop in CD4 T-cell counts from normal level between 500 and 1500 cells/mm3)
  • HIV asymptomatic (more than 500 CD4+ T lymphocytes/mm3)
  • HIV symptomatic (200-499 CD4+ T-lymphocytes/mm3)
  • AIDS (fewer than 200 CD4+ T lymphocytes/mm3)

Risk Factors

HIV is transmitted through bodily fluids by high-risk behaviors such as heterosexual intercourse with an HIV-infected partner, injection drug use, and male homosexual relations.Also at risk are people who received transfusions of blood or blood products contaminated with HIV, children born to mothers with HIV infection, breast-fed infants of HIV-infected mothers, and health care workers exposed to needle-stick injury associated with an infected patient.


Clinical Manifestations:

Symptoms are widespread and may affect any organ system. Manifestations range from mild abnormalities in immune response without overt signs and symptoms to profound immuno-suppression, life-threatening infection, malignancy, and the direct effect of HIV on body tissues.

Respiratory

  • Shortness of breath, dyspnea, cough, chest pain, and fever are associated with opportunistic infections, including Pneumocystis jiroveci pneumonia (PCP), the most common infection, and the immune reconstitution syndromes, such as Mycobacterium avium complex(MAC)/Mycobacterium avium intracellulare (MAI), which is a leading bacterial infection in AIDS patients. Legionella and CMV are other opportunistic organisms.
  • HIV-associated tuberculosis occurs early in the course of HIV infection, often preceding a diagnosis of AIDS.

Gastrointestinal

  • Loss of appetite
  • nausea and vomiting
  • Oral and esophageal candidiasis (white patches, painful swallowing, retrosternal pain, and possibly oral lesions)
  • Chronic diarrhea, possibly with devastating effects (eg, weight loss, fluid and electrolyte imbalances, perianal skin excoriation, weakness, and inability to perform activities of daily living)

Wasting Syndrome (Cachexia)

  • Multifactorial protein-energy malnutrition
  • Profound involuntary weight loss exceeding 10% of baseline body weight
  • Chronic diarrhea, chronic weakness, and documented intermittent or constant fever with no concurrent illness
  • Anorexia, diarrhea, gastrointestinal malabsorption, lack of nutrition, and for some patients a hyper metabolic state.

Neurologic

Neurologic complications involve central, peripheral, and autonomic functions

  • HIV encephalopathy (AIDS dementia complex [ADC]) occurs in two thirds of patients with AIDS. Symptoms include memory deficits, headache, lack of concentration, progressive confusion, psychomotor slowing, apathy and ataxia, and in later stages global cognitive impairments, delayed verbal responses, spastic paraparesis, hyperreflexia, psychosis, seizures, incontinence, mutism, and death.
  • HIV – related peripheral neuropathy is thought to be a demyelinating disorder; it is associated with pain and numbness in the extremities, weakness, diminished deep tendon reflexes, orthostatic hypotension, and impotence.
  • Cryptococcus neoformans, a fungal infection (fever, stiff neck, nausea and vomiting, seizures)
  • Central and peripheral neuropathies, including vascular myelopathy (spastic paraparesis, ataxia, and incontinence)
  • Progressive multifocal leukoencephalopathy (PML), a central nervous system demyelinating disorder, can occur.
  • Other neurologic disorders include Toxoplasma gondii, CMV, and Mycobacterium tuberculosis infection, with symptoms ranging from confusion to blindness, aphasia, paresis, and death.

Integumentary

  • Kaposi’s sarcoma (KS), herpes simplex and herpes zoster viruses, and various forms of dermatitis associated with painful vesicles.
  • Folliculitis, associated with dry flaking skin or atopic dermatitis (eczema or psoriasis)

Reproductive (female)

  • Persistent recurrent vaginal candidiasis may be the first sign of HIV infection
  • Ulcerative sexually transmitted diseases, such as chancroid, syphilis, and herpes, are more severe in women with HIV.
  • Veneral warts and cervical cancer/cervical intraepithelial neoplasia (CIN) may be noted.
  • Women with HIV have a higher incidince of pelvic inflammatory disease (PID) and menstrual abnormalities (amenorrhea or bleeding between periods).

Hematologic / Lymphatic

  • B-cell lymphomas, such as non-Hodgkin’s lymphoma, are the second most common AIDS-related cancer (the first is KS). These lymphomas usually  differ from those in the general population because they develop outside the lymph nodes (mostly in the brain, bone marrow, and GI tract), grow aggressively, affect multiple organs, and exhibit resistance to treatment, which may be complicated by severe hematologic toxicity.

Other: Chronic Illness and Cancers

Early diagnosis and treatment of opportunistic diseases and antiviral therapy have brought HIV infection into the chronic illness category. Additional clinical manifestations follow:

  • Fatigue, headache, profuse night sweats, unexplained weight loss, dry cough, shortness of breath, extreme weakness, diarrhea, decreased endurance, edema, blindness, swallowing difficulties, and possible neurologic involvement resulting in dementia, hemiplegia, spastic paraparesis, painful neuropathies, proximal and distal muscle weakness, and persistent lymphadenopathy.
  • Higher than usual incidence of cancer, including KS, B-cell lymphomas and carcinomas of cervix, skin, stomach, pancreas, rectum, and bladder.
  • Depressive symptoms from multiple causes, including preexisting mental illness, neuropsychiatric disturbances, and psychosocial factors
  • Irrational guilt, loss of self-esteem, helplessness,worthlessness, and suicidal ideation.

Assessment and Diagnostic Methods

Confirmation of HIV antibodies is done using enzyme immunoassay(EIA; formerly enzyme-linked immunosorbent assay [ELISA]), Western blot assay, and viral load tests such as target amplification methods.

Medical Management

Currently there is no cure for HIV or AIDS, although researchers continue to work on developing a vaccine. Treatment decisions for an individual patient are based on three factors: HIV RNA (viral load), CD4 T-cell counts, and the clinical condition of the patient (severity of symptoms and patient’s commitment to participate in lifelong therapy). The goals of treatment are maximal  and durable suppression of viral load, restoration and/or preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. To determine and evaluate the treatment plan, viral load testing is recommended at diagnosis and then 3 to 4 months thereafter in the untreated person. CD4+ T-cell counts should be measured at diagnosis and generally every 3 to 6 months thereafter.

Combination therapy is defined as a regimen containing at least two antiretroviral agents; highly active antiretroviral therapy (HAART) includes at least one nucleoside reverse transcriptase inhibitor plus various other drug combination. As new medications are developed, the number of combinations continues to increase. High cost of medications, difficulties with adherence to the regimen, drug resistance, and drug toxicities present problems in drug therapy. Intermittent therapy is under investigation as an alternative regimen.

Pharmacologic Therapy

Antiretroviral Therapy (ART)

  • Nucleoside/nucleotide reverse transcriptase inhibitors (NRTI)
  • Non-nucleoside reverse transcriptase inhibitors (NNRTI)
  • Protease inhibitors (PI)
  • Fusion inhibitors (FI)

Drug Resistance Testing

Helps determine which antiretroviral agents to eliminate from the antiretroviral regimen (rather than which agents should be used)

Treatment Interruption and Reinstitution

Depending on the patient and CD4 cell count, ART may be temporarily discontinued when immune competence recurs and stabilizes (eg, sustained CD4 count between 500 and 800 cells/mm3). Then, when CD4 count fall between 350 and 400 cells/mm3, ART should restart.

Medications for HIV-related Infections

  • PCP: trimethoprim-sulfamethoxazole (TMP-SMZ) and antibacterial agents, such as dapsone, alternatively, pentamidine, an antiprotozoal agent
  • MAC: treatment for MAC infections involves use of either clarithromycin (Biaxin) or azithromycin (Zithromax). The combinaiton of azithromycun with rifabutin (Mycobutin) is more effective but costly, with more adverse effects and interactions.
  • Cryptococcal meningitis:  intravenous amphotericin B with or without antifungal agents, such as fluconazole (Diflucan) or flucytosine (Ancobon).
  • CMV retinitis: ganciclovir, foscarnet, or cidofovir
  • Encephalitis: pyrimethamine (Daraprim) and sulfadiazine or clindamycin (Cleocin)
  • Candidiasis: clotrimazole (Mycelex), ketoconazole, or fluconazole

Anticancer Agents

  • KS: alpha-interferon, surgical excision of lesions, liquid nitrogen to lesions, vinblastine injected into intraoral lesions, interferon;  chemotherapy with doxorubicin (Adriamycin), bleomycin, and vincristine (ABV); radiation
  • Lymphomas: limited successful treatment; chemotherapy and radiation therapy may be used

Immunomodulators

  • Alpha-interferon
  • Other substances under evaluation (interleukin-2, interleukin-12, and other cytokines and lymphokines)

Antidepressants

Psychotherapy is integrated with pharmacology (imipramine [Tofranil]), desipramine [Norpramin], fluoxetine [Prozac], methylphenidate [Ritalin]; electroconvulsive therapy if depression is severe).

Antidiarrheal Agents and Appetite Stimulants

Octreotide acetate (Sandostatin) is given to treat diarrhea and megestrol acetate (Megace) or dronabinol (Marinol) to stimulate appetite.

Reference:

Brunner & Suddath’s

Textbook of Medical-Surgical Nursing 11th edition

Lippincott Williams & Wilkins pp.1-7