Antiviral, TB, and Antifungal Drugs

Topic 20: Antiviral, Antitubercular, and Antifungal Drugs

• Focuses on pharmacology, specifically the mechanisms, uses, and nursing considerations for drugs in these categories.

Objectives

• Differentiate between non-HIV antivirals and HIV antiretrovirals.
• Explain the mechanism of action, indications, contraindications, cautions, administration, and adverse/toxic effects of both non-HIV and HIV antiviral drugs.
• List first-line and second-line drugs used for TB treatment.
• Describe the pharmacology of antitubercular drugs, including mechanisms, dosages, side effects, routes of administration, dosing, cautions, contraindications, and interactions.
• Identify various antifungal drugs and their uses.
• Discuss the mechanisms, uses, contraindications, administration, side effects, and interactions for antifungal medications.

General Principles of Virology

• Viruses cannot replicate without a host.
• Viruses attach and enter a host cell, then utilize the host's energy to synthesize protein, DNA, and RNA.

Viral Illnesses

• Includes Smallpox (poxviruses), sore throat and conjunctivitis (adenoviruses), warts (papovaviruses), influenza (orthomyxoviruses), respiratory infections (coronaviruses, rhinoviruses).
• Also includes Gastroenteritis (rotaviruses, Norwalk-like viruses), HIV/AIDS (retroviruses), herpes (herpesviruses), and hepatitis (hepadnaviruses).

Antiviral Drugs

• Destroy virions or inhibit virus replication.
• Immunoglobulins are concentrated antibodies that attack and kill viruses.
• Current antiviral therapy controls viruses like cytomegalovirus (CMV), hepatitis viruses, herpesviruses, HIV, influenza, and respiratory syncytial virus (RSV).

Key Characteristics of Antiviral Drugs

• Penetrate infected cells.
• Disrupt viral nucleic acid synthesis or regulation.
• Prevent fusion and/or stimulate the body’s immune system.

Opportunistic Infections

• Occur in immunocompromised patients and can be caused by viruses, fungi, bacteria, or protozoa.
• Require long-term prophylaxis and anti-infective drug therapy.

Classes of Viruses and Antiviral Drugs

• Minimum of 6 DNA and 14 RNA virus classes known to infect humans.
• Antiviral drugs treat infections other than HIV.
• Antiretroviral drugs treat HIV, which causes AIDS.
• Few viruses are controlled by current drugs; this group includes CMV, hepatitis, herpes, HIV, influenza, and RSV.

Hepatitis C

• Leading cause of chronic liver disease and most common reason for liver transplantation.
• Ribavirin (Virazole®) is administered orally for treatment.

Non-HIV Antiviral Drugs

• Block the polymerase enzyme to prevent the synthesis of new viral genomes.
• Commonly treat influenza viruses, HSV, VZV, CMV, and Hepatitis A, B, and C.

Adverse Effects and Interactions of non-HIV Antiviral Drugs

• Adverse effects vary by drug; healthy cells are also killed, resulting in toxicities.
• Interactions with other medications are a concern.

Specific Non-HIV Antiviral Drugs

• Amantadine hydrochloride (Dom-Amantidine®) used for influenza A, but recent guidelines discourage its use.
• CNS effects include insomnia, nervousness, and light-headedness while gastrointestinal effects include anorexia and nausea.
• Acyclovir (Zovirax®) is a synthetic nucleoside analogue that suppresses replication of HSV 1, HSV 2, and VZV.
• Acyclovir (Zovirax®) comes in oral, topical, and parenteral forms and is the top choice for initial and recurrent episodes.
• Ganciclovir hydrochloride (Cytovene®, Valcyte®) is a synthetic nucleoside analogue of guanosine used to treat CMV infections and CMV retinitis.
• Valacyclovir hydrochloride and famciclovir are oral alternatives for less severe infections.

Neuraminidase Inhibitors

• Oseltamivir phosphate (Tamiflu) and zanamivir (Relenza) are active against influenza types A and B.
• Oseltamivir phosphate is oral and causes nausea/vomiting.
• Zanamivir is inhaled, causes diarrhea, nausea and sinusitis.
• Treatment should start within 2 days of influenza symptoms.

Ribavirin

• Synthetic nucleoside analogue given orally or nasally.
• Inhalation form (Virazole) treats respiratory syncytial virus infections in hospitalized infants.

HIV and AIDS

• Worldwide, 36.9 million are infected with HIV, a retrovirus transmitted via sexual activity, IV drug use, or perinatally.
• Risk of transmission to healthcare workers from a needle-stick injury is approximately 0.3%.
• Hand hygiene and standard precautions are important

Stages of HIV Infection

• Stage 1: Asymptomatic infection.
• Stage 2: Early, general symptoms.
• Stage 3: Moderate symptoms.
• Stage 4: Severe symptoms leading to AIDS and potentially death; these stages are part of the World Health Organization model.

Opportunistic Infections

• Caused by organisms that do not harm immunocompetent people.
• Commonly affects cancer patients, transplant recipients, and individuals with AIDS.
• Can be caused by viruses, bacteria, fungi, or protozoans and require long-term anti-infective therapy.

Antiretroviral Drugs: Enfuvirtide (Fuzeon®)

• Highly active antiretroviral therapy (HAART).
• Reverse transcriptase inhibitors block reverse transcriptase.
• Protease inhibitors stops the protease retroviral enzyme to prevent viral replication.
• Fusion inhibitors prevent virus fusion, and entry inhibitors like CCR5 co-receptor antagonists target integrase.

Adverse Effects of Antiretroviral Drugs

• Numerous and vary by medication.
• Drug therapy adjustments are necessary due to unwanted effects.
• Finding a tolerable regimen that effectively controls the infection is the goal.
• Medication regimens change during the course of the illness

Nursing Implications for Viral Infections

• Before initiating therapy, assess underlying disease, medical history, and allergies.
• Assess baseline vital signs and nutritional status.
• Watch for contraindications, conditions for cautious use, and potential drug interactions.
• Key to instruct patients to take medications exactly as prescribed for the full treatment course.
• Start antiviral medication at the earliest sign of a recurrent episode.
• Watch for a decreased incidence of flulike symptoms, a lessening in the frequency of herpetic flare-ups, or crusting of herpetic lesions when looking at therapeutic effects.

Antitubercular Drugs

• Tuberculosis (TB) is caused by Mycobacterium tuberculosis.
• Antitubercular drugs treat all forms of Mycobacterium.
• TB is characterized by granulomas in the lungs, composed of inflammatory cells within clear boundaries and a caseated center.

Mycobacterium Infections

• Common infection sites include the lungs (primary site), brain (cerebral cortex), bone (growing end), liver, kidney, and genitourinary tract.
• It can infect virtually every tissue and organ in the body.

Multidrug-Resistant Tuberculosis (MDR-TB)

• MDR-TB is resistant to both isoniazid (isonicotine hydrazine [INH]) and rifampin.
• Close contacts of patients with MDR-TB require 6-9 months of treatment.
• Isoniazid is a primary and widely used drug.
• Therapy involves an initial intensive two-drug phase and a continuation phase with three or more medications.

Antitubercular Drugs: First and Second Line

• First-line drugs: isoniazid, ethambutol hydrochloride, pyrazinamide, and rifampin.
• Second-line drugs: amikacin sulphate, levofloxacin hemihydrate, and moxifloxacin hydrochloride.

Tuberculosis-Related Injections

• Purified protein derivative (PPD) (Mantoux®) is a diagnostic injection with 5 tuberculin units to detect TB exposure.
• A positive result is indicated by induration at the injection site.
• Bacille Calmette-Guérin (BCG) is a vaccine from an inactivated strain of Mycobacterium bovis.
• BCG is used in areas with high TB prevalence for young children; it does not prevent infection but reduces active TB by 60-80%.
• BCG vaccine may cause false positives results on tuberculin skin tests.

Antitubercular Drug Therapy Considerations

• Major effects include reduced cough, reducing infectiousness.
• Effects typically occur within 2 weeks if the TB strain is drug sensitive.
• Most cases of TB are curable.
• Successful treatment usually requires several antibiotics for at least 6 months, up to 12 months in total.
• Perform drug-susceptibility testing on the first isolated Mycobacterium to prevent MDR-TB.
• Start a regimen with multiple antitubercular drugs(even before susceptibility results arrive).
• Adjust drug regimen when susceptibility test results are available.
• Problems stem from patient nonadherence and drug-resistant organisms.

Mechanisms of Action of Antitubercular Drugs

• Act by disrupting protein wall (streptomycin, rifampin, rifabutin, rifapentine) or cell wall (isoniazid) synthesis
• Can also disrupt the formation of the tuberculous cell wall by blocking arabinosyl transferases (ethambutol, isoniazid, pyrazinamide).

Antitubercular Therapy: Factors of Effectiveness

• Effectiveness relies on the type of infection, adequate dosing, sufficient duration, adherence, and an effective drug combination.
• Problems include drug resistance, toxicity, nonadherence, and MDR-TB.

Isoniazid (Isotamine®)

• First-line drug of choice.
• Resistance of Mycobacterium is emerging.
• Metabolized via acetylation in the liver; watch for “slow acetylators”.
• Given alone or in combination with other drugs.
• Contraindicated in previous isoniazid-associated liver injury or acute liver disease.

Adverse Effects of Antitubercular Drugs

• INH: peripheral neuropathy, hepatotoxicity, optic neuritis, visual disturbances, and hyperglycemia.
• Ethambutol: retrobulbar neuritis and blindness.
• Rifampin: hepatitis, hematological disorders, and red-orange-brown discoloration of urine, stools, sputum, and tears.

Nursing Implications for Tuberculosis

• Important to perform liver function studies in patients receiving INH or rifampin.
• Assess contraindications, conditions for cautious use, and potential drug interactions.
• Patient education is critical; therapy may last up to 24 months.
• Tell pt to take medications as scheduled and emphasize adherence.
• Remind patients that they are contagious during the initial period of illness and instruct on proper hygiene.
• Instruct patients to take care of themselves, including adequate nutrition and rest.
• Warn patients to to consume alcohol nor take other medications without first checking with their prescribers.
• Rifampin will cause oral contraceptives to be ineffective
• Patients taking rifampin may experience reddish-orange body fluids and staining of contacts.
• Pyridoxine may be needed to combat neurological effects associated with INH therapy.
• Oral preparations can be given with food to combat GI upset.
• Observe for and monitor effects like fatigue, nausea, vomiting, numbness/tingling, fever, loss of appetite, depression, and jaundice.
• Patients need to report any visual changes.
• Watch or a lack of a clinical response to therapy.

Antifungal Drugs

• Fungal infections, aka mycoses contain some normal floras like the skin, mouth, intestines, and vagina.
• Yeast is a single cell fungi

Characteristics of Fungi

• Yeast are single-cell fungi that reproduce by budding, used in baking and brewing.
• Moulds are multicellular and characterized by long, branching filaments aka hyphae

Mycotic Infections

• Includes cutaneous, subcutaneous, superficial, and systemic categories.
• Systemic is life threatening, and common in immunocompromised hosts.
• Candida albicans is a mycotic infection
• Vaginal candidiasis is a yeast infection
• Common in pregnant women, women with diabetes, and women on oral contraceptives.

Antifungal Drugs

• Treat infections caused by fungi.
• The systemic medications amphotericin B, caspofungin, fluconazole, itraconazole, are used for systemic infections.
• Also used for isavuconazole, ketoconazole, micafungin sodium, nystatin, posaconazole, and anidulafungin, ravuconazole (in clinical III trials), terbinafine, and voriconazole in systemic infections.
• Topical drugs are also used.

Major Groups of Antifungal Drugs

• Triazoles: fluconazole, itraconazole, voriconazole, and posaconazole.
• Echinocandins: caspofungin, micafungin sodium, and anidulafungin.
• Imidazoles: ketoconazole.
• Polyenes: amphotericin B and nystatin.

Mechanism of Action: Antifungal Drugs

• Amphotericin B, Flucytosine, Griseofulvin, Nystatin, ketoconazole, fluconazole, itraconazole, voriconazole

Indications of Antifungal Drugs

• Treat systemic and topical infections depending on type and location.
• Amphotericin B: Many severe fungal infections.
• Fluconazole inhibits cryptococcal fungi growth in cerebrospinal fluid and treats cryptococcal meningitis.

Antifungal Drugs: Contraindications and Adverse Effects

• Most Common Contraindications: Drug allergy, liver failure, kidney failure, and porphyria (for griseofulvin).
• Contraindications with itraconazole: Treatment of onychomycoses with severe cardiac problems.
• Voriconazole Adverse Effects: Fetal harm in pregnant women.
• Cardiac dysrhythmias, pulmonary infiltrates.
• Neurotoxicity leads to tinnitus, visual disturbances, paresthesias, and convulsions.
• Kidney toxicity with potassium loss and hypomagnesemia.
• Fever, chills, headache, nausea, occasional hypotension, gastrointestinal upset, and anemia.

Amphotericin B Adverse Effects: Prevention

• Premedications commonly ordered: antiemetics, antihistamines, antipyretics, and corticosteroids.
• Infusion-related reactions minimized by prevention and longer infusion times (2-6 hrs).

Antifungal Drugs: Additional Contraindications

• Liver/Renal failure, Porphyria (griseofulvin), Drug allergy and Pregnancy (voriconazole).

Antifungal Drugs: Interactions

• Many are metabolized by the cytochrome P450 enzyme system.
• Co-administration may lead to competition, increasing levels of one or both drugs.

Nursing Implications: Antifungal Drugs

• Assess for hypersensitivity, possible contraindications, and conditions that require cautious use beforehand.
• Vital signs, CBC, liver/renal functions, and ECG need to be monitored
• Assess other prescribed/over-the-counter drugs for interactions.
• Dilute/Administer: Manufacturer’s directions.
• Monitor vital signs every 15-30 minutes during IV infusions.
• During IV infusions, monitor input and output to identify effects.

Amphotericin B Considerations

• Pretreatment is helpful to reduce the severity of the infusion-related reactions
• An antipyretic, antihistamines, antiemetics, and corticosteroids may be given.
• Use IV infusion pumps and the most distal veins possible

Monitoring of Antifungal Drugs

• Improves energy levels and normalizing vital signs
• Easing signs of infection helps monitor therapeutic effects
• Must also carefully monitor effects