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Antifungal Drugs

The body contains a variety of potentially pathogenic fungi which can cause local inflammation or disease if:

• a person becomes immunocompromised
• the balance of resident bacterial flora is suppresed by broad-spectrum antibiotics
• or if an inhaled corticosteroid is used without a reservoir device.

Drugs that are antifungal include amphotericin B, nystatin, and some newer azole antifungal agents.

Amphotericin B, which is administered by IV, has been the drug of choice for serious fungal infections since the 1950s, but its toxic effects such as nephrotoxicity, fever, and hypotension have limited its use. Nystatin is applied topically, and is effective against yeast-like infections.

Antituberculosis Drugs

First line agents to treat against tuberculosis include isoniazid, rifampin, pyrazinamide, ethambutol, and streptomycin. These primarily inhibit the growth of the mvcobacterium tuberculosis, but can be bactericidal with proper dosage. Usually two or more of the above agents are given simultaneously for 6-9 months. Isoniazid is the most effective, and is believed to act as an antimetabolite in the bacilli. This inhibits most enzyme systems in the organism. Side-effects are directly related to dosage, duration of treatment, and increasing patient age. Complications include: mouth dryness, visual problems, headache, insomnia, constipation, anemia, orthostatic hypotension, skin rashes, seizures, peripheral neuritis and hepatitis. Vitamin B₆ (pyridoxine) can decrease the neurotoxic effects.

Resistant strains develop rapidly when any of the above are given by themselves, so multidrug combinations are used to fight TB. Second-line antituberculosis drugs consist of: capreomycin, kanamycin, ethionamide, paraaminosalicylic acid, and cycloserine.

Pentamidine

Pentamidine Isoethionate is an antiprotozoal drug which is active against pneumocystis carinii pneumonia (PCP). It can be given either parenterally or via aerosol, and aerosolized pentamidine reaches significantly higher concentrations in the lung than when given by IV. Inhaled pentamidine (NebuPent) is specifically approved for the prevention of PCP in HIV-infected patients who:

• have a history of one or more episodes of PCP

• have a peripheral CD4⁺ lymphocyte count of 200/mm₃, or less

The aerosol form has also been used in the treatment of acute episodes of PCP. Dosage approved for prophylaxis of PCP in AIDS subjects is 300 mg, given by inhalation once every 4 weeks. If there is a response to pentamidine, respiratory function may improve within 24-48 hours. Improvement generally takes between 2-8 days for most patients. Improvement in the chest X-ray may take a week or longer, particularly with an AIDS patient.

While pentamidine administered by aerosol has fewer side effects than it does when given parenterally, it still has the potential for side effects, including: cough and bronchial irritation, shortness of breath, bronchospasm and wheezing, conjunctivitis, rash, renal insufficiency. Using a beta adrenergic bronchodilator before inhaling aerosolized pentamidine can reduce or prevent local airway reaction.

The greatest danger of inhaling aerosol pentamidine exists when the patient coughs or removes the mouthpiece from their mouth while nebulization continues. Proper instruction of the patient on controlling aerosol particles by coughing into a tissue minimizes the former.