McKenna's Pharmacology for Nursing, 2e

172

P A R T 2  Chemotherapeutic agents

OTHER ANTIPROTOZOAL AGENTS Drugs that are available specifically for the treatment of these various protozoan infections include many of the malarial drugs; chloroquine is effective against extraintestinal amoebiasis, and pyrimethamine is effec- tive in treating toxoplasmosis. Other drugs, including some tetracyclines and aminoglycosides, are used for treating these conditions at various stages of the disease. Other antiprotozoals include atovaquone ( Wellvone ), metronidazole ( Flagyl , Metronide ), pentamidine ( DBL Pentamidine Isethionate ), pyrimethamine ( Daraprim ) and tinidazole ( Fasigyn, Simplotan ). (See Table 12.2.) Therapeutic actions and indications These antiprotozoal agents act to inhibit DNA synthe- sis in susceptible protozoa, interfering with the cell’s ability to reproduce, subsequently leading to cell death (see Figure 12.1). These drugs are indicated for the treat- ment of infections caused by susceptible protozoa. See Table 12.2 for usual indications for each of these agents. Pharmacokinetics Atovaquone is slowly absorbed and is highly protein bound in circulation. It is excreted slowly through the faeces, with a half-life of 67 to 76 hours. Metronidazole is well absorbed orally, reaching peak levels in 1 to 2 hours. It is metabolised in the liver with a half-life of 8 to 15 hours. Excretion occurs pri- marily through the urine. Pentamidine is readily absorbed through the lungs. Excretion occurs in the urine, with traces found in the urine for up to 6 weeks. Pyrimethamine is readily absorbed from the GI tract, with peak levels occurring within 2 to 6 hours. It is metabolised in the liver and has a half-life of 4 days. It usually maintains suppressive concentrations in the body for about 2 weeks. Tinidazole is rapidly absorbed after oral administra- tion, reaching peak levels within 60 to 90 minutes. It is excreted in the urine with a half-life of 12 to 14 hours. Contraindications and cautions Contraindications include the presence of any known allergy or hypersensitivity to any of these drugs and pregnancy because drug effects on developing fetal DNA and proteins can cause fetal abnormalities and even death. Use caution when administering these drugs to people with CNS disease because of possible disease exacerbation due to drug effects on the CNS ; hepatic disease because of possible exacerbation when hepatic drug effects occur ; candidiasis because of the risk of superinfections ; and women who are breast- feeding because these drugs may pass into breast milk

Trypanosomiasis Trypanosomiasis is caused by infection with Trypano- soma. Two parasitic protozoal species cause very serious and often fatal diseases in humans: • African sleeping sickness, which is caused by Trypanosoma brucei gambiense, is transmitted by the tsetse fly. After the pathogenic organism has lived and grown in human blood, it eventually invades the CNS, leading to an acute inflammation that results in lethargy, prolonged sleep and even death. • Chagas disease, which is caused by Trypanosoma cruzi, is almost endemic in many South American countries. It is passed to humans by the common housefly. This protozoan results in a severe cardiomyopathy that accounts for numerous deaths and disabilities in certain regions. Trichomoniasis Trichomoniasis , which is caused by another flagellated protozoan, Trichomonas vaginalis , is a common cause of vaginitis. This infection is usually spread during sexual intercourse by men who have no signs and symptoms of infection. In women, this protozoan causes reddened, inflamed vaginal mucosa, itching, burning and a yellowish-green discharge. Trichomoniasis is par- ticularly prevalent among the Aboriginal and Torres Strait Islander population in Australia. Giardiasis Giardiasis , which is caused by Giardia lamblia , is a very commonly diagnosed intestinal parasite in Australia. This protozoan forms cysts, which survive outside the body and allow transmission through contaminated water or food, and trophozoites, which break out of the cysts in the upper small intestine and eventually cause signs and symptoms of disease. Diarrhoea, rotten egg–smelling stool, and pale and mucus-filled stool are commonly seen. Some individuals experience epigastric distress, weight loss and malnutrition as a result of the invasion of the mucosa. Pneumocystis carinii pneumonia Pneumocystis carinii is an endemic protozoan that does not usually cause illness in humans. When an individual’s immune system becomes suppressed because of acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC), the use of immunosuppressant drugs or advanced age, this parasite is able to invade the lungs, leading to severe inflammation and the condition known as Pneumocystis carinii pneumonia (PCP) . This disease is the most common opportunistic infection in people with AIDS.