This child has acute falciparum malaria, and her lethargy and abnormal laboratory tests are consistent with progres-sion to severe disease. She should be hospitalized and treated urgently with intravenous artesunate or, if this is unavailable, intravenous quinine or quinidine. She should be followed closely for progression of severe malaria, in particular neu-rologic, renal, or pulmonary complications, and if treated with quinine or quinidine should have cardiac monitoring for potential toxicities.
Clinical Pharmacology of the Antihelminthic Drugs
Philip J. Rosenthal, MD
A 29-year-old Peruvian man presents with the incidental finding of a 10 × 8 × 8-cm liver cyst on an abdominal com-puted tomography (CT) scan. The patient had noted 2 days of abdominal pain and fever, and his clinical evaluation and CT scan were consistent with appendicitis. His clinical find-ings resolved after laparoscopic appendectomy. The patient immigrated to the USA 10 years ago from a rural area of Peru where his family trades in sheepskins. His father and sister have undergone resection of abdominal masses, but details of their diagnoses are unavailable. What is your differential diagnosis? What are your diagnostic and therapeutic plans?
Helminths (worms) are multicellular organisms that infect very large numbers of humans and cause a broad range of diseases. More than 1 billion people are infected with intestinal nematodes, and many millions are infected with filarial nematodes, flukes, and tapeworms in other organs. Many drugs, directed against a number of different targets, are available to treat helminthic infections. In many cases, especially in the developing world, the goal is control of infection, with elimination of most parasites, alleviating disease symptoms, and decreasing the transmission of infection. In other cases, complete elimination of parasites is the goal of therapy, although this goal can be challenging with certain helminthic infections, because of both limited efficacy of drugs and frequent reinfection after therapy in endemic areas.
Table 53–1 lists the major helminthic infections and provides a guide to the drug of choice and alternative drugs for each infection. In the text that follows, these drugs are arranged alphabetically. In general, parasites should be identified before treatment is started.
Albendazole, a broad-spectrum oral antihelminthic, is the drug of choice and is approved in the USA for treatment of hydatid disease and cysticercosis. It is also used in the treatment of pinworm and hookworm infections, ascariasis, trichuriasis, and strongyloidiasis.
Albendazole is a benzimidazole carbamate. After oral administration, it is erratically absorbed (increased with a fatty meal) and then rapidly undergoes first-pass metabolism in the liver to the active metabolite albendazole sulfoxide. It reaches variable maximum plasma concentrations about 3 hours after a 400-mg oral dose, and its plasma half-life is 8–12 hours. The sulfoxide is mostly protein-bound, distributes well to tissues, and enters bile, cerebrospinal fluid, and hydatid cysts. Albendazole metabolites are excreted in the urine.
Benzimidazoles are thought to act against nematodes by inhibiting microtubule synthesis. Albendazole also has larvicidal effects in hydatid disease, cysticercosis, ascariasis, and hookworm infection and ovicidal effects in ascariasis, ancylostomiasis, and trichuriasis.