Side Effects

Nalidixic acid, the first quinolone, first introduced in 1962, is now only rarely used and has been supplanted by the fluoroquinolones. It is almost completely absorbed from the gastrointestinal tract and is rapidly eliminated by the kidneys, resulting in urinary concentrations 4-6 times higher than plasma concentrations.

The tetracyclines are a closely related group of antibiotics with comparable pharmacological properties but different pharmacokinetic characteristics. They have both the advantages and disadvantages of broad-spectrum antibiotics. Tetracyclines are effective not only against bacteria and spirochetes, but also against some forms of Mycoplasma, Chlamydia, and Rickettsia, as well as protozoa.

Cardiovascular reactions to tetracyclines have often been associated with other symptoms of hypersensitivity, such as urticaria, angioedema, bronchial obstruction, and arterial hypotension. Such reactions occurred in patients who had tolerated tetracyclines previously and were therefore considered as anaphylactic. Tetracyclines rarely cause benign intracranial hypertension. This syndrome has primarily involved children, although it has also been observed in adults.

Chloroquine and its congeners can cause two typical effects in the eye, a keratopathy and a specific retinopathy. Both of these effects are associated with the administration of the drug over longer periods of time. Chloroquine-induced keratopathy is limited to the corneal epithelium, where high concentrations of the drug are readily demonstrable. Slit lamp examination shows a series of punctate opacities scattered diffusely over the cornea; these are sometimes seen as lines just below the center of the cornea, while thicker yellow lines may be seen in the stroma.

The “gray syndrome” is the term given to the vasomotor collapse that occurs in neonates who are given excessive parenteral doses of chloramphenicol. The syndrome is characterized by an ashen gray, cyanotic color of the skin, a fall in body temperature, vomiting, a protuberant abdomen, refusal to suck, irregular and rapid respiration, and lethargy. It is mainly seen in newborn infants, particularly when premature.

Albendazole has been used in the treatment of human hookworm and trichuriasis. In a mass-treatment report from Western Australia 295 individuals in a remote rural area were treated with albendazole 400 mg/day for 5 days because of possible Giardia lamblia and hookworm infections. The 37% prevalence of Giardia fell to 12% between days 6 and 9, but rose again to 28% between days 18 and 30. The effect on hookworms (Ankylostoma duodenale) was more pronounced and more sustained with a reduction of the pretreatment prevalence of hookworm infections from 76% before treatment to 0% after 3^1 weeks.

In 2917 adults, adverse effects of roxithromycin occurred in 4.1% at a dosage of 150 mg/day. Nausea (1.3%), abdominal pain (1.2%), and diarrhea (0.8%) were the most frequently reported events, whereas rash, vomiting, headache, dizziness, pruritus, urticaria, and constipation were reported only rarely. Treatment had to be withdrawn in 0.9% of the patients because of adverse effects. In an uncontrolled study in 24 HIV-infected patients, roxithromycin (300 mg bd for 4 weeks) was effective against cryptosporidial diarrhea.

In a double-blind, multicenter study 171 patients who had acute pyelonephritis were given intravenous cefuroxime for 2-3 days, followed by ceftibuten 200 mg bd or norfloxacin 400 mg bd for 10 days. There were fewer bacterial relapses after oral norfloxacin than ceftibuten. Adverse events were reported by 47% of the patients taking ceftibuten and by 38% of those taking norfloxacin. This difference was not significant, but diarrhea or loose stools occurred more often with ceftibuten.

Over a number of years, ivermectin has shown excellent results in the treatment of onchocerciasis, both in controlled studies and in the field, including use in the WHO-sponsored program of treatment. This experience has provided a thorough picture of its adverse effects. The effective dosage is of the order of 50-200 micrograms/kg.

Supine and postural tachycardia with postural hypotension can occur; in one large study, such effects were found in three of 40 patients. In another there was hypotension in 13 of 69 cases, but in some series these effects have not been observed at all. A massive community study in Ghana noted hypotension in only 37 of nearly 15 000 patients treated.