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ANNEX 3. Pharmacology of antimalarial medicines

Tetracyclines are inhibitors of aminoacyl-tRNA binding during protein synthesis.
They have a broad range of uses, including treatment of some bacterial infections:
Chlamydia, Rickettsia, Mycoplasma, Lyme disease, Brucella, tularaemia, plague and
cholera. Doxycycline is a synthetic tetracycline with a longer half-life, which makes
dosing schedules easier.

Formulations
• Capsules and tablets containing 250 mg of tetracycline hydrochloride, equivalent to
231 mg of tetracycline base.
A3
Pharmacokinetics
Some 60–80% of tetracycline is absorbed from the gastrointestinal tract following oral
administration. Absorption is reduced by the presence of divalent and trivalent metal
ions with which it forms stable, insoluble complexes. Thus absorption may be impaired
with food or milk. Formulation with phosphate may improve absorption. Peak plasma
concentrations occur 1–3 h after ingestion. Tetracycline is 20–65% bound to plasma
proteins. It is widely distributed throughout the body, although less so than the more
lipophilic doxycycline. High concentrations are present in breast milk (around 60% of
plasma levels), and also diffuse readily across the placenta, and are retained in sites of
new bone formation and teeth development. The half-life of tetracycline is around 8 h;
40–70% is excreted in the urine via glomerular filtration. The remainder is excreted in
the faeces and bile. Enterohepatic recycling slows down complete elimination.

Toxicity
All the tetracyclines have similar adverse effect profiles. Gastrointestinal effects, such as
nausea, vomiting and diarrhoea, are common, especially with higher doses, and are due to
mucosal irritation. Dry mouth, glossitis, stomatitis, dysphagia and oesophageal ulceration
have also been reported. Overgrowth of Candida and other bacteria occurs, presumably
due to disturbances in gastrointestinal flora as a result of incomplete absorption of the
drug. This effect is seen less frequently with doxycycline, which is better absorbed.
Pseudomembranous colitis, hepatotoxicity and pancreatitis have also been reported.
Tetracyclines accumulate in patients with renal impairment and this may renal failure. In
contrast doxycycline accumulates less and is preferred in patient with renal impairment.
The use of out-of-date tetracycline can result in the development of a reversible Fanconi-
type syndrome characterized by polyuria and polydipsia with nausea, glycosuria,
aminoaciduria, hypophosphataemia, hypokalaemia, and hyperuricaemia with acidosis
and proteinuria. These effects have been attributed to the presence of degradation
products, in particular anhydroepitetracycline.

Tetracyclines are deposited in deciduous and permanent teeth during their formation and
cause discoloration and enamel hypoplasia. They are also deposited in calcifying areas in

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