Page 108 - 80 guidelines for the treatment of malaria_opt

N
N
CI
2
CH 3
NH
2
CH 3
F HN H 3 C N CH 3 CI HN OH N CH 3 CH 3 H N O S O N H N O N O CH 3 H N N N 2 CH 3 CI
H 3 C H 3 C H 3 C
F F
F
F Guidelines for the treatment of malaria – 2 edition
nd
N O O O
O C O C O C
F O O O
ÿ O CH 3 bone and the nails and interfere with bone growth in young infants or pregnant women. CH 3
CH 3
O
O
O
H
H
H
H H H Raised intracranial pressure in adults and infants has also been documented. Tetracyclines H
H 3 C
HO
HO O O O
H
H use in pregnancy has also been associated with acute fatty liver. Tetracyclines should
H
HN O
therefore not be given to pregnant or lactating women, or children aged up to 8 years.
CH 3
CH 3
CH 3
Hypersensitivity reactions occur, although they are less common than for β-lactam
antibiotics. Rashes, fixed drug reactions, drug fever, angioedema, urticaria, pericarditis
H 3 C H 3 C CI
and asthma have all been reported. Photosensitivity may develop, and, rarely, haemolytic
anaemia, eosinophilia, neutropenia and thrombocytopenia. Pre-existing systemic lupus
CH 3
O O
NH
O C O C erythematosus may be worsened and tetracyclines are contraindicated in patients with 2
HN
O O
CI
CH 3 CH 3 the established disease. CI N
O O
H H H H
Drug interactions H 3 C
H 3 C
HO H 3 C O O
H H There is reduced absorption of tetracyclines with concomitant administration of cations,
H 3 C N
CH 3 CH 3
such as aluminium, bismuth, calcium, iron, zinc and magnesium. Administration with
OH
antacids, iron preparations, dairy products and some other foods should therefore
be avoided. Nephrotoxicity may be exacerbated with diuretics, methoxyflurane or
other potentially nephrotoxic drugs. Potentially hepatotoxic drugs should be avoided.
CI
CI Tetracyclines produce increased concentrations of digoxin, lithium and theophylline,
H H H
N N N CH 3 and decrease plasma atovaquone concentrations and also the effectiveness of oral
CI
O
H NH NH CH 3
contraceptives. They may antagonize the actions of penicillins so should not be given
NH
H N
S
2
2
NH NH CH 3 concomitantly.
CI H H H O
O N N N CH 3
H
OH
O
a3.13 doxycycline (see also Tetracycline)
Molecular weight: 444.4
Doxycycline is a tetracycline derivative
H 2 C H H 3 C CH 3 OH with uses similar to those of tetracycline.
CI
HO CH 3 H N OH O O O CH 3 O CH 3
N
OH OH It may be preferred to tetracycline because
NH of its longer half-life, more reliable N
H
N 2 absorption and better safety profile in
H
H 3 C
HO H NH 2 O CH 3
H
HO
OH patients with renal insufficiency, where it S
OH H H
O OH O OH O O may be used with caution. It is relatively
H 3 C H 3 C OH N water insoluble but very lipid soluble. It OH
HO
H 3 C CH 3 may be given orally or intravenously.
N
It is available as the hydrochloride salt or phosphate complex, or as a complex prepared
from the hydrochloride and calcium chloride.
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