Page 106 - 80 guidelines for the treatment of malaria_opt

N
N
CI
2
HN
CH 3
H
NH
2
H 3 C N CH 3 CI HN OH N CH 3 CH 3 H N O S O N N O N CH 3 O CH 3 H N N N 2 CH 3 CI
nd
Guidelines for the treatment of malaria – 2 edition
F
H 3 C H 3 C H 3 C
F F
F
F
N in endemic areas are a common cause of sciatic nerve palsy. Hypotension and cardiac O O C
O
O
C
O
C
O
F arrest may result from rapid intravenous injection. Intravenous quinine should be given O
O
O
ÿ
only by infusion, never injection. Quinine causes an approximately 10% prolongation of O O CH 3
CH 3
CH 3
O
O
H
H
H
H
H the electrocardiograph QT interval – mainly as a result of slight QRS widening (75). The HO H H
H 3 C
HO effect on ventricular repolarization is much less than that with quinidine. Quinine has O
O
O
H
H
HN been used as an abortifacient, but there is no evidence that it causes abortion, premature O CH 3 H
CH 3
CH 3
labour or fetal abnormalities in therapeutic use.
Overdosage of quinine may cause oculotoxicity, including blindness from direct retinal
toxicity, and cardiotoxicity, and can be fatal (76). Cardiotoxic effects are less frequent
CI
H 3 C H 3 C
than those of quinidine and include conduction disturbances, arrhythmias, angina, CH 3
O hypotension leading to cardiac arrest and circulatory failure. Treatment is largely
O
O C O C NH 2
O
O supportive, with attention being given to maintenance of blood pressure, glucose, and HN
CH 3 renal function and to treating arrhythmias. CI CI N
CH 3
O O
H H H H
Drug interactions H 3 C H 3 C
HO H 3 C O O
H H
H 3 C
N
CH 3 There is a theoretical concern that drugs that may prolong the QT interval should
CH 3
OH
not be given with quinine, although whether or not quinine increases the risk of
iatrogenic ventricular tachyarrhythmia has not been established. Antiarrhythmics,
such as flecainide and amiodarone, should probably be avoided. There might be an
increased risk of ventricular arrhythmias with antihistamines such as terfenadine, and
CI
CI with antipsychotic drugs such as pimozide and thioridazine. Halofantrine, which causes
H
H
H
marked QT prolongation, should be avoided but combination with other antimalarials, O
CI
N
N
N
CH 3
H NH NH CH 3
such as lumefantrine and mefloquine is safe. Quinine increases the plasma concentration H N S NH 2
2
NH
NH
of digoxin. Cimetidine inhibits quinine metabolism, causing increased quinine levels and O
CH 3
CI
H
H
H
O rifampicin increases metabolic clearance leading to low plasma concentrations and an CH 3
N
N
N
H increased therapeutic failure rate (77).
OH
O a3.12 tetracycline
Molecular weight: 444.4
The tetracyclines are a group of antibiotics
H 2 C H H 3 C CH 3 originally derived from certain OH CI
HO CH 3 H N Streptomyces species, but used mostly in O O CH 3 O CH 3
OH
O
OH OH N
synthetic form. Tetracycline itself may be N
N administered orally or intravenously as the NH 2 H 3 C H H
HO H NH 2 hydrochloride salt or phosphate complex. OH H HO O S CH 3
OH Both are water soluble, although the H
H
O OH O OH O O
OHble for
H 3 C
H 3 C intravenous preparation is only sta N HO OH
a few hours.
N H 3 C CH 3
92