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Biomedical subjects

G Koren

Publications and source records attributed to G Koren.

713 records · Page 40Linked to original sources

Deferoxamine (desferrioxamine). New toxicities for an old drug.

Iron is an essential element for body homoeostasis, but there is no effective mechanism for elimination of an excess of this mineral. Deferoxamine (desferrioxamine) is currently the treatment of choice for iron overload states from both acute iron intoxication and transfusion-dependent anaemias. The pharmacokinetics of deferoxamine are confounded both by its ability to chelate endogenous and exogenous iron and by the laboratory techniques used for its determination. Its iron-complex (ferrioxamine) has different pharmacokinetic properties. Because of its effectiveness, the use of deferoxamine is becoming more common, involving long term and high dose regimens. As a result of this, more and more toxicities that were not known in the past have been described and characterised. The most serious of these include hypotension, renal insufficiency, neurotoxicity, growth retardation and opportunistic infections: some of these side effects may be attributed to or aggravated by ferrioxamine. The pharmacological and toxicological literature on deferoxamine, and possible mechanisms for its toxicity, are reviewed and discussed.

Animals↗

Anticonvulsants and breast feeding: a critical review.

Progress in the diagnosis and management of seizure disorders and the availability of effective anticonvulsive medications has enabled increasing numbers of epileptic women of child-bearing age to raise families. Breast feeding, which these women may wish to choose, provides health, nutritional, immunological, developmental, social, economic and environmental benefits. The traditional anticonvulsants, such as phenytoin, carbamazepine and valproic acid (valproate sodium), are generally considered safe for use during breast feeding; however, observation for adverse effects is recommended. The use of phenobarbital while breast feeding is controversial because of its slow elimination by the nursing infant. The newer anticonvulsants, such as clobazam, felbamate, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and vigabatrin, are used mainly as adjunctive therapy. Data on the use of these drugs in pregnancy and lactation, and regarding long term effects on cognition and behaviour, are sparse. Weighing the benefits of breast feeding against the potential risk to the nursing infant, breast feeding is considered to be safe when the mother is taking carbamazepine, valproic acid or phenytoin. Infant monitoring for potential adverse effects is advisable when the mother is taking phenobarbital, clobazam, gabapentin, lamotrigine, oxcarbazepine or vigabatrin. Monitoring of infant serum drug concentrations is advisable but not compulsory. The use of felbamate, tiagabine and topiramate during breast feeding should await further study.

Adult↗

Fetal distribution of cocaine: case analysis.

The implications of gestational cocaine use are widely documented. There is evidence that cocaine crosses the placenta in animals and humans; however, the fetal distribution of the drug and its metabolites has not been documented. We describe the distribution of cocaine and benzoylecgonine (BE) in the fetus of a cocaine user mother. Cocaine and BE were detected in brain, scalp, liver, kidney, heart, placenta, blood, and hair. The liver contained substantially more cocaine than other tissues, whereas the brain had more BE than any other sample.

Cocaine↗

Bias in maternal reports of smoking during pregnancy associated with fetal distress.

BACKGROUND: Studies examining the adverse effects of smoking during pregnancy commonly use maternal reports. We hypothesized that if an adverse event occurred during pregnancy, women may underreport smoking. This study looked for bias in maternal report of smoking if fetal distress occurs. METHODS: Data were collected prospectively from patients attending The MotheRisk Program who smoked during pregnancy, and were categorized by delivery outcome, maternal and neonatal characteristics, and the raw number of cigarettes smoked per day during pregnancy reported at clinic and at follow-up. The difference between these two values was compared. RESULTS: 95 women had uneventful deliveries and 25 had fetal distress. Women who reported fetal distress decreased their report of smoking after delivery compared to their original report during pregnancy, whereas women with an uneventful labour did not (p = 0.04). CONCLUSIONS: Our results suggest that if an adverse pregnancy outcome occurs, mothers may tend to underreport their cigarette consumption.

Adult↗

Digoxin-verapamil interaction: in vitro studies in rat tissue.

Recent studies have shown a significant increase in plasma digoxin concentration during verapamil treatment. This phenomenon has been attributed in part to reduced renal clearance of digoxin owing to inhibition of the digoxin tubular secretory process. We studied the influence of digoxin-verapamil interaction on [125I]digoxin uptake by various rat tissues in vitro, employing the tissue slice technique. Slice/medium digoxin ratios (mean +/- SD) were: kidney, 4.09 +/- 0.60; heart, 3.63 +/- 0.41; liver, 3.93 +/- 0.39; and muscle, 3.55 +/- 0.55. Addition of verapamil to the incubation medium resulted in a 15.6% reduction of digoxin uptake by kidney tissue, to 3.38 +/- 0.49 (p less than 0.0005). Verapamil failed to reduce digoxin uptake in liver, heart, or striated muscle. We conclude that the renal cortical transport mechanism of digoxin may be inhibited by verapamil. In contrast, the unaffected uptake of digoxin in heart or muscle indicates that the increase in serum digoxin concentration in the presence of verapamil is not caused or accompanied by redistribution of digoxin from the heart or striated muscle.

Animals↗