deamino-arginine-vasopressin and Drug-Overdose

Adenosine diphosphate (ADP)-receptor antagonists are widely used for thrombus prevention, although reversing their platelet dysfunction is difficult. This study evaluated the ability of desmopressin to reverse clopidogrel-induced platelet dysfunction. Sprague-Dawley rats received either clopidogrel (30 mg/kg) or placebo, followed 4 h later by saline or desmopressin (0.15, 0.3, or 0.6 μg/kg). Bleeding times and platelet aggregation studies were subsequently performed. A bleeding time >25 min was considered "prolonged." The median bleeding time for clopidogrel-exposed rats was 21 min, vs. 6 min for controls (p < 0.01). Progressively higher doses of 1-deamino-8-D-arginine vasopressin (DDAVP) were associated with a reduced number of rats with prolonged bleeding time (p = 0.001). Higher doses of DDAVP were also associated with a reduction in the median (IQR) bleeding time; 29 (13.5-30) min in rats receiving clopidogrel without DDAVP vs. 19 (12-28) min in rats receiving clopidogrel and 0.6 μg/kg DDAVP. The step-wise dosing of DDAVP resulted in a 54 % reduction in meeting the endpoint of prolonged bleeding time (OR 0.46; p = 0.025; 95 % CI 0.23-0.91). Platelet aggregation was observed in all control rats, but only some of those clopidogrel-treated rats who received 0.6 μg/kg DDAVP. In this model of an ADP-receptor antagonist, DDAVP results in partial reversal of clopidogrel-induced platelet dysfunction.

Topics: Animals; Antidiuretic Agents; Bleeding Time; Clopidogrel; Deamino Arginine Vasopressin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Overdose; Hemostatics; Injections, Intravenous; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Prodrugs; Purinergic P2Y Receptor Antagonists; Pyridines; Random Allocation; Rats; Rats, Sprague-Dawley; Ticlopidine

Hyponatremic encephalopathy is a potentially lethal condition with numerous reports of death or permanent neurological injury. The optimal treatment for hyponatremic encephalopathy remains controversial. We have introduced a unified approach to the treatment of hyponatremic encephalopathy which uses 3% NaCl (513 mEq/L) bolus therapy. Any patient with suspected hyponatremic encephalopathy should receive a 2 cc/kg bolus of 3% NaCl with a maximum of 100 cc, which could be repeated 1-2 times if symptoms persist. The approach results in a controlled and immediate rise in serum sodium with little risk of inadvertent overcorrection.

Topics: Brain; Brain Diseases, Metabolic; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Drug Overdose; Humans; Hypernatremia; Hyponatremia; Iatrogenic Disease; Sodium Chloride

Water intoxication is a serious condition which may be caused by desmopressin overdose, with reversible or irreversible neurological complications. In the past, desmopressin was used in endocrinological centers for the treatment of antidiuretic hormone deficiency (central diabetes insipidus). Indications for hormone treatment have since widened, especially as an effective solution for nocturnal enuresis. It is now often prescribed in community clinics, and its use has been encouraged by extensive promotion. We describe a 15-year-old boy with primary nocturnal enuresis who started treatment with desmopressin 1 year prior to admission. He was allowed to use the drug without supervision, and drank excessively. The result was water intoxication which required admission for intensive care because of loss of consciousness and convulsions for 36 hours.

Topics: Adolescent; Critical Care; Deamino Arginine Vasopressin; Drug Overdose; Enuresis; Humans; Male; Renal Agents; Water Intoxication

The effects of concentration, amperage and duration on the antidiuretic response induced by iontophoretic delivery of desmopressin acetate (DDAVP) were examined using a diabetes insipidus model in rats. A higher current density brought about a larger and longer antidiuretic response. Prolonged iontophoretic duration caused an overdose. Repeated short iontophoretic treatments with lower current density maintained a constant response with a short lag time and a rapid disappearance of pharmacological response immediately after cessation of the final treatment. This type of iontophoresis substantially reduced the inter-subject variability of response as compared to the response using an intranasal route of administration.

Topics: Administration, Cutaneous; Administration, Intranasal; Animals; Deamino Arginine Vasopressin; Diabetes Insipidus; Disease Models, Animal; Diuresis; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug Overdose; Iontophoresis; Male; Rats; Rats, Wistar; Skin Absorption