Carbamazepine Diminishes the Sensitivity of the Plasma Arginine Vasopressin Response to Osmotic Stimulation

Abstract

Carbamazepine, a drug used to treat manic-depressive illness, has been reported to possess antidiuretic properties, but its effects on arginine vasopressin (AVP) secretion are controversial. Consequently, we examined plasma AVP secretion during hypertonic (5%) saline infusion in seven manic-depressive patients while on placebo and after 3-5 weeks of carbamazepine treatment. We also measured carbamazepine's effects on basal levels of the hormone in cerebrospinal fluid. Carbamazepine significantly reduced the sensitivity of the plasma AVP response to osmotic stimulation without affecting the osmotic threshold for AVP secretion. Moreover, carbamazepine did not affect baseline weight, plasma osmolality, plasma sodium, urine output, plasma AVP, or cerebrospinal fluid AVP. Although the functional significance of these findings remain to be fully determined, the fact that carbamazepine significantly reduced AVP secretion without inducing diuresis supports previous suggestions that carbamazepine enhances renal responsivity to available AVP. In addition, since carbamazepine failed to affect the osmotic threshold, the reported cases of carbamazepine-induced inappropriate AVP secretion and water intoxication must be very uncommon and probably represent idiosyncratic responses.

Metoclopramide Increases Plasma but Not Cerebrospinal Fluid Vasopressin Levels in Man: Study in Hydrocephalic Patients

“…Therefore, the possibility that metoclo pramide may act as a dopamine receptor blocker [5], thus removing a possible dopaminergic inhibitory influence on AVP release, may be suggested. Otherwise, since the drug may also act as an indirect cholinergic agonist, a possible AVP-releasing effect exerted in this way may also be hypothesized [9], Our results showing that after metoclopramide the AVP release occurs in plasma but not in CSF are in agreement with experimental and clin ical findings showing that pharmacological stimuli (acute nicotine and histamine administration [12], or carbamazepine treatment [ 13]) are able to modify plasma but not CSF AVP concentrations. Furthermore, they are in keep ing with the opinion that CSF and plasma AVP may arise from different sources: increased CSF AVP levels in hypophysectomized rats [2] and in patients with diabetes insipidus [ 14] in association with a low plasma AVP con centration have been shown.…”

Influence of Sodium Valproate on Sodium and Chloride Urinary Excretion in Rats, Gender Differences

“…An increased sensitivity of Na transport systems in the renal tubules to circulating vasopressin cannot be excluded. It has been proposed that antiepileptic medicines cause an increase in vasopressin secretion or have a direct tubular effect in the kidney, but the data are confl icting [17,18] . The classical short-term effect (within minutes) of vasopressin consists in increasing Na, Cl and water transport in kidney cells.…”

Clinical management of SIADH

“…The secretory patterns do not show any specific relationship to underlying pathology [Berl and Robertson, 2000]. Second, measurement of ADH in patients with SIADH receiving agents such as carbamazepine, cyclophosphamide or others [Gold et al 1983] may yield low concentrations of ADH. This has been attributed to direct tubular actions of these drugs [de Braganca et al 2010], resulting in enhancement of water reabsorption that is not exclusively mediated by ADH.…”