Rocuronium-induced Neuromuscular Block Is Affected by Chronic Carbamazepine Therapy 

Abstract

The authors conclude that the duration of the rocuronium-induced neuromuscular block is significantly shortened by preceding chronic carbamazepine therapy.

Efeitos neuromusculares in vitro e in vivo do atracúrio e do rocurônio em ratos submetidos a tratamento de sete dias com carbamazepina

“…Those factors influence the pharmacology of neuromuscular blockers increasing or decreasing and prolonging or shortening the muscular blockade 6,15,20,[23][24][25][26] . Among those drugs, anticonvulsants, widely used in the treatment of seizures, bipolar disorder, trigeminal neuralgia and diabetic neuropathy [8][9][10][11][12] can, by themselves, interfere with the neuromuscular junction, change, or not interfering at all with the pharmacodynamic and pharmacokinetic properties of neuromuscular blockers [13][14][15][16][17][18][19][25][26][27][28][29][30][31][32][33][34] . Pharmacologic and clinically, carbamazepine is similar to phenytoin, but with fewer undesirable effects and, although effective and useful in the treatment of partial complex seizures, it is also used in the treatment of several types of neuropathic pain.…”

“…Additionally, those drugs also affect the membrane of the nerve ending in a manner similar to curare 35 . It is a potent inducer of hepatic microsomal enzymes and consequently it has important drug interaction by accelerating the metabolism of several drugs such as oral contraceptives, corticosteroids, phenytoin, warfarin and neuromuscular blockers especially the aminosteroids 6,9,19,24,25 . Although the inhibition of calcium channels and glutamate receptors is involved in the effects of several anticonvulsants the main mechanism of action of carbamazepine seems to be due to changes in membrane excitability through the inhibition of voltage-gated sodium channels that transport the current to the interior of the cell which is necessary for the generation of an action potential 9,36 .…”

“…This reduced sensitivity to neuromuscular blockers is not clearly established. The etiology of this interaction seems to be multifactorial and the mechanisms most likely to be involved are: enzymatic induction, with an increase in hepatic metabolism and clearance, increased inactivation and elimination of those drugs; increased concentration of acid α 1 -glycoprotein, resulting in greater protein binding, reduced fraction of free cationic drugs and change in distribution; reduced sensitivity of the receptor to acetylcholine; proliferation of receptors in the muscular membrane 6,13,17,19,25,32,34,41,[44][45][46][47][48][49][50] . The attempt to correlate the in vitro results with clinical practice is a difficult task and for this reason in vivo assays, more appropriate in the pharmacological study of drugs, were undertaken.…”

“…Embora inúmeros estudos tenham sido realizados para investigar os efeitos dos anticonvulsivantes nas respostas musculares e sua interação com bloqueadores neuromusculares, os resultados ainda são conflitantes. Alguns estudos mostraram que os anticonvulsivantes modificam as respostas aos bloqueadores neuromusculares, potencializando, diminuindo ou mesmo não alterando os seus efeitos [13][14][15][16][17][18][19] . Portanto, o estudo dessas interações pode ser interessante na prática anestésica ou em pacientes críti-cos. O estudo realizado em ratos tratados (CBZ t ) ou não (CBZ st ) com carbamazepina, por um período de sete dias, teve por objetivo avaliar in vitro e in vivo o efeito da carbamazepina na transmissão neuromuscular e a sua influên-cia no bloqueio neuromuscular produzido pelo atracúrio e pelo rocurônio, bem como as concentrações de citocromo P450 e b5 redutase em microssomos hepáticos.…”

“…Although several studies have investigated the effects of anticonvulsants in the neuromuscular response and their interaction with neuromuscular blockers, the results are conflicting. Some studies have demonstrated that anticonvulsants modify the response to neuromuscular blockers, potentiating, decreasing, or not interfering with it [13][14][15][16][17][18][19] . Therefore, the study of those interactions can be interesting in the anesthetic practice or in critical patients.…”