Pharmacokinetic Origin of Carbamazepine-induced Resistance to Vecuronium Neuromuscular Blockade in Anesthetized Patients

Abstract

The twofold increase in clearance provides evidence of a pharmacokinetic origin to the carbamazepine-vecuronium interaction; however, the possibility of a concurrent pharmacodynamic alteration cannot be assessed. Greater knowledge of protein drug binding needs to be acquired to give a meaningful interpretation to the similar EC50 values observed in the two groups.

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.…”

“…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.…”

Phenobarbital influence on neuromuscular block produced by rocuronium in rats

“…Among these drugs are local anesthetics, volatile anesthetic agents, antibiotics aminoglycosides, anticonvulsants, antiarrhythmic, magnesium, lithium, calcium channel blockers and others [1][2][3][4][5][6][7][8][9][10][11][12] . Although countless studies have been accomplished to investigate anticonvulsants effects in the neuromuscular transmission and its interaction with neuromuscular blocking, the results are contradictory [6][7][8][9][10][11][12][13][14][15] .…”