Neuromuscular blocking effect of fluoxetine and its interaction with rocuronium

Abstract

As selective serotonin reuptake inhibitors have an inhibitory effect on nicotinic acetylcholine receptors, they may affect the neuromuscular transmission and interact with neuromuscular blockers. This study was designed to observe the effect of fluoxetine on neuromuscular transmission and its interaction with rocuronium using the rat phrenic nerve hemidiaphragm and rabbit head drop methods. Rat phrenic nerve hemidiaphragms were mounted and stimulated using a train of four pulses (TOF). The effect of fluoxetine was studied on both indirectly and directly stimulated basal twitch responses by plotting cumulative dose response curves (DRCs). DRCs of rocuronium were obtained in the absence, and presence of 5 μm and 20 μm fluoxetine to study its interaction. ED5 , ED50 and ED95 values of rocuronium DRCs in absence and presence of fluoxetine were calculated. Fluoxetine significantly inhibited twitch responses in both indirect and directly stimulated preparations. Fluoxetine (20 μm) caused an increase in the potency of rocuronium such that the ED50 and ED95 values of rocuronium DRCs were significantly decreased. Partially inhibited twitch responses by fluoxetine (100 μm) were not reversed by neostigmine (3.3 μm) or 3,4 diaminopyridine (0.25 μm). Rabbits were given fluoxetine 0.25 mg kg(-1) and 1 mg kg(-1) orally for 15 days, and on 15th day, rocuronium infusion was given, and time for head drop was recorded. The time of head drop was significantly reduced in fluoxetine pretreated as compared to control group. Fluoxetine blocks the neuromuscular transmission and increases the potency of rocuronium-induced neuromuscular block.

The SLCO1A2 -189_-188InsA polymorphism reduces clearance of rocuronium in patients submitted to elective surgeries

“…Estimated glomerular filtration rate (eGFR) was estimated from serum creatinine values using CKD-EPI equation [12]. All patients taking fluoxetine, carbamazepine, aminoglycoside antibiotics (gentamicin, amikacin, neomycin, streptomycin, tobramycin), or OATP1A2 inhibitors such as rifampicin and verapamil were excluded due to potential pharmacokinetic interaction with ROC [10,13,14].…”

Nefopam does not influence onset and recovery profiles of rocuronium-induced neuromuscular block: a prospective, double-blinded, randomized, controlled study

“…5-hydroxytryptamine 3 (5-HT 3 ) receptor antagonists have an inhibitory effect on nicotinic acetylcholine receptors and affect neuromuscular transmission, because of the structural similarities and common evolutionary origin of muscle nicotinic acetylcholine and 5-HT 3A receptors [7,8]. Therefore, serotonin reuptake inhibitors may interact with non-depolarizing NMBs.…”

“…Therefore, serotonin reuptake inhibitors may interact with non-depolarizing NMBs. In an animal study, Patel et al [7] showed that serotonin reuptake inhibitors significantly inhibited twitch responses by blocking neuromuscular transmission and increasing the potency of rocuronium-induced neuromuscular block. The interaction of 5-HT 3 receptor antagonists with non-depolarizing NMBs is related to antiemetic potency [14].…”

“…Nefopam was reported to be an effective alternative to opioids without significant changes in the Richmond Agitation Sedation Scale score, ventilatory frequency, and oxygen saturation [3]. Therefore, we can frequently encounter patients with many kinds of analgesic taken via infusions or single bolus injections, in the clinical setting requiring the control of preoperative pain such as disease-related pain and drug injection pain.In general, neuromuscular blockers (NMBs) may interact with several drugs, including anticonvulsants, steroids, calcium channel blockers, antidepressants, antibiotics, and anti-arrhythmic drugs, resulting in potentiation of action or rapid recovery of blockade [4][5][6][7][8]. Hence, monitoring of neu-…”

“…In general, neuromuscular blockers (NMBs) may interact with several drugs, including anticonvulsants, steroids, calcium channel blockers, antidepressants, antibiotics, and anti-arrhythmic drugs, resulting in potentiation of action or rapid recovery of blockade [4][5][6][7][8]. Hence, monitoring of neu-…”