buprenorphine and Seizures

Topics: Animals; Animals, Newborn; Anxiety; Behavior, Animal; Buprenorphine; Female; Locomotion; Male; Maze Learning; Methadone; Morphine; Narcotics; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Seizures; Sex Factors; Tramadol

We report the case of a hypotrophic twin who presented neonatal abstinence syndrome to buprenorphine and developed neonatal seizures when the substitutive treatment by morphine was stopped. The other eutrophic twin did not develop withdrawal symptoms. This case demonstrates the unpredictable nature of transplacental transfer of buprenorphine. It also shows that neonatal abstinence syndrome can be potentially severe and that morphine treatment is not without risk.

Topics: Buprenorphine; Humans; Infant, Newborn; Morphine; Narcotics; Neonatal Abstinence Syndrome; Seizures; Twins

Buprenorphine safety in overdose has been debated recently, but no mortality data related to this compound from the UK have been published. To gather together all of the buprenorphine mortality figures, a number of different sources have been checked. To inform on buprenorphine safety issues, accessible information related to its availability indicators (i.e. prescriptions; seizures) data for the 1980-2002 time frame have been sought. In the UK, during this period, buprenorphine was mentioned in 43 fatalities. Typically, victims were males in the 25-44 age group. In 12 cases (28% of total), a verdict of suicide was given. Buprenorphine was detected on its own in seven cases; more frequently, it was found together with benzodiazepines and other opiates. Large quantities of buprenorphine were prescribed both in England in 1985-1989 and in 1991-1992 in Scotland, where seizures reached their highest levels. Buprenorphine prescriptions seemed to peak again after 1999, when high dose buprenorphine formulations entered the UK market. No positive correlation was found between the number of buprenorphine deaths over the years and either buprenorphine dispensings/prescriptions or seizures. However, an increase in buprenorphine-related deaths since 1999 was identified and this may be an issue which should be carefully monitored over the next few years.

Topics: Adult; Aged; Buprenorphine; Drug Overdose; Drug Utilization; Female; Humans; Male; Middle Aged; Mortality; Seizures; Time Factors; United Kingdom

To report a seizure occurring secondary to meperidine treatment despite normal renal and central nervous system (CNS) function, and to provide a review of meperidine's role in pain management, including its use in pancreatitis and sphincter of Oddi dysfunction.. A 55-year-old white woman with a history of sphincter of Oddi dysfunction presented to the emergency department with severe abdominal pain. On admission to the hospital, the serum creatinine level was 0.6 mg/dL with slightly elevated aspartate aminotransferase of 56 U/L (normal range 0-31) and alanine aminotransferase of 34 U/L (0-31). The patient received repeated and escalating doses of intravenous meperidine, resulting in a generalized seizure on day 4 of hospitalization. The accumulated meperidine dose was 2125 mg. Buprenorphine was substituted in place of meperidine, and the patient had no further reported complications. She was then transferred to a tertiary-care facility for sphincter of Oddi reevaluation. An objective causality assessment revealed the adverse drug event as probable.. Despite alternative opioids, meperidine continues to be used in pain management. Meperidine is different from other opioids because its active metabolite, normeperidine, is neurotoxic. Patients with renal insufficiency, liver failure, or CNS dysfunction are at increased risk for adverse drug reactions related to normeperidine accumulation. Due to normeperidine's extended half-life, however, accumulation of normeperidine can occur in any patient receiving repeated doses of meperidine.. This case demonstrates the potential hazards that exist when using meperidine in any patient. Meperidine's inherent risks of both undertreating pain and causing adverse drug reactions should prompt clinicians and health organizations to restrict its use in pain management. This restriction should not make exceptions to meperidine's traditional use in pancreatitis or sphincter of Oddi dysfunction.

Topics: Analgesics, Opioid; Buprenorphine; Common Bile Duct Diseases; Female; Humans; Meperidine; Middle Aged; Seizures; Sphincter of Oddi

N-Cyclopropylmethyl-[7alpha,8alpha,2', 3']-cyclohexano-1'[S]-hydroxy-6,14-endo-ethenotetrahydronororip avine (BU48) is a novel, ring-constrained analog of buprenorphine. In vivo, BU48 (0.1-10 mg/kg s.c.) produced brief, nonlethal convulsions in mice followed by brief Straub tail and a short period of catalepsy characteristic of BW373U86 and other nonpeptidic delta-receptor agonists. BU48-induced convulsions were sensitive to antagonism by naltrindole (10 mg/kg s.c.) and were also prevented by administration of the putative delta(1) antagonist 7-benzylidenenaltrexone and the putative delta(2) antagonist naltriben, with the latter being more potent. In the abdominal stretch assay in the mouse, only low-efficacy antinociceptive activity of BU48 (0.1-10 mg/kg) was seen. This was reversed by the kappa-opioid antagonist norbinaltorphimine (32 mg/kg s.c.) but not by the delta-opioid antagonist naltrindole (10 mg/kg s.c.). BU48 (10 mg/kg s.c.) acted as a delta-antagonist in this assay. In mouse brain homogenates, BU48 had high (nanomolar) binding affinity for all three opioid receptors in the order mu > delta = kappa. In vitro, the compound acted as a potent (EC(50) = 1.4 nM) kappa-opioid agonist in the guinea pig ileum and a potent (EC(50) = 0.2 nM) delta-opioid agonist in the mouse vas deferens but showed partial agonist activity at the rat cloned delta-opioid (40%) and human cloned kappa-opioid (59%) receptors with very low efficacy at the rat cloned mu-opioid receptor (10%); findings consistent with its in vivo profile. BU48 is the first described compound that produces delta-opioid-mediated convulsions without any evidence of delta-opioid-mediated antinociception and will be a useful tool in investigations of the delta-opioid receptor.

Topics: Analgesics, Opioid; Animals; Benzamides; Brain; Buprenorphine; Convulsants; Electric Stimulation; Guanosine 5'-O-(3-Thiotriphosphate); Guinea Pigs; Ileum; In Vitro Techniques; Male; Mice; Muscle Contraction; Muscle, Smooth; Naltrexone; Narcotic Antagonists; Pain Measurement; Piperazines; Radioligand Assay; Rats; Receptors, Opioid, delta; Receptors, Opioid, kappa; Seizures; Vas Deferens

Buprenorphine (0.3-3.0 mg/kg) produced dose-dependent protection against the lethal effects of cocaine in mice. The (+)-enantiomer of buprenorphine did not protect up to doses over 100 times greater than the lowest effective dose of its (-)-enantiomer. The protective effects were also produced by the opioid agonists morphine and methadone, but not by the opioid antagonist, naltrexone. Low doses of naltrexone (0.3-1.0 mg/kg) blocked the protective effects of buprenorphine. Protection conferred by buprenorphine was not observed in CXBK mice, a recombinant inbred strain relatively devoid of mu-opioid receptors. Thus, buprenorphine appears to protect against the lethal effects of cocaine by a process mediated by mu-opioid receptors. The present results should provide some additional safety assurance in future clinical trials with buprenorphine, especially in outpatient trials where cocaine abuse may continue along with treatment.

Topics: Animals; Brain; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Methadone; Mice; Mice, Inbred Strains; Morphine; Naltrexone; Receptors, Opioid; Receptors, Opioid, mu; Seizures