Benzodiazepine interactions

Figure 4.1 Benzodiazepines interact with the GABA receptor in the brain and activate the ceii membrane of neurons to open and allow negative chioride ions (Cl ) to enter the neuron (a, ), y subunits form the Cl- ion). This entry inhibits that neuron s ability to fire an action potential. The GABA receptor also has binding sites for other substances, such as steroids, barbiturates, and alcohol.

Haefely, W. The GABA-benzodiazepine interaction fifteen years later. Neurochem. Res. 15 (1990) 169-182. 

Benzodiazepines interact at the GABA receptor to increase the duration of chloride flow into the synapse. The end result is an increase in seizure threshold and inhibition of the spread of discharges from the epileptic foci. 

Schuster R, Bodem M Evaluation of ethanol-benzodiazepine-interactions using blood sampling protcxiol data. Blutalkohol (1997) 34,54-65. 

Orser BA, Miller DR. Propofol-benzodiazepine interactions insights from a bench to bedside" approach. Can J Anesih (2001) 48, 431-4. 

Kfeirti-Masso JF, Lopez de Munain A, Lopez de Dicastillo G. Ataxia following gastric bleed-ii due to omeprazole-benzodiazepine interaction Ann Pharmacother( 99 26,429-30. 

Benzodiazepines. Several BZs have anticonvulsant activity and ate used for the treatment of epilepsy producing their anticonvulsant actions via interactions with the GABA /BZ receptor complex to enhance inhibitory GABAergic transmission (1). The anticonvulsant actions of the BZs tend to tolerate upon chronic usage in six months, and BZs also lead to withdrawal symptomatology. Other side effects include sedation, ataxia, and cognitive impairment. 

Nonbenzodiazepine Benzodiazepine Receptor Ligands. The simultaneous discovery of the molecular target for the BZs, the GABA /BZ receptor complex, by two teams of workers (34,35) resulted ia the identification of a number of atypical or anxioselective anxiolytics that, whereas not having the BZ pharmacophore, interacted direcdy with the central BZ receptor. The anxioselective nature of such agents was considered to be... 

Synthesis of imidazo[l,2-d]pyridazines and their interaction with central and peripheral-type (mitochondrial) benzodiazepine receptors 98JHC1205. 

The anxiolytic agent buspirone (131) is notable for the fact that it does not interact with the receptor for the benzodiazepines. This difference in biochemical pharmacology is reflected in the fact that buspirone (131) seems to be devoid of some of the characteristic benzodiazepine side effects. The spiran function is apparently not required for anxiolytic activity. Alkylation of 3,3-dimethylglutarimide with dichlorobutane in the presence of strong base yields the intermedi-... 

Phenytoin interacts widi many different drugp. For example isoniazid, chloramphenicol, sulfonamides, benzodiazepines, succinimides, and cimetidine all increase phenytoin blood levels. The barbiturates, rifampin, theophylline, and warfarin decrease phenytoin blood levels. When administering the hydantoins with meperidine, die analgesic effect of meperidine is decreased. 

Valerian Valeriana officinalis Restlessness, sleep disorders Rare if used as directed. May interact with the barbiturates (eg, phenobarbital), the benzodiazepines (eg, diazepam) and the opiates, (eg, morphine). 

Sporadic use (e.g., for the induction of sleep after a psychostimulant binge) does not require specific detoxification. Sustained use can be treated as described in the previous sections on detoxification from therapeutic or high dosages but with added caution. In mixed opioid and benzodiazepine abuse, the patient should be stabilized with methadone (some clinicians use other oral preparations of opioids) and a benzodiazepine. Buprenorphine should not be administered with benzodiazepines, because a pharmacodynamic interaction is possible (Ibrahim et al. 2000 Kilicarslan and Sellers 2000) and fatalities have been reported with the combination (Reynaud et al. 1998). Sedative-hypnotic withdrawal is the more medically serious procedure, and we usually... 

Kilicarslan T, Sellers EM Lack of interaction of buprenorphine with flunitrazepam metabolism. Am J Psychiatry 137 1164-1166, 2000 King SA, Strain JJ Benzodiazepines and chronic pain. Pain 41 3-4, 1990a King SA, Strain JJ Benzodiazepine use by chronic pain patients. Clin J Pain 6 143-147, 1990b... 

White et al. 1982). Benzodiazepines may be useful, particularly if agitation is present, although clinicians must be mindful of a possible interaction leading to a prolonged half-life for ketamine (Lahti et al. 1995 Lo and Gumming 1975). In general, because of the short half-life of ketamine, patients usually require observation only for several hours and can then be released home (Koesters et al. 2002). 

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