Benzodiazepines tolerance

Lechin F, van der Dijs B, Benaim M (1996) Benzodiazepines tolerability in elderly patients. Psy-chother Psychosom 65(4) 171-182... 

Drug and alcohol dependent patients Use with caution in patients with alcoholism and other drug dependencies due to the increased frequency of benzodiazepine tolerance and dependence observed in these patient populations. 

Tolerance to many of the effects of the depressants develops. Unlike opioids, barbiturate and benzodiazepine tolerance develops slowly. Also, tolerance is incomplete in some instances or does not influence some pharmacological effects. One such exception is the lack of tolerance to barbiturate lethality. The lethal dose in a tolerant individual is not much different from that of the general population. Cross-tolerance develops to some degree between the depressant classes of drugs. 

Miller NS, Gold MS. Benzodiazepines tolerance, dependence, abuse, and addiction. J Psychoactive Drugs 1990 22(l) 23-33. 

Benzodiazepine tolerance and dependence are avoided by using low-dose therapy for the shortest possible duration. 

Promethazine 25-50 mg PO/IM 100 mg Sedating antihistamine - useful if benzodiazepine tolerant Wait longer to assess effect before repeating (IM = onset 1-2 h PO longer)... 

The CCK system shares one property with the opioid system, ie, the existence of selective nonpeptide antagonists. These include aspedicine, a natural benzodiazepine (136), and Devazepide (L-364,718 MK-329) (137). Selective, potent peptide antagonists for CCK, eg, Cl-988 and PD 134308, have been developed that maybe useful as anxiolytics and as dmgs which increase the analgesic effect of morphine but at the same time prevent morphine tolerance (138) (see Hypnotics, sedatives, anticonvulsants, and anxiolytics). 

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. 

Bleich A, Gelkopf M, Weizman T, et al Benzodiazepine abuse in a methadone maintenance treatment clinic in Israel characteristics and a pharmacotherapeutic approach. Isr J Psychiatry Relat Sci 39 104-112, 2002 Bohn LM, Gainetdinov RR, Lin FT, et al Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature 408 720— 723, 2000... 

Pharmacodynamic tolerance to the psychomotor effects of benzodiazepines has been demonstrated after single or multiple doses (File 1985 Greenblatt and Shader 1978 Rosenberg and Chiu 1985). Pharmacodynamic tolerance to the anxiolytic effect (over a 6-month period) has not been demonstrated (Rickels et al. 1983), and clinical experience supports the view that many patients with anxiety disorders require long-term therapy with benzodiazepines or alternative antianxiety agents. An important clinical consequence of tolerance to sedative effects is observed in benzodiazepine overdoses, when patients may initially be... 

Benzodiazepines do not induce their own metabolism, and thete is no evidence for the development of pharmacokinetic toletance (Gteenblatt and Shader 1986). The behavioral tolerance seen with chronic dosing is explicable entirely on the basis of pharmacodynamic tolerance (as described earlier in the overview of neuropharmacology). 

Not cross-tolerant to benzodiazepines and should not be used for acute withdrawal high doses may be used to treat anxiety disorders to help maintain long-term discontinuation after abstinence has been achieved. 

Darragh A, Lambe R, Kenny M, et al Tolerance of healrhy volunteers to intravenous administration of the benzodiazepine antagonist Ro 15-1788. EurJ Clin Pharmacol 24 569-370, 1983... 

File SE Tolerance to the behavioral actions of benzodiazepines. Neurosci Biobehav... 

Greenblatt DJ, Shader RI Dependence, tolerance, and addiction to benzodiazepines clinical and pharmacokinetic considerations. Drug Merab Rev 8 13-28, 1978... 

Greenblatt DJ, Shader RI Long-term administration of benzodiazepines pharmacokinetic versus pharmacodynamic tolerance. Psychopharmacol Bull 22 416 23, 1986... 

Miller LG, Greenblatt DJ, Barnhill JG, et al Chronic benzodiazepine administration, I tolerance is associated with benzodiazepine receptor downregulation and decreased gamma-aminobutyric acidA receptor function. J Pharmacol Exp Ther 246 170-176, 1988a... 

Perera KM, Jenner FA Some characteristics distinguishing high and low dose users of benzodiazepines. Br J Addict 82 1329-1334, 1987 Perez MF, Salmiron R, Ramirez OA NMDA-NRl and -NR2B subunits mRNA expression in the hippocampus of rats tolerant to diazepam. Behav Brain Res 144 119-124, 2003... 

Clonazepam, a typical 1 4 benzodiazepine, is effective in absence seizures, myoclonic jerks and tonic-clonic seizures and given intravenously it attenuates status epilepticus. It is less sedative than phenobarbitone but tolerance develops and its withdrawal, as... 

P-adrenergic blockers or clonidine may be utilized in conjunction with benzodiazepines in patients with coronary artery disease who may not tolerate adrenergic excess ° Limited experience with dexmedetomidine... 

Assess patients for improvement of anxiety symptoms and for return to baseline occupational, social, and interpersonal functioning. With effective treatment, the patient should have no or minimal symptoms of anxiety or depression. While drug therapy is being initiated, evaluate patients more frequently to ensure tolerability and response. Increase the dose in patients exhibiting a partial response after 2 to 4 weeks on an antidepressant or 2 weeks on a benzodiazepine. Individualize the duration of treatment because some patients require up to one year of treatment.27... 

---