Alprazolam drug dependence

Alprazolam has caused a lower incidence of drowsiness, light-headedness and depression than diazepam. Alprazolam, like other benzodiazepines, has the potential for the development of tolerance and withdrawal symptoms, although the incidence is lower than that seen with other benzodiazepines. Alprazolam s potential for drug dependence is less in comparison to other benzodiazepines. 

Klein E, Uhde TW, Post RM Preliminary evidence for the utility of carbamazepine in alprazolam withdrawal. Am J Psychiatry 143 235—236, 1986 Kouyanou K, Pither CE, Wessely S Medication misuse, abuse and dependence in chronic pain patients. J Psychosom Res 43 497-304, 1997 Kryspin-Exner K [Misuse of bezodiazepine derivatives in alcoholics] (German). Br J Addict Alcohol Other Drugs 61 283-290, 1966 Kryspin-Exner K, Demel 1 The use of tranquilizers in the treatment of mixed drug abuse. Int J Clin Pharmacol Biopharm 12 13-18, 1973... 

The speciflc clinical use of the numerous available benzodiazepines depends on their individual pharmacokinetic and pharmacodynamic properties. Drugs with a high affinity for the GABAa receptor (alprazolam, clonazepam, lorazepam) have high anxiolytic efficacy drugs with a short duration of action (temazepam) are used as hypnotics to minimise daytime sedative effects. Diazepam has a long half-life and duration of action and may be favoured for long-term use or when there is a history of withdrawal problems oxazepam has a slow onset of action and may be less susceptible to abuse. 

Most sedative drugs, including narcotics and alcohol, potentiate the sedative effects of benzodiazepines. In addition, medications that inhibit hepatic cytochrome P450 (CYP) 3A3/4 increase blood levels and hence side effects of clonazepam, alprazolam, midazolam, and triazolam. Lorazepam, oxazepam, and temazepam are not dependent on hepatic enzymes for metabolism. Therefore, they are not affected by hepatic disease or the inhibition of hepatic enzymes. 

Insomnia is a common complaint in the elderly. As people age they require less sleep, and a variety of physical ailments to which the elderly are subject can cause a change in the sleep pattern (e.g. cerebral atherosclerosis, heart disease, decreased pulmonary function), as can depression. Providing sedative hypnotics are warranted, the judicious use of short half-life benzodiazepines such as temazepam, triazolam, oxazepam and alprazolam for a period not exceeding 1-2 months may be appropriate. Because of their side effects, there would appear to be little merit in using chloral hydrate or related drugs in the treatment of insomnia in the elderly. It should be noted that even benzodiazepines which have a relatively short half-life are likely to cause excessive day-time sedation. The side effects and dependence potential of the anxiolytics and sedative hypnotics have been covered elsewhere in this volume (Chapter 9). 

Fig. 23. Effects of diazepam, alprazolam and buspirone on drug discrimination in rats trained to discriminate 2 mg/kg i.p. diazepam from saline. Note the dose-dependent generalization of lower doses of diazepam towards responding on die lever associated with the training dose of diazepam, with a similar generalization curve for alprazolam. Buspirone does not generalize to diazepam.

CANNABIS ANXIOLYTICS AND HYPNOTICS-BZDs-alprazolam, diazepam, midazolam, triazolam Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index Induction or inhibition of CYP3A4-mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes... 

Other clinical uses Tricyclic drugs are also used in the treatment of bipolar affective disorders, acute panic attacks, phobic disorders (compare with alprazolam Chapter 22), enuresis, and chronic pain states. Clomipramine and the selective serotonin reuptake inhibitors, including fiuvoxamine, are effective in obsessive-compulsive disorders. SSRls are also effective in patients who suffer from panic attacks, social phobias, bulimia, and premenstrual syndrome (PMS) and may also be useful in the treatment of alcohol dependence. Bupropion is used for management of patients attempting to withdraw from nicotine dependence. 

As with depression, those who are battling or have battled cancer sometimes report feelings of anxiousness that may also respond to medications. Benzodiazepines (BZs) are one class of drugs used in the treatment of anxiety and insomnia. Unlike antidepressants, they work almost immediately. The drugs include lorazepam (Ativan), alprazolam (Xanax), diazepam (Valium), clonazepam (Klonopin), chlordiazepoxide (Librium) and triazolam (Halcion). Some people do become dependent upon BZs, but the drugs are generally safe... 

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