Tolerance, physical

Changes have also been reported to occur in the sub-unit composition of the GABA-A receptor following chronic exposure to barbiturates, neurosteroids, ethanol and benzodiazepine agonists. These changes may underlie the development of tolerance, physical dependence and the problems which are associated with the abrupt withdrawal of such drugs. 

With frequently repeated therapeutic doses of morphine or its surrogates, there is a gradual loss in effectiveness this loss of effectiveness is denoted tolerance. To reproduce the original response, a larger dose must be administered. Along with tolerance, physical dependence develops. Physical dependence is defined as a characteristic withdrawal or abstinence syndrome when a drug is stopped or an antagonist is administered (see also Chapter 32). 

Tolerance, physical dependence and addiction are possible with the benzodiazepines but less likely to occur than with barbiturates. In general this class of compounds does not cause induction. The potential for suicide is also lessened with these compounds. It has been estimated that physical dependence occurs in one person out of five million. Withdrawal symptoms are real but usually not life-threatening (fatigue due to REM rebound, dizziness, CNS disturbances). In general, benzodiazepines do not cause induction. 

Tolerance, physical dependence and receptors. A theory of the genesis of tolerance and physical dependence through drug-induced changes in the number of receptors, 3, 171... 

Barbiturates (a class of drugs with more effective sedative-hypnotic effects) replaced bromides in 1903. Depending on the dose, frequency, and duration of use, however, tolerance, physical dependence, and psychological dependence on barbiturates can occur relatively rapidly. With the development of tolerance, the margin of safety between the effective dose and the lethal dose becomes very narrow. That is, in order to obtain the same level of intoxication, the tolerant abuser may raise his or her dose to a level that can produce coma and death. 

Three factors are generally involved in drug dependence tolerance, physical dependence and psychological dependence. 

It must be emphasized that the relationship between tolerance, physical dependence and compulsive drug use is complex and depends both on the category of drug and the personality of the abuser. For example, it appears that the majority of patients prescribed benzodiazepines for periods of many months experience relatively minor withdrawal symptoms when the drugs are abruptly stopped. Others, however, experience severe anxiety states and have extreme difficulty in stopping the drug. 

Tolerance, physical dependence and withdrawal are a natural consequence of the properties of drugs of dependence. They can be produced in experimental animals as readily as they can in man but the symptoms do not always imply that the individual is dependent on a drug of abuse. For example, a patient with hypertension who is receiving a beta-adrenoceptor antagonist such as propranolol will probably exhibit a withdrawal syndrome consisting of a rebound hypertension when the drug is abruptly withdrawn. 

Morphine tolerance, physical dependence, and synthesis of brain 5-hydroxytryptamine... 

Tolerance, Physical Dependence, and Withdrawal Frequent, repeated use of psychedehc drugs is unusual, and thus tolerance is not commonly seen. Tolerance does develop to the behavioral effects of LSD after 3-4 daily doses, but no withdrawal syndrome has been observed. 

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