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Flashcards in Tolerance and Withdrawal Deck (21)
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Psychiatric Tolerance

The need to increase the dose in order to achieve the desired effect or progressive loss of effect while taking the same dose. The need may not be connected to a bodily function, but could be based on belief that they need to take the drug


Psychiatric Dependence

The continued use of a drug resulting in significant consequences for either the patient individually or for his or her close environment


WHO Dependence

A strong compulsion to take the drug on a continuous or periodic basis


WHO Tolerance

Neuroadaptive or altered changes that occur with repeated exposure to a drug that results in a measured reduction in response to a constant dose. usually takes from days to weeks


Time Course of Responses

Activation of ion channels- ms
Second messenger formation- s
Activated enzyme- 1 hr
RNA synthesis- 1 day
Protein synthesis- 1-3 days
Enzyme Activity- 1-10 days


Tolerance Biological

State in which an organism no longer responds to a drug or the response is attenuated
Higher dose is required to achieve the same effect


Pharmacodynamic Tolerance

Altered response to drug at cellular level
Rate depends on particular drug, dosage and frequency of use
Differential development for different effects of same drug
1. Response to drug attenuates as a result of adaptations in the body that reduce activity at the receptor
2. Signal intensity remains the same, but initial response is counteracted by homeostatic changes in biochemical, cellular or effector systems


Pharmacodynamic Tolerance Model

Altered reactivity to the drug may be due to changes in brain chemistry, second messenger, receptor sensitivity or density
May also involve protein synthesis
May also be explained by differential expression of genetic characteristics


Pharmacodynamic Tolerance- Protein Synthesis

Weekly injections of morphine cause tolerance to the analgesic effects
Cyclohexamide, a protein synthesis inhibitor, dramatically decreases this tolerance
Effect took 2-3 weeks to develop and persisted for a number of weeks


Pharmacodynamic Tolerance- Dosing

Key is continued dosing of drug. Interrupting exposure prevents tolerance from fully developing
Balance must be maintained with duration of action-- sustained release can develop tolerance fairly quickly because doses are not often missed


Metabolic Tolerance

Reduced drug effect due to enhanced metabolism or elimination by the body due to increase in catalytic enzymes
Most commonly observed as an increase n the production in enzymes that break down or metabolize the drug
Alcohol dehydrogenase breaks down alcohol and liver enzymes break down barbiturates


Behavioral Tolerance

The degree to which an individual can learn to compensate for the effects of a drug
Thought to be related to conditioned cues associated with the drug
These elicit a response that opposite that of the drug
Rats that did not overdose in their home cage overdosed in a stranger cage
May contribute to higher amount of overdoses in shooting galleries because people are in a foreign environment


Cross Tolerance

When tolerance has developed to one drug, drugs within the same class will have attenuated responses
Methadone tolerant individuals are cross tolerant to heroine
Does not work with drugs not in the same drug class


Reverse Tolerance

Tolerance can decrease with drugs that damage brain tissue
This lost brain tissue can cause the entire drug experience to be different and less pleasurable
ex. MDMA


Acute Tolerance

Developing tolerance to a drug within hours
Usually happens when several doses are taken in a short amount of time


Selective Tolerance

Tolerance can develop to different effects of the same drug at different rates
One may build up a tolerance to the analgesic effects of morphine without building a tolerance to the physical effects
This can often times be the cause of overdose


Inverse Tolerance

Repeated use of a drug can cause an increased sensitivity to it.
Brain anticipates the effects and enhances them
Marihuana and cocaine users become more sensitive, and can have reactions even with non-drug substitutes


Physical Dependence

The physiological and biochemical changes that take place during continued exposure to a drug that result in withdrawal signs and symptoms if the drug is aborted
Reactions to termination of drug is called withdrawal or abstinence syndrome
Magnitude and duration of withdrawal can be manipulated by how the drug is withdrawn


Psychological Dependence

The perceived need for a drug to relieve pain, suffering, or withdrawal
Tied to drug related cues


Withdrawal Symptoms

When chronic exposure to a drug is terminated
Usually the opposite of the effects of the drug
Time course and severity dependent on the drug half life and how rapidly the drug was withdrawn
Signs and symptoms immediately reversed if drug, or drug in the same class, is administered
Also seen with non-drugs of abuse
Symptoms precipitated with agonist


Dose Tapering

Technique used to limit the amount of drug withdrawn
Doses gradually reduced over time
Prevents too rapid of a decline in blood levels