Tolerance and Withdrawal

Question 1

Psychiatric Tolerance

Answer 1

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

Question 2

Psychiatric Dependence

Answer 2

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

Question 3

WHO Dependence

Answer 3

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

Question 4

WHO Tolerance

Answer 4

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

Question 5

Time Course of Responses

Answer 5

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

Question 6

Tolerance Biological

Answer 6

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

Question 7

Pharmacodynamic Tolerance

Answer 7

Altered response to drug at cellular level
Reversible
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

Question 8

Pharmacodynamic Tolerance Model

Answer 8

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

Question 9

Pharmacodynamic Tolerance- Protein Synthesis

Answer 9

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

Question 10

Pharmacodynamic Tolerance- Dosing

Answer 10

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

Question 11

Metabolic Tolerance

Answer 11

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

Question 12

Behavioral Tolerance

Answer 12

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

Question 13

Cross Tolerance

Answer 13

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

Question 14

Reverse Tolerance

Answer 14

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

Question 15

Acute Tolerance

Answer 15

Developing tolerance to a drug within hours

Usually happens when several doses are taken in a short amount of time

Question 16

Selective Tolerance

Answer 16

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

Question 17

Inverse Tolerance

Answer 17

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

Question 18

Physical Dependence

Answer 18

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

Question 19

Psychological Dependence

Answer 19

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

Question 20

Withdrawal Symptoms

Answer 20

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

Question 21

Dose Tapering

Answer 21

Technique used to limit the amount of drug withdrawn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