Chapter 3

Question 1

Define drug tolerance.

Answer 1

Drug tolerance is either the decreased effectiveness (or potency) of a drug that results from repeated administrations, or as the necessity of increasing the dose of drug in order to maintain its effectiveness after repeated administrations.

Question 2

Do all of the drug effects diminish at the same rate?

Answer 2

Not usually. Tolerance grows for different effects at different rates, some quickly, some longer. Better to think of tolerance for each of the drugs effects, rather than the whole drug itself.

Question 3

What is a synonym for tolerance?

Answer 3

Tachyphylaxis.
Latin: tachy = accelerated
phylaxis = protection.
Sometimes used to describe an rapidly developing tolerance to a drug effect. (also called Acute tolerance).

Question 4

What is acute tolerance?

Answer 4

Tolerance to a drug developed over a single administration.

Question 5

Describe an illustration for drug tolerance.

Answer 5

The drug effect shifted to the left of the drug level in blood. I.e., the effect peaks before the blood level peaks.

Question 6

Does drug tolerance last forever?

Answer 6

No, tolerance may disappear after the drug has not been taken for a while.

Question 7

What is cross-tolerance?

Answer 7

When tolerance to one drug diminishes the effect of another drug. Usually seen with members of the same class of drug. E.g., Opioids. It is likely that drugs that cause cross tolerance work with the same mechanisms.

Question 8

What are the four mechanisms of tolerance?

Answer 8

1. Pharmacokinetic Tolerance;
2. Pharmacodynamic Tolerance;
3. Functional Disturbances;
4. Behavioural Tolerance.

Question 9

What is Pharmacokinetic Tolerance?

Answer 9

(Also called metabolic tolerance or dispositional tolerance) results from an increase in the rate or ability of the body to metabolize a drug, resulting in fewer drug moleules reaching their sites of action.
This is usually caused by an increase in enzyme concentrations that destroy the drug.
This affects all of the drug effects equally, because blood level of the drug is diminished.

Question 10

What is Pharmacodynamic Tolerance?

Answer 10

Also known as physiological or cellular tolerance. Arises from the body adjusting to the effects of the drug - a result of homeostasis (mainly homeostatic feed back loops). Thermostat example of a feedback loop.
When a drug is taken and alters some aspect of functioning, the body’s response is controlled by a homeostatic mechanism - which will detect the disruption and sends this information to the control center responsible for this function. The control center responds by compensating for the disruption (e.g., the thermostat turning the heat on when it gets too cold).

Question 11

What happens to pharmacodynamic tolerance over time?

Answer 11

When the drug has been discontinued, the compensatory processes weaken. Some are weakened rapidly, others more slowly. Some weeks to months.

Question 12

Give an example of pharmacodynamic tolerance.

Answer 12

Upregulation and downregulation of neurotransmitter receptors. If the drug blocks the receptor sites on the postsynaptic plate, the cell may respond by creating more receptor sites. This is an example of upregulation. If the drug was stimulating the receptors, the cell may reduce the amount of receptors, which would be downregulation.

Question 13

What are functional disturbances as they relate to tolerance?

Answer 13

Tolerance to a drug effect is dependent upon the presence of the symptom. For example, the analgesic effect of morphine will not diminish by much if the rat is not subjected to pain. If pain is present, then tolerance to morphine’s analgesic effect will occur more quickly.

Question 14

What is behavioural tolerance?

Answer 14

The organisms ability to learn how to decrease the effect of the drug.

Question 15

What are withdrawal symptoms?

Answer 15

Withdrawal symptoms are physiological changes that occur when the use of a drug is stopped or the dosage is decreased. Families of drugs will often produce similar withdrawal symptoms.
These withdrawal symptoms vary in intensity from drug to drug.
Can be produced much more quickly by giving the antagonist drug. E.g., giving Nalozone to organisms dependent on morphine.

Question 16

What is dependence?

Answer 16

When a person who takes a drug will experience withdrawal when a drug is discontinued. Also called physical dependence, and physiological dependence.

Question 17

What is opponent process theory?

Answer 17

Tolerance and withdrawal are thought to be linked. Withdrawal symptoms are thought to be the result of the body’s physiological response to the drug’s effects when the drug is no longer producing those effects. It takes the body some time to readjust to the physiological changes it has made in response to the drug to maintain homeostasis. During the readjustment, it is these compensatory response that cause withdrawal symptoms.

Question 18

What are the dynamics in opponent process theory?

Answer 18

Abused drugs stimulate an A process that creates a euphoric state, but soon after, a compensatory B process is evoked that creates a dysphoric state. During a single drug administration, first the A process dominates, but but once the B process kicks , it very uickly dcancesl out some of the euphoria. As the drug wears off, so does the A process, but the B process endures for a while. E.g., a hangover (sensitive to bright lights and noises) the result of compensatory responses.

Question 19

Explain opponent process theory as it relates to acute tolerance.

Answer 19

When you take a drug, its effect will be greatest before the B processes build up. As the B processes get stronger, the strength of the A process will diminish. This explains why a drug effect could e greater at a particular blood level as the drug levels are rising than at the same point as the blood levels of a drug are falling.

Question 20

Explain how classical conditioning relates to drug stimuli and responses.

Answer 20

Giving a dog a drug which causes salivation is the Unconditioned Stimulus (US), the salivation to the drug is the Unconditioned Response (UR). Over trials, the dog will begin to salivate to the stimuli that are present before drug administration because an association between the two has been made. So the stimuli preceding the drug becomes the Conditioned Stimulus (CS) and salivation to this preceding stimuli before the drug has been administered is the Conditioned Response (CR).

Question 21

Explain Classical Conditioning of Compensatory Responses.

Answer 21

Often, the Conditioned Response will not be the drug’s effect, but the body’s compensatory response to the drug. So if you walk into Tim Hortons to get coffee you would become tired because your body has already started to use compensatory responses to work against caffeine before you even take it, due to classical conditioning.

Question 22

Explain Classical Conditioning of Drug Tolerance.

Answer 22

Read textbook section.

Environment repeatedly associated with the drug acts like a conditioned stimulus, but rather than becoming a CS for the effect the drug is having, it becomes a CS for the physiological changes the body is making to compensate for the drugs effect. The environment associated with the administration of the drug elicits physiological responses opposite to the effect of the drug. These changes help prepare the body of the drug and diminish its effect.

Question 23

Explain classical conditioning of withdrawal.

Answer 23

Learning may be responsible for some withdrawal symptoms. A recovered heroin addict who no longer experiences withdrawal may experience withdrawal symptoms when they return to places where they frequently took the drug.

Question 24

Explain Operant conditioning of drug tolerance.

Answer 24

Read textbook section.

Question 25

What is sensitization?

Answer 25

When a drug is administered repeatedly, it can sometimes result in the opposite of tolerance, that is the body becomes more sensitive to the effects of the drug.

This is much less common.

Question 26

Explain the placebo effect.

Answer 26

It is clear that the context in which a drug is administered is capable of having a significant influence on the effect of that drug. One of the most powerful contextual effects is whether you know a dug is being administered at all, that is, whether you are expecting a drug effect and what you think that effect will be like. This is the placebo effect.

It is a part of the therapeutic effect of many drugs, even up to 70%!

Question 27

Describe a placebo effect study with unexpected results.

Answer 27

Four groups:

1. No treatment.
2. Placebo pill.
3. Drug (Proglumide).
4. Not aware of receiving drug.

Result was that placebo was more effective than no treatment, and drug was more effective than placebo. However, when subjects did not know they were getting the drug, the drug had no effect.

Possible explanation is an “expectation mechanism” - a top down pain relieving pathway from the cortex to a pain control center in the lower brain that is capable of blocking pain. Proglumide was not relieving pain directly, but stimulating this expectation mechanism, which is why it was more effective than placebo.

Question 28

What are the factors that modify the placebo effect?

Answer 28

• The biggest factor is the strength of expectation.
• Belief that subject (who is in the placebo group) is in the treatment group rather than the placebo group.
• Desire for an effective treatment.

Question 29

What is the “nocebo effect”?

Answer 29

Subjects in the placebo group experiencing side effects, likely because of expectations from reading packaging labels, hearing side effects listed on commercials.

Question 30

What is the effect of self administration on drug effectiveness?

Answer 30

There are differences when a drug is administered by the subject and by other people. Studies have shown that levels of dopamine in the nucleus accumbens were higher in rats that were allowed to press a lever to give themselves injections of cocaine than in rats that passively received an injection every time the rats in the self-administration group gave themselves an injection.

Question 31

What is the influence of novel environments on taking a drug?

Answer 31

Research shows that drug effects are different when the drug is administered in a novel environment.
Stimulant drugs like cocaine and amphetamine tend to cause increases in motor behaviour after they are administered, and with repeated administrations (sensitization). If the drug is administered in a novel environment, the amount of locomotor stimulation is considerably more than would be seen if the drug had been administered in a familiar setting.

Sensitization of this effect is much more rapid and can be induced at a lower dose if the drug is given in a novel setting.

When drugs are administered in a novel setting it can have different effects on the nervous system.

Question 32

Describe a study on the placebo effect that found some unexpected results.

Answer 32

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