Chapter 3: How We Adapt to Drugs – Tolerance, Sensitization, and Expectation

Flashcards covering key definitions and mechanisms of drug tolerance, including pharmacokinetic, pharmacodynamic, and behavioral tolerance, as well as related concepts like functional disturbances, cross-tolerance, and acute tolerance, based on Chapter 3 Part I (p. 36-38).

How is drug tolerance defined according to the lecture notes?

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

Why is it often more useful to think of developing tolerance to drug effects rather than to the drugs themselves?

Because tolerance to different effects of a drug develops at different rates; some effects develop quickly, some slowly, and some not at all.

What is an example of differential tolerance using morphine?

Tolerance to morphine's nausea develops very quickly, but no tolerance develops to its ability to constrict the pupils of the eyes.

What is pharmacokinetic tolerance also known as, and how does it arise?

Also known as Metabolic or Dispositional Tolerance, it arises from an increase in the rate or ability of the body to metabolize a drug, resulting in fewer drug molecules reaching their sites of action.

What is generally the mechanism of pharmacokinetic tolerance, and what is its consequence for drug effects?

It is generally the result of enzyme induction, which diminishes all effects of the drug and can create cross-tolerance with other drugs metabolized by the same enzyme.

What is pharmacodynamic tolerance also called, and how does it occur?

Also called Physiological or Cellular Tolerance, it arises from adjustments made by the body to compensate for an effect of the continued presence of a drug, largely due to homeostasis.

What is homeostasis?

The ability or tendency of a living organism, cell, or group to keep the conditions inside it the same despite any changes in the conditions around it.

How does homeostasis contribute to pharmacodynamic tolerance during repeated drug administration?

If a drug is repeatedly administered, the body gets better at restoring normal function and diminishing the disruptive effect of the drug, due to homeostatic feedback loops.

How do receptors contribute to pharmacodynamic tolerance?

Repeated activation of receptors leads to receptor down-regulation (fewer receptors), while decreased receptor activation induces up-regulation, both attempting to restore the normal level of information flow through the synapse.

What is behavioral tolerance?

It is when an organism learns through experience with a drug to decrease the effect the drug is having, involving both operant and classical conditioning.

What is required for drug-induced physiological changes to lead to tolerance, beyond just physiological disruption?

The drug-induced change usually needs to be of some significance to the animal; disruptions of physiology alone are not always sufficient to cause tolerance.

Provide an example illustrating the concept of functional disturbances and tolerance development.

Amphetamine causes anorexia in rats; tolerance develops only when administered to hungry rats in the presence of food, allowing the drug to interfere with the organism's functioning. If no food is present, tolerance to the anorectic effects does not develop.

What is cross-tolerance?

It is when tolerance to one drug diminishes the effect of another drug, often between drugs with similar functions or effects (e.g., alcohol and sedatives) by acting on the same cell receptor or affecting the transmission of certain neurotransmitters.

What are the mechanistic bases for cross-tolerance?

Cross-tolerance may be mechanistically pharmacokinetic, pharmacodynamic, and/or behavioral.

What is acute tolerance?

With some drugs, the effect can be greater at a specific blood level during absorption than it is at the same blood level during elimination.

What did the study by Cromer et al. (2010) find regarding acute tolerance to alcohol?

While subjective perception of intoxication and visuomotor speed showed acute tolerance, executive functions and short-term memory showed no significant difference, implying that people might feel less intoxicated but still have impaired 'higher order' cognitive functions.