Pharmacology of Tolerance: Types, Mechanisms, and Homeostasis

Tolerance

A decreased effect of a drug after repeated use or the need to take a higher dose to get the same effect.

Acute Tolerance

When a drug's effect is stronger during absorption than it is at the same blood level during elimination (happens within a single use).

Cross Tolerance

When tolerance to one drug causes reduced sensitivity to another drug that works similarly (e.g. alcohol and sedatives).

Pharmacokinetic Tolerance (Metabolic / Dispositional Tolerance)

When the body becomes faster at metabolizing (breaking down) the drug, meaning fewer drug molecules reach the target site.

Pharmacodynamic Tolerance (Physiological / Cellular Tolerance)

When the body or brain adjusts to maintain balance (homeostasis) despite continued drug use, making the drug less effective.

Homeostasis

The body's ability to maintain stable internal conditions (like temperature or chemical balance) despite outside changes.

Feedback Loops

Body systems that automatically adjust functions to maintain normal balance.

Up-Regulation

When the body increases the number of receptors because drug effects are too low.

Down-Regulation

When the body reduces the number of receptors because drug effects are too strong.

Behavioral Tolerance

When experience or learning helps reduce the drug's effects — the person learns to function under the influence.

Functional Disturbance

Tolerance develops only when a drug disrupts a function that's important or active at that moment.

Pharmacokinetic Mechanism

Tolerance caused by changes in metabolism or drug movement through the body.

Pharmacodynamic Mechanism

Tolerance caused by changes in the brain or body's physiological response to the drug.

Conditioning (Classical & Operant)

Learning processes that can contribute to behavioral tolerance through repeated association of cues or actions with drug effects.