General Pharmacology - lecture series

1. Drug Tolerance
Shivankan Kakkar, MD

2. Definition
Pharmacological concept describing a
subject’s
Reduced reaction
to a drug following its
Repeated use

3. Examples
•barbiturates,
•opiates,
•nitrates,
•xanthines,
•alcohols

4. Mechanism
•Pharmacokinetic (METABOLIC)
changes in drug pharmacokinetics (metabolism) leading to
decreased contact between a given drug and the target tissue.
•Pharmacodynamic
changes in the target tissue, that make them less sensitive to a
given drug concentration (cellular changes).

5. Mechanism
•Pharmacokinetic- e.g., induction of hepatic
microsomal enzyme systems after repeated
administration of barbiturates
•Pharmacodynamic- e.g., decrease in drug receptors
(down-regulation) after repeated administration of
opiates

6. Good to know
Tissue tolerance
•Development of tolerance is confined to certain effects or to
certain systems,
•E.g., morphine produces tolerance for its euphoriant effect, but
the pupils and the GI tract do not become tolerant.
•Thus, the same dose of morphine produces miosis and
constipation but may FAIL to produce euphoria.

7. Good to know
Cross tolerance
•If an individual initially develops tolerance to a drug
belonging to a particular group, he also shows tolerance
to other drugs from the same group.
•This phenomenon is known as cross tolerance e.g., that
between alcohol and the general anesthetics like ether.