Chapter 1: Pharmacodynamics, Tolerance, Pharmacogenetics

Slide 80-109

Pharmacodynamics

Study of the interaction of drug molecules with specific receptors

Surface receptors

most drugs do not pass cell membranes, but act on the surface of them via receptors to cause chemical changes

Receptor Agonist

have high affinity for a receptor; binds to the receptor and initiates a cellular response

Receptor Antagonist

bind to receptors but produce no effect (low efficacy) and prevents other agonist from binding

Partial agonist

have intermediate efficacy

inverse agonist

initiate an action opposite to that produced by a regular agonist

Receptor Lifespan

The number and sensitivity of a receptor can change based on how much it is used.

Up-Regulation

number of receptors increases

chronic receptor antagonist —> upregulation

Down-Regulation

Number of receptors is reduced in response to the absence of a ligand or constant activation

Agonists —> downregulation

Receptor Subtypes

Receptors with different characteristics in different tissues

Dose-Response Curve

Describes extent of biological or behavioral effect produced by a given drug concentration (dose)

50% Effective Dose (ED50)

the dose that produces half the maximal effect; half receptors are occupied

Maximum Response/Effective Dose (ED100)

Assume all receptors are occupied

Threshold

dose that produces the smallest measurable response

Potency

Amount of drug necessary to produce a specific effect

Comparing ED50 shows potency of drugs despite them having the same efficacy

Efficacy

The capacity of drugs to be effective

Toxic Dose 50% (TD50)

a dose at which 50% of the population experiences a toxic effect

Therapeutic Index (TI)

TD50/ED50

Competitive Antagonists

Compete with agonist to bind receptors but don’t initiate effects, reducing effects of the agonist

Can be displaced by excess of agonist

think of the caterpillar

EX: Naloxone is a competitive antagonist of morphine

Noncompetitive Antagonist

Binding to receptor at a site other than the agonist binding site, and prevents the agonist from binding to its site

disturbing the cell membrane supporting the receptor

Think of the brick under the faucet

Physiological Antagonism

Two drugs interact and reduce the effectiveness of each other

EX: A positive and negative effect both becoming milder

Additive Effects

The two drugs are similar, and therefore add their effects together to become more potent

EX: Taking two different pain meds

Potentiation

The combination of two drugs produces effects greater than the sum of their individual effects

Tolerance

Repeated drug exposure causes a diminished response to the drug, to achieve the same effect the dose must increase

• dependent on dose and frequency

• may occur rapidly, after long periods of chronic use, or never

• not all effects show the same degree of tolerance

Is reversable when stopping taking the drug

Cross Tolerance

Tolerance to one drug can diminish effectiveness of a second, different drug

Sensitization

the effects of the drugs are increased after repeated exposure

AKA reverse tolerance

These effects can persist over long periods of abstinence

Cross-sensitization can occur

Metabolic Tolerance (Drug Disposition Tolerance)

When drugs increase their own rate of metabolism by liver microsomal enzyme induction

Pharmacodynamic Tolerance

Neural function changes to adapt to continued presence of the drug by up or down regulation

Contributes to withdrawl

Behavioral Tolerance

When in the same environment as the drug being administered, you can experience tolerance

Acute Tolerance

After one administration

Pavlovian Tolerance

The drug-taking procedure or environment elicits a conditioned response

Operant Conditioning Tolerance

Learning to cope;

EX: an individual with alcohol use disorder learns to maneuver efficiently while intoxicated

State-Dependent Learning Tolerance

The state you are in can influence tolerance

Tasks learned under the influence of a psychoactive drug may then be performed better in the drugged state compared to the sober state

Pharmacogenetics

Study of genetic basis for variability in drug response among individuals

Drug dosage can be adjusted if an individuals genetic make up is known

Pharmacoepigenetics

Take into account epigenetic modifications (demographic factors, environmental factors, ect) that can alter gene function

Genetic Screening

To perfectly administer a dose for a patient, genetic screening must take place

Trial and Error, the current method, is timely and costly

However genetic screening is limited, expensive, laborious, and requires large amounts of data but holds promise for psychiatric treatment