Psychopharmacology(psychoactive drugs)

1. Name ways to get a drug into your system (sources of drug administration)

2. Rank those sources based on how fast they reach blood & thus the brain

3. List the factors that determine the effect of a drug on an individual. (In other words, what makes a psychoactive drug be more effective in one person than another)

Group activity

Outline

• Pharmacokinetics– Dose-response curve

• Pharmacodynamics– Drugs vs. NTs– Agonists vs. Antagonists– Receptor types

• Tolerance

• Specific Neurotransmitter Systems (& drugs that affect them)

• Whatever the body does to the drug

• how drugs are– absorbed, – distributed within the

body, – metabolized, and– excreted.

• Whatever the drug does to the body

• Main effect: increasing or decreasing the effect of neurotransmitter X

• Side effects (unwanted effects)

PharmacodynamicsPharmacokinetics

Pharmacokinetics

• Sources of administration: oral, intranasal, inhalation, topic, intravenous (i.v), sublingual, intramuscular (i.m.) subcutaneous, intraperitoneal

• Distribution: – Lipids (fats) vs. non-lipids (proteins, ionized molecules)

• Metabolization: liver• Excretion: kidneys

– Half-life: time it takes to eliminate half the drug from the bloodstream. It is used to determine inter-dose interval

Ways to administer a drug (& time to reach blood)

Dose-response curve: Effect of a drug as a function of the amount of the drug administered.

Therapeutic index: The ratio between the dose that produces the desired effect in 50% of the animals and the dose that produces toxic effects in 50% of the animals.

Pharmacodynamics

• A drug can do only two things, either: – Increase the effect of neurotransmitter X (agonist)– Decrease the effect of neurotransmitter X (antagonist)

Thus, in order to understand the action of a ‘drug X’, we need to understand the neurochemical system it interacts with.

In other words, we need to understand how Neurotransmitter X - is produced & released from the pre-synaptic neuron - acts on the receptors of the post-synaptic neuron- is removed from the synaptic cleft

Pre-synapticNeuron(axon)

Post-synapticneuron

(dendrite)

1. produce

precursors

2. pack 3. release 4. Bind 5. Post-synapticchanges

(e.g., epsp)

6.A Recycle

synapticcleft

6.B Destroy

Post-synaptic receptors

Pre-synaptic receptors

NT ‘x’

AP Ca++ inflow

- -

+ +

Copyright © Allyn & Bacon 2004

Receptors• Receptors are specific for individual neurotransmitters• More than one receptor for each neurotransmitter. e.g., Acetylcholine

(muscarinic & nicotinic receptors)

Ionotropic Receptors(e.g., nicotinic) Metabotropic Receptors

(e.g., muscarinic)

Agonists and Antagonists

• Agonist (Greek: Agon, meaning contest)– Substance that facilitates post-synaptic

effects

• Antagonist – Substance that inhibits or blocks the post-

synaptic effects

• Exogenous vs. Endogenous (drugs vs. neurotransmitters)• Agonist vs. Antagonist: Both bind to a receptor. The agonist

activates it, the antagonist does not (antagonists block the receptor) • Competitive vs. non-competitive: whether the drug works at the

same receptor as the NT or at a different receptor as the NT, but one that modifies the NT’s action

1. Will an antagonist produce a rightward shift or a leftward shift in the dose-response curve? (graph)

2. How would a competitive antagonist modify the curve? (draw with a solid line)

3. How would a non-competitive antagonist modify the curve (draw with a dotted line) Group activity

Tolerance a decreased response due to frequent use.

• Metabolic tolerance: faster metabolism of the drug.This is a pharmacokinetic mechanism (e.g., alcohol metabolization by hepatic enzimes)

• Cellular-adaptive tolerance: down-regulation of receptors (a pharmacodynamic mechanism)

Before drug

After Drug

Factors that determine the effect of a drug on an individual

• Age• Weight• Setting in which the drug is used• History of use (tolerance)• Level of proteins in blood • Time of day drug is consumed

• These effects are underlined by both pharmacokinetic and pharmacodynamic modulations