Ch 1: Principles of Psychopharm Flashcards
Drugs have biological effects because
They interact with receptors of target tissues
Define: Receptor
Define: Ligand
A ligand that are high affinity for the receptor is..
Receptor: large protein molecules located on a cell; INITIAL site of action of all ligands
Ligand: any molecules that binds to a receptor with some selectivity
a ligand that most readily attaches to the receptor
Define Antagonist
Capable of binding but produces no physiological change; they ‘block agonist activity” by preventing agonists from binding to the same receptor
ligands with low efficacy
Inverse agonists
Binds to a receptor and initiatives a biological response that is opposite of the one produced by the agonist
Is binding of a specific ligand to a receptor reversible?
generally, yes
What is the number of receptors influenced by?
stimulation
prolonged stimulation - causes down regulation
absences of stimulation - causes up regulation
What does a dose-response curve show?
with an increasing dose, the effect also increases in a linear fashion UNTIL maximum effect is reached
What is an ED50 dose?
a dose that produces a half-maximal effect (50%)
The MORE potent drug is the one with a lower ED 50
What is the TI?
Therapeutic Index
Compares the TD50 (50% toxic dose ) with the ED 50 - provides a measurement for drug safety
What effect do competitive receptor antagonists have on the potency of an agonist? What effect does this have on the dose-response curve?
Competitive receptor agonists REDUCE potency of an agonist
Dose-response curve shifts (parallel) to the right, with NO change in maximum effect
What effect can biobehavioural interactions of drugs produce?
Physiological antagonism
Additive effects
Potentiation
Potential results of chronic drug use:
1) may lead ro a reduction in biobehavioural effects (TOLERANCE)
or sometimes
2) SENSITIZATION
What is cross tolerance?
When repeated use of one dru reduced the effectiveness of a second drug
Is tolerance reversible? What is this dependent on?
Generally reversible
Dependent on: dose, frequency of use, and drug-taking environment
- not all drugs induce tolerance
- not all effects of a given drug undergo tolerance to the same extent/same rate
What is pharmodynamics?
What is pharmodynamic tolerance?
Pharmacodynamics: the study of the physiological and biochemical interaction of drug molecules with target tissue, which is ultimately responsible for drug effects
Tolerance: the adaptation of the nervous system to continued presence of the drug by increasing or decreasing receptors or producing other compensatory intracelluar processes
What is behavioural tolerance?
When learning processes and environmental cutes contribute to the reduction in drug effectiveness
e.g. pavlovian conditioning/operant conditioning
What is sensitization? How is it difference from tolerance?
Dependent on dose, intervals between treatments and drug-taking environment
Cross-sensitization with other drugs can occur
UNLIKE TOLERANCE:
- sensitization is not readily reversible
- persists long periods of abstinence caused by LONG-TERM physiological changes to the cells.
Define: Psychopharmacology
The scientific study of the actions of drugs and their effects on a living organism : specifically the drug-induced changes on mood, thinking and behaviour
Define: Phamacokinetics
Interacting Pharamokinetic factors determine HOW MUCH free drug is in the blood (bioavailability)
5 pharmokinetic factors that influence the bioavilability of the drug:
- method of admin
- rate of absorption/distribution
- binding at inactive sites (drug depots) e.g plasma proteins, bone, fat (
- biotransformation (INACTIVATION - occurs in the liver)
- excretion
What are lipid soluble drugs?
NOT ionized, and readily pass through fatty membranes, through passive diffusion based on concentration gradient (higher to lower concen)
Lipid solubility increases the absoprtion of a drug into the blood and determines readiness for brain entry
ONLY lipid soluble drugs can enter the brain
What is the importance of the blood-brain barrier
ONLY lipid soluble drugs can enter the brain
Drug distribution is usually determied by volume of blood flow to the tisues EXCEPT for the brain due to specialized brain capilarries
Effect of drugs are determined by:
1) How much of drug reaches target site
2) How quickly the drug reaches that site
What factors is absorption dependent on?
Absorption: movement or drug from site of admin to blood circulation; mostly occurs in small intestine
- method of admin
- soluability and ionization of the drug
- individuals differences: age, sex, body size
Define Half Life
HALF LIFE: the rate at which a drug is removed from the body
Drug clearance usually occurs by first-order kinetics - where a CONSTANT fraction of the free drug is removed during each time internal (the internal is called the half life)
some drugs have zero-order kinetics : clearance occurs at constant rate regardless of drug concentration
Important because it determines the internals required between doses
What is enzymatic drug metabolism/biotransformation?
Occurs in liver - produces chemical change to drug molecule that makes in inactive and more water soluable
Cytochrom P450 family of enzymes is the most important type of liver enzyme for transforming psychotropic drugs
Describe the process of drug metabolism
Phase 1: oxidation, reduction or hydrolysis to produce a ionized metabolically that may less, equally or more active that parent drug. (NONSYNTHETIC)
Phase 2: Conguation of drug with a simple molecule provided by the body e.g. glucuronide or sulfate. Products are ALWAYS inactive and more water soluble (SYNTHETIC).
Contrast drug action vs drug effects
Drug action: specific molecular changes produced by drug when it binds to a target site/receptor
Drug effects: when molecular change leads to more widespread physiological/psychological effects
Site of drug action may not be the same as site of drug effects
Contrast drug action vs drug effects
Drug action: specific molecular changes produced by drug when it binds to a target site/receptor
Drug effects: when molecular change leads to more widespread physiologica/psychological effects
Site of drug action may not be the same as site of drug effects
Contrast specific drug effect with non-specific drug effect
Specific: based on physical and biochemical interactions of a drug with target site in living tissue
Nonspecific drug effects: based on unique individual’s background e.g. mood, expectations, attitude et.c
What is depot binding? What are the effects?
Binding of a drug to an inactive site e.g. plasma, bone, fat
Has significant effects on the magnitude and the duration of the drug action
- reduces concentration of the drug at action site due to lower concentration of free circulating drug
- onset of drug may be delayed
Can also cause overdose because binding to inactive sites is over nonselective: therefore increasing competition between drugs : may results in a higher blood concentration than anticipated
- cannot be processed by liver
