Introduction Flashcards
Drug
Chemical compound that may produce physiological, behavioural and physiological effects
Psychoactive effects
Alterations to cognition, behaviour and motor processes
4 drug names
Chemical
Generic (Non-proprietary)
Trade (Proprietary
Street
Heroin
Diacetylmorphine– morphine with 2 acetyl groups so it enters the brain quicker
Pharmokinetics
Administration Absorption Distribution Metabolism Elimination
Pharmodynamics
Interaction between drug and receptors at site of action
Path of oral administration
Stomach
Small intestine
Blood stream
Alkaline Drugs
Bases– Become ionized in stomach acid and can’t pass into bloodstream– go to small intestine which is a more alkaline environment
How do drugs pass into the blood stream in the small inetstine
Passive diffusion following the alkaline concentration gradient
First Pass metabolism
Drugs are routed to the liver where most is metabolized
Cytochrome P-450
Very large group of enzymes in the endoplasmic reticulum of liver cells
Inducible
Activity may be potentiated
Mucous membrane administration
Snorting or absorbing through skin
How fast does inhalation get drugs to the brain?
5-8 seconds
– faster than intravenous
Regions in order of blood supply
Peritoneal cavity
Muscles
Under the skin
What injection site absorbs the quickest
Intraperitoneal– the most blood
Mainlining
Intravenous injection– blood flow in region is irrelevant
Skin popping
Subcutaneous injection
Where do drugs given by injection or pulmonary routes distribute to?
Diffuse through pores in capillary walls and into bloodstream
Oral distribution
Must be lipid soluble to be absorbed by digestive system beacause there are no pores in GI tract lining
How often is total blood volume circulated
Once a minute
Ionization
Weak acids readily ionize in alkaline environments and become less ionized in acidic environments – Reverse is true for bases
Are ionized molecules readily absorbed?
No
What determines rate of absorption
% of non-ionized molecules
What part of the GI tract absorbs drugs better
Further away from stomach where its less acidic
Lipid Solubility
Lipid soluble compounds penetrate cell membranes more readily
What types of molecules does the blood brain barrier limit
Water soluble
Ionized
Fetal blood supply
75-100% of mothers blood concentration in 5 minutes
Receptor binding
Drugs interact with receptors at relevant targets – receptors are oppositely charged from groups on drugs
Agonist
Mimics the effects of a neurotransmitter
– bind to receptors, block reuptake, inhibit breakdown
Antagonist
Reduce the effects of a receptor agonist by binding to active receptors but producing no effect
Dose response curve
Vertical axis– % of subjects exhibiting measured effect
– Allows comparison of potency of drugs
Are the DRC of more potent drugs to the left or the right?
Left– Smaller dose is required to produce the same effect
ED50
Dose of drug that produces a response in 50% of the subjects
LD50
Dose that kills 50% of subjects (lethal dose)
Therapeutic index
Ratio of LD50/ED50 for a given drug effect
– the higher the ratio, the less chance that lethal effects will occur
Margin of safety
More conservative measure of safety
LD1/ED99
Tolerance
Progressive attenuation of a drug effect
Which way does tolerance shift DRC
Right– more dose needed to produce the same effect
Sensitization
Drug effects are augmented over time
Which way does sensitization shift DRC
Left– Less dose needed to produce the same effect
Routes of elimination
Skin
Lungs
Kidneys
Sweat/Exhalation
Major site for enzymatic breakdown
Liver– Cytochrome P-450
Which drug inhibits Cythochrome p450 activity
SSRI
What is renal absorption dependant on?
pH— acids are excreted easier when urine basic
Elimination half-life
Time needed for half of a drug dose to be eliminated
How many half lives for a drug to be eliminated?
6
Steady stae concentration
Steady blood concentration needed for best therapeutic results
Interneuronal Synaptic junction
Presynaptic element and post-synaptic receptor area
Autoreceptors
Presynaptic receptors play a negative feedback role in regulating release of NT
Precursor substances
Amino acids from diet are building blocks of neurotransmitters
Synthesis of Neurotransmitters
Precursor + synthesizing agents– sent to presynaptic terminal for storage, release and bind to recptors
Acetylcholine
Broken down by acetylcholinesterase
Responsible for learning and memory
Dopamine
Broken down by MAO
Pleasure, movement, schizophrenia
Norepinephrine
Broken down by catechol-o-methyl-transferase
– Mood and affect
Serotonin
Broken down by MAO and aldehyde dehydrogenase
– Mood, appetite, sex, sleep, aggression, hallucinations
Glutamate
Excitatory NT involved in neural plasticity
GABA
Inhibitory NT involved in anxiety
Opioid Peptides
Endorphins and enkephalins interacting with mu, kappa, delta and sigma receptors
Behavioural pharmacology paradigms
Specific experimental procedures designed to provide standardized data about certain aspects of drug effect
Withdrawal symptoms
Exact opposite of drug effects
Reactive Adaptation
Body anticipates changes from drug and homeostatic processes take place in advance
Classic Conditioning
Uncontrolled stimulus does not elicit a response of interest in the beginning, is paired with another controlled stimulus that does elicit response of interest
What does CS elicit
CR
Situational specificity of drug tolerance
Predrug cues must be present to show tolerance– CS must be present for CR to occur
Placebo CR Test
See the drug compensatory CR when the CS drug cues are presented but no drug is administered
How does a placebo test differ from a SSDT test?
In a placebo test, all animals receive saline injections during the test phase (no drug is administered)
How long does withdrawallast
7-10 days
Priming Effect
Returning to same environment after treatment can produce subclinical withdrawal symptoms
Subclinical Withdrawal Symptoms
Presence of pre drug cues with no drug produces a compensatory CR and some withdrawal symptoms
Extinction
Presenting the CS and not following it with the expected UCS – Can’t just withhold UCS
How is self administration maintained
Positive and negative reinforcement
Operant Self-Administration Paradigm
See if animals will press a lever to be rewarded with drug injections– gage reinforcement properties of drugs against other natural reinforcers like food and sex
Breaking point
The largest number of responses an animal will make to obtain a drug
Which type of drugs have the highest breaking points
Stimulants
Which drugs have the lowest breaking point
Hallucinogens
What NT system is important for positive reinforcement
Dopaminergic activity in ventral tegmental and in nucleus accumbens
Disadvantages of Operant SA
Requires surgical preparation of animals and is expensive
- Difficult to determine aversive effects
Advantages of operant SA
Allows for more obvious comparisons of reinforcing effects an shows patterns of self-administration
Conditioned Place-Preference Paradigm
Uses two boxes differing in tactile and visual stimulation
- If drug is positively reinforced , rats will spend more time in that box as opposed to where they received a saline injection
