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PHARMACOLOGY:
THE SCIENCE OF
DRUG ACTION
Chapters 4 and 5
Pharmacology
Pharmacokinetics
Explains the processes involved in administration,
absorption, distribution, transformation, and
elimination a drug
Pharmacodynamics
Explains the nature of physiological and
biochemical interactions between a drug and the
target tissue responsible for the drug effect
Pharmacokinetics
Administration
Absorption
Distribution
Biotransformation
Excretion
Routes of Administration
Oral
Intramuscular (IM)
Intraperitoneal (IP)
Intravenous (IV)
Inhalation
Intracranial (IC)
Intracerebroventricular
Topical
Absorption
Moving from the site of administration to the
bloodstream
Drugs exert effects by first traveling into the
bloodstream
How fast do drugs leave the site of administration?
Route
Acidity/Alkalinity
Absorption relates to bioavailability
The amount of the drug that reaches the bloodstream
and/or site of action
Distribution
Refers to a drug’s ability to reach a wide
range of tissues
Solubility – Lipid solubility. Highly lipid soluble =
greater distribution and effect.
Blood Brain Barrier
Depot binding: Drug binding to inactive sites
Fat, Protein, Muscle
THC testing
Blood-brain barrier limits
drug access to brain
Biotransformation
Drug Metabolization – Mainly in
LIVER
Many drugs are broken down into
other compounds. Some are not
transformed at all
Enzymes break down drugs into
metabolites
Drugs that use the same enzyme
interact
Metabolites can be active or
inactive
Metabolization occurs in an
ordered manner
Half-life – The amount of time it
takes for drug plasma level to be
reduced by half
THC – 20 hours – 9 days
Cocaine – 45 minutes
Zoloft 2-3 days Prozac 7-9 days
Drug Elimination
Drugs are excreted in a variety of ways
Urine
Breath
Feces
Sweat
Can be excreted changed or unchanged
(alcohol vs. psylocibin)
Target - Receptor
Depot – Bone & Fat
Blood Plasma
Absorption &
Distribution
Administration
Oral, IV, IM, IP, SC,
Inhalation, TC
Plasma Protein
Binding
Metabolites
Liver
Excretion
Intestines, Kidneys,
Lungs, etc.
Feces, Urine,
Sweat, Saliva
Pharmacodynamics
Interaction between the drug and the target
tissue
For psychoactive drugs target tissues are
receptors in CNS
General Terms
Receptor
Site of initial interaction
Ligand
Any molecule that binds to a receptor
Agonists
Increases NT for a transmitter system
Antagonists
Decreases NT for a transmitter system
Receptors
IONOTROPIC
Work rapidly. Involved
in “fast” NT
Ion channels open when
NT occupies
Sodium
Calcium
Chloride
METABOTROPIC
Slower, longer lasting
Work through a “second
messenger”
Agonist/Antagonist
Agonist
Drug binds and induces full pharmacological effect
Partial Agonist
Drug binds and exerts only a partial effect
Competitive Antagonist
Binds to same receptor as agonist
Reduces the effect
Effect can be overcome by sufficient dose
Noncompetitive Antagonist
Binds in other ways, but disrupts agonist binding
Reduces the effect
Effect can not be overcome by sufficient dose
Forms of Drug Action at the Synapse
Ways to agonize
Stimulate release
Receptor binding
Inhibition of reuptake
Inhibition of deactivation
Promote synthesis
8.
Autoreceptors
Ways antagonize
Block release
Receptor blocker
Prevent synthesis
Acetylcholine
Agonists
Nicotine
Physostigmine
Antagonists
Muscarinic receptor Atropine
Nicotinic receptor Curare
GABA
•Valium, Xanax, Ativan
•Act as GABA agonists
•GHB, Rohypnol
•GABA agonist
Dopamine
Cocaine
dopamine reuptake
inhibitor
Amphetamine
increases DA release
Antipsychotics
block post-synaptic
dopamine receptor
Serotonin
Selective-serotonin
reuptake inhibitors
(SSRIs) – used to treat
depression
Dose Issues
General Drug Effects
Main Effect – The reason why the drug is taken
This may be therapeutic or recreational
Side Effects – All effects other than the main
effect
One person’s side-effect is another person’s main
effect.
Ultimately drugs have an effect, we label it base on
need or context.
Dose Response Curve
Dose-Response Curve
Plots the relation between the dose of the
drug and the size of the effect
Specific to the behavior you are
measuring
Drugs have multiple effects and curves
DRC Characteristics
Slope
gradual versus steep
Potency
amount required to
produce effect
Maximum efficacy
upper end where
response levels out
100
80
% of
Maximal
60
Effect
40
20
0
0
200
400
600
Drug Dose
800
Effective vs. Lethal Dose
Effective Dose (ED)
Dose level for chosen
effect in % of population
ED50, dose in which
drug is effective for 50%
of population
Lethal Dose (LD)
Dose level for death in %
of population
LD50 = lethal dose for
50% of the population
Therapeutic Index
LD50/ED50 - Serves as margin
of drug’s safety
Higher ratio more
safe/less toxic
20 or more = relatively
safe, 100 preferred
Drug Interactions
Using multiple drugs increases the complexity of
the experience
Antagonism – One drug inhibits the effect of another
drug
Cocaine and alcohol (Pharmacodynamic)
St. John’s Wort and Birth Control Pills (Pharmacokinetic)
Potentiation – The two drugs together produced and
enhanced effect
Alcohol and nicotine
Street “dynamics”
Reality is that with illicit drugs,
pharmacodynamics is ignored
Most drugs are diluted
Changes ED
Most are “cut” with dangerous compounds
Changes LD
Sometimes dose is too high, leading to acute
toxicity
Potentiation and Antagonism work here
ISSUES OF REPEATED USE
Tolerance Sensitization Dependence and Withdrawal
Tolerance
Decreased response to drug with repeated
use
Shifting DRC to the right
3 types
Metabolic
Liver enzymes
Cellular
Receptor down-regulation
Learned
Context/cues
Acute vs. Protracted
Acute is within a single administration
Cross-tolerance
Tolerance to one drug leads to tolerance
of other drugs in the same class.
Sensitization
Increased response to a drug
with repeated use
Shifting DRC to the left
Cocaine-induced, movement,
cataplexy and seizures
Cocaine is a good example of
a drug induces tolerance
(euphoria) and sensitization
(movement)
Repeated Self-Administration
Mesolimbic dopamine
system
Abused drugs all tend to
activate this system
3 stages
Pleasure
Associative learning
through classical
conditioning
Incentive salience
Craving (wanting)
Get DA release by
cues/context alone
Dependence/Withdrawal
Physiological Dependence
Body adapts to presence of drug. Needs drug on
board to maintain homeostasis
Indicated by the display of withdrawal symptoms
upon cessation of drug use
Withdrawal symptoms
Behaviors displayed by a user when drug use ends
Typically the opposite of the drug effect
BEHAVIORAL PHARMACOLOGY
Behavioral Pharmacology
Study of the relationship between the physiological
actions of drugs and their effects on behavior and
psychological function
Drugs do not create behaviors outside the normal species-typical
repertoire
They alter the probability or form of behaviors
Uses the principles of operant and classical conditioning
to examine the effects of drugs as well as the differences
and similarities between drugs
Self-administration studies
Discrimination studies
Conditioned place preference studies
Conflict paradigm studies
Self-administration
Train animal to press
lever for drug
administration
All drugs shown to be SA
by animals are SA by
humans
Alcohol
Cocaine
THC
Drug Discrimination
Drugs can serve as discriminative
stimuli
Animals learn to respond in certain
ways in the presence of a drug
Discrimination is related to
interoceptive cue
Using these techniques, it appears
that animals classify drugs just like
humans
Amphetamine and cocaine
alike, but different from
morphine, while morphine is
like heroin and other opiates
Method to ask animals about the
interoceptive cues associated
with different drugs
Press left lever if on morphine >
get food
Right lever if given saline > get
food
Give new drug - is it like
morphine?
Left lever - Yes
Right lever - No
Conditioned Place Preference
Pair drug
administration with a
place in the
environment
Give animal a choice of
where to hang out.
Measure where animal
spends time
Conflict Paradigm
Train animal to
associate both
reinforcement and
punishment with a
certain behavior
Tail-flick
test
Food and shock
Hot plate
test
w/lever press
Administer a drug to
test effects
Xanax
Light
source