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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