Chapter 1 Flashcards
psychopharmacology
study of actions of substances and their effects on mood, cognition, and behavior
neuropharmacology
study of substance-induced brain changes at the physiological, receptor, biochemical, and molecular levels
pharmacokinetics
how our bodies affect the actions of a substance (ADME)
ADME
absorption, distribution, metabolism, elimination
pharmacodynamics
how a substance affects our bodies and brains
How do substances cause molecular changes in a cell?
substances are ligands that selectively act on receptors or target sites
therapeutic effect
when substance-receptor interaction produces desired physiological/behavioral changes
side effects
other effects that accompany the desired/main effect
physiological factors affecting substance action
dose and chemical structure of substance
bioavailability
amount of the substance in the blood that is free to bind at a target site
inactivation
body changes substance to make it easier to get rid of through excretion
types of administration
oral
intravenous
instramuscular
intraperitoneal
inhalation
subcutaneous
topical
transdermal
epidural
effect of drug administration type
drug concentration varies based on administration type
factors affecting absorption
membrane structure
lipid soluble substances
ionized substances
pH
pKa
higher absorption of organs (small intestines)
size of individual
sex
pKa
pH of aqueous solution at which 50% of the substance would be ionized
selective barriers to substances
fenestrae (pores; allow substance to move from blood plasma to ECF fairly freely)
blood brain barrier (prevents certain compounds from entering the brain)
placenta (separates blood of mother from fetus)
acute toxicity
high substance level in mother is amplified in fetus
teratogens
induce developmental abnormalities
substance depots
substances can bind at inactive sites where no physiological effect is initiated
can have major impact on substance magnitude and duration
first-order kinetics
metabolism/biotransformation that occurs at an exponential rate
50% of substance removes at each time interval
zero-order kinetics
metabolism/biotransformation that occurs at a constant rate
half-life
t (1/2) ; time required to remove 50% of substance in blood
type I biotransformation
nonsynthetic
oxidation (loss of H or gain of O)
reduction (gain of H or loss of O)
hydrolysis (split H2O into H+ and OH-)
type II biotransformation
synthetic reactions
combine substance with some other molecule to inactivate or ionize it
enzyme induction
increase in liver enzymes
can lead to tolerance because metabolism is sped up
enzyme inhibition
inhibit enzyme activity and reduce metabolism of other substances
can cause more intense or prolonged effect
substance competition
two substances compete for the same enzyme
an elevated concentration of either drug reduces the metabolic rate of the second, causing potentially toxic levels
genetic polymorphism
genetic variation produces a variety of active forms proteins
can explain why some individuals need higher or lower doses than others to achieve the same effect
how are drugs excreted?
mostly through the kidneys
also sweat, saliva, feces, breast milk, breath
conditions needed for drugs to be excreted
water soluble and ionized
how does pH affect excretion
drugs w/ opposite pH of tubular urine are more ionized and less easily reabsorbed, so they are excreted more easily
conformational change
change in receptors due to ligands temporarily binding to them
initiates a cascade of biochemical events
up regulation of receptors
number of receptors increasing due to absence of substance
down regulation of receptors
number of receptors decrease due to abundance of substance
why is it important to design substances that bind to one subtype of receptors?
fewer side effects
what causes a drug action/effect?
agonist-receptor interaction
agonist
ligand that activates the receptor
has affinity and efficacy
affinity
ability to bind or fit into receptor
high affinity = best fit = strong drug effect
antagonist
ligands that bind to receptors but do not cause effect
can have high affinity but still no efficacy
competitive antagonist
ligand and antagonist compete for one receptor
noncompetitive antagonist
ligand and antagonist bind to different receptors but activation is still stopped
minimal effects upstream or downstream of receptor sites
types of receptor competition
physiological antagonism (two drugs cancel out each other’s effects)
additive effects (outcome is sum of two reactions)
potentiation (both drugs together has greater results than the singular effect of either)
orthosteric site
where ligands bind to activate receptor
what effect?
no ligand in orthosteric site
no ligand in allosteric site
no signal / closed
what effect?
no ligand in orthosteric site
ligand in allosteric site
no signal / closed
what effect?
ligand in orthosteric site
positive allosteric modulator in allosteric site
increased signaling / enhanced opening
what effect?
ligand in orthosteric site
negative allosteric modulator in allosteric site
decreased signaling / smaller opening
what effect?
ligand in orthosteric site
neutral allosteric modulator in allosteric site
unaltered signaling
dose response curves
used to compare amount of biological response for a given dosage
the closer the curves are on the x-axis, the less safe it is for that effect
ED(50)
dose that produces half the maximal effect (ED(100))
ED(100) can be toxic so middle effect is desired
potency
absolute amount needed to produce the effect
TD(50)
dose at which 50% of people suffer a toxic/undesirable effect
formula for TI
therapeutic index = TD(50) / ED(50)
tolerance
needing higher dose of substance after repeated use
can be due to physiological mechanisms
generally reversible depending on dose and frequency of use
rates differ depending on substance
cross tolerance
tolerance to one substance builds tolerance for another
acute tolerance
rapid, after one use
metabolic tolerance
aka substance disposition tolerance
repeated use decreases amount of substance that reaches the target tissue
pharmacodynamic tolerance
aka cellular tolerance
change in neuronal function or receptor regulation
behavioral tolerance
tolerance showed in environment/behavior but not in a neuronal or cellular level
