Fundamental techniques and knowledge Flashcards
types of drug names (4)
(1) chemical, (2) generic (nonproprietary), (3) trade and (4) street
what does the stem (last part of name) of a generic drug name indicate?
class or function
stem that indicates an antidepressant
-oxetine
what is the trade name for diazepam?
Valium
stem for local anaesthetics
-caine (eg.dibucaine)
stem for antianxiety agents
-azepam (eg. lorazepam)
which type of drug name is capitalized?
trade names
excipients
fillers, coloring agents, binding agents, and coatings
what is the common street name for MDMA?
ecstasy
drug dosages are in ____
milligrams (mg)
a milligram is 1/____ of a gram
1000
behavioural and physiological effects of a drug are related to its _______ rather than the absolute amount of drug administered
concentration in the body
dose-response curve (DRC)
a graph with the dose on the x-axis and effect on the y-axis
the horizontal axis of a DRC curve is usually plotted ____
logarithmically
ED50
median effective dose
LD50
median lethal dose
median effective dose
the does that is effective in 50% of the individuals tested
median lethal dose
the does that is lethal in 50% of tested individuals
therapeutic index (TI)
the ratio of the LD50 to the ED50 (higher is safer)
TI = LD50/ED50
potency
differences in the ED50 of two drugs with the same effect (lower is more potent)
effectiveness
differences in the maximum effect that drugs will produce at any dose
antagonism
when one drug diminishes the effect of another
what shift would you see in a DRC if antagonism was occuring?
a shift to the right
additive effect
when one drug increases the effect of another
what shift would you see in a DRC if a drug was having an additive effect?
shift to the left
superadditive effect or potentiation
drugs have an effect together that is greater than might be expected simply by combing their effects
pharmacokinetics
the study of how drugs move into, get around in, and are eliminated from the body
processes of pharmacokinetics (3)
(1) absorption, (2) distribution and (3) elimination
sites of action
the area of the body where a drug has an effect
parenteral routes of administration
injection through the skin into various parts of the body using a hollow needle and syringe
divisions of parenteral routes of administration (4)
(1) subcutaneous, (2) intramuscular, (3) intraperitoneal, (4) intravenous +other
vehicle
the liquid in which a powder drug is dissolved or suspended (usually a weak salt solution)
common vehicle
normal or physiological saline (0.9% sodium chloride)
example of a non-water based vehicle and why it might be used
vegetable oil; if drug is not water soluble it may be lipid-soluble (slows rate of absorption and prolongs drug’s effect over several days)
bolus
the small bubble of drug and vehicle that is injected into the body
subcutaneous (s.c. or sub-q)
drug is injected to form a bolus just under the skin or cutaneous tissue (eg. arm, thigh)
intramuscular (i.m.)
needle is inserted into a muscle and a bolus is left there (eg. deltoid, gluteus maximus); usually absorbed through the muscle’s capillaries within about an hour
intraperitoneal (i.p.)
needle inserted directly into the peritoneal cavity
peritoneum
sack containing the visceral organs (eg. intestines, liver and spleen)
intravenous (i.v.)
needle is inserted into a vein and the drug is injected directly into the bloodstream (very quick distribution)
other parenteral routes (3)
(1) intrathecal (nervous system via space between the base of skull and first vertebra), (2) intracerebroventricular (brain’s ventricles) and (3) intracerebral (brain tissue)
cannula
like a catheter, except a rigid tube that is often attached to the animal’s skull using dental cement and can remain permanently implanted
absorption is NOT necessary in what type of parenteral route?
intravenous (i.v.)
which parenteral site absorbs the fastest?
intraperitoneal (i.p.)
which parenteral site absorbs the slowest?
subcutaneous (s.c)
which factors can speed up absorption from i.m. and s.c. sites?
heat and exercise (increases blood flow to skin and muscle)
which substances CANNOT move in and out of capillaries?
RBCs and large protein molecules
diffusion
the process by which a substance tends to move from an area of high concentration to an area of low concentration until the concentrations are equal in both areas
why is absorption faster from i.m. sites than s.c. sites?
muscles need oxygen so there is a richer capillary supply than the skin
how many litres of blood are in the body and how fast does the heart pump them?
about 6L; all 6 are pumped in about a minute
depot injections
the drug is dissolved in a high concentration in a viscous oil (often sesame) which is then injected into a muscle (usually the buttock); slowly diffuses over a long period of time (up to 4 weeks)
intranasal administration (insufflation)
sniffing/ snorting drugs
per oral/ per os (p.o.)
drugs absorbed into the body through the digestive system by swallowing
intrarectal administration
suppositories inserted into the rectum
olive oil partition coefficient
equal amounts olive oil and water are placed in a beaker and a fixed amount of drug is mixed in; later the oil and water are separated and the amount of drug dissolved in each is measured
when a molecule of a drug carries an electric charge (ion) it ____ it’s ability to dissolve in lipids
loses
percentage of ionized molecules in a solution is determined by what? (3)
(1) whether the drugs is a weak acid or a weak base, (2) whether it’s an acid or a base and (3) its pKa
pKa
pH at which half of the molecules are ionized
transdermal administration
absorbed through the skin
drugs must be _____ soluble for transdermal administration
lipid
highly lipid-soluble drugs tend to concentrate in ____ ___ outside the ___
body fat; CNS
when a drug is dissolved in fat it is, in effect, ____
inactive
because of ion trapping, drugs that are weak bases will be concentrated in the fluid on the side of a membrane that is more ___
acidic
difference is pH is logarithmically related to ______ difference
concentration
a pH difference of 3.0 across a membrane will create what size difference in concentration?
1000
blood-brain barrier
a special barrier of cells wrapped around capillaries and blocking pores separates blood and the brain (CNS); a solid lipid barrier
what are two examples of brain areas with weak/incomplete blood-brain barriers?
area postrema of the medulla oblongata (vomit response to toxins in the blood); subfornical organ (hormone level detecting)
passive transport mechanism
large protein molecules create channels that allow non-lipid-soluble molecules to pass through in response to diffusion; or carrier protein
active transport mechanism
works against normal diffusion by concentrating a substance on one side of a membrane; requires energy and only takes place in living membranes (eg. ion pump)
protein binding
drugs may attach to a protein that is too large to diffuse out of the capillary pores; remains attached until metabolized or never get to action site; may act like depot injections
placental barrier
similar to the blood-brain barrier
drug concentration in the blood of a fetus usually reaches ___-___% of that of the mother within ____ of administration
75-100%; 5 minutes
what is the dynamic duo of excretion?
(1) kidneys and (2) liver
liver function
comparable to that of a chemical factory; molecules are modified to form useful substances and toxic molecules are made less harmful and ready to be filtered out by kidneys
enzymes
catalyst; substance that controls a certain chemical reaction
metabolism
process of restructuring molecules
products of metabolism are ____
metabolites
in terms of drugs, metabolic processes are sometimes called _____
detoxification
does detoxification always lead to less harmful metabolites?
no; example is THC (causes prolonged action)
are metabolites usually more likely or less likely to ionize?
more likely
why is it important that metabolites often ionize?
ionized molecules cannot be reabsorbed by through the nephron wall, meaning it is easier to excrete them
first-pass metabolism
when drugs are absorbed from the digestive system and pass through the liver before going anywhere in the body; subject to a certain amount of metabolism by liver enzymes before reaching target site; can also experience some metabolism in the stomach and intestines before absorption (eg. alcohol)
primary function of kidneys
maintain correct water/salt balance in body fluids
the kidney acts as a ____
filter
what is the functional unit of the kidney?
nephron
Bowman’s capsule
one end of the nephron; contains a clump of capillaries called the glomerulus
glomerulus
clump of capillaries inside Bowman’s capsule
collecting tube
back end of the nephron which empties into the ureters/ urinary bladder
what passes through the pores in the capillaries of the glomerulus?
most things except RBCs, WBCs and large proteins
what passes through the pores in the capillaries of the glomerulus (out of the blood and into the nephron)?
most things except RBCs, WBCs and large proteins
the kidney does not filter out impurities, it _____
filters everything out and then selective reabsorbs what is required
mechanisms of kidney reabsorption (3)
(1) diffusion, (2) lipid solubility and (3) active/passive transport
pH of urine
6.0
pH of blood
7.5
at low concentrations, the rate of metabolism will be ___
lower
half-life of a drug
rate of excretion; time taken for the body to eliminate half of a given blood level of a drug
first order kinetics
when the elimination of a drug changes with concentration
what is an important example of a drug that CANOOT be described in terms of a half-life (has zero order kinetics)?
alcohol
the excretion curve for alcohol is a ____ line
straight
what is the general rate of alcohol excretion?
15mg of alcohol/ 100 ml blood/ hour
zero order kinetics
when the rate of elimination of a drug is a straight line
alcohol is converted into ______ by _____
acetaldehyde; alcohol dehydrogenase
acetaldehyde is converted into ___ ____ by the enzyme ______ ______
acetyl coenzyme; aldehyde dehydrogenase
levels of a given enzyme can be increased by what?
previous exposure to a specific drug that uses that enzyme or some other enzyme system (enzyme induction)
example of enzyme induction
heavy drinkers have increased levels of alcohol dehydrogenase in their liver
issue with St. John’s wort
used to treat depression but can reduce the effectiveness of many other drugs because of enzyme induction (including oral contraceptives)
how are enzyme systems depressed?
when two drugs that use the same enzyme are introduced into the body at the same time they compete for it causing reduced metabolism of both drugs
why is it dangerous to take Disulfiram (Antabuse) with alcohol?
it competes for aldehyde dehydrogenase which is needed to convert acetaldehyde into acetyl conenzyme A…. causes a build up of acetaldehyde which is toxic; sometimes used to stop alcoholics from drinking
how can age affect enzyme function?
infants have immature enzyme systems that cause different pathways or lack of drug metabolism; elderly people have less efficient liver function so dosage has to be decreased
time course
effect of a drug (Y) over time (x) plotted on a graph (absorption and excretion)
therapeutic window
the range of blood concentrations of a drug between a level that is ineffective (therapeutic level) and a level that has toxic side effects (toxic level)
example of a drug with a narrow therapeutic window
lithium carbonate (bipolar disorder)
why does risk of overdosing on morphine increase with use?
tolerance to the therapeutic effect increases faster than tolerance to the toxic effects, narrowing the therapeutic window over time (dose required for therapeutic effect gets closer to dose that causes toxic effects)
behavioural pharmacology (vs psychopharmacology)
investigation of drug effects using operant analysis of behaviour; psychopharmacology is more often used to refer to research studying drug treatments of mental illness or psych disorders
when and by whom was the term “behavioural pharmacology” coined?
Peter Dews; 1950s
aims of behavioural pharmacology (2)
(1) observing behavioural changes produced by drugs and (2) analyzing the mechanisms of the drug’s effect
what made the scientific study of behavioural pharmacology possible?
19th century development of modern chemical techniques that permitted isolation of drugs and synthesis of substances
when did interest grow among pharmacologists with regard to how drugs affecting the CNS alter behaviour?
1940s and 1950s
what was chlorpromazine marketed as in 1952?
antipsychotic
what was the first antipsychotic drug?
chlorpromazine
what did the success of chlorpromazine demonstrate?
the tremendous economic potential of behaviorally active drugs
escape-avoidance test
measures the ability of rats to avoid and escape electric shock by climbing up a pole; used to examine the effect of antipsychotic drugs
pentobarbital is a ____
sedative
Peter Dews pigeon experiment
looked at the effect of different doses of pentobarbital on the rate of key pecking of pigeons responding for food on two different schedules of reinforcement; showed that different dosages/ reinforcement schedules had different effects on behaviour
when was the behavioural pharmacology society founded?
1957
what is the independent variable in behavioural pharmacology?
drug dose
what is the dependent variable in behavioural pharmacology?
some change in behaviour
within-subjects design
compare the behaviour of a drugged participant with the drug-free behaviour of that participant under similar conditions
between-subjects design
compare the behaviour of a drugged participant with the behaviour of other drug-free participants under similar conditions
balanced placebo design
two groups are told they are getting the drug, but only one is and another two groups do not expect to get the drug, but one does
three-groups design
one group is given the drug, second group is given a placebo (left out for life-threatening diseases) and third group is given an established drug with known therapeutic effects
nonexperimental research
looks for a relationship between two measured events (eg. link between smoking during pregnancy and increased infant mortality); no cause-and-effect inferences
spontaneous motor activity (SMA)
measure of behaviour as how much there is
open field
a large open box
stereotyped behaviour
the continuous repetition of simple, purposeless acts such as rearing or head bobbing
methods of measuring unconditioned behaviour (4)
(1) spontaneous motor activity (SM), (2) inclined plane test, (3) elevated plus maze and (4) paw lick latency test
inclined plane test
animal is placed on a board that can be tilted to various degrees; the degree of tilt where the animals cannot hold on and slides off is a measure of muscle tone
elevated plus maze
narrow boards in the shape of a plus raised a foot or more off the ground, two opposite arms of the plus have walls and the other two do not; whether they venture to the unprotected arms is a measure of anxiety
paw lick latency test
rats placed on metal surface that is heated to about 500 degrees celsius; the time it takes for them to raise their hind paw to their mouth as though they were licking (paw lick latency) it is a measure of analgesic effect
manipulandum
something that an animal can manipulate or move (eg. bar, lever) (usually in Skinner box)
avoidance-escape task
light is warning of shock coming, if animal responds than the light is turned off (avoidance); animal can escape shock by responding once it has started
what are avoidance-escape tasks used for?
determining if anti-psychotic drugs will work; interferes with an animal’s ability to avoid the shock but not to escape it
apparatuses used for the avoidance-escape task (3)
(1) skinner box, (2) shuttle box and (3) pole climbing
dissociation or state-dependent learning
events experienced in a drugged state might not have the ability to control behaviour when the organism is not drugged and vice-versa (eg. T-Maze avoidance-escape task)
substitution test
animal is taught to discriminate between saline and a drug, then given a substitute drug (see how similar to original drug)
abuse liability
the reinforcing property of a drug is an indication of its potential for abuse
techniques for determining abuse liability (4)
(1) rate of responding, (2) progressive ratio schedule of reinforcement, (3) choice and (4) conditioned place preference
problems with the technique: rate of responding (2)
(1) different durations of action and (2) many drugs have effects that interfere with self-administration
breaking point
the point on a progressive ratio schedule of reinforcement in which the demand is too high and the animal will stop responding
higher breaking points are usually a sign that there is more potential for ___
abuse
visual analog scale (VAS)
participant makes a mark on a line between the two extreme alternatives to indicate how the variable applied to them
profile of mood states (POMS)
paper-and-pencil test that ask participants to indicated on a five-point scale how each of 72 adjs apply to them in the moment (8 subscales)
addiction research center inventory (ARCI)
developed so each class of drug has a unique profile of mood and physical changes; new drugs can be assessed in comparison to existing profiles
liking scale
indicate how much the drug is liked
absolute threshold
lowest value of a stimulus that can be detected by a sense organ
difference thresholds
measures of the ability of a sense organ to detect a change in level or locus of simulation
critical frequency at fusion
with increased speed of light flickering, eventually it will appear steady
tests of motor performance: reaction time (2)
(1) simple reaction time and (2) complex reaction time
test of hand-eye coordination
pursuit rotor; holding a stylus on a spot contained on a rotating disk
test for attention and vigilance
mackworth clock test; clock hand moves at regular intervals but occasionally will move two places instead of one, participant must click the button
test of short-term memory
N-back test; when a target stimulus appears, participant must recall the stimulus that was shown previously
tests of long-term memory (2)
(1) free recall and (2) cued recall
tests of inhibition (impulse control) (2)
(1) go-no go task and (2) go-stop task
main cell types in the nervous system (2)
(1) glial cells and (2) neurons
Glial cell function (3)
(1) structure, (2) protection, and (3) metabolic role (transport materials), (4) maintenance (destroy dead neurons), (5) active communicators
assumptions made for membrane potentials (2)
(1) relative (comparing inside to outside) and (2) the outside of the membrane is always considered equal to zero
passive processes (3)
(1) diffusion, (2) electrostatic charge, (3) differential permeability
nongated ion channels are always ___ but are specialized so that only ____ ions are permitted to pass through
open; certain
if Na+ wants to diffuse into the cell, why is it at higher concentrations outside the cell?
active transport via ion pumps
sodium-potassium pumps
transport three Na+ ions out of the cell for every two K+ ions they move in; more positive outside the cell
threshold
-55mV
what happens when the potential is reduced beyond the threshold?
voltage-gated ion channels open allowing the free flow of ions across the membrane; Na+ rush into cell; triggers K+ to leave cell; Na+ closes, K+ stays open for a bit longer
rising phase of an action potential
Na+ channels open (enters cell), causes depolarization which triggers K+ channels to open (leave cell)
where is the action potential generated
adjacent to the axon hillock
how do action potentials move down the neuron
Na+ that enter travel sideways along the insider surface; depolarizing the next section of axon
how does an action potential travel down myelinated neurons?
passively under section of myelin sheath and then retriggered by opening of Na+ channels at each node of ranvier
what is meant by saying action potentials are non-decremental?
they reach the axon terminal with the same strength as which they were initiated near the axon hillock
do action potentials move faster or slower along myelinated neurons?
much faster (salatory conduction)
salatory conduction
action potentials jumping from node to node along an axon
action potential speed
120 m/sec (431 km/hr)
all-or-none law
APs are always the same. As long as a stimulus is strong enough to depolarize a cell to its threshold, it will occur; increased the magnitude of depolarizing beyond the threshold does not change the size of the AP.
how are stimulus strengths conveyed?
RATE LAW; rate at which action potentials are generated
graded (postsynaptic) potentials
depolarization in the cell body and dendrites
intensity of GPs are proportional to the ____ of the disturbance
magnitude
the intensity of GPs ____ as the distance from the site of stimulation lengthens
decreases
EPSP
stimulation of dendrites or the cell body results in the opening of voltage-gated Na+ channels; Na+ will rush into the cell and depolarize it; enough EPSPs will cause depolarization past the threshold and an AP
IPSP
opening of voltage gated K+ channels; K+ will leave the cell causing hyperpolarization; making it harder for an AP to occur
can also be Cl- channels allowing, so they will enter (again hyperpolarizing the cell)
major types of integration (2)
(1) temporal summation and (2) spatial summation
temporal summation
when a neuron experiences several GP/PSPs closely in time
spatial summation
when two or more GP/PSPs occur in close proximity on a neuron
synapse
terminal buttons of one cell intertwine with structures of another cell
how are NTs released?
AP causes opening of Ca2+ voltage-gated channels, influx of Ca2+, triggers fusion of synaptic vesicles with membrane and subsequent exocytosis of NTs
neuromodulator
chemical that is synthesized and released by neurons and that modulates the effects of NT; short- or long-term effects
differences between neuromodulators and NTs
NMs are released in greater amount and travel further distances
how can a single NT produce a variety of results?
receptor subtypes
ionotropic receptors
binding sites directly connected to a gated ion channel; rapid action; brief affect
metabotropic receptors
indirect activation; cascade of events; slower and longer lasting; intracellular portion of protein is linked to G protein; subunit breaks away and activates nearby ion channel to stimulate an EPSP or IPSP; or synthesis of a second messenger
second messenger example
cAMP or cGMP; often interacts with gated ion channels from inside the cell (longer lasting effects compared to ionotropic receptors)
how can second messengers cause permanent effects?
activation of kinase proteins that are more persistent and remain active for longer than 2nd messengers; these can then influence transcription factors and gene expression
heteroreceptors
receptors on the presynaptic cell that respond to chemicals from the postsynaptic cell
autoreceptors
receptors on the presynaptic cell that respond to NTs from their own cell
retrograde signaling
transmission of chemical info from a post to presynaptic cell; mechanism by which the postsynaptic neuron can modulate its level of stim
ways postsynaptic cells modulate stim via retrograde signaling (2)
(1) depolarization-induced suppression of excitation (DSE) or (2) depolarization-induced suppression of inhibition (DS1)
terminating synaptic action (2)
(1) reuptake (most common) or (2) enzymatic degradation or deactivation
in the PNS, groups of cell bodies are called ___
ganglia
in the PNS, bundles of axons are called _____
nerves
in the CNS, cell body groups are called ___
nuclei/ centers
in the CNS, bundles of axons are called ___
tracts
nerves and tracts are ___ matter
white
unmyelinated cell bodies are called ___ matter
gray
primary NT of the sympathetic NS
epinephrine
primary NT of the parasympathetic NS
Acetylcholine
location of neurogenesis in adult humans (2)
(1) a region of the HC involved in the formation of new memories, (2) subventricular zone (lines brain’s lateral ventricles)
number of neurons in the human brain
100 billion (10^11)
on average, each neuron has synapses on ____ other neurons and receives an average of ____
10; 10 000
the spinal cord arises from the _______
medulla oblongata
vomiting center
area postrema
locus coeruleus
group of cell bodies in the pons; uses NE as a NT; depression is associated with it (arousal, fear, panic, and anger); inhibition causes anxiety relief and excitatory action causes anxiety
RAS function
maintain levels of activation in the cortex (arousal, selective attention, wakefulness)
example of how barbiturates work
enhance GABA which inhibits nueron activity in the RAS; decreases arousal
NT of raphe nuclei
serotonin
PAG functions (2)
(1) pain sensation and (2) defensive behaviour
stimulation of the PAG causes an immediate ___ of pain sensation
loss
cell bodies in the substania nigra produce which NT
DA
degeneration of DA cells is associated with which disease
Parkinson’s disease
VTA contains neurons that produce ____, _____, and ______
dopamine; GABA; glutamate
largest component of the basal ganglia is the ____
striatum
projections from the striatum are sent to the ____
globus pallidus
components of the motor loop
basal ganglia, thalamus and cortex
malfunction of the basal ganglia is associated with what disease?
Parkinson’s
pyramidal motor system
connects the motor cortex tot he muscles
extrapyramidal motor system
the basal ganglia and substania nigra
hippocampus function
learning and memory
ways hypothalamus restores balance (2)
(1) sending info to medulla and (2) regulating pituitary gland (tuberoinfundibular)
functional teratology
low levels of behaviourally active drugs during certain stages of fetal development can cause alterations in the functioning of the nervous system
criteria to be a NT (4)
(1) synthesized within the neuron by coexisting enzymes, (2) released in response to cell depolarization, (3) binds to receptors to alter the postsynaptic cell, (4) removed or deactivated by some mechanism within the synaptic cleft
many large molecule NTs are also ____
hormones
Whereas ____ carry messages over very short distances, a ____ circulates throughout the body and has an effect on some biological process distant from the place where it is released.
NTs; hormone
acetylcholine (ACh) is a __ molecule neurotransmitter
small
monoamines - catecholamines (small molecule)
DA, NE, E
monoamines - indoleamines (small molecule)
serotonin (5-HT) and histamine
excitatory amino acid
glutamate (and aspartate)
inhibitory amino acid
GABA (and glycine)
large molecule neuropeptides
opioid peptides (morphine-like molecules)
Dale’s law
a neuron always produces the same NT at every one of its synapses (now we know it’s true most of the time but not always)
neurons that release ACh are called ____
cholinergic
synapses that use epinephrine and norepinephrine are called _____ and ______
adrenergic; noradrenergic
synapses that use dopamine are called ____ and those that use serotonin are ____
dopaminergic; serotonergic
Even though each neuron almost always releases the same transmitter(s), its ____ on various cells can be quite different.
effect (based on receptor site to which it binds)
direct agonist
drug binds to and activates a receptor, mimicking the effects of a neurotransmitter
partial agonist
hat has a high binding affinity (attraction) for a particular receptor but that activates that receptor only weakly, to a lesser degree than would its natural ligand (neurotransmitter), is referred to as a partial agonist.
mixed agonist - antagonist
rug that acts as an agonist at one receptor subtype while also acting as an antagonist at another receptor subtype
receptor blockers or direct antagonists
Drugs that bind to receptor sites but do not activate them at all, instead preventing the neurotransmitter from binding and exerting its effect
