Exam 1 Flashcards
(265 cards)
1
Q
pharmacology
A
uses, effects, and modes of actions of drugs
2
Q
psychopharmacology
A
Influence of drugs on behavior and psychological function
3
Q
neuropharmacology
A
Influence of drugs on brain function
4
Q
neuropsychopharmacology
A
Influence of drugs on brain, behavior and psychological function
5
Q
psychoactive drug
A
chemical substance that alters perception, mood, or consciousness
6
Q
purposes of psychoactive drugs
A
recreational, ritual/spiritual, therapeutic
7
Q
classification by source
A
natural, synthetic, semisynthetic
8
Q
classification by behavioral/psychological effects (5)
A
stimulants, depressants, analgesics, hallucinogens, psychotherapeutics
9
Q
classification by pharmacological action
A
often drugs have multiple pharmacological actions, so it’s difficult to classify
10
Q
other ways to classify drugs
A
chemical structure, legal status
11
Q
what terms have been synonymous with addiction?
A
dependence and drug abuse
12
Q
physical dependence
A
body relies on drug to prevent withdrawal
13
Q
addiction
A
- uncontrollable cravings
- inability to control drug use
- compulsive drug use
- use despite doing harm to oneself or others
- classified as a disease
14
Q
in the last month, __% of the U.S. population has used illicit drugs
A
13
15
Q
most common illicit drug used in the U.S.
A
marijuana
16
Q
age group in which drug use is most common
A
young adults (18-20)
17
Q
percentage of people with substance use disorder
A
14.5% (40.3 million people)
18
Q
most common substance abused & diagnosed
A
alcohol
19
Q
binge drinking
A
at least 5 drinks in one session for men; at least 4 drinks in one session for women
20
Q
heavy drinking
A
at least 5 binge days out of last 30 days
21
Q
daily marijuana use has ___ among college students
A
increased
22
Q
binge alcohol use is ___ in college students than in non-college peers
A
greater
23
Q
marijuana and nicotine vaping are ___ among college students
A
increasing
24
Q
illicit drug use in high school students
A
- steady in 12th graders over the years
- decreased alcohol use across all grades over the last decade
25
cigarette use in high-school students has ___ over the last 10 years
decreased
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nicotine and THC vaping have ____ in high-school students
increased
27
psychoactive substances used throughout history (5)
nicotine, caffeine, morphine, cocaine, and THC
28
alcohol temperance movement's effects on attitudes towards drugs/alcohol
did not outlaw alcohol, but drug use in general was socially unacceptable
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prohibition
alcohol is outlawed and seen as criminal behavior
30
scientific advancements that led to greater drug use
increased addictive potential of drugs and development of hypodermic syringes
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approach to drug control that led to increased drug use
increased drug availability and lack of drug control laws
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changes in treatment of addiction
medicalization led to categorizing addiction as a disease
33
effects of Nixon's War on Drugs in 1971
expanded incarceration, drug crimes more severely punished and policed
34
targets of the War on Drugs
Black population, anti-war left
35
effects of the War on Drugs in the 80s
mandatory minimum prison sentences, increased penalties for posession
36
Anti Drug-Abuse Act of 1986
created a big sentencing disparity between crack and powder cocaine, which further fueled racial disparities in incarceration
37
top consumer of illicit drugs in the world
USA
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race typically subjected to higher rates of arrests and incarceration
Black population
39
past approach to the war on drugs
- viewed drugs as a criminal justice problem
- law enforcement
- penalization
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science's influence on drug policy
little to none
41
what method is effective when tackling a drug problem
treatment programs
42
future of war on drugs
- drugs are a public health problem
- increased treatment availability
- focus on education, prevention
- reduced drug sentences
- legalization of marijuana
- harm reduction (syringe programs)
43
DSM-5 definition of substance use disorder
significant impairment in at least 2 categories in a 12-month period: impaired control, social impairment, risky use, pharmacological properties
44
changes from DSM-I to DSM-V when discussing addiction
gradual transition from stigmatizing to biological basis
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addiction is NOT
physical dependence and withdrawals
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addiction IS
craving and relapse
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definition of addiction
chronic, relapsing brain disease characterized by compulsive drug seeking/use, despite harmful consequences, major impairment to self-control
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bioavailability
amount of drug available to bind to target sites and elicit drug action
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absorption
movement from site of administration to blood circulation
50
oral route of administration
- aka preoral, PO
- absorption in the GI tract
- slow, variable
- undergoes first-pass metabolism in the liver before entering the bloodstream
51
first-pass metabolism
aids in drug degradation and sometimes drug design
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routes of administration that typically avoid first-pass metabolism
intranasal (bypasses BBB), inhalation, sublingual, rectal, transdermal
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injection routes of administration
subcutaneous, intramuscular, intravenous (IV)
54
factors affected by route of administration
onset, peak concentration, and duration
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slow route of administration
typically for medical use, longer duration
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fast route of administration
typically associated with drug use/abuse, used to achieve highest peak concentration with rapid onset
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oral and transdermal administration
slow absorption
58
intravenous injection or inhalation/smoking (route of administration)
rapid drug entry, fast onset
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increased addictiveness is associated with...
fast onset and short duration
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how route of administration affects absorption rate
- blood circulation and surface area
- amount of drug destroyed by digestive or metabolic processes
- transport across membranes
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drug properties that affect absorption rate
solubility, ionization
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most drugs easily diffuse across membranes when they are
lipid-soluble, non-ionized
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lipid solubility of heroin vs morphine
heroin reaches the brain much faster than morphine because of increased lipid solubility
64
drug ionization
occurs when drugs are dissolved in water (neutral pH) due to them being a weak acid or base
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lipid solubility of ionized drugs
not readily lipid soluble, making diffusion difficult
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factors affecting drug ionization
different bodily fluids (different pH)
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ion trapping
concentration of drug in one compartment
68
distribution (ADME)
movement from blood to target site
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factors affecting distribution
depot binding and the blood-brain barrier (BBB)
70
blood-brain barrier
selectively permeable (lipophilic) to keep a stable brain environment
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weak BBB areas
area postrema, median eminence
72
depot binding
can occur in albumin (plasma), fat, and muscle, where the drug remains in an inactive state in the system and is protected from metabolism
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factors affected by depot binding
peak concentration and duration of drug concentration
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example of depot binding
THC: depot binding in fat leads to slow release, making THC detectable in urine days after the initial dose
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metabolism and excretion (ADME)
movement out of the system
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drug inactivation (biotransformation)
usually by metabolism, occurs in the liver by microsomal enzymes
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phase I metabolism
oxidation, reduction, or hydrolysis (non-synthetic)
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phase II metabolism
- addition of small molecules (glucuronide, sulfate, methyl groups (synthetic)
- products ionized and less lipid soluble so they become inactive metabolites
79
active metabolites
- have biological activity of their own
| - need further metabolism to become inactive metabolites
80
drug clearance: first order kinetics
- drugs cleared at exponential rate
- based on half-life
- most common
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drug clearance: zero-order kinetics
- drugs cleared at constant rate (linear)
| - example: alcohol
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individual variation in drug metabolism
- sex differences
- individual adaptation (tolerance)
- age effects
- genetic differences
83
drug therapy for alcoholics (Disulfram/Antabuse)
blocks ALDH
84
pharmacokintetics
how drugs move throughout the body
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pharmacodynamics
- how drugs affect the body
| - actions of drugs at receptor sites
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ligand
neurotransmitter or drug that fits a given receptor
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receptor
protein a ligand interacts with to initiate biological effects
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drug + receptor =
drug effects
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agonists
ligands that bind to a receptor to initiate a cellular response
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antagonists
- ligands that bind to a receptor to block the action of an agonist or endogenous ligand at the same receptor
- do NOT reverse the effects of an agonist or cause an opposite reaction
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receptors are bound at the ___ of the cell
membrane
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a drug can be ___ specific for the receptor than the endogenous neurotransmitter
more
93
T/F: drugs can show agonist or antagonist actions
T
94
drug-receptor interaction
modulate normal neuronal functioning by mimicking, increasing, or inhibiting normal physiological/biochemical processes
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characteristics of drug-receptor binding
temporary and reversible
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binding affinity
determines speed of dissociation
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law of mass action
- more drug molecules = increased receptor occupancy
- maximum drug effect = all receptors occupied
- cellular response proportional to degree of receptor occupancy
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dose-response curve
relationship between cellular response and receptor occupancy
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reversibility of drug-receptor interactions
- most are reversible
| - some form long lasting, irreversible bonds
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ED100
- effective dose that gives maximum response
- all receptors occupied
- giving more of the drug does not increase observed drug effect
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ED50
dose that produces half the maximum effect
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dose-response curve shape
sigmoid
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therapeutic index
evaluates all desirable and undesirable drug effects
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TD50
dose that produces a given toxic effect in 50% of all subjects
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LD50
dose that kills 50% of subjects (lethal dose)
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therapeutic index (TI, margin of safety)
LD50 / ED50
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potency
amount of drug needed to produce an effect
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efficacy
maximum effect that can be produced
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factors that affect potency
- pharmacokinetics
| - binding affinity for certain receptors (does not determine maximum possible effect however)
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factors that affect efficacy
- act by different mechanisms (different receptors)
| - different activity at the same receptor
111
competitive antagonists
- bind to the same receptor binding site as agonist
- shifts DRC for agonist to the right
- antagonist effect can be overcome by adding more agonist
112
non-competitive antagonists
- do not compete with agonists for receptor binding site
- shifts DRC to the right for agonist, but also changes shape
- cannot be overcome by adding more agonists, there is a decrease in maximum effect
113
partial agonists
- efficacy is lower than full agonist, higher than antagonist
- in the presence of a full agonist, they act as antagonists
114
inverse agonists
- bind to receptors and initiate a cellular response that is opposite to the agonist
- descending DRC
115
allosteric modulators
ligands/drugs that indirectly influence the effects of a primary ligand
116
positive allosteric modulators (PAMs)
amplify primary ligand effects
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negative allosteric modulators (NAMs)
reduce primary ligand effects
118
tolerance
- drug effect gets smaller
- more drug required for same effect
- DRC shifts to the right
119
sensitization
- drug effect gets bigger
- less drug required for same effect
- DRC shifts left
120
acute tolerance
- aka tachyphylaxis
| - drug effect decreases rapidly within a single session
121
example of acute tolerance
when blood-alcohol level is rising vs falling
122
cross-tolerance
drug effect decreases due to repeated administration of another drug
123
cross-sensitization
drug effect increases due to repeated administration of another drug
124
pharmacokinetic (metabolic) mechanism of tolerance/sensitization
- changes in metabolism
| - enzyme induction
125
pharmacodynamic mechanism of tolerance/sensitization
- changes in receptors and corresponding signaling pathways
| - change in receptor number/sensitivity
126
behavioral mechanism of tolerance/sensitization
- changes due to learning factors
| - can be context-specific
127
pavlovian/classical conditioning
conditioned stimulus (CS) training can contribute to sensitization or tolerance effects depending on conditioned reactions (CR)
128
context-specific tolerance/sensitization
tolerance/sensitization effects only expressed in a specific environment that was previously paired with the drug
129
context-specific tolerance related to heroin
this type of tolerance contributes to fatal heroin overdoses
130
signals sent within a neuron
electrical local and action potentials
131
signals send between neurons
chemical signals transported via neurotransmitters
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post-synaptic potentials
local changes in electrical activity at the dendrites/input zone
133
action potentials
generated down the axon if a post-synaptic potential is large enough to reach the soma, all-or-nothing
134
resting membrane potential
difference in electrical charge inside vs. outside the cell (polarized)
135
ions
electrically charged molecules
136
ions
electrically charged molecules
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anions
negatively charged
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cations
positively charged
139
movement of potassium (K+) in a neuron at resting membrane potential
electrical pressure to enter the cell, but chemical pressure to leave the cell
140
movement of sodium (Na+) in a neuron at resting membrane potential
electrochemical pressure to enter the cell
141
movement of calcium (Ca2+) in a neuron at resting membrane potential
electrochemical pressure to enter the cell
142
movement of chloride (Cl-) in a neuron at resting membrane potential
chemical pressure to move out of the cell
143
triggers that can open an ion channel (4)
- ligand binding
- change in membrane potential
- phosphorylation
- G proteins
144
inhibitory post-synaptic potential (IPSP)
Cl- or K+ ion channels open, making the cell more negative
145
excitatory post-synaptic potential (EPSP)
Na+ ion channels open, making the cell more positive
146
threshold for an action potential
around -40 mV
147
what happens during an action potential?
membrane potential reverses (inside of cell becomes positive)
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an action potential is caused by a rush of ___ ions into the axon
Na+
149
hyperpolarization is the same as...
IPSP
150
depolarization is the same as...
EPSP
151
function of voltage-gated Na+ channels
conduct the action potential down the axon
152
synapse
site of action for most psychoactive drugs
153
axoaxonic synapse (pre-synaptic facilitation/inhibition)
- open ion channels → affect NT release
| - signaling cascade → protein function
154
axodendritic and axosomatic synapse
- open ion channels → EPSP, IPSPs
| - signaling cascade → protein expression or function
155
presynaptic side of synapse
axon terminal contains synaptic vesicles that contain neurotransmitter
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postsynaptic side of the synapse
Receptors respond to the neurotransmitters
157
classical neurotransmitters (4)
- amino acids
- monoamines
- acetylcholine
- purines
158
non-classical neurotransmitters (3)
- neuropeptides (opioids)
- lipids (endocannabinoids)
- gases
159
retrograde neurotransmitters
lipids and gases
160
examples of amino acid neurotransmitters (2)
glutamate and GABA
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examples of monoamine neurotransmitters
DA (dopamine), NE (norepinephrine), 5-HT (serotonin)
162
steps in chemical synaptic transmittion
- synthesis
- release
- inactivation
163
synthesis of classical neurotransmitters
- synthesized from dietary precursors
- enzymes in axon terminals synthesize NTs
- then transported into small vesicles (~40 nm radius)
164
synthesis of neuropeptides
synthesized in cell body → packaged into large vesicles → transported down the axon
165
neuropeptide synthesis is dependent on ___
protein-synthesis
166
neurons that release neuropeptides can also release ___
classical neurotransmitters
167
classical NTs require ___ transport
active
168
vesicular transporters
move transmitters into vesicles
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steps for NT release
- action potential reaches terminal
- activation of voltage-gated calcium channels
- influx of calcium
- calcium mediates fusion of vesicle
- NT is released via exocytosis
170
SNARE proteins
mediates vesicle fusion with the cell membrane
171
Botulinum toxin (Botox)
cleaves proteins involved in vesicle fusion
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endocytosis
Vesicle membrane is retrieved from the terminal membrane
173
vesicle recycling
New (empty) vesicles can be refilled with NT rapidly
174
NTs rapidly diffuse across narrow synaptic cleft and bind to receptors in vicinity, including on:
post-synaptic neuron
175
There is also significant “spillover” at most synapses, or diffusion out of the cleft to reach receptors (3) on:
- presynaptic neuron (autoreceptors)
- astrocytes (glia)
- nearby synapses
176
autoreceptors
receptors on the same neuron releasing the NT and provide feedback (usually negative feedback)
177
terminal autoreceptors
modulate NT release
178
somatodendritic autoreceptors
modulate NT synthesis or firing
179
inactivation of NT via:
- enzymatic degradation (metabolism via enzymes)
| - Plasma membrane transporters present in nerve terminal (2, reuptake) or glia
180
retrograde transmission
- Signaling from post-synaptic to pre-synaptic cell
| - different than anterograde transmission used in most signaling
181
drug-receptor interactions
Drugs primarily act outside the cell on targets (receptors) on the cell membrane
182
receptor activation
activated by the binding of ligand (neurotransmitter, drug)
183
categories of neurotransmitter receptors
ionotropic and metabotropic
184
ionotropic receptors
- ligand-gated ion channels
- 4-5 subunits (separately encoded proteins) bound together to form an ion channel
- fast, rapidly reversible
185
metabotropic receptors
- G-protein coupled receptors
- use second messengers to open an ion channel or trigger cellular changes
- 1 subunit with 7 transmembrane domains coupled to intracellular G protein
- slower, long lasting
186
nAChR
- aka nicotinic acetylcholine receptor
| - gates a cation channel
187
GABAa
gates a chloride ion channel
188
second messenger system - sequence
- activation of G protein
- change in activity of effector enzyme
- change in second messenger levels
- activation of protein kinase
- phosphorylation of of a substrate protein
189
families of G proteins
- α subunit
| - βγ subunit complex
190
α subunit
Gs (stimulatory), Gi (inhibitory), Gq (quirky?)
191
all neurotransmitters have _____ receptors, but only some utilize _____ receptors
metabotropic, ionotropic
192
receptors that utilize ionotropic receptors
glutamate, GABA, acetylcholine, and serotonin (only one)
193
receptors determine whether effects are ____ or ____
excitatory, inhibitory
194
calcium regulation
tightly regulated due to playing a large part in neuronal function
195
protein kinase
modify other proteins by adding phosphate groups to them (phosphorylation).
196
protein kinase targets
ion channels, receptors, cytoskeletal proteins, transcription factors, etc.
197
protein phosphatastes
dephosphorylate proteins
198
phosphorylation
changes the structure/function of a protein to activate or inhibit
199
transcription factors
- family of proteins that bind to regulatory sites on genes to promote or suppress transcription of DNA to mRNA.
- activation can cause second messengers to alter gene regulation
200
immediate early genes (IEGs)
- first genes to be transcribed into mRNA and then translated into protein quickly
- include transcription factors
201
c-Fos
- a transcription factor and immediate-early gene
| - marker of neuronal activation
202
epigenetics
can potentially change gene expression for a lifetime
203
unconditioned animal behavior
- simple behavior observation
- motor activity
- analgesia
- anxiety
204
locomotor activity chamber
measures horizontal and vertical movement using infrared beam breaks
205
analgesia tests
tail flick and hot plate tests measure reduced pain sensation (analgesia)
206
elevated plus maze test
used to measure anxiety
207
light-dark box and open field
both measure anxiety
208
classical conditioning examples
fear conditioning, conditioned place preference
209
instrumental conditioning examples
operant chamber learning
210
fear conditioning
test of learning and remembering emotionally aversive events
211
drug discrimination
used to assess stimulus properties, "what does the drug feel like?"
212
drug discrimination test findings
- animals classify drugs just like humans
| - predictions have been highly sensitive and accurate
213
reward
something that is "wanted" or "liked," drives appetite behavior
214
positive reinforcement
when adding something increases the probability of a behavior
215
negative reinforcement
when removing something increases the probability of the behavior
216
conditioned place preference
- used to assess rewarding properties
| - do you "like" the drug?
217
conditioned place aversion
occurs when the drug is aversive and causes the animal to avoid the context they were in when given the drug
218
drug self-administration
- measures whether subject wants the drug and whether they will work for it
219
drugs that do not maintain self-administration
most hallucinogens (aspirin, LSD, mescaline, etc)
220
fixed ratio schedule
reinforced after every nth response
221
variable ratio schedule
reinforced on average after every nth response
222
progressive ratio schedule
each reinforcement requires more responses
223
cocaine self-administration in rats
rats will adjust rate of cocaine self-administration according to dose
224
dose-response curve of fixed-ratio schedule
inverted U shape
225
drug satiety
may explain why replacement therapy works
226
breakpoint (progressive ratio schedule)
- highest ratio attained before the animal “gives up.”
- measure of drug motivation.
- “How hard are you willing to work for the drug?”
227
rate of responding changes with dopamine antagonist
DA antagonist will increase FR responding and decrease PR responding
228
dose-response curve for progressive ratio schedule
just increases (not inverted U shape)
229
ligand binding
used to visualize receptors
230
antibody binding
used to visualize proteins
231
hybridization
used to visualize mRNA
232
tissue extract
provides quantification; in vitro
233
tissue slice
provides localization; in situ
234
living organism
in vitro
235
autoradiography
radioligand (radioactive ligand) shows location and density of receptors
236
autoradiography with PET
used to visualize receptors in live human brains (in vivo), injected intravenously
237
striatum
high concentration of dopamine receptors
238
immunohistochemistry
binding of specific antibodies to visualize location of proteins
239
primary antibody
binds to protein of interest
240
secondary antibody
binds to primary antibody
241
label (immunohistochemistry)
colored product from enzyme reaction
242
CLARITY
- 'dissolves' fats/lipids
| - no sectioning of the brain, whole cellular brain architecture
243
in situ hybridization (ISH)
complementary RNA/DNA probes bind to mRNA
244
advantages of static visualization techniques
high specificity, full brain coverage, high spatial resolution
245
electroencephalogram (EEG)
non-invasive, good time resolution, poor spatial resolution
246
functional magnetic resonance imagine (fMRI)
non-invasive, detects blood flow changes
247
techniques requiring intracranial surgery
electrophysiology, neurotransmitter detection, lesions, and local drug delivery
248
another term for intracranial surgery
stereotaxic
249
stereotaxic surgery
allows for accurate targeting of specific brain structures
250
intracranial electrophysiology
record activity from (and stimulate) neurons in specific brain areas
251
microdialysis / voltammetry
can be used in freely moving animals to measure neurotransmitter levels and see how they change over time
252
common property in addictive drugs
evoke dopamine release in the ventral striatum (nucleus accumbens, NAc)
253
why do we need manipulation of variables in an experiment?
- to determine causation
- determine whether a specific brain area is necessary for a certain behavior
- is it necessary or sufficient for a drug effect?
- where in the brain is the drug rewarding?
- can we block the effects?
254
general neurotoxin lesion example
NDMA, toxic to all neurons
255
specific neurotoxin lesion example
6-OHDA toxic only to catecholamine neurons
256
local drug delivery (intracranial manipulation)
drug gets microinjected into a specific brain area of an awake animal
257
genetic manipulation techniques
- mutations
- gene silencing
- gene editing
- viral vectors
258
3 different kinds of mutants (usually mice)
- knockout
- knockin
- transgenic
259
knockout (genetic mutation)
removal of a gene, loss of function
260
knockin (genetic mutation)
replace gene, gain of function
261
transgenic (genetic mutation)
introduce new gene
262
gene silencing
performed via injection of RNA interference
263
gene editing
performed via CRISPR-Cas9; can remove, replace, or add DNA
264
viral vectors
- used for gene therapy in humans
- replication-disabled viruses that can infect cells, integrate into the host genome and cause stable expression of introduced genes
265
optogenetics
- incorporate light-gated ion channels and pumps into neurons
- allows depolarization/hyperpolarization of cells using light
