Neuropsychopharmacology Test 1
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- What is the difference between medicine and drug?
- There is none. They both alter biological functions.
- What is the definition of drug at the molecular level?
-
Drugs are molecules that bind with either a receptor
or an enzyme within the biological system, which produce
a chemical signal to the cell. - What is the definition of drug at the cellular level?
-
Drugs are the signaling mechanisms for cells to turn
on or off some cellular processes. - Where are drugs synthesized?
- Outside the body (exogenous). Endogenous chemicals are biochemicals.
- What are the two rules to follow biochemical ethics?
-
1.Reduce the pain/suffering of the patient.
2.Weigh the beneficial effects against the detrimental to decide. - What does a drug bind to?
- receptors or enzymes
-
Drug+Receptor=
Drug+Enzyme= -
Drug-receptor complex
Drug-enzyme complex - Receptor molecules lie in a cell's __
- membrane
-
What is the definition of drug at the physiological
level? -
Drugs are the induction mechanisms for altering the
physiological functions of an animal (or plant). - What is the definition of drug at the neural level?
-
Drugs are the chemical signals that turn on (or off)
specific neural circuitry. - Can oxygen or food be considered drugs?
- Yes
- Where do drugs join with the receptor?
- Binding site
- What is a ligand?
-
A ligand is simply the chemical that binds to a
receptor. - What is a receptor?
- A macromolecule comprised of long chains of amino acids.
- What is an ionotropic receptor (ionic channel)?
- A receptor with a channel pore that ions can flow through.
- Any receptor that is not ionotropic is ___
- Metabotrophic
- An ion channel can either be ___ (+excitory) or ___ (-inhibitory)
-
depolarized
hyperpolarized - Gs proteins ___ the production of chemicals while Gi ___ it
-
stimulate
inhibit - What are drug effects?
- consequence produced by drug behaviorally, psychologically, physiologically
- What is a drug action?
- molecular/biochemical action at the binding site
- What is a therapeutic effect?
- the desirable effect
- What is a side effect?
- an undesirable effect
- Self-medication can be beneficial or detrimental based on ___
- pre-existing conditions
- What is an agonist?
- a drug that acts as a real biochemical or neurotransmitter.
- What is an antagonist?
- a drug that blocks biological effects.
-
What is a full agonist?
What is a partial agonist?
antagonists? -
full produces 100% of what it is supposed to.
partial produces partial.
same but with blocking - What is an inverse agonist?
- renders real neurotransmitters useless in their presence
- What is potency?
- more potent if small concentration=high effect
- What is efficacy?
- how strong an effect is at the synapse level (measured in %)
- What is affinity?
- the attractive force of a drug at the receptor level. More attractive, higher affinity.
- What is competitive binding?
- binding can be displaced by another molecule
- What does GABA stand for and what is its function?
-
gamma amino butric acid
inhibitor of neurotransmitter - What are the receptors that GABA binds to? (subtypes)
- GABAa and GABAb
- GABAa has how many binding sites and what ion passes through the channel?
- at least 5, Cl-
- GABAb has how many binding sites and what ion passes through the channel?
- 1, K+
- What is a benzodiazepine?
- a class of drugs that are believed to cause the GABA receptor GABAa to have a higher affinity for GABA
- How does an NMDA receptor function?
- The NMDA receptor (NMDAR) is an ionotropic receptor for glutamate. Activation of NMDA receptors results in the opening of an ion channel. Calcium flux through NMDARs is thought to play a critical role in synaptic plasticity, a cellular mechanism for associative learning and memory.
- What does NMDA stand for? What is NMDA?
- N-methyl-D-aspartate is the agonist for the NMDA receptor.
- PCP acts as a ___ for NMDAR
- noncompetitive channel blocker (doesn't interfere with glutamate binding to site). This antagonism causes pdychosis.
- What is anandamide basically and what receptor does it bind to?
- bliss synthesiaed on demand, CB(cannabinoid) receptor
- What do PCP(phencyclidine), katamine, and DXM(dextromorpha) have in common?
- They are dissociative anesthetics (blocks signals, usually physical, to the brain)
- What is specificity(selectivity)?
- something selectively binds to a receptor
- What is SSRI(selective serotonin reuptake inhibitor) selective to?
- serotonin
- What is dose?
- The amnt of drug being used (mg)
- What is dosage?
-
It is the dose normalized by the body weight, i.e., it is
the dose per body weight. (mg/kg) - Why do most drugs have side effects?
-
It is because there are many similar receptors all over
the body, not just at the target site. - What is toxic effect?
-
It is the undesirable biological effect that a drug may
produce. Usually it is damaging to the biological system. - What is effective dosage?
-
It is the dosage that produces the desirable biological
effects. - What is ED50?
-
It is the effective dosage in which 50% of the
population experiences the desirable effects. - What is TD50?
-
It is the toxic dosage in which 50% of the population
experiences toxic effects. - What is LD50?
-
It is the lethal dosage in which 50% of the population
would die from it - What is a dose-response curve?
-
It is a graph that plots the relationship between
dosage and the population response to that drug. - When is the maximal response is reached?
- when all the receptors at the target site are occupied.
-
Where are the ED50, TD50 and LD50 relative to one
another in the dose-response curve? - ED50 < TD50 < LD50
- What is therapeutic index?
-
TI = TD50/ED50
It is a quantitative
measure for estimating how “safe†a drug is with respect
to the toxic dosage. - If the TI is close to 1, how safe is the drug? More than 1?
- unsafe, safe
- In a graph, the more the dose-response curve is to the right,it is (more,less) potent?
- less
- When a NT is in the presence of a competitive antagonist, the graph shifts ___ and the max effect ___.
- to the right, stays the same
- When a NT is in the presence of a non-competitive antagonist, the graph shifts ___ and the max effect ___.
- to the right, is lowered
- what do hydromorphine, morphine, codeine, and aspirin have in common? How is aspirin different?
- They are all anesthetics. Aspirin is weaker and doesn't bind to an opioid receptor.
- What is the cycle of drugs?
- administration route, absorption, distribution, elimination
- What are different routes of administation?
- intravenous(IV), intramuscular(IM), oral administration
- What is unique about IV?
- it's fast (takes a few minutes), it needs to be administered in an aseptic(clean) condition
- What is unique about IM?
-
-slower than IV (10-30 min)
-the drug can affect vasoconstriction/vasodilation (constriction of blood vessels)
-rate of absorption is more even - What is unique about oral administration?
-
-can be recalled by stomach pumping
-30 min on empty stomach to 2 hrs on full stomach -
The absorption of drug through the stomach
lining is dependent on the ___ of the drug
molecule because of the acidic environment in the
stomach. This is determined by ___ - ionization, pH in gastric juices
- The effective concentration(distribution) of a drug is ___ concentration.
- unbounded
- What happens if the concentration of a drug is bounded?
- The drug is unavailable for biological effects in other sites.
- What are some examples of silent receptors?
- Mainly plasma proteins as well as fats, muscles, and bones.
- What is the function of silent receptors?
- Silent receptors soak up the drug and act as a buffer(minimizes change in pH)
- What is the half-life of distribution?
-
It is the amount of time that takes the drug to
decrease the original amount by half. -
How is half-life used to determine the dosage intervals
for administering a drug? -
If a drug is taken at equal time-intervals at each halflives, it takes 5-6 half-lives to reach steady-state
concentration level in the plasma. - Can a drug have multiple half-lives?
-
Yes, there are often a half-life for drug distribution
and a different half-life for drug elimination. - What affects the drug absorption rate?
- solubility, pH
- What are the characteristics of lipid soluble drug absorption?
-
It passes through the
membrane easily, and is absorbed easier. - What are the characteristics of water soluble drug absorption?
-
It can be ionized, and
ionization reduces the absorption through membrane. Less absorbed than lipid soluble. -
• Gastric juice, pH=
• Small intestine, pH= 5 – 6.6
• Blood, pH= 7.4
• Urine, pH= 4.5 – 7 -
• Gastric juice, pH= 2 - 3
• Small intestine, pH= 5 – 6.6
• Blood, pH= 7.4
• Urine, pH= 4.5 – 7 - The Aspirin molecule is ___able. In the stomach, aspirin is less ionized because of the ___ (by donating the protons). This increases the ___ through the stomach lining.
-
ionizable
gastric juice
absorption -
Once inside the blood , aspirin
becomes more ___ (by accepting the protons), and thus “___†in the bloodstream and cannot return to the stomach. It is becomes more basic and close to ___. -
ionized
trapped
neutral - Most drugs do not get absorbed in the stomach, rather they are absorbed in the ___.
- small intestine
- In the intestine, aspirin is ___ and ___
- less acidic, less absorbed
- The ___ of a drug affects elimination.
- ionization
- What does TDM stand for?
- Therapeutic drug monitering
- What is TDM?
- Threshold plasma concentration of a drug needed at the receptor site.
- TDM is needed in order to know the ___ dosage and ___ dosage to achieve the pharmacological response.
- initial, maintenances
- TDM is also used to ___.
-
-correlate with tissues and receptor concentration
-detect signs of toxicity
-used to determine the delay on
the onset of the therapeutic response from the initial
administration of drug. - Drug excretion mainly occurs in the ___ but is also in the ___
- kidneys, lungs
- Drug metabolism occurs in the ___.
- liver
- Renal clearance is a measurement that allows one to analyze the ___.
- activity of the kidneys
- The kidney filter is leaky to everything except ___.
- large molecules (eg. red blood cells, white bc, plasma, and proteins. The drug reabsorbs what is needed (eg. H2O, Na, Cl, Glucose)
- Some drugs can be rebsorbed back after leaking through the kidney filter. Drug reabsorption is higher if the drug is more ___.
- lipid-soluble
- If a drug is water-soluble, the reabsorption depends on the ___. When drugs are ionized to be more acidic or basic, the reabsorption rate is ___
- pH, lower
- Ionized drugs are often ___ inside the renal tubules, so they are then ___.
- "trapped", excreted
- Filtration depends on:
-
hydrostatic pressure
osmotic pressure
renal clearance - In drug metabolism, drug molecules are modified by ___
- biotransformation
- A biotransformation can be either a ___ or ___ reaction.
- synthetic, non-synthetic
- In biotransformation, a synthetic reaction is a ___ or the chemical coupling of a drug with another molecule.
- conjugation
- In a synthetic reaction, an ___ alters the new molecule by making it more or less ___ or ___.
- enzyme, water soluble, lipid soluble
- An enzymes in the liver can change foreign drug molecules into ___, thus inactivating the molecule's functions.
- metabolites
- Drug testing tests for ___ which is ranked either false or positive.
- metabolites
- Conjugation groups:
-
carboxyl -COOH
hydroxyl -OH
amino -NH_2_
sulfhydryl -SH - In a non-synthetic reaction, the parent drug is modified by:(3)
- oxidation, reduction, hydrolysis
- What is biotransformation?
-
the transformation of a drug molecule into a
different molecule in the body - What are the effects of the chronic use of a drug?
- increases the amount of hepatic (liver) enzymes which lowers the plasma concentration of the drug
- After the first exposure of alcohol, the amount of ___ increases, therefore therefore there is a lesser effect the next time.
- enzymes
- Alcoholics have so many enzymes that ___.
- It overflows the liver, essentially killing it which stops the production of hepatic enzymes.
- What is a chronic drug's half life
- infinite
- What is drug tolerance?
-
the changes in the system that result in requiring
taking more amount of drug to get the same initial effect
after first exposure to the drug - Types of drug tolerance:(3)
-
Pharmacological tolerance
Cellular adaptive tolerance
Behavioral tolerance - What is metabolic tolerance?
- There is a faster metabolic rate if there is a higher enzyme concentration. There is a higher need for drugs to achieve the same effect.
- What is cellular adaptive tolerance?
- the changes of receptor sensitivity and/or receptor density (number of receptors at the target site) in response to the continual presence of the drug.
- What is up-regulation?
- The number of receptors in the target site increases, thus the system responds with higher sensitivity to the same drug.
- What is down-regulation?
- The number of receptors in the target site decreases, thus the system responds with lower sensitivity to the same drug, i.e., becomes tolerant to the drug.
- In order to make up for a low amount of neurotransmitters, there is a raise in receptor density. This leads to ___. Therefore, the limiting factor is ___
- depression, receptor occupancy
- What is cross-tolerance?
-
It is the tolerance resulted from the interaction of
different drug molecules that share similar properties.
Tolerance to one drug can result in tolerance to another
drug that the user has never been exposed to before. - What is reverse tolerance?
- sensitization (opposite effect of tolerance)
- What does negative feedback lead to?
- homeostasis
- What does positive feedback lead to?
- amplification
- What is an example of positive feedback in the respiratory system.
- There is low O2, which is amplified by lowering the respiration rate. This leads to more shutdown in the respiratory center of the brain which leads to the shutdown of the lungs. This leads to respiratory arrest.
- What is hypoxia?
- A deficiency of oxygen in tissues.
- What is an example of negative feedback in the respiratory system?
- If there is low O2, the respiratory center can detect the higher CO2. The respiration rate increases to get more oxygen.
- What is the function of CNS depressants?
- lowers the excitability of neurons
- What are the effects of CNS depressant administration from lowest to highest dosage?
- relief from anxiety, disinhibition, sedation, hypnosis(sleep), general anesthesia, coma, death
- What is behavioral tolerance?
- It is the tolerance developed by environment factors rather than the drug itself. It is induced by learned association with the environment in which the drug is taken. The tolerance is established by paired association between the effects of the drug and the environmental cues.
- Why is behavioral tolerance sometimes called contigent tolerance?
- It is dependent on the context of the usual pre-drug cues in the environment.
- Contingent tolerance is an ___ response in which the tolerance is a compensatory conditioned to diminish the effect.
- over-conditioning
-
What often happens to behavioral tolerance after a period of
abstinence? What does this make it? - disappears, reversible
- What is blood-brain barrier (BBB)?
-
It is the tight junction formed by the feet of the glial
cells at the capillary walls in the brain. It prevents many
molecules from leaking into the CNS. - What does CNS stand for?
- central nervous system
- Most molecules are selectively pumped into the brain by the ___ system.
- carrier-mediated transport
- What is Parkinson's disease?
- the degeneration of dopamine neurons in the basal ganglia
- What is a stereoisomer?
- two compounds that have the same order of chemical, but have different spatial arrangements
-
l means:
d means: -
levo (left)
dextro (right) - what do l-DOPA and d-amphetimine have in common?
- they are both active (can cross the bbb)
- What are the mechanisms for behavior tolerance?(3)
- conditioning, expectancy, self-liberation of endogenous neurotransmitters (eg. endorphins, enkalphalins, adrenaline)
- Which drug blocks opioid receptors and is used for emergencies for heroin users?
- naloxone
- What type of learning includes a reward?
- reinforcement learning
- What is the difference between adaptation and conditioning?
- with adaptation, there is only one event (stimulus)
- What is cognitive learning?
- using instructions
- What is sensitization?
- the continued use of a drug amplifies the effect
- What is habituation?
- after continued use of a drug, there is a diminuation of behavioral response
- what are examples of adaptation?
-
aphesia-gill withdrawl reflex
light sensitivity
socks - What does Pavlovian (classical) conditioning prove?
- behavioral tolerance is in part due to the effects of a drug and the environment
- What are the stimuli and responses in the Pavlovian experiment?
-
US-unconditional stimulus (food)
UR-unconditional response (salivaition)
CS-conditional stimulus (bell)
CR-conditional response (salivation) - What are neurons like before training?
- the US has strong synaptic weight the UR, but the CS has no relation
- What are neurons like during training?
- the US and CS axons start to associate, increasing the CS synaptic weight
- What are neurons like after training?
- the CS can independantly affect the UR because the synaptic strength is raised to 1.
- The UR's synapse that has adapted is a ___, or changeable
- modifiable synapseq
- What does the stimulus-response graph look like before learning?
- a horizonal line (no matter the amount of input, output is always the same)
- What does the stimulus-response graph look like after learning?
- diagonal, linear, increasing line (the more stimlus, the more response)
- What does a typical stimulus-response graph look like in most biological systems?
- sigmoidal with a threshold for the drug and a maximal response.
- What is the linear section of a stimulus-response graph and what does it mean?
- the physiological range-the system acts on this
- What is a reflex?
- the stimulus-response curve is inborn
- what is a conditioned reflex?
- the natural reflexes are modified
- What does the stimulus response graph look like for sensitization?
- the slope increases (less input than original for same result)
- What is synaptic plasticity?
- the ability of the connection, or synapse, between two neurons to change in strength
- What how does an NMDA receptor function?
- Na+ and Ca+ pass through the ligand channel. Glutamate is the agonist. Mg++ is a non competitive channel blocker.
- What is the difference between the NMDA receptor and a normal ligand gated receptor?
- ligand only requires 1 event while NMDA requires 2
- What two events need to happen for NMDA to open its ionic channel?
-
-bind with glutamate
-depolarization to unblock Mg++ - Why is the NMDA receptor important?
- it is key for associative learning/memory
- What is the function of a non-NMDA receptor on a neuron?
- they are just normal exciting synapses
- what is excitotoxicity?
- too much glutamate opens NMDA too much which leads death or secondary injury of the postsynaptic neuron cell. This is why we don't use NMDA as a drug to improve learning.
- What is the difference between positive and negative reinforcement?
-
pos.-there is a reward so the animal has a seeking behavior
neg.- there is punishment so the animal has avoidance behavior - What is an example of conditioned fear?
- pair the bell with a shock
- What is extinction?
- pair UR with a neutral simulus and repeat. The CR will go extinct. They don't unlearn, they learn a new concept that CS does not lead to reward.
- what is PTSD?
- post-traumatic stress disorder is the feeling of being in an inescapable situation and where there is an establishment of an emotional memory with the environment.
- what is secondary TSD?
- learned helplessness that is caused by abuse. the victim toleratesthe abuse and inhibits the avoidance escape behavior when punished repeatedly without escape.
- What are the biomedical ethics related with animals?
- reduce suffering, therefore reduce the number of animals used in experiments
- what box is used in the lever-pressing test?
- skinner box
- what is the difference between classical conditioning and operant conditioning?
-
classical-requires a teacher
operant-self-learning - how does self-administration work in operant conditioning?
- the animal presses the bar to recieve a reward or avoid punishment
- what is a fixed ratio schedule (FR)?
- the schedule of reinforcement that uses a number of trials
- what does FR10 mean?
- there is a reward every 10 trials
- what does FI10 mean?
- there is a reward every 10 seconds
- what is a fixed interval schedule (FI)?
- the schedule of reinforcement that uses a time interval
- What is a variable ratio schedule? variable interval?
- reward on an average, but is random, unpredictable, and addictive (hard to extinguish)
- What does ISI mean?
- inter stimulus interval (time between stimulus)
- What is the Differential Reinforcement of Low Rate of Responding (DRL) schedule?
- make the animal wait. if the animal responds before the time period, the timer is reset and started over
- What does the DRL prove?
- animals have a sense of time. they are able to monitor the elapsed time.
- In a test preparatory step, what do the different colors of lights mean?
-
yellow-prepare/anticipatory signal
green-reward
red-punishment -
What is an example of drug discrimination stimulus?
(stimulus generalization)
(drug discriminative learning) - the animal presses the bar on green light instead of red because green=good drug.
- What is the type of signal that is avoided?
- noxious stimulus
- What is signal avoidance?
- a light or sound stimulus leads to aversion. the animal actively tries to predict and terminate the delivery of the noxious stimulus. it only postpones
- What is an escape procedure?
- actively run away from stimulus
- What is CAR?
- conditioned avoidance response is conditioned fear (includes avoidance, learned helplessness, escape)
- What is place conditioning?
- there is a preference in the location of the Skinner box and the time spent in the compartment
- What do mazes test?
- spacial memory and learning a task
- what are some types of mazes?
- T arm, 4 arm, 8 arm. These are all radial.
- How do scientists test animals for anxiety?
- they use an underwater submerged platform and a rotating rod. (if the animal is anxious, it will run faster)
- How do scientists test animals for analgesia (no pain)?
- tail flick test-induce heat on tail and test latency (express)
- what is the double-blind experiment?
- it is a clinical trial in which neither the subject nor the experimenter knows whether the real drug or the placebo is given.
- what is a placebo?
- a substance that has no known biological effect
- What is the point of the double-blind experiment?
- eliminate the suggestive effects
- what tools are used to see if a drug is working?
- fluorescent labeling, PET scan (Position Emission Tomography), MRI (Magnetic Resonance imaging)
- What is an fMRI?
- an MRI that is used for neuroimagery. tests for BOLD(Blood Oxygen Level).
- What does BOLD indicate?
- neural activity
- What is the order of structures from inside out of the brain?
- thalamus, basal ganglia, limbic system, archicortex, neocortex
- What does the thalamus control?
- gateway for sensation/motor
- What does the basal ganglia control?
- motor initiation and termination
- What does the limbic system control?
- memory/emotion
- What does the archicortex control?
- memory/emotion
- What does the neocortex control?
- sensory, spatial, motor commands, language/conscious thought
- What is the meso limbic system?
- midbrain; includes the prefrontal cortex, hypothalamus, pituitary, VTA, and N. Acc.
- What does the pituitary gland control?
- releases hormones from hypothalamus
- What does the hypothalamus control?
- drive/thirst, sends message to VTA, pituitary
- What does the VTA (ventral tegmental area) control?
- motivation (gives reward), sends message to N. Acc.
- What does the N. Acc. (Nucleus Accumbus) control?
- reward, reinforcement
- What does the prefrontal cortex control?
- cognition for decisions and integration of emotions
- What does dopamine (cocaine) function as in the brain?
- neurotransmitters