Dose response curve

Question 1

DOSE RESPONSE CURVES
* In addition to showing ED50 and LD50, DRCs illustrate
four other characteristics of a drug

Answer 1

– Dose that produces max effect
– Potency of drug
– Intenseness of response to dose increases
– Drug interactions: affecting potency of drug

Question 2

TYPES OF DRUG INTERACTIONS
(1) ANTAGONISM

Answer 2

(a) Pharmacological antagonism (interacting at sites of action (neuronal level)
– Competitive vs. noncompetitive

• competitive : drug competing fro same receptor site (naloxone competes vs opioids) –> can have a higehr affinity for the receptor site than the drug
• reduces the potency of the other drug***** –> this is binding to the drugs receptor sites (they would have to take more of the drug)
• will eventually dissociate from the receptor
• potency affected**

noncompetitive: drug wont bind to same receptor sites
- binds to a receptor (allosteric site) that then can interfere with the agonist action
- effects the structure of the receptor the drug wants to attach to –> makes it more difficult for the drug to bind to the receptors
- in some cases –> that drug that has binded the allosteric site cannot be dislodged (can affect the receptor of the other drug for a very long term)
- the overall effectiveness of the drug is affected***

(b) Physiological antagonism (interaction not at neurological level but offsetting effects) (like increase HR from one drug to decrease in HR from another drug)
- like taking a drug to deal with the side effects of another drug

Question 3

(2) SYNERGISM

Answer 3

(a)Additive effects
- when combined, drugs will increase the effect/potency of another drug
- ex: mug of beer + drug that is the same as 1 mug of beer = 2 mugs

(b) Superadditive effects (potentiation)
- when combined, effect is much greater than just summing the 2 drugs
- beer + drug that’s like 4 mugs = 5 beers
- can be unpredictable (may have not happened before0
- ex: sedatives can be combined with existing states of people –> already tired and take a drug and another to combine = extreme sedation (from existing physical impairment)

not clear from DRC if it is either add or super
- hint for super: one drug by itself has no effect on something, but when combined with another drug : increase in overall potency of the drug

Question 4

TOLERANCE

Answer 4

• Occurs as a result of repeated use/administrations of
  drug
• State of decreased effectiveness and/or need to
  increase dosage for same level of effect
• Varies as a function of drug effects (some effects reduced)
• ex opiates (vomiting effect reduced after first intake)
• Eventually dissipates
• ex: cocaine –> 24hrs and you can return to normal dose levels
• if having a lot in the same day may increase tolerance

Question 5

MECHANISMS OF TOLERANCE
Pharmacokinetic Tolerance

Answer 5

• Aka Metabolic Tolerance
• Increase in production in number of drug metabolizing
  enzymes (e.g., cytochrome P450) in liver
• have to increase doasge of drug to compensate this

Question 6

MECHANISMS OF TOLERANCE
Pharmacodynamic Tolerance

Answer 6

• Aka Physiological Tolerance
• Homeostatic adjustments to continued presence of
  drug through processes of down regulation (decrease in # of receptor sites) or up regulation occuring (increased in # receptor sites for the drug to interact with)
  desnsitization: less affinity for receptor
  sensitization: more affinity of receptor for drug

these vary from a drugs effects
- down reg or desensitization –> agonsit
- up reg or sensitization –> antagonsit

• Type of adjustment made will vary as function of
  drug effect

Question 7

MECHANISMS OF TOLERANCE
Cross Tolerance

Answer 7

• Repeated use of one drug, diminishes effect of other
  drug not used by individual
• Partly function of non-specificity of drug
  metabolizing enzymes in liver (they will be increased and will take any drig down the same way)

cross tolerance with a class of drugs
ex: sed/hypnotics

cross tolerance with drugs of similar effects
ex: alcohol and opiates

Question 8

median effective dose (ED50) in mg/kg

Answer 8

dosage will be effective

Question 9

MECHANISMS OF TOLERANCE
Reverse Tolerance

Answer 9

• State of increased sensitivity to drug effects (need less of drug for an effect to be realized)

ex: seizures with cocaine –> repeated use of coke can lead to a seizure occuring more times (called a kindling effect)

• Hypothesized factors behind phenomenon:
  – Lipid solubility of drug (more LS , more sucked up by tissue and slowly released) –> continued use, already is some in cirulation –> new amount is added to old amount in system) –> for high LS

– Subjective expectations: greater familiarity of drug allows them to consciously experience the drug at a lower dose (cognizant of drugs effects)

Question 10

median lethal dose (LD50) in mg/kg

Answer 10

dosage that will produce death

Question 11

MECHANISMS OF TOLERANCE
Acute Tolerance

Answer 11

• Aka tachyphylaxis
• sudden onset and doesn’t last very long
• Rapid developing tolerance
• one does not need repeated use for drug for tolerance to be experienced**

Question 12

MECHANISMS OF TOLERANCE
Behavioral Tolerance

Answer 12

• Due to habituation and conditioning
• Involves body’s physiological attempt to resist conditioned response to drug

drug uncontrolled stimulus + neutral stimulus (syringe) –> euphoria
- over time you can eliminate Uncontrolled stimulus and the syringe can produce the euphoria and now can cause a conditioned response
- looking at a syringe can give effects of the drug
- body is trying to stop this and return to homeostatic conditions
- taking a drug in a different location can cause an overdose from the tolerance as the location reduced the tolerance

ex: THC we can turn off our sensation of being high

• we can learn to decrease the effect the drug is having on us
• develop compensatory strategies to offset the effect the drug will have on us

Question 13

DEPENDENCE

Answer 13

• Compulsive use of drugs despite adverse
  including health, life situation , school,
• is not addiction
• shows how powerful effects of drug can be
  -from a learning perspective what control behvaiour (rewards) the timing of rewards (more immeditate= more effect reward has)
• immediate consequence of using drug is euphoria from taking it –> long term consequences like losing job, health etc is not immediate enough to help

Question 14

TI = therapeutic index

Answer 14

notation showing the safety of the drug
- computed as a ratio of LD50/ED50

Question 15

dependance consequences (3)

Answer 15

Types include:
– Physiological dependence (when we talk abotu addiction) –>
– Psychological dependence
– Cross dependence

Question 16

TI above 100 =

Answer 16

safe

Question 17

TI below 10=

Answer 17

hazardous to take

Question 18

PHYSIOLOGICAL DEPENDENCE

Answer 18

• Experiencing a cluster of unpleasant physical and
  psychological effects upon termination of drug use
  i.e., presence of withdrawal symptoms**/abstinence
  syndrome
• The effects experienced opposite of drug effects
• ex euphoria vs depression afterwards
  ex: keep you up vs sleep all day
• Severity, length, timing of withdrawal influenced by
  dose, manor of administration, and rate of elimination
• IV withdrawal is more severe than Oral
• elimination: dependant on drugs half life (large half life, longer elimination) IV = withdrawal happens quickly

if you have withdrawal that comes up quickly, tends not to last as long

Question 19

PSYCHOLOGICAL DEPENDENCE
* Two types

Answer 19

Primary: dependence that people think about when someone is addicted
- craving people have for positive effects of the drug
- euphoria craving, relief from anxiety, calms them, makes them feel different

Secondary: craving for drug to eliminate withdrawal symptoms (Dean Wilson in movie)
- usually have gone through withdrawal at least once

Question 20

CROSS DEPENDENCE

Answer 20

• Phenomenon in which use of a drug (typically from
  same class) stops withdrawal symptoms

Question 21

Addiction

Answer 21

– Characterized by tolerance, psychological, and
physical dependency, and organ changes

Question 22

• 3 C’s of addiction

Answer 22

– Compulsion: fear that people will have of being w/o drug –> will do anything to get the drug (looking for drug, looking for money for the drug) thoughts of the drug make up an entirety of a persons day –> will us another drug if the preferred is not available to them

– Loss of Control: only have 1 beer and have many ‘
- cannot control their use, drinking and drinking and drinking
- cannot stop using the drug if they go somewhere where its avaiable

– Continued use despite adverse consequences
- binge usage –> get sick for a while –> then binge it
- affects life, health

Question 23

Ti different for a drugs effect:
so a TI to treat migraines vs treat arthritis =

Answer 23

is lower in migraines

Question 24

main effect vs side effect

Answer 24

main effect: desired outcome of taking drug
side effect: not desired outcome of taking drug

Question 25

a side effect of a drug may be sought after … ex aspirin

Answer 25

main effect: reduce pain, inflammation,
side effect: slow blood clotting (cause internal bleeding) –> reduced the likelihood of having a stroke with less blood clotting

Question 26

Substance Use Disorder (DSM V)
* Diagnostic Criteria

Answer 26

• Tolerance
• Craving or strong desire to use drug
• Withdrawal
• Great deal of time is spent in activities necessary to obtain drug, use drug or recover from its effects
• Continued use having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the drug
• Continued use despite having a persistent or recurrent physical or psychological problem that is likely to have bee caused orexacerbated by the drug
• Persistent desire or unsuccessful efforts to cut down or control drug use
• Important social, occupational, or recreational activities are given up or reduced because of drug use
• Recurrent drug use resulting in failure to fulfill major role obligations at work, school, or home

Question 27

FACTORS IN DEPENDENCE
Sociological (3)

Answer 27

• Selling of drug (high risk of dependancy) (strongest most direct factor of drug abuse) –> associated with drug availbaility, associated with deviate behaviour, weak family influence (relationship an individual has with their mother) –> close bond b/t mother and child (communication with mother) less bond/commnication with mother = greater selling of drug and using it
• Exposure to Drugs
• Religion (more religious, lower risk of substance abuse)

Question 28

FACTORS IN DEPENDENCE
Psychological

Answer 28

personality: Sensation seeking, (- looking for some fun, or bored)
Impulsivity (without fully thinking, more likely to try the drug without thinking of consequences), narcissism (very strong relationship with substance abuse) someone who thinks they are superior to people (obsessed with fame and power) associate with people who are a superior quality (linked to excessive alcohol usage, harm avoidant temperament (apprehensive in behaviour –> correlated with extensive alcohol use)

social learning (in video), talked about how they didn’t belong–> use drugs to feel more connected to people (subculture in the world), peer pressure,

self medicating: treat a variety of psychological states
- angry all the time –> to calm them, reduces tension they feel
- allows them to escape, feel different

• Low self-esteem
• Anxiety/depression

Question 29

FACTORS IN DEPENDENCE
Genetic

Answer 29

• Several hundred family, twin, adoption studies
  provided evidence of genetically related variability in
  individuals’ sensitivity to and bodys’ handling of
  drugs –> in turn plays a role in drug seeking behaviour
• ex: stumbling right away with drinking—> decreases likelihood of drinking
• ex: low rate of alcohol abuse in asian cultures cuz the enzyme in their body makes them sick

Question 30

less potency doesnt mean it is more _____

Answer 30

effective

Question 31

less ED50 drugs means they are ______

Answer 31

less effective

Question 32

tolerance vs dependant

Answer 32

many people develp tolerance but doesnt mean they are depends
tolerance preceeds dependancy
dependance does not always occur with tolerance

Question 33

dev and maintenance of addiction

Answer 33

drugs and reinforces
- positive reinforcing effects: use the drug experiences positive effect (euphoria)

• neg reinforcing effects: the removal of an adverse stimulus (anxiety) –> does a drug removes anxiety

reinforcement increases the likelihood of doing drug again (both above)

• stress and reinforcement: experiencing stress (shocking animal) causes self admin of drugs in animals to increase. current AND past stress increases the strength of reinforcing stimuli
• immediate vs delayed consequences: drugs alter the function of motivational control system and then modify behaviour
  ex:

drugs alter functioning of the motivation control system and hence behaviour

Question 34

cortex controls what we’re going to do

Answer 34

towards or away from the stimulus

Question 35

motivation control system

Answer 35

when there are homeostatic imbalances in body that in of goes to
VTA then stimulates the Nucleus incumbens then passes infomation to BG —> thalamus –> cortex (reach out arm to grab muffin) (muffin) sends to BG

Question 36

drugs will alter the functionaing of motivational control system

Answer 36

VTA: affected = release of dopamine –> leads to cascaded of NI–> BG–> TH–> cortex –>

VTA affects this whole thing

drugs cause a surge in the VTA –> initiates behaviiour (get ball rolling for behaviour)
if the stimulus is good from hipocampus

Question 37

development and maintenance of addiction

Answer 37

any stimuli that activate the MLDS (mesolimbic dopamine system) (reward pathway –> reward system have a lot of dopamine receptors) have incentive salience
- is a stimulus that is very easily noticed and attended to
- the stronger the Insentive salience, the stronger our motivates behaviour towards it

drugs activate the MLDS so thus have incentive value and so presence of drug or stimuli (positive stimuli) associated with drug (needle, person they do drugs with) will lead to drug use behaviour
- what happens here is that we are already primed to recognise and find the drug n their environment which leads to the behaviour to get and use the drug
- repeated use of the drug = increase of incentive salienc e

ex: hungry animal –> sees food –> bahviour is acted to get food

Question 38

disruption of brain control circuits

Answer 38

a dysfunction in information processing and integration
amongst multiple brain regions

circuits that:
- regulate reward/saliency (NA, VTA)

• motivatio/drive (Orbitofrontal cortex and motor cotrtes –> amygdala and hippo and affect inhibitory control (executive fucntioing of prefrontal cortex (hypoactivity) –> involved with making decisions/reasoning and perseving consquences of a current behaviour**and inhbiting behaviors (this decision process part is impaired in people who are addicted to drugs cuz the function of the brain has been disrupted
  —> reduces saliency of natural rewards (natural high from roller cosaters (this is not rewarding anymore and replaced by the drug)
• memory/conditioning: amygdala and hippo

inhibotry control/executive function: dorsolateral prefrontal cortex and anterior cingulate cortex

Question 39

rest on slides