Dose response curve Flashcards
DOSE RESPONSE CURVES
* In addition to showing ED50 and LD50, DRCs illustrate
four other characteristics of a drug
– Dose that produces max effect
– Potency of drug
– Intenseness of response to dose increases
– Drug interactions: affecting potency of drug
TYPES OF DRUG INTERACTIONS
(1) ANTAGONISM
(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
(2) SYNERGISM
(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
TOLERANCE
- 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
MECHANISMS OF TOLERANCE
Pharmacokinetic Tolerance
- 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
MECHANISMS OF TOLERANCE
Pharmacodynamic Tolerance
- 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
MECHANISMS OF TOLERANCE
Cross Tolerance
- 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
median effective dose (ED50) in mg/kg
dosage will be effective
MECHANISMS OF TOLERANCE
Reverse Tolerance
- 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)
median lethal dose (LD50) in mg/kg
dosage that will produce death
MECHANISMS OF TOLERANCE
Acute Tolerance
- 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**
MECHANISMS OF TOLERANCE
Behavioral Tolerance
- 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
DEPENDENCE
- 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
TI = therapeutic index
notation showing the safety of the drug
- computed as a ratio of LD50/ED50
dependance consequences (3)
Types include:
– Physiological dependence (when we talk abotu addiction) –>
– Psychological dependence
– Cross dependence
TI above 100 =
safe
TI below 10=
hazardous to take
PHYSIOLOGICAL DEPENDENCE
- 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
PSYCHOLOGICAL DEPENDENCE
* Two types
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
CROSS DEPENDENCE
- Phenomenon in which use of a drug (typically from
same class) stops withdrawal symptoms
Addiction
– Characterized by tolerance, psychological, and
physical dependency, and organ changes
- 3 C’s of addiction
– 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
Ti different for a drugs effect:
so a TI to treat migraines vs treat arthritis =
is lower in migraines
main effect vs side effect
main effect: desired outcome of taking drug
side effect: not desired outcome of taking drug