lecture 4 - pharmacodynamics Flashcards
know the diagram in lecture
what is a ligand?
molecule that binds to a receptor with some selectivity
what are receptors?
proteins on cell surfaces or within cells
what are types of receptors?
- heteroreceptors: regulate the release of neurotransmitters other than their own (pre and post)
- autoreceptors: regulate the release of their own neurotransmitter (pre)
what are allosteric binding sites?
distinct site on the surface of the receptor different from where the neurotransmitter binds – impacts function of receptor
what is binding affinity?
refers to strength of the bond between drug and receptor
when changes can occur when a drug (ligand) binds?
produced an EPSP (depolarizes - more likely for an AP)
produced and IPSP (hyperpolarizes - less likely for an AP)
what are characteristics of the receptors of the drug itself?
- have a particular life span
- number and sensitivity of receptors can also change
what is up regulation?
making MORE receptors - so more receptors available to interact with drugs
what is down regulation?
make LESS receptors in response to absence of ligand or chronic activation
what is a receptor efficacy?
drug’s ability to alter the activity of the receptor (ex. can the key actually turn the lock)
basically comparing the response that the drug produces compared to what an endogenous ligan would normally produce there
what are full agonists interactions?
- has binding affinity (drug fits into lock)
- has receptor efficacy
- produced SAME biological response as the endogenous ligand would and ACTIVATES the neurotransmitter receptor
if an agonist binds to a neurotransmitter receptor, what occurs?
depends on type of receptor
so either EPSPs or IPSPs
what are receptor antagonist interactions?
- binding affinity (a stick fits in the lock)
- low or NO receptor efficacy (the stick jams it)
- can prevent the active ligands from binding
if an antagonist binds to an excitatory receptor, what happens?
nothing happens
if an antagonist binds to an inhibitory receptor, what happens?
EPSP - the activity continues
what interaction does a competitive antagonist do?
- binds to same site as neurotransmitter
- prevent neurotransmitter from binding
BLOCKS
- they can be overwhelmed if too much agonist drug is given*
what interaction does a non competitive antagonist do?
- binds to allosteric sites and makes conformational change
- prevents neurotransmitter binding or prevents activation of the receptor
- irreversible
DISTORTS
what are partial agonists?
- binding affinity
- lower receptor efficacy than full agonist
what are inverse agonist?
- binding affinity
- initiate a biological action that is opposite to that produced by an agonist
what are allosteric modulators?
- positive modulators (PAM)
- negative modulators (NAM)
what are positive modulators?
- bind to allosteric sites
- increase the ability of a neurotransmitter to bind to and/or activate the receptor
what are negative modulators?
- bind to allosteric sites
- decrease the ability of a neurotransmitter to bind and/or activate the receptor
what are indirect agonists?
- enhances receptor activity without directly binding to receptor
how..
1. RELEASING AGENTS - more transmitter release from presynaptic neuron (ex. amphetamine)
2. REUPTAKE INHIBITORS - makes them stay in the synaptic cleft and not taken back in
3. ENZYME INHIBITORS - keeps them in synaptic cleft
4. PRESYNAPTIC REGULATOR - interact with auto/hetero receptors on presynaptic neuron
what are implications of drug receptor interactions?
- drugs can alter rate of bodily/brain function
- drugs cannot impart entirely new functions to cells, only modify existing functions
- drugs can produce effects outside of normal physiological range (SUPRAPHYSIOLOGICAL RESPONSE)
what are dose response curves?
it shows the magnitude of a drug’s effects (response) produced by a given drug concentration (dose)
what is on the x and y axis of a dose response curve?
X-axis: drug dose (concentration)
Y-axis: biological response/ efficacy/ binding
what is the threshold dose on a dose response curve?
the minimum amount of drug needed to provide a measurable change in your physiology
what is the maximum effect/ ceiling effect on a dose response curve?
the strongest biological effect that can be produced by the drug
what does ED50 / EC50 mean on a dose response curve?
ED50: effective dose in 50%
EC50: effective concentration in 50%
same thing!
can be used to see…
1. how much drug needs to be given to reach the half maximal (50%) response
or
2. dose of drug that produced a response in 50% of a test population
what does ED100 mean on a dose response curve?
dose that produces maximal effect in 100% of the population
what is the potency of a drug?
amount of drug needed to produce a given effect (on X axis ALWAYS)
high potency means low dose needed so the graphs will be near the 0 of the graph (increases as you go left)
what is the efficacy of a drug?
maximum effect/ response drug can produce (on Y axis ALWAYS)
high efficacy means it will be higher up on the y axis. (increases as you go up)
what does the slope of a dose response curve indicate?
the more steeper the curve the more sensitive to small changes in dose.
less drug causes a high biological response
threshold & maximum response are closer together with steep slope and contributes to saftey of drug
what can dose responses tell us?
ED: effective dose
TD: toxic dose (ex. TD50 dose at which 50% of population experiences adverse reactions)
LD: lethal dose (ex. LD50 dose at which 50% of population dies)
in an ideal world you want your LD line to be super far away from ED.
what helps determine how safe a drug is?
therapeutic window: separation between effective & toxic (or lethal) dose
how is therapeutic window calculated?
therapeutic index = TD50/ED50
higher TI = more separation between curves - GOOD
what is certain saftey index/certain saftey factor/ margin of saftey and how is it calculated?
is more conservative because we don’t want it to be toxic to 50% of population so we look at 1%
CSI = TD1/ED99
higher CSI = more separation between curves - GOOD
how do competitive antagonists change dose response curves?
competitive antagonist will cause a right ward shift – more of drug is needed to produce same biological response – reduced potency of drug
how do non competitive antagonists change dose response curves?
- binding to the receptor at a site other than the agonist binding site.
- disturbing the cell membrane supporting the receptor.
- interfering with cell processes that were initiated by the agonist.
what are pharmacokinetic drug interactions?
one drug affects the absorption, distribution, metabolism, or excretion of another
what is pharmacodynamic drug interactions?
two drugs have interactive effects in the brain (at level of the receptor)
what are cumulative effects of a drug?
repeated administration of the SAME drug may produce effects that are more pronounced than those produced by the first dose
what are additive effects of a drug?
The effect of two chemicals is equal to the sum of the effect of the two chemicals taken separately
Example: aspirin (5) + acetaminophen (6)=
total effect: 11
what are synergistic effects of a drug?
The effect of two chemicals taken together is greater than the sum of their separate effect at the same doses. both drugs individually have an action
Example: alcohol + redbull
what are potentiation effects of drugs?
One drug has minimal/no effect by itself but enhances the effects of a second drug. it intensifies morphine by itself.
Example: acepromazine (drug with little/ no analgesic effects) + morphine
what are antagonistic effects of drugs?
The effect of two chemicals taken together is less than the sum of their separate effect at the same doses. reduced response if taken together but not if taken separately
Example: caffeine + melatonin
heroine + naloxone
what are objective effects of drugs?
can be directly observed by others
ex. stumbling when drunk
what are subjective effects of drugs?
can be felt by the individual but not directly observed by others
ex. seeing the world spinning when laying down
what is symptom that has both subjective and objective effects?
objective: high heart rate
subjective: feeling excited
what is drug tolerance?
reduced response to a drug after repeated exposure and an increased dosage must be taken to get the same magnitude of biological effect
what is cross tolerance?
tolerance to one drug can reduce effectiveness of a second drug that you make take in the future
what are the characteristics of tolerance?
- tolerance is reversible if you stop using the drug
- depends on dose, frequency, and environment
- can occur rapidly, after chronic use, or never
- not all effects of a drug show the same degree of tolerance
- several different mechanisms explain multiple forms of tolerance
what is acute tolerance (tachyphylaxis)?
rapid decrease in response to drug after initial dose
what is behavioral tolerance?
experience with a drug leads to reduced impairment
ex. you adapt to walking when drunk or you act sober when intoxicated
what is metabolic tolerance (drug disposition tolerance)?
repeated use of a drug reduces amount of the drug available at the target tissue
liver enzyme induction causes the liver to break down the active drug and speed up its removal
ex. repeated use of the drug causes your body to protect you from yourself and thats when liver enzyme induction occurs
what is pharmacodynamic tolerance?
changes in nerve cell function to compensate for continued presence of drug
ex. receptor down-regulation
what is sensitization (reverse tolerance)?
- increased drug effects after repeatedly taking the same dose
- less drug needed to achieve the same effect
what is cross sensitization?
Taking 1 drug can make a person more sensitized to other drugs in the future
