Intro to Pharmacodynamics Flashcards
Receptor:
what role does it play?
initiates what events?
regulatory role
interacts with a drug and initiates the biochemical events leading to drug effect
Drug-Receptor Interaction–> Covalent
- can it be reversed?
- reactivation requires?
Irreversible and reactivation requires resynthesis of the receptor or enzymatic removal of the drug
Drug Receptor Interaction–> Noncovalent
- is it reversible?
- how common
reversible, most drugs bind to receptors via non-covalent bonds
Strongest to weakest drug receptor interactions
(four)
Ionic>hydrogen>hydrophobic>Van der waals
Hyperbolic curve
x axis?
y axis?
drug dose on the x axis
drug effect on the y axis
how do you get a sigmoidal dose response curve?
-x, vs y axis
log of drug dose on x
response on y
more common than hyperbolic curve
Emax
-define
The maximal effect that can be produced by the drug
ED50
The dose of the drug that produces 50% of its maximal effect
Graded Response curve:
- what question does it answer?
- What varies continuously?
- represents mean value of what?
Answers the question how much
magnitude of a response varies continously
typically represents the mean value within a population or a single subject
Quantal Response:
- question it answers
- type of response
- requires what
- used for what?
all or none; yes-no binary response
- does the response occur or not?
- in how many?
- requires a pre-defined response (death, falling asleep, 10% reduction in bp)
- used to examine the frequency of the number of individuals showing a response within a large population
non-cumulative quantal dose-response curve
-define
number or percent of individuals responding at a certain dose of a drug and only at that dose
Cumulative quantal dose response curve
-define
number or percent of individuals responding at a certain dose of a drug AND at all doses lower than that dose
Therapeutic index:
- what ratio?
- meaning of the value?
TD50/ED50
higher the TI the safer the drug
Therapeutic window:
-define
range of doses of a drug or of its concentration in a bodily system that provides for the safe and effective therapy
KD:
- meaning of this value
- unit
- low vs high
KD is the equilibirum dissociation constant, which is the drug concentration at which 50% of the drug receptor binding sites are occupied by the drug
- unit is molar concentration
- lower the value, higher the affinity of a drug for a receptor
Where [L], [R] and [LR] represent molar concentrations of ligand, receptor, and their complex
What is the EC50
-how is it different than KD
- It is simply the concentration of agonist required to provoke a response halfway between the baseline and maximum responses. Because the EC50 defines the location of the dose-response curve for a particular drug, it is the most commonly used measure of an agonist’s potency.
- However, the EC50 is usually not the same as the Kd for the binding of agonist to its receptor – it is not a direct measure of drug affinity.
-Magnitude of a drug’s effects will be proportional to what?
proportional to the degreee of its interaction with a receptor
Drug selectivity:
- define
- measured how?
- property of a drug determined by its affinities at various binding sites
- measured by comparing affinities of a drug to different receprots
- a more selective drug would affect fewer targets over a specific concentration range (therapeutic range)
Intrinsic activity:
-define
ability of a drug to change a receprot function and produce a physiological response upon its binding to a receptor
Agonist
-definition, does it have intrinsiv activity?
bind to the receptor and stabilize it in a particular conformation (usually active), producing a physicological response
*have an intrinsic activity*
Antagonist
- define, does it have intrinsic activity?
- effect in absence of an agonist?
- receptor antagonists bind to the receprot but do not change its function. however, they prevent activation of the receport in the presence of an agonist
- don’t have intrinsic activity
- don’t change function of receptor upon binding
- no pharmacological effect in the absence of an agonist
Full agonist:
- when do they produce maximal pharm. effect?
- intrinsic activity levels?
fully activate receptors producing a max pharm effect when all receptors are occupied
-maximal intrinsic activity
partial agonist:
- describe activation of receptor
- pharm effect
- intrinsic efficacy
partially activate the receptor upon binding
- produce a sub-maximal pharm effect when all receptors are occupied
- intrinsic efficacy varies depending on drug, but ALWAYS submaximal
Inverse Agonists:
- effect on receptor signaling
- constitutive receptor activity?
- intrinsic activity, why?
- decrease receptor signaling
- decrease response at receprotrs with a significant level of constitutive receptor activity
- intrinsic activity is present and related to the inhibition of receptor function
Pharmacologic antagonism
Chemical antagonism
Physiologic antagonism
Pharm: (receptor) antagonism action at the same receptor as endogenous ligands or agonist drugs
Chemical: when chemical antagonist makes the other drug not available
Physiologic: occurs between endogenous pathways regulated by different receptors
Competitive antagonist:
- compete with what?
- can be displaced by what
- compete with endogenous chemicals or agonist drugs for binding to the receptor
- can be displaced from the receptor by other drugs (effects are surmountable)
Non-competitive antagonists:
types, define (x2)
-receptor inactivation is not surmountable
Irreversible antagonists: irreversibly bind to and occlude the agonist site on the receptor by forming covalent bonds
Allosteric antagonists: bind to a site other than the agonist site to prevent or reduce agonist binding or activation of the receptor
Competitive antagonism:
- EC50 effect
- Emax effect
-EC50 increases, Emax does not change
Noncompetitive antagonism:
- effect on EC50
- effect on Emax
EC50 does not change, but Emax decreases
Drug Potency:
- define
- what drugs tend to be more potent
- what value represents drug potency? (lower vs higher)
- Potency describes the amount of drug required to produce a specific pharmacological effect
- drugs with higher affinities for a receptor–> lower KD tend to be more potent
- potency describes the amount of drug required to produce a specific effect and is represented by the ED50–> the lower the value, the more potent
*determines the drug dose that will be used clinically*
Drug Efficacy:
- define
- represented by what value?
- efficacy is related to total number of?
- determines clinical what?
- describes the maximal pharmacological effect the drug can produce
- represented by the Emax, the greater the Emax the more efficacious the drug
- efficacy is related to the total number of receptors available to bind a drug, and it determines the clinical effectiveness of a drug
Describe increasing potency vs increasing efficacy graphs
microgram
-define
1/1000th of a milligram, which is 1/1000th of a gram
1 kg = how many pounds?
2.2
Volume:
-tsp, tbsp, ounce, cup
Volume:
- ml/cc
- quart=how many ml? how many pints in quart?
- pint=ml? how many oz in one pint?
- gallon=how many L? quarts in a gallon? pints in gallon?
Dosing Frequency abbreviations:
- qd
- bid
- tid
- qid
- qod
- q”x”h
Dosing frequency:
- qam
- qpm
- qhs
- prn
- ac
- pc
Routes of administration:
- od
- os
- ou
- ad
- as
- au
- gtt
Routes of administration:
- po
- sl
- iv
- im
- sq
- pr
- NGT
- OGT
abbreviations:
- ut.dict.
- tra
- kvo
- as directed
- to run at
- keep vein open
of gms in 100ml
W/V%
