Pharmacodynamics and drug-receptor interaction Flashcards
pharmacodynamics
study of biochemical, cellular, and physiological effects of drugs and their mechanics of action
Chemical mechanism of drug action
chemical nature of the drug alters the physiologic environment of the target tissue to produce an effect
Antacids
increase pH of gastric lumen to neutralize gastric acid thereby decreasing irritation to the lining of the stomach
Osmotic diuretics
increase osmolarity of tubular fluid in kidney to decrease the reabsorption of water which increases urine output
chelating agents
drugs that chemically bind to target molecules
digibind
used as an antidote for digoxin toxicity
deferoxamine
used as an antidote for iron toxicity
Receptor binding
drug functions as ligands that bind to receptors that regulate cellular processes
Agonist
when it binds to the receptor, results in producing a desired response of the receptor
Antagonist
when it binds to the receptor, it stops producing a desired response of the receptor
Receptor types
ligand gated ion channels
GPCR
enzyme linked receptors
intracellular receptors
What is Kd
equilibrium dissociation constant
ratio of the dissociation rate to the association rate
Affinity
strength of interaction between a ligand and its receptor
Kd= ?
([L][R])/ [LR]
The formation of the ligand/drug-receptor complex is determined by?
affinity
Affinity constant
Ka
reciprocal of the equilibrium dissociation constant
Drugs with a high affinity have what kind of Kd?
low
Fraction occupancy of receptors= ?
[LR]/([R]+[LR])
describes the magnitude of biological effect related to the amount of active receptors— agonists can infect this
When the concentration of free drug increases the concentrations of bound receptors to total receptors plateaus. This is known as?
the maximal effect
potency
amount of drug needed to produce an effect
EC50
concentration of the drug that produces 50% of the maximum effect; determines potency
Efficacy
ability of ligand to produce a pharmacological response
Emax
maximal effect of a drug
factors that affect biological response
[agonist]
affinity of agonist for the receptor
fraction of occupied receptors
intrinsic activity
ability of a drug to fully/partially activate the receptors
Full agonists
intrinsic activity ~ 1
can produce a maximal response
Partial Agonists
0 < intrinsic activity < 1
produces less than a maximal response
Inverse agonists
intrinsic activity < 0
reverse the activation state of receptors
exert opposite pharmacological effect of agonists
Competitive antagonists
bind reversible to the receptor on the same site
interferes with binding to its receptor
maintain the receptor in the active states
reduces antagonist potency, incr EC50
Non competitive antagonists
bind irreversibly and covalently to the receptor on the same site
reduces the number of receptors available to the agonist permanently
decr Emax
no shift of EC50 values
As concentration of antagonist increase in competitive antagonism, response curves shift to the?
right
Which way do response curves shift in non competing antagonism?
right and down
Allosteric antagonists
bind to allosteric site
decr Emax
no shift of EC50 value
decrease affinity of receptor for the against
can potential effects of primary agonists
ED50
median effective dose
dose required to produce a desired effect in 50% of the population
ED99
dose of a drug that produces a desired effect in 99% of the population
LD50
median lethal dose
dose producing toxicity in 50% of the population
LD1
dose producing toxicity in 1% of the population
Therapeutic index
ratio that compares [blood] at which a drug becomes toxic and the concentration at which the drug is effective
LD50/ED50
measure of a safety of a drug
large therapeutic index indicates
a wide margin between effective dose and lethal dose
therapeutic window
range of steady-state concentrations of drug providing therapeutic efficacy with minimal toxicity
In most drugs, what kind of therapeutic index values are required?
high
factors affecting the response to a prescribed drug dose
medication errors
patient compliance
factors affecting administered dose
rate and extent of absorption
body size and composition
distribution in body fluids
binding in plasma and tissues
rate of metabolism and excretion
factors affecting concentration at site of action
physiological variables
pathological factors
genetic factors
interaction with other drugs
development of tolerance and desensitization
factors affecting drug effects
drug receptor interaction
functional state of targeted system
selectivity of drug propensity to produce unwanted effects
placebo effects
resistance
