Pharmacodynamics Flashcards
pharmacodynamics
the study of the pharmacologc and biochemical effects of a drug and its mechanism of action
a ligand can be classified as
a chemical messenger
what are receptors
proteins that receive a chemical signal from a protein ligand which binds to a protein receptor
characteristics and roles and protein ligands - 3
- they determine the quantitative relation between dose/concentration and its pharmacologic effects
- responsible for selectivity of drug action, the size, shape and electric charge, whether it will bind and it if does, at what affinity
- mediate the action of pharmacologc agonists and antagonist
orthosteric binding - 3
- binding of receptor or enzyme to the primary binding site of an agonist or antagonist
- involves the interaction between the ligand and the active binding site of a receptor or enzyme
- cause direct change in the receptor or enzyme activity
allosteric binding - 3
- occurs at the site of the receptor that is different from the active binding site of a receptor or enzymes
- can either enhance or inhibit the receptor enzyme activyt
- has fewer side effects that orthosteric bc it doesnt result in full actions but rather partial
receptor classification - 4
- ion channels
- GPCR
- enzyme linked - tyrosine kinase
- intracellular
4 main targets for drug action
- receptor
- ion channels
- carrier molecules
- enzymes
voltage gated ion channels - 4
- on electrically charged cells or nerve tissue like the cardiac
- open or close in response to change in membrane potential not just by the binding of a ligand
- open when the cell is depolarised
- CCB
ligand gated receptors
- open in response to the binding of one or more ligands
- Ach, GABA
GPCR
- secondary messengers
- regulate the activity of enzyme and ions
Enzyme-linked receptors
- mainly respond to protein mediators
- has an ELBD and a CED
- insulin/EGFR
intracellular receptors
- nuclear receptors that regulate gene transcripton
- lipid soluble agents = steroid and thyroid hormones
dose response relationship - 3
- an increase in dose will increase the pharmacologic effects
- where all receptors are occupied
- because the point of maximal response is reached
Ec50
concentration of a drug that produces 50% of the maximal effect (potency)
potency
- the amount of drug needed to produce a given effect
- it is dependant on the affinity of the receptor to the drug
- drugs with high potency produce effects at low concentration
efficacy
- the ability to exert a response
- the maximal effect an agonist can produce
all receptors are occupied and increasing the dose will not have any an=dditional effects
therapeutic window
the range of steady state concentrations which orovides therapeutic efficacy with minimal toxicity
therapeutic index
how selective a drug is in producing the desired effects/ therapeutic vs its adverse effects
what do they mean when they say a drug has a narrow TI
therapeutic concentration is closer to the toxic concentration
5 drugs with a low/narrow TI
- Lithium
- Digoxin
- Carbamazepine
- Phenytoin
- Theophylline
Affinity
the strength of the interaction between a drug and receptor determined by the Kd
Intrinsic activity
the capacity to induce a functional change in the receptor
Specificity
when a ligand binds to a single type of receptor that is only expressed in a limited number of cells
Different dissociation constants
- electrostatic interactions
- van der waals forces
- hydrogen bonding
Kd affects - 2
affinity and specificity
chemical structure affects - 2
intrisic activity and affinity
partial agonists
drugs that are only partly effective regardless of the concentration employed
inverse agonists
drug that has constituitive activity in the absence of a regulatory ligand, and their effects are opposite that of agonists
Antagonist
reduce or block the action of an agonist
Antagonism
competition with an agonist for the same or overlapping site of a receptor
Chemical antagonism
combines with a substance chemically
Physical antagonism
binds to a drug and decreases its absorption
Physiological antagonism
produces an action that is opposite to that of a substance by bindging to a different receptor
Pharmacological antagonism
produces no effect, no intrinsic activity
Reversible antagonism
readily dissociates from the receptor
Irreversible antagonism
stable, permanents/ nearly permananet chemical bond with their receptor
- e.g = alkyation
competitive antagonism explained
the binding of an antagonist prevents the binding of an agonist to the receptor
noncompetetive antagonism explained
agonist and antagonist can bind simultaneously but the antagonist prevents or reduces the action of the receptor
- basically both can binds, its not that deep man.. mara se salang antagonist yo winna.. its giving self cav
reversible competitive antagonims - 3
- agonist and antagonist form short-lasting bonds with the receptor
- steady state of the 3 is recahed
- can be overcome by increasing drug concentration
what changes occur in competetive reversible antagonism
- antagonist competes with agonist for receptor binding and more agonist is required n the presence of antagonist to have the same effect
- emax unchanged
-potency decreases - ec50 increases
what changes occur in noncompetetive irreversible antagonism
- antagonists form covalent irreversible bonds with the rece[tor
- emax decr
- efficacy dec
-ec50 remains the same
pseudoirreversible antagonists
dissociates slowly from the receptor and mimics an irreversible antagonist
allosteric antagonism effects - 2
- after binding to a different site, it causes conformational changes that prevent the agonist from binding
- REDUCES MAXIMAL EFFECT
Antagonism potentiation
