Pharmacodynamics Flashcards
which one of Paul Ehrlich’s theories used the analogy of a lock & key?
the side chain theory & concept of the receptor
what was the lock and key analogy implying relating to a ligand & a receptor?
- key goes in and out (reversible binding)
- key must fit lock (selective binding)
- only certain keys turn the lock (selectivity of action)
- thermodynamic (energetically favorable to obtain binding/action)
most receptors have endogenous naturally occurring molecule that
bind to them
exogenous drugs have to be designed to
bind and mimic the endogenous substance at the same receptor
give an example of an endogenous molecule and exogenous drug acting through the same receptor class
endorphins & morphine bind to opiate receptors in the brain
what chemical bond determines if a drug-receptor complex is irreversible
covalent
what chemical bond determines if a drug-receptor complex is reversible by altering pH
ionic
what chemical bond determines if a drug-receptor complex is readily reversible
- hydrogen
- hydrophobic
- van der Waals
define stereoisomers
chemical structures that are chemically identical but have different orientations around the single bond
what effect can stereoisomers have on drug affinity?
it can alter affinity of a drug to its receptor therefore affecting its potency
define hydrophobic
- water hating
- fat loving
- nonpolar
define hydrophilic
- water loving
- fat hating
- polar
define lipophilicity
allows drugs to move among body compartments and bind to receptors
what are the 4 requirements for good drug binding
- receptor specificity
- type of bond formed
- stereoselectivity
- solubility characteristic
define agonists
bind to produce and elicit
- max. activation of receptor
- max response from the tissue
define antagonists
bind but produce
- NO activation of receptor
- block response from tissue
define partial agonists
produce weaker activation of receptor than full agonists or endogenous ligands
define inverse agonists
inhibit rather than activate the receptor
define allosteric modulators
bind to receptors at alternate binding site
define potency
the measure of the amount of drug necessary to produce an effect of a given magnitude
what is EC50
the [] of a drug needed to produce 50% of the maximum effect
what is ED50
dose that produces 50% of maximal response
define efficacy
ability of a bound drug to change the receptor in a way that produces an effect
what is Emax
the maximal efficacy of a drug
define therapeutic index (TI)
ratio of LD50/TD50 and ED50
which if the 2, efficacy or potency, is a more useful value?
efficacy
why is the efficacy a more clinically useful value than potency?
b/c a drug with greater efficacy is more therapeutically beneficial that one that is more potent
what is LD50
the dose at which 50% of patients die
what is TD50%
the dose at which toxicity occurs in 50% of patients
drugs with which type of therapeutic window are more desirable?
those with a greater/wider therapeutic window
drug binding specificity involves
molecular recognition between ligand and receptor
drug binding specificity requires
spatially & energetically complementary domains
explain the concept of binding affinity/ binding energy
- recognition between receptor and ligand
- spatially/ energetically complementary domains
equilibrium binding constant KD represents…
rate of dissociation/ rate of association
what information does KD provide about a drug?
drugs w/ a high affinity display a small KD value
KD= the drug concentration that gives
50% bound receptors
KD is inversely related to
drug binding affinity
receptor classifications are named after an
endogenous ligand w/ various subtypes of receptors named for exogenous agents
what is an example of a ligand gated ion channel?
in skeletal muscles for movement of NA+ and Ca2+
- nicotinic cholinergic receptors
- endogenous ligand acetylcholine
explain GPCRs
G-protein coupled receptors
7 transmembrane domains spanning region of the receptor w/ few allosteric modulator binding sites
GPCRs activate
2nd messenger systems within the intracellular space
which receptors represent the largest protein class of receptors in the human genome?
GPCRs
gives examples of GCPR receptors
- muscarinic cholinergic receptors
- adrenergic (a & b )
- dopaminergic
- serotonergic
give examples of endogenous ligands that bind to GCPRs
- acetylcholine
- epinephrine
- norepinephrine
- dopamine
- serotonin
- GABA
- glucagon
the GCPR are found in the
- heart
- respiratory system
- digestive system
- blood vessels
what are RTKS
receptor tyrosine kinases
single transmembrane spanning regions
describe the mechanism of RTKs
binding of ligand causes dimerization of the kinases following phosphorylation by ATP
give examples of ligands that bind to RTKs
- insulin
- GF
GH
ligand binding occurs on what side of the cell?
on the extracellular side
nuclear receptors are ..
receptor residues that are on the inside of the cell or within the nucleus
in nuclear receptors the ligand-receptor complex binds to
DNA segment for transcription
what is a unique characteristic of nuclear receptors?
they have longer lasting effects than other ligand-binding receptors
what are some examples of endogenous receptors that bind to nuclear receptors?
- corticosteroids
- mineralocorticoids
- sex steroids (estrogen & testosterone)
- vit. A and D
what are the 4 known changes that can occur in receptor quantities?
- receptor quantities are not constant
- internalization & degradation
- change in receptor synthesis rate
- can be unregulated or downregulated
describe upregulation
receptor number increase due to a decrease of activity in the receptor
describe downregulation
receptor number decreases due to an increase making the cell less sensitive to the ligand
describe desensitization/tolerance
continued stimulation of a receptor system will depress the effect produced by an administered drug
- a higher dose is requires to each the same effect
