Block 1 Lecture 3 -- Pharmacodynamics I Flashcards
ligand:
molecules that binds to some other type of biological entity
receptor:
protein that interacts with a ligand resulting in a change in physiological activity
drug mechanism of action:
the physicochemical relationship between a drug and its specific target, and the cascade of biochemical signaling that ensues
placebo response:
inert substance given to a patient that leads to clinical improvement
nocebo response:
inert substance that causes a worsening of Sxs or development of ADRs
adverse drug response:
undesirable drug response
idiosyncratic drug response:
a quantitatively abnormal drug response
drug allergy:
an adverse immunologic reaction to a drug
agonist:
ligand that binds receptor and activates it
partial agonist:
a drug with less than maximal effect in comparison to a full agonist
indirect-acting agonist:
drug that increases synaptic concentration of endogenous neurotransmitter
allosterically-acting ligand:
ligand that interacts at a non-orthosteric site where it can potentiate functional response to an endogenous ligand
chemical antagonist:
a compound that chemically combines with a xenobiotic to prevent delivery of that substance to its normal site of action
physiologic antagonist:
a drug that blocks a physiological response related to a particular condition without actually affecting the state of that condition
receptor (pharmacological) antagonist:
drug that prevents formation of agonist-receptor complexes
competitive antagonist:
drug that competes with NTs for access to orthosteric binding sites
non-competitive antagonist:
drug that binds receptor at a non-orthosteric site
irreversible antagonist:
drug that binds covalently to a receptor
indirect antagonist:
drug that decreases synaptic concentration of NT
inverse agonist:
drug that produces physiological effects opposite to those of an agonist
potency:
the relationship between a drug concentration and its biological response in comparison to another drug
Quantal Dose Response Curve:
graph used to plot “all or nothing” drug responses; commonly used to assess responses across large patient population
efficacy
the ability of a drug to produce a desired effect
constitutive activity:
activity present in the GPCRs of some systems to produce physiologically active effects even in the absence of agonist
on-target ADR:
drug hits intended target excessively or in the wrong location
off-target ADR:
drug interacts with unintended targets
direct-acting agonist:
drug with enough structural similarity to an endogenous ligand to bind to and directly activate NT receptors
Partial agonists are aka…
functional antagonists
What are the mechanisms by which indirect-acting agonists might work?
1) block NT degradation
2) block re-uptake transporters
3) increase pre-synaptic release
What are the types of antagonism?
1) PK
2) chemical
3) physiologic
4) receptor (pharmacological)
Describe the structure of the nAChR
5 subunits like GABAa but excitatory
Describe structure of the GABAa receptor
5 subunits surrounding inhibitory Cl- channel
- 2 orthosteric GABA sites
- allosteric: EtOH, BZDs, neurosteroids, barbiturates
Axes of a DRC:
% response vs. [drug]
ED50:
[agonist] that produces a 50% maximal response
IC50
ED50 for antagonist–
[antagonist] to decrease agonist response by 50%
examples of irreversible antagonists:
organophosphates
snake toxins
examples of chemical antagonism:
1) mercury + dimercaprol
2) anti-venoms
3) immunotherapy for addiction
examples of physiologic antagonism:
1) epinephrine + histamine
2) beta-blockers in hyperthyroidism
example of receptor antagonism:
propranolol + NE
What are the mechanisms by which indirect antagonists might work?
1) block NT synthesis
2) decrease pre-synaptic NT release
What factors could cause an idiosyncratic drug response?
1) reactive metabolites
2) non-allergic changes in pt immune system
3) specific gene mutations in receptor
