Final Flashcards
Routes of administration and characterization of each route
Oral (metabolism); intravenous (nonlipid, fast onset); intramuscular (lipid, slow, long release); inhalation (gas, lipid (gas exchange), Topical (lipid, slow, long release); subcutaneous (like IM); Intraperitoneal (rat stomach), intracranial (spinal cord)
phenomenon by which concentration of administered drug is greatly reduced before reaching circulation via _____
First pass effect, metabolism
how do orally administered drugs cross PPB of cell membranes?
achieve neutrality after metabolism
places drug can go from bloodstream
tissue reservoirs, proteins, tissues, metabolism and elimination
“bi-functional role of receptor” meaning and who?
Langley, “binding and transduction”
lock and key metaphor, who?
Ehrlich
Gs (short)
stimulates adenylyl cylase
Gi (short)
inhibits adenylyl cyclase
Gq (short)
stimulates PLC
Go (short)
couples directly to ion channels
Gs/Gi (whole sequence)
ligand binds, alpha subunit disconnects, activating adenylyl cyclase, converts ATP to cAMP, cAMP goes on to rearrange regulatory subunits and release catabolic subunits of PKA
Gq
ligand couples to receptor, stimulates PLC to phosphorylate PIP2 into DAG and IP3. DAG activates PKC and IP3 stimulates calcium calmodulin action
Go
ligand couples, receptor opens K+ pathways and they exocytose, leading to inhibition?
affinity
ability of drug to bind receptor
Kd
(affinity constant) concentration of drug at which 50% receptors are bound. (looks logarythmic, the one that is sharper slope is more effective (less concentration) (drug concentration vs %maximal binding)
IC50
(Competitor) concentration at which 50% of binding sites have now been taken over (like a backwards S, negative slope)
Efficacy
ability of a ligand to activate a receptor (full, partial, antagonistic)
Full agonist
intrinsic efficacy of 1
partial agonist
efficacy between 0 and 1
antagonist
bonds to receptor, intrinsic efficacy of 0
EC50
concentration of drug at which 50% of population exhibits response over certain time period (survey “has pain been relieved) (forwards s, sharper slope and smaller EC50 means better drug)
mechanisms of tolerance:
desensitization and downregulation
desensitization
when sudden, high concentrations of agonist and receptor become phosphorylated, inactivated, and internalized
Downregulation
when chronic levels of agonist, receptors become phosphorylated multiple times, inactivated, and internalized for degradation (may be way diabetes works with insulin detection / release?) not sure
what molecule flags for degradation?
B-arrestin
TD50
concentration of drug at which 50% of the population shows toxicity (S shape)
TD50-Ed50=______; (Larger = _____)
Therapeutic window; (larger=safer)
Metabolism types (4)
Oxidation, reduction, hydrolysis, conjugation
oxidation
R-CH2-CH3 —ctochrome P450)—> R-CH(OH)-CH3
reduction
R-NO2 —–> R-NH2
hydrolysis
R-CO2R’ —esterases—-> R-CO2H + R’OH
conjugation
R-OH + R’ —–> R-O-R’
example of the way enzymes responsible for metabolism are inhibited
Grapefruit juice contains furanocoumarins that inhibit cytochrome P450, leading to increased levels of circulating drug
Regulation of Choline Acetyltransferase amounts in the synapse (3)
End product inhibition
Neuronal Stimulation
Mass Action
negative feedback loop used to regulate production of a given molecule; prevents excess buildup of end-product
end-product inhibition
if a neuron is stimulated by depolarization from action potential, ACh will be released/used up, so choline acetyltransferase will become activated to produce more ACh and compensate for its use
Neuronal stimulation
principle on the equilibrium of a process (hypothetical)
mass action
terminates the action of acetylcholine action by breaking ACh into acetate and choline
Acetylcholinesterase