Midterm 1 Flashcards
the action of a drug on an individual
pharmacodynamics
substance used in the diagnosis, treatment, or prevention of an illness
drug
anti-emitic, specific muscarinic acetylcholine receptor antagonist of vestibular pathway, decreases ACh input
scopolamine
vestibular, sensory, emotional, chemoreceptors, GI tract are all things that project to what
vomition center
the way botox achieves specificity
local administration
the study of drug administration, absorbtion, distribution, action, and excretion
pharmacokinetics
routes of administration
oral, IV, intramuscular, inhalation, topical, subcutaneous, intraperitonial, intracranial
Problems with oral administration
acidic environment in stomach, first pass effect (liver metabolism often reduces efficacy, but not loarsitan)
first pass effect
drug must enter bloodstream: portal vein - liver - drug metabolism. Both acidic stomach env. and liver metabolism can reduce function of drug
works better after metabolism
loarsitan
MEC (desired response)
minimum effective concentration (always exists)
point at which drug exceeds threshold
onset of effect
point of drug being toxic
MEC (adverse response)
Difference between drug threshold and toxic threshold
therapeutic window
Time it takes for half of drug to leave system
Half-life (T1/2)
Repeated doses to achieve steady state leads to this curve shape
sigmoidal
Fast onset, large volumes, sterility problem, must be hydrophilic
IV
Steady absorbiton, hydrophobic, sterility problems, sometimes irritating
Intramuscular
Gaseous (volatile), fast onset, sometimes requires flame
Inhalation
slow, steady absorption, only hydrophobic
Topical
implantation of pellet, slow, steady absorption, sterility problems, removal problems
subcutaneous
injection into abdomen, fast availability, sterility problem, used for lab rats
Intraperitoneal
drug effectiveness/absorbtion graph
IV, IP, IM, oral(PO)
directly to CNS, sterility problem, (epidurals)
Intracranial
drug enters and exits body tissues
Equilibrium
Drug doesnt know where you want it to go
hydrophilic, hydrophobic, specific receptors, etc.
tissue drug has no effect in and gets trapped in, no receptors
drug reservoir
example of drug reservoir
adipose tissue
nonspecific assoiation, other drug reservoir that isnt drug reservoir, is reversible, amino acids attractive to drug
proteins
liver chemically alters drugs to make removal easier
metabolism
metaolized drug
metabolite
why is transformation from ph 2 to 7 necessary
make absorption possible, must be nonpolar to cross lipid bilayer
why weak bases are good oral candidates
protonation in stomach, becomes neutral
BBB is different in this way
tight junctions and astrocytic feet
R-CH2-CH3 –>(cytochrome P450) –> R-CH(OH)-CH3
oxidation
R-NO2 –> R-NH2
reduction
R-CO2R’–>esterases>R-CO2H+R’OH
hydrolysis
R-OH + R –> R-O-R’
conjugation
contains furanocoumarins which inhibit a P450 enzyme, increases levels of lipitor in bloodstream | can also block transporters in intestine which are responsible for uptake (allegra)
grapefruit juice
urination, sweat, exhalation, liver–bile
excretion
bifunctional role of receptor, one “thing” for which atropine and pilocarpine are competing in salivary glands (DATE, PERSON, THEORY NAME)
john langley (1878)- receptor theory
coined the term “receptor,” lock and key metaphor (person and dates)
Paul Ehrlich (1854 - 1915)
molecules that bind receptors
ligands
cause a positive response (biological), can initiate second messenger response
agonist
binds with high affinity, but doesn’t have biological effect (nothing turned on in cell), no second messenger pathway, blocks normal chemical binding, blocked cellular activity
antagonist
one example antagonist can be used for response
narcan for heroin overdose
Gs
stimulates adenylyl cyclase - takes ATP and forms cAMP, alters PKA, catalytic subunits run free and phosphorylate downstream targets
Gi
inhibits adenylyl cyclase
Gq
stimulates PLC - DAG–>PL(K?)C
Go
couples directly to ion channels
how many transmembrane domains do G protein receptors have?
7
nicotine is agonist for this type of channel
ligand-gated ion channel
transporter: just takes one
uniporter
transporter: picks up one from inside, one from outside, and swaps them
antiporter
transporter: takes multiple things at once and moves them to other side of membrane
symporter
transporter: uses ATP
ATP-driven transporter
proteins which interact with DNA following binding of a ligand (e.g. estrogen)
Transcriptional activator
receptor where each monomer has half of the receptor sites, presence of ligand bring 2 monomers together, they phosphorylate each other, then phosphorylates downstream intracellular target
Tyrosine Kinase Receptor
Drug binding to receptor is:
reversible
computer runs water molecule over protein surface, this helps us determine:
protein shape
how much drug wants to get into and stay in binding pocket | “ability of drug to bind receptor”
affinity
4 factors that determine drug affinity
steric interactions, ionic bonds, hydrogen bonds, hydrophobic interactions (all reversible), covalent bonds rare
Concentration at which 50% of receptors are bound
Kd (affinity constant), logarithmic curve, smallest concentration that achieves Kd has highest affinity, Kd is inflection point
concentration of competitor at which we lose 50% of first drug binding
IC50
binding assay demonstration
once receptors are filled, more drugs wont bind
how fast drug associates with receptor
k1- forward rate constant
how long it takes drug to come off of receptor
k-1 - reverse rate constant
k-1/ k1
reflects affinity
ability of drug bound to receptor to induce intracellular activity
efficacy
intrinsic efficacy of 1
full agonist
intrinsic efficacy btw 0 and 1
partial agonist
intrinsic efficacy of 0
antagonist
regions responsible for making associations with drug - influences affinity
binding domain
region that interacts with drug that “turns on” receptor (conformational change)
activation domain
____ is a measure of how well a drug binds; ____ is a measure of how well a drug can produce desired effect
affinity, efficacy
dose response curves can tell you response to drug, but neither ___ or ____ specifically
affinity, efficacy
concentration of drug at which 50% of population exhibits a response after a certain period
EC50, lower EC50 is a better drug
receptor expression, ligand affinity, and intrinsic efficacy, all constitute:
drug effectiveness
receptor expression is not ___ within population, or even within people
constant
with sudden high concentrations of agonist, receptor becomes phosphorylated, inactivated, and internalized/sequestered
desensitization
with chronic levels of agonist, receptors become phosphorylated multiple times, inactivated, and internalized, having been tagged for degradation, B- arrestin involved
downregulation
administration of 2nd drug to allow re-sensitization of 1st drug’s receptors
drug vacation
drug binding and biological response are ___ correlated
directly
Therapeutic index
TD50/ED50 (2 is not safe drug, doubling dose causes side effects in 1/2 of population
Therapeutic window
TD50 - ED50
3 categories of neurotransmitters of ANS
ACH, catecholamines (NE and E), and indolamines (serotonin)
