Exam 1 Flashcards
insulin works via?
receptor tyrosine kinase
glucocorticoids work via?
intracellular receptors
platelet growth factors work via?
receptor tyrosine kinases
nerve growth factors work via
receptor tyrosine kinases
platelet-derived growth factors work via?
receptor tyrosine kinases
kinase activity is a separate protein for?
cytokine receptors
NO is synthesized via what signaling pathway
cyclic GMP/guanylyl cyclase
decreased response because the enzymes that metabolize the drug are induced
(increased drug metabolism = decreased response)
is??
pharmacokinetic tolerance
decreased response due to change in receptor # or function is?
pharmacodynamic tolerance
what is physiologic tolerance?
when 2 agents w/ opposing physiologic effects are administered together
what is competitive tolerance
receptor antagonist w/ an agonist
what is potency
the dose required to produce a particular effect
a basic drug in an acidic medium will…?
become ionized & accumulate
then be eliminated
drugs with high first pass metabolism?
lidocaine, morphine
how does first pass metabolism influence oral availability
decreases
drugs with low first pass metabolism
diazepam, digitoxin
CNS & autonomic drugs, cardiovascular drugs target?
G protein coupled receptor
local anesthetics and anticonvulsants target?
voltage-gated ion channels
nicotine targets?
ligand-gated ion channel
benzodiazepienes target?
ligand gated ion channels
MAO inhibitors and cholinesterase inhibitors target?
enzymes
antidepressants target? (and 2 examples?)
transport proteins (DAT, SERT)
anticancer and antiviral drugs target?
nucleic acids
codeine is metabolized to what?
morphine (active metabolite)
metabolism of diazepam
diazepam –> nordiazepam (longer half-life) –> oxazepam
acetaminophen metabolite?
N-acetyl-p-benzoquinone imine (toxic metabolite)
affinity is designated by?
Kd
what reactions are the most common phase I reactions?
oxidation
whats the most common phase II reaction?
conjugation
CYP2D6 polymorphism results in
decreased codeine metabolism to morphine –> less analgesic effect
acidic mediums trap which drugs?
basic drugs
basic mediums trap which drugs?
acidic drugs
what cytochrome metabolizes > 50% of drugs?
CYP 3A4
which CYP metabolizes alcohol?
CYP 2E1
alcohol’s effect of CYP2E1 (2)
induction- more activity —> EtOH tolerance
induction of CYP2E1 also increases acetaminophen metabolism
primary enzymes in Phase I metabolism?
Cytochrome P 450 (CYPs)
two CYP-independent oxidation reactions?
alcohol dehydrogenase
monoamine oxidase
grapefruit juice inhibits what enzyme?
CYP450 3A4
Examples of substrates inhibited by grapefruit juice?
Acetaminophen, diazepam, lidocaine
Quinidine inhibits what enzyme?
CYP 2D6
examples of substrates inhibited by quinidine?
Codeine, oxycodone
what is a common endogenous compound used in Phase II conjugation reaction?
glucuronic acid
Phase II conjugation reaction w/ glucuronic acid?
UDP-glucuronic acid + R-OH —> glucuronic acid-R + UDP
renal excretion is influenced by 3 factors:
glomerular filtration rate
active tubular secretion or reabsorption
passive diffusion across tubular epithelium
(all of these can be impacted by pathology)
describe enterohepatic circulation
conjugated metabolites released into the bile are cleaved by bacterial enzymes in the SI, releasing the drug for reabsorption
effect of enterohepatic circulation on drug half-life
and an example?
increases the drug’s half-life
example: estrogen in BC
biotransformation of drugs?
lipid-soluble, non-ionized —> water-soluble, ionized metabolites
large Vd signifies? re: distribution
extensive distribution, binds to peripheral tissues (not plasma- not bioavailable)
small Vd signifies? re: distribution
drugs that are highly concentrated in the plasma
examples of drugs with large Vd?
Acetaminophen, Propranolol
examples of drugs with small Vd?
Heparin, Warfarin
spare receptors effect on the concentration-response curve
shifted left to smaller concentrations
competitive antagonist effect on the curve
dose response curve shifts to the right
noncompetitive agonist effect on the curve
Emax and Bmax decrease
partial agonist effect on curve
lower Bmax and Emax than the full agonist
graded dose response curve measures?
response in an individual
on a graded dose response curve, the position on the X-axis indicates
potency
contraindications for gastric lavage (4)
more than 4 hours since ingestion of most poisons
more than 30 min since ingestion of corrosive
not used for hydrocarbon solvents
or if coma, stupor, delirium are present
methods of increasing excretion rate to treat toxicity (4)
osmotic diuretics, alter urine pH, hemodialysis, hemoperfusion
single/multiple exposure to a poison over 1-2 days
acute toxicity
repeated exposures to a poison <3 mo.
subacute toxicity
repeated exposures to a poison > 3 mo.
chronic toxicity
nicotine toxicity mechanism
interference w/ receptor-ligand interactions
local anesthetic toxicity mechanism
interference w/ membrane fxn
toxicity mechanism of cyanide
interference w/ cellular energy fxn
toxicity mechanism of organophosphates
binding to biomolecules
toxicity mechanism of ethylene glycol
perturbation in calcium homeostasis
toxicity mechanism of MPTP
toxicity from selective cell loss
toxicity mechanism of carcinogens
non-lethal alterations in somatic cells
toxicity mechanism of dioxins
interference w/ cellular transcription factors
toxicity mechanism of Acetaminophen
induction of programmed cell death
Poisoning treatments that reduce absorption or increase elimination (3)
Activated charcoal Ammonium chloride (acidifies urine- basic drugs) Sodium bicarbonate (alkalinizes the urine- acidic drugs)
chelator of arsenic, gold, mercury, and acute lead
Dimercaprol
chelator of copper
Penicillamine
chelator of iron
Deferoxamine
tx for lead poisoning
calcium disodium edatate
tx for acetaminophen poisoning (drug)
Acetylcysteine
antidote for cholinesterase inhibitor
Atropine
sx of organophosphate poisoning
SLUD
Salivation, Lacrimation, Urination, Defecation
Kayser-Fleischer rings indicate?
copper accumulation
competitive agonist effect on curve (2)
increased Kd
right shift
noncompetitive antagonist effect on curve (2)
Emax and Bmax decrease
efficacy of partial agonists?
lower
Administration of agonist and allosteric activator effect the curve how?
same Emax, shift left
Administration of agonist and competitive antagonist affect the curve how?
shift right
No Emax
Administration of Agonist & Noncompetitive Antagonist affect the curve how?
No Emax
decreased response because the enzymes that metabolize the drug are induced
pharmacokinetic tolerance
examples of pharmacokinetic tolerance
barbiturates, EtOH, warfarin
decreased response due to change in receptor number or function
pharmacodynamic tolerance (desensitization, receptor down-regulation)
example of pharmacodynamic tolerance
B-adrenergic agonists (Albuterol)
occurs when two agents with opposing physiologic effects are administered together
physiologic tolerance
example of physiologic tolerance?
histamine and norepinephrine
vasodilation and vasoconstriction
administration of receptor antagonist along with receptor agonist results in?
competitive tolerance
example of competitive tolerance
Yohimbe & clonidine
two methods of desensitization?
- continuous exposure to an agonist –> conversion of an ion channel to an altered, closed state
- receptor coupling effector is phosphorylated to an inactive form
chronic administration of agonists can result in?
down-regulation = degradation of receptors