I. PPT Flashcards
Determines the fraction of drug molecules charged (ionized) vs uncharged (non-ionized)
pH
a neutral molecule that can reversibly dissociate into an anion and a proton
weak acid
a neutral molecule that can form a cation by combining with a proton
weak bases
(weak acids)
unprotonated form is more ____
water soluble
(weak acids)
protonated is more ___
lipid soluble
(weak acids)
better clearance
protonated/unprotonated
unprotonated
(weak acids)
cross biological membrane easily
protonated/unprotonated
protonated
(weak bases)
more lipid soluble, cross biological membrane easily
protonated/unprotonated
unprotonated
(weak bases)
more water soluble, better clearance
protonated/unprotonated
protonated
excretion of weak acid is accelerated by ___
alkalinizing the urine
excretion of weak base is accelerated by ____
acidifying the urine
the component of a cell or organism that interacts with a drug and initiates the chain of events leading to the drug’s observed effects
receptor
responsible for selectivity of drug action
receptors
largely determine the quantitative relations between dose or concentration of drug and pharmacologic effects
receptors
mediate the actions of both pharmacologic agonists and antagonists
receptors
receptors (3)
enzymes
transport proteins
structural proteins
responses to low doses of a drug usually increase in ___ to dose
direct proportion
as doses increase, the response increment __
diminishes
the transduction process that links drug occupancy of receptors and pharmacologic response
coupling
it is possible to elicit a maximal biologic response at a concentration of agonist that does not result in occupancy of all of the available receptors
spare receptors
may be demonstrated by using irreversible antagonists to prevent binding of agonist to a proportion of available receptors and showing that high concentrations of agonist can still
produce an undiminished maximal response
spare receptors
bind to receptors but do not activate them
antagonist
prevents agonists from activating receptors
antagonist
antagonists 2 types
competitive (reversible)
non-competitive (irreversible)
___ agonist binds to receptors in a reversibleway
competetive
the presence of antagonist increases the agonist concentration required for a given degree of response, and so the agonist concentration-effect curve is shifted to the ___
right
the degree of inhibition produced by a competitive antagonist depends on the ____
concentration of antagonist
cause downward shift of DRC
non competitive antagonist
agonists 2 types
full a.
partial a.
capable of fully activating the effector system
full agonist
high affinity for the activated receptor conformation
full agonist
produce less than the full effect, even when it has saturated the receptors
partial agonist
in the presence of an agonist, it acts as an inhibitor
partial agonist
Interact directly with the drug being antagonized to remove it or to prevent it from reaching its target
Chemical antagonist
Does not depend on the interaction with the agonist’s receptor
Chemical antagonist
Binds to a different receptor, producing an effect opposite to that produced by the drug it is antagonizing
Physiologic Antagonist
Response of a particular receptor-effector system measured against increasing drug concentration
dose-response curve
Emax, EC50
Maximal effect an agonist can produce
Efficacy
Determined mainly by the nature of the receptor and its associated effector system
Efficacy
refers to the concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug’s maximal effect
Potency
Determined mainly by the affinity (Kd) of the receptor to the drug
Potency
Minimum dose required to produce a specified response is determined in each member of a population
QUANTAL DOSE-EFFECT CURVES
the measure of the ability of the body to eliminate the durg
clearance
the factor that predicts the rate of elimination in relation to the drug concentration
clearance
two major sites of drug elimination:
kidneys and liver
clearance will vary depending on the concentration of drug that is achieved
capacity-limited elimination
also known as saturable, dose- or concentration-dependent, nonlinear, and Michaelis-menten elimination
capacity-limited elimination
drugs are cleared very readily by the organ of elimination, so that at any clinically realistic concentration of the drug, most of the drug in the blood perfusing the organ is eliminated on the first pass of the drug through it
flow-dependent elimination
the elimination of these drugs will depend primarily on the rate of drug delivery to the organ of elimination
flow-dependent elimination
is the time required to change the amount of drug in the body by one-half during elimination/ during constant infusion
half life
indicates the time required to attain 50% of steady state
half time
defined as the fraction of unchanged drug reaching the systemic circulation following administration by any route
bioavailability
for a drug administered orally, bioavailability may be less than 100% for 2 reasons:
- incomplete extent of absorption
- first-pass elimination
different routes of administration
IV
IM
SC
PO
Rectal
Inhalation
Transdermal
following absorption across the gut wall, the portal blood delivers the drug to the liver prior to entry into the systemic circulation
first-pass elimination
____ plays a pivotal role in terminating the biologic activity of some drugs
renal excretion
converts the parent drug to a more polar or more reactive product by unmasking or inserting a polar functional group
PHASE 1
phase 1 reactions examples
oxidation
reduction
deamination
hydrolysis
also called mixed-function oxidases
cytochrome P450
Cytochrome P450 is found in the
SER of liver
reactions that makes the drug more polar and less lipid-soluble
Phase II reactions
Phase II reactions examples
glucoronidation
acetylation
glutathione conjugation
glycine conjugation
sulfation
methylation
metabolized to products that irreversibly inhibit the metabolizing enzymes
suicide inhibitors
