Pharmacology Synopses 1 Flashcards
ideal for lipid soluble drugs that would otherwise be metabolized in the gut or liver
sublingual route
route reserved for nitrates or certain hormones
sublingual route
rate and completeness of absorption
factors comprising bioavailability
bioavailability of drug types, most to least
solution> suspension >capsule >tablet >coated tablet
route commonly used in children, slow absorption
rectal (no villi in rectum)
route for rapid clinical response, precise plasma concentrations, no issues of bioavailability
intravenous injection
route to deliver high concentrations of drugs to a particular tissue
intraarterial injection
route to bypass blood-brain barrier
intrathecal, via lumbar puncture to subarachnoid space
intramuscular absorption rates, high to low
arm> thigh> buttocks
subcutaneous injections absorb ____ than intramuscular
slower than
heat, massage, vasodilators
increase rate of subcutaneous absorption
coadministration of vasoconstrictors, as with local anesthetics
slows rate of subcutaneous absorption
route for volatile anesthetics or drugs for pulmonary function, not subject to first-pass liver metabolism
inhalation
drug patches enter system via
zero order kinetics (amount constant per unit time)
occurs only for molecules less than 150-200 MW
passive aqueous diffusion
allows molecules of 20-30,000 MW to pass through via aqueous diffusion
endothelial capillary lining (but not in brain)
occurs for drugs that are analogs of endogenous compounds
carrier mediated facilitated transport
may reduce the amount of drug reaching target tissue, or metabolically activate an inert pro-drug
first pass effect (via liver)
will increase rate of passive absorption by maintaining concentration gradient of free drug
drug binding to plasma protein
gastrointenstinal absorption rate, but not extent of absorption
reduced by the presence of food in the gut
equation for Ka
[H+][A-]/[HA]
equation for pH of acids
pKa + log [A-]/[HA]
equation for pH of bases
pKa + long [B]/[BH+]
more rapid than elimination, accomplished via circulation, influenced by regional blood flow
distribution
peripheral compartments
adipose and skeletal, less well perfused, drug equilibrates more slowly
special compartments
CNS, CSF, pericardial fluid, bronchial secretions, middle ear fluid (difficult to treat infections)
weak acids and neutral drugs bind particularly to
albumin
basic drugs tend to bind
alpha-1-acid glycoprotein (orosomucoid)
protein binding ____ the net transfer of drugs across membrane
decreases
at equilibrium, the total drug concentration in plasma is usually ____ than in extravascular fluid
higher (due to protein-drug in plasma)
for drugs secreted renally, protein binding
decreases the rate of elimination
for drugs eliminated hepatically, protein binding
may promote drug elimination
apparent blood volume
amount of drug injected/blood concentration at time zero
if plasma binding is marker, apparent volume will be
small
if there is extracellular binding, storage in fat or other tissues, apparent volume will be
large
generally bind plasma proteins and have small Vd
acidic drugs
generally bind extravascular sites and have large Vd
basic drugs
capable of eliminating drugs with low molecular weight or polar and fully ionized at body pH
the kidneys
most important extrahepatic site of drug metabolism
GI tract
sites of drug metabolizing action
Liver, Gi tract, intestines, skin, placenta, lungs
most enzymes involved in drug metabolism are located within
the lipophilic membranes of the smooth endoplasmic reticulum
the enzymes that carry out metabolism on the SER are called
the MFO system (microsomal mixed-function oxidase system)
phase I reactions convert a drug to a more polar compound by adding or unmasking
polar functional groups: OH, NH2, SH
phase II reactions conjugate the compound with wndogenous compounds such as
glucuronic acid, sulfuric acid, acetic acid, or amino acids (glycine!)
the most common phase II reaction is
glucuronide formation
terminal oxidizing enzyme in most MFO reactions
cytochrome P450
receptors for exogenous ligands
ion channels, enzymes, ion transporters, carriers and pumps, structural proteins
glomeruli permit the passage of most drug molecules, except
protein bound drugs
can kidney actively transport some protein bound drugs?
yes, though associated protein dissassociates
renal tubules reabsorb
nonionized, lipid-soluble drugs
alkalinized urine promotes excretion of
drugs that are weak acids
acidified urine promotes excretion of
weak bases
drugs and metabolites passed into the small intestine via bile may undergo
enterohepatic cycling
receptor types for endogenous ligands
Ligand-gated ion channels, G-protein receptors, tyrosine kinase receptors
See 7 transmembrane passes, think
G-protein coupled receptor
Adrenergic and muscarinic Ach receptors are in this family
single subunit receptor protein
receptors for insulin and growth factors are in this class
tyrosine kinase
steroid hormone receptors are of this class
intracellular, hormone-receptor complex binds to DNA
for a congerneric series of agonists, lower ED50 means
lower dissociation constant (tighter receptor binding)
the effect of a competitive agonist is
to reduce apparent affinity of D for R
competitive antagonist bind
reversibly with same site on receptor as the agonist
with competitive inhibitor, curve shifts
right
with competitive inhibitor, slope and maximum response
do not change
the effect of the inhibitor may reversible or irreversible, but the agonist has no influence on the extent of antagonism
noncompetitive inhibition
with noncompetitive inhibitor, curve shifts
generally not (kd isn’t changing)
with noncompetitive inhibitor, maximum response
is decreased
no drug effect seen until minimum occupancy is achieved
fractional occupancy threshold
effect of fractional occupancy threshold on slope
increases
effect of fractional occupany threshold on curve shift
shifts to the right
with fractional occupancy threshold, the ED50
overestimates the dissociation constant (ED50>Kd)
drug maximal effect achieved without occupying all receptors
spare receptors
in the presence of spare receptors, curve shifts
to the left
in the presence of spare receptors, ED50
is less than (underestimates) Kd
incapable of causing a maximal response at any concentration
partial agonist
describes the binding forces between drug and receptor
affinity
describes the physiological effectiveness of the drug receptor complex
efficacy
partial agonists act as antagonists by
binding receptors but having low intrinsic activity
slope of an LDR curve indicates
how steeply the drug effect varies with dose = one indication of the margin of safety
curve that shows a normal distribution around the average dose patients first respond to
Non-cumulative dose-response frequency curve
dose at which 50% of patients show a toxic response
TD50
equation for therapeutic index
TD50/ED50
rapid decrease in the magnitude of response due to the action of a drug
tachyphylaxis
decrease in response to a given does resulting from prolonged administration
tolerance
what follows zero order kinetics?
constant IV infusion
more rapid absorption will ____ peak plasma concentration, ____latency, and ____duration
increase, decrease, decrease
increase in dose will ____ latency, ____ peak plasma concentration, and ____ duration of effect
decrease, increase, increase
more rapid elimination will ____ peak plasma concentration and duration of effect
decrease
when repeated doses of a drug are given at short intervals and elimination is a first order process, plasma concentration will
plateau
when a drug is administered at a constant rate IV, and eliminated first order, plasma concentration will
plateau
approximate total body storage equals
1.44 times the amount administered per half life
avoiding toxicity and maintaining steady state is easier when drugs have
a long half life
in zero order elimination, k=
Er
in first order elimination, k=
.693/halflife
typically, absorption follows
first order kinetics
equation for bioavailability
F=AUCoral/AUCiv
equation for relative bioavialability
AUCgeneric/AUCtradename
triphasic curve, rapid peak and decline, slow decline
Single-dose IV, long decline=Ke
level of drug in blood rises slowly until elimination = absorption. Bioavailability=1
subcutaneous or intramuscular single dose
blood level rises until equal to elimination, Cmax is slower, tmax is later
oral, single dose
