lecture 4 part 3 Flashcards
name 3 body compartments into which the drug may be distributed
water
fat
bone
what drugs will get distributed to:
-total body water
-extracellular water
-blood
blood = heparin, strongly plasma bound and large molecules
total body water = small, water soluble molecules like ethanol
extracellular water = large, water soluble molecules like gentamicin
name drugs that will get distributed into the bone
certain ions like lead and fluoride
what things will get distributed into the fat
highly lipid soluble molecules
rank the following according to their Vd:
digoxin
acetaminophen
chloroquine
highest = chloroquine
digoxin
lowest = acetaminophen
true or false
clearance is additive
TRUE
function of elimination by ALL participating organs like the liver and kidney
name the 2 most important sites for drug elimination
liver and kidney
what are the units for clearance
mL/min
name the 2 main factors in renal excretion
-glomerular filtration
-passive tubular reabsorption
true or false
if a drug is strongly bound to protein, it will be filtered
FALSE – it will not be filtered and will go back to the blood
true or false
enhanced lipid solubility favors reabsorption
true
give an example of a drug that is completely reabsorbed
thiopental and all barbiturates
** name 4 things that affect renal tubular reabsorption rate
pH
pka compared to urine pH
weak acid or weak base
rate or renal tubular blood flow
what does it mean if a drug is “transferred to glomerular filtrate?”
it is secreted out of the body
true or false
when lipid soluble drugs are reabsorbed back into the body, the mechanism is through active transport
FALSE - passive
how does chronic ethanol use affect metabolism
it induces CYP2E1
therefore, the effect of ethanol won’t happen (or not as much) because it gets metabolized quickly
grapefruit juice
potent inhibitor of CYP3A4 (localized in intestinal wall mucosa)
genetic polymorphism of CYP2D6
5-10% of caucasians are poor metabolizers but only 1-2% for asian population
genetic polymorphism of CYP2C19
20% of asians are poor metabolizers and only 4% caucasian
**** explain enterohepatic cycling and what xubstances go through it
glucuronide conjugates – hydrolyzed in GI back to the parent molecule.
parent molecule gets reabsorbed back into the body again and again – duration of action prolonged.
VITAMIN B12, VITAMIN D3, FOLIC ACID, ESTROGENS
define half life
the time required to decrease the amount of drug in the bpdy by HALF during elimication
explain what 1st order elimination is
a constant fraction of the drug dissapears from the body in an equal interval of time
true or false
most elimination mechanism are through first order
true
true or false
the concentration of drug in the plasma drops exponentially with time
true - 1st order kinetics
explain zero order
elimination is constant and INDEPENDENT of drug concentration
very few drugs eliminated this way
true or false
disease states do not affect half life
false – they do bc disease states affect clearance and VD
** what is the average amount of half lives for a drug to be fully excreted
around 7
one half life will reduce the drug by 50%
how much drug will be remaining after 2 half lives?
25%
one half life will reduce the drug by 50%
how much drug will be remaining after 5 half lives?
3.12%
one half life will reduce the drug conc in the body to 50%
how many half lives are needed to get to 12.5%?
3 half lives
the half life is useful in estimating the time to reach……
steady state
approximately ___ half lives are required to reach about ____% of a new steady state
4 half lives, 94%
drug accumulation will be observed if…
the dosing interval is less than 4 half lives
in the simplest case, drugs are directly related to…..
plasma concentration
give reasons for delayed drug effects
the time required for the drug to distrubute from the plasma to the site of action
slow turnover of physiologic substances involved in producing the drug effect
warfarin inhibits vitamin k epoxidase in the liver. this forms a clotting complex with a long half life (14 hours)
what is the “maintenance dose”
just enough drug is given in each dose to replace what has been eliminated since the preceding dose
why might a loading dose be required?
to produce effective blood levels without delay
loading dose formula
target concentration * VD /f
f can be ignored if IV
true or false
the vd is different for every drug
true
what is a useful indicator of renal function
creatinine clearance
when drugs bind to tissues, is Vd higher or lower?
higher
when drugs bind to plasma proteins, is vd higher or lower?
lower
older people have decreased muscle mass and thus tend to have a _____ Vd of digoxin
smaller
if a drug is highly lipid soluble, does vd increase or decrease?
give an example
increase
diazepam
absorption usually occurs within the first _____ after a drug dose and varies according to food intake, posture, and activity
2 hrs
