Lecture 5- Pharmokinetics Flashcards
what are the pros or oral administration of drugs
convenient
economic
safe (drug absorp. slow so OD less likely)
what are the cons of oral administration of drugs?
patient compliance
drug absorp slow (rapid metabolism may cause failure of drug to reach optimum concentration)
what are the most important sites of absorption of drugs taken orally?
stomach
small intestine
what molecule structures will reduce solubility in lipid (diminish the partition coefficient) and imede absorption?
- charge
- polar moities
(makes water more likely to surround and less likely to go through membrane)
the …. is the solubility of a drug in a non polar environment
partition coefficient (PC)
the larger the PC of a drug, the more likely that the drug will be …
absorbed by passive diffusion
… molecules are more likely to be absorbed by passive diffusion than … molecules
smaller
larger
pH of stomach that is at rest/empty?
pH of stomach immediately after high protein meal?
4-5
1-2
… can dramatically passive diffusion of drugs that are acids and bases
pH
aspirin has a pKa of 3.4 so it is better absorbed in the …
stomach
codeine has a pKa of 8.1 so it is better absorbed in the …
small intestine
facilitated diffusion can happen through …. which are always open or … that let things in when activated
pores
channels
facilitated diffusion through pores and channels work …. the concentration gradient
with
active transport of drugs are done through … and … transporters
ABC
SLC
ABC transporters can …
kick drugs out of cells (*if over expressed, get drug resistance)
SLC transporters (exchange Na or K) are important for transport of certain drugs that are…
organic acids or bases
5 factors that affect oral absorption of drugs
pH surface area gastric emptying dosage form drug inactivation
other routes to administer drugs other than oral
inhalation intravenous intramuscular subcutaneous topical
parenteral routes to administer drugs
intravenous
intramuscular
subcutaneous
capillary penetration:
lipophilic drugs is ….
water soluble drugs through endothelial gaps is….
bigger proteins (>20kd) happens through…
fast
slower
transcytosis
bigger proteins penetrate the capillary through transcytosis which is when
vesicles form and are internalized
equation for volume of distribution (Vd)
Vd= Q/C
Q=known amt of drug (mg)
C=concentration of drug in blood some time after administration (mg/L)
the average person has about … liters of plasma, … liters interstitial space and …. liters of cells
3
9
29
41 total liters
if a drug has a large Vd then not much of the drug will be in the …. because it has been distributed to other places (on proteins, in tissues)
plasma
the …. is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the plasma. It is defined as the distribution of a medication btn plasma and the rest of the body
volume of distribution
the … of a drug represents the degree to which a drug is distributed in body tissue rather than plasma
Vd
a …. Vd indicates a greater amount of tissue distribution
higher
is a Vd greater than the total volume of body water possible?
yes (indicates that the drug is highly distributed into tissue)
drugs with a high lipid solubility, low rates of ionization, or low plsma binding capabilities have …. Vd values
higher
drugs that are polar, more highly ionized or exhibit high plasma binding have …. Vd values
lower
Vd may be …. by renal failure and/or liver failure
increased
Vd may be …. during dehydration
decreased
the general strategy of metabolism of drugs is for the liver to make drugs more … for excretion in the urine
water soluble
metabolism of drugs:
phase 1 is to ….
phase 2 is to…
add functional group (make more polar)
conjugation
the … is the most important place for drug metabolism
liver
