Pharmacokinetics - Lecture 5 Flashcards
What are some pros of oral absorption?
Convenient, cheap, and fairly safe
What are some cons of oral absorption?
We have less control if we just tell a patient to take a pill
What are the most important sites of absorption for oral drugs and why?
Stomach (pH = 1.4) and Small intestine (pH = 3.0-7.0)
If a pill absorbs at a lower pH, it can spend more time in the stomach, but needs to get through quick if it is absorbed at a higher pH
What kind of drugs can passively diffuse through a membrane?
Lipophilic molecules
What is the partition coefficient, and why is it important?
[X1]/[X2] = PC
The larger the PC, the more likely a drug will be absorbed by passive diffusion
Smaller molecules are more likely to be absorbed by passive diffusion
What is the most important aspect affecting drugs that are acids or bases?
pH
Drugs with a low pKa (asprin) should be absorbed in the stomach - by the time it gets to the intestine, the higher pH will make it charged and it won’t get absorbed
Drugs with a high pKa (codeine) need to be absorbed in the intestine, because in the stomach it will charged and can’t be absorbed
What is the significance of facilitated diffusion to drug absorption?
Most small molecules can get taken up by passive diffusion, but some drugs taken orally require facilitated diffusion
What are the ways Active transport effects drug absorption?
1) ABC transporters can kick drugs out of cells when necessary
2) SLC transporters (exchange Na or K) are important for transport of certain drugs that are organic cids or bases
What factors affect oral absorption of drugs?
pH Surface area Gastric emptying Dosage form Drug inactivation
How does surface area affect oral drug absorption?
More area = more absorption
Typically, the small intestine has the most surface area
What sort of drugs should be taken with food, why?
Acidic pills should be taken with food.
When you eat something, everything leaves the stomach in 30 min-4 hrs. Acidic pills want to spend as much time in the stomach as possible, because they’re best absorbed at low pH
What sort of drugs should be taken without food, why?
Basic pills.
When you drink water and take a pill, everything leaves your stomach in 15 min - 1 hr. Basic pills don’t want to be in the stomach long, because they’re charged in the stomach and can’t be absorbed there, so we want to get them through the stomach and to the intestines as quickly as possible
How does dosage form affect drug absorption?
Solids (pills) have to dissolve, and this can be controlled easier than some other forms
What are some other routes to administer drugs other than orally?
Inhalation Parenteral injection Intravenous Intramuscular Subcutaneous Topical
What sort of treatment is best suited for inhalation?
Asthma treatment
Profusion of the tissue is most important for what types of drug administration?
Intramuscular and Subcutaneous
What ways can drugs be distributed to tissues?
Capillary penetration
Entry into cells from interstitial fluid
Why is it difficult for drugs to get to the CNS?
Blood-brain barrier
Why are water soluble drugs slower to get to tissues than lipophilic drugs?
They have to go through endothelial gaps as opposed to going directly through the membrane
What can the volume of distribution tell us?
IT provides an indication of how a drug is distributed, based on how much is in the plasma and how much was added
This is true if the drug is water soluble
How many liters of plasma, interstitial space, and cells are there in the average person?
3 L of plasma
9 L of interstitial space
29 L cells
41 total L
What is the equation for the volume of distribution?
Q/C = Vd Q = amount of drug administered C = concentration of drug in the plasma
If an administered drug never leaves the plasma, what would the Vd be?
3L
Q/(Q/3) = 3L
If an administered drug goes to the plasma and interstitial space, but not into the cells, what would the Vd be?
12 L
Q/(Q/12) = 12L
