Absorption, Distribution, and Fate of Drugs. Exam 1 Flashcards
What are the sites of absorption for oral drugs?
Stomach and small intestine
What is the pH of the stomach?
1.4
What is the pH of the small intestine?
3.0-7.0
How are oral drugs absorbed?
drugs enter from the lumen, through endothelial cell membranes, and into the bloodstream
What are the four basic steps of a drugs life in your body?
absorption, distribution, metabolism, excretion
_______ molecules can cross down a concentration gradient (passive diffusion) through the membrane.
Lipophilic
_______ is the ratio of the compound’s concentration in a known volume of n-octanol to its concentration in a known volume of water after the octanol and water have reached equilibrium
Partition Coefficient
The _______ the partition coeffcient, the more likely a drug will be absorbed by passive diffusion. Why?
larger
passive diffusion occurs with lipoPHILIC molecules and PC is essentially a ratio comparing concentration in oil to water
_______ molecules are more likely to be absorbed by passive diffusion.
Smaller
More _______ moieties will make a compound more soluble in water and ______ likely to cross a membrane by passive diffusion.
polar
less
Why is pH important when considering absorption of drugs?
pH of drugs that are acidic or basic will dramatically affect the location at which it is absorbed
Aspirin has a pKa of 3.4 and will be absorbed in the ______.
Stomach
Codeine has a pKa of 8.1 and will be absorbed in the ______.
small intestine
A lower pKa indicates that the drug will be absorbed in a more _______ environment.
acidic
A higher (more positive) pKa indicates that the drug is more ______ and will be absorbed in a similar environment such as the _______.
basic
small intestine
Facilitated diffusion across a cell membrane utilitzes ________ or carrier proteins.
protein channels
What are the three methods of diffusion that are used by drugs?
Passive, Facilitated, Active Transport
_____ transporters are active transporters that use ATP to kick drugs out of cells.
ABC
____ transporters exchange Na+ for K+ to transport drugs that are organic acids or bases.
SLC
What are the two transporter types used to actively transport drugs?
ABC and SLC
True or False: SLC Transporters exchange Cl and K to move organic drugs.
False: exchange of Na and K
Name five factors that affect oral absorption of drugs.
- pH
- Surface area
- Gastric emptying
- Dosage Form
- Drug inactivation
How does surface area affect oral absorption of drugs?
Greater surface area = more time Small intestine (6-8 hrs) > stomach (30min-4hrs)
What administration instructions would reflect gastric emptying properties?
“take with food”
if a drug needs to pass more quickly, it should be taken on an empty stomach. if a drug needs lipid transport, it should be taken with food
Slow Release Tablet is an example of ________ and the variations exist due to presence or absence of _______.
dosage form
surface proteins
Other than orally, what are five additional methods for drugs administration?
- Inhalation (asthma, COPD)
- Intravenous
- Intramuscular (gaps in endothelium)
- Subcutaneous
- Topical
Greater amount of blood getting to the tissue, known as increased ________, will increase the amount of drug entrance.
profussion
Lipophilic drugs are fast; whereas, water soluble drugs must pass through _______ and are much slower.
endothelial gaps
Similar to absorption from the lumen, drugs may enter cells from the ________.
interstitial fluid
Name a critical location where drug distribution is restricted.
CNS-blood brain barrier
What is the volume of distribution?
an indication of how a drug is distributed, based on how much is in the plasma and how much was added.
Vd = Q/C
Vd = amt. administered/ concentration at equilibrium
An average person contains 41 total liters: ____ liters of plasma, ____ liters of interstitial space, and _____ liters of cells.
3 plasma
9 space
29 cells
If a drug is _____ soluble, you can administer the drug, measure concentration in plasma, and calculate the Vd to get an idea where it is distributing.
Water
If a drug goes to plasma and interstitial space, but not into cells, the Vd would = ______
12 liters
If a drug goes only to plasma, the Vd would =______
3 liters
If a drug goes to cells but not plasma or interstitial space, the Vd would =_______.
29 liters
If a drug distributes everywhere, such as urea, what would its volume of distribution be?
41 liters
What are the phases of drug metabolism?
phase I: Add/Uncover functional group, make it polar
phase II: Conjugation, link something to it
phase III: processed and pumped out of cells
Where does most drug metabolism take place?
liver
What are microsomes?
membrane bound enzymes that metabolize drugs
Where do microsomes bind?
smooth ER of hepatocytes
Phase I reactions can be broadly grouped into what three categories?
Oxidations
Reductions
Hydrolysis
What is the most important of the phase 1 oxidation systems?
P450 enzymes
Cytochrome ____ enzymes catalyze the oxidative metabolism of xenobiotics, the initial step in the biotransformation and elimination of a wide variety of drugs and environmental pollutants
P450
Where are cytochrom P450 enzymes found?
smooth ER of liver cells
Reductions most commonly occur in _________.
enteric bacteria
Drug hydrolysis involves splitting of ____ or ____ to yield an acid and an alcohol.
esters
amides
__________ metabolism occurs in the liver and other tissues when a drug mimics a natural substance.
Non-microsomal
What are six factors that will affect drug metabolism?
- Entry to liver
- Enzyme inhibition
- Enzyme induction
- Genetics
- Age
- Pathology
When metabolizing drugs, there are two rates k1 and k2. k1 is the movement to the liver, k2 is the metabolism. Which rate is typically limiting (slower)?
k1 (movement to the liver) is typically slow
Protein binding will ______ drug metabolism.
slow down
Transporters will ______ drug metabolism.
speed up
Where are drugs typically excreted?
the kidney
What are the three components of the kidney filtration?
glomerular filtration
tubular reabsorption
active transport
A major area of filtration within the glomeruli occurs at ________.
The basement membrane
The glomerulus sits within _________.
Bowmans Capsule
Tubular reabsorption includes passive transport of _____, active transport of _____, and ____ via osmosis.
Cl-
Na+
water
True or False: Some compounds are actively pushed out from the capillary endothelium into the urine.
True
What does half-life of a drug measure?
the speed at which half of the drug has cleared
How many half-lives must occur in order to have only 6% of drug remaining?
four
50, 25, 12, 6
If you have two drugs and neither is reabsorbed. Drug 1 is filtered, Drug 2 is actively secreted. Which drug will clear faster?
Drug 2
Aspirin is absorbed in the stomach where pH is low. If pH is increased, what will happen?
more aspirin will be ionized and it will be less likely to be absorbed out of the blood or reabsorbed by the kidney
