Pharmacology: Pharmacokinetics Absorbtion Flashcards
What determines if a drug can get into its target site through passive diffusion?
The partition coefficient. (Drug size, ability to dissolve through lipids, and drug ionization)
What determines if molecules can pass to target site through filtration?
Size
What four ways can drugs get to their target site?
Passive diffusion, filtration, active transport and endocytosis
How does blood help maintain a gradient so drug can continually cross the gut membrane?
Blood whisks away drug so the gradient is constantly lower on the vessel side.
How does plasma affect drug movement from gut to vessel?
If drug binds to plasma proteins, it is no longer included in the equilibrium of free drug and shifts equilibrium to inside of gut.
For weak acids, which species is lipid soluble and which is charged?
The acid is lipid soluble and the base is charged.
For weak bases, which species is lipid soluble and which is charged?
The acid is charged and the base is lipid soluble.
How do you know how much of your drug will pass through lipid membranes?
Henderson-Hasselbach: pH=pK + log(base/acid)
Why is morphine not absorbed from the stomach as well as aspirin?
It is a weak base, is charged at the stomach pH and cannot pass through the membrane. Aspirin is not ionized at stomach pH and gets across the membrane more easily.
How could you excrete barbiturates more quickly?
Increase urine acidity. Barbituates are noncharged weak bases. The higher plasma pH (7.5) will drive the drug into the urine.
What type of drug will enter the CNS the quickest?
Nonionized and hydrophobic molecules. The blood-brain barrier is a thick lipid membrane.
2 families of active transport mechanisms
ABC and SLC
How do ABC family transporters function?
They cleave ATP and use the energy to force the drug out against the concentration gradient.
How do SLC family transporters function?
The transporter uses the concentration gradient of a different ion. When the other drug comes in the drug of concern goes out against its gradient.
Why is it difficult to get anti-tumor drugs into tumor cells?
They have high expression of ABC family transporters. Drugs enter by diffusion, but are picked up by the ATP transporter and are transported out of the cell. Specifically MDR1/ABCB1/P-glycoprotein.
Where does the anti-depressant drug Prozac act?
SLC family transporter. It is a serotonin uptake transporter that inhibits uptake so serotonin stays in the blood longer.
How does drug movement happen in the liver?
Hepatocytes metabolize drugs and have ABC transporters that lead to the blood vessels or bile. SLC transporters carry the drugs either way.
How does drug movement occur in the kidney?
ABC transporters pump drugs out of endothelial cells and into tubules for secretion. SLC transporters work in both directions.
How does drug movement occur in the small intestine?
Both ABC and SLC transporters work in both directions (lumen and blood stream)
How does drug movement occur in the brain?
ABC transporters keep things out of the brain and SLCs work in both directions.
Where is the major site of enteral drug absorption?
Small intestine
What is the major mode of parenteral drug absorption?
I.V.
Where do many lipophilic drugs bind?
Albumin in plasma. Although plasma proteins have low affinity for drugs, there are many more of them than the actual target receptors.
How could you release more drug into the body after it has been administered hours ago?
Give a drug with a higher affinity for plasma protein.
How can you get a high volume of distribution in a fat ass?
Lipid soluble molecules get sucked into the fat depot.
What are the protected compartments?
CNS, eye, joints and fetus
Through what do drugs need to pass to get to the brain?
Blood-brain barrier which is closed off by tight junctions. Drugs must pass through astrocytes if they want to get to the capillaries.
Blood-brain barrier characteristics
Few pores, lipid solubility facilitates penetration, ABC transporters in and out
What transporter acts as the brain’s gate keepers?
MDR1 (P-glycoprotein) expressed on endothelial cells and in choroid plexus. Specifically pumps HIV proteases, anti-cancer drugs, morphine)
Why does transport occur so slowly to the placenta?
Blood volume is low in the placenta
How does the kidney get rid of metabolites?
Filtration
How do you figure adult creatine clearance in the kidney?
Schwartz Equation
How are organic cations transported in tubular secretion?
OCT1 and OCT2 present on the blood side of the proximal tubule transport cations from the blood into the cells. MDR1 and OCT3 are present on the urine side of the cell and transport molecules into the urine.
How are organic anions transported in tubular secretion?
OATs transport ions into the epithelial cells from the blood and MDRs transport them into the urine
