3 - Pharmacokinetics 2a Flashcards
(52 cards)
Absorption, distribution, and excretion of drugs all involve what?
The movement of drugs across cell membranes.
What types of molecules can diffuse readily through the membrane via passive diffusion?
Lipophilic compounds.
What is the rate of passive diffusion across a cell membrane determined by?
The partition coefficient of the drug into oil from water AND the concentration gradient across the membrane.
Most drugs are _____ acids or _____ bases and can exist in either _____ or _____ forms.
Weak acids or weak bases
and can exist in either charged or uncharged forms.
What version of a weak acid will likely passively diffuse through cell membranes?
HA, the protonated uncharged version.
Low pH means that an acid is most likely in what form? What happens as you increase the pH?
Protonated form.
As you increase the pH, the concentration of H ions will decrease and the weak acid will exist mostly in the A- form.
What is the pKa?
The pH at which there’s an equal amount of the protonated and unprotonated forms of an acid.
The negative log of the acid dissociation constant.
What is [HA]/[A-] determined by?
The pH of the environment and the pKa of the drug.
Write out the Henderson-Hasselback equation?
Log([protonated]/[unprotonated]) = pKa - pH
What form is a weak base in when it’s charged? What about when its uncharged?
Protonated when charged.
Unprotonated when uncharged.
When can weak acids or bases cross a membrane?
When they’re UNcharged.
What are the principles of ion trapping?
Acidic drugs accumulate on the side of the membrane that’s more BASIC (because A- can’t cross the membrane)
Basic drugs accumulate on the side of the membrane that’s more ACIDIC (because BH+ can’t cross the membrane).
Morphine, a weak base, can sometimes be detected in the stomach contents following an IV overdose. How can this happen?
Because weak bases accumulate on the side of the membrane that’s more acidic because BH+ can’t cross the membrane.
The stomach is more acidic than the plasma.
Describe the movement of passive diffusion.
Bidirectional
Driven by the concentration gradient.
What is carrier mediated transport?
Transport of a molecule across a barrier that’s mediated by binding of the solute to a protein transporter.
- can move hydrophilic molecules
- can move molecules against their gradient
- provides specificity
What is facilitated diffusion?
Carrier mediated diffusion, but driven by the concentration gradient (ie no energy input is needed).
What is an example of facilitated diffusion?
Glucose transporters allow the movement of glucose into the cell; this is driven by the concentration gradient of glucose.
Allows for selectivity (ie can tell glucose from fructose).
What is the p-glycoprotien “ABC” pump? Where does the energy come from?
ATP binding cassette family of proteins.
Binds lipophillic drugs that have entered cells and mediates their efflux through the cell.
Energy from ATP hydrolysis.
What are ABC pumps encoded by?
The multidrug resistant gene; this means that they can be induced in response to exposure to various drugs
What are two types of secondary active transport?
Co-transport and anti-transport (exchangers).
Move two different solutes, one of which is against its concentration gradient coupled to the movement of the other down its conncentration gradient (usually Na or H).
What is bioavailability (F)? What is the bioavailability of an IV administered drug?
The fraction of the administered dose of drug that reaches the circulation.
IV administered drug would have an F=1.
What is the first pass effect and enterohepatic cycling?
First pass: drug metabolized in the liver or excreted back into the intestines through biliary excretion during its “first pass” through liver.
Enterohepatic cycling: goes around in useless circle and doesn’t make it to total circulation.
Never reaches systemic circulation and therefore reduces the bioavailability considerably.
What does it mean if the preparations of two drugs are bioequivalent?
They are the same drug, with the same route of administration, with the same amount of drug entering the circulation at the same RATE.
Describe the route of orally administered drugs? What type of drugs are absorbed?
Absorbed from the GI tract mostly via passive diffusion (absorption) which favors absorption of unionized drugs.
Weak acids in the protonated form and weak bases in the unprotonated form absorbed.
