Intro to Pharmacokinetics

Question 1

list and describe the 4 processes of drug pharmacokinetics

Answer 1

absorption: drug entering blood circulation

distribution: the dissemination of a drug into body fluids and tissues

metabolization: the transformation or inactivation of the drug

excretion: the removal of a drug from the body

Question 2

what is bioavailability and why is this important?

Answer 2

the fraction of a drug that is absorbed and available to produce its systemic effect; classified by the extent of absorption (amount) and the rate of absorption (amount per unit of time) across the gut lumen and gut wall, which is then sent to the liver for 1st pass metabolism

this is important because it describes how much of a given drug will actually be able to be used by the body

(if you give a drug IV the bioavailability will be 100%)

Question 3

describe phase I and phase II metabolism

Answer 3

phase I: often oxidation reactions to make a compound more polar; occurs mainly in the liver endoplasmic reticulum by cytochrome P450 enzymes (a large family of heme proteins)

phase II: synthetic reactions that involve conjugation that usually inactivates the drug and makes it more polar and available to the excretory processes of the kidney or the liver; the most common conujugation is with glucuronide requiring glucuronyl transferase (this enzyme is DEFICIENT in cats, which is why they are prone to acetaminophen and propofol toxicity), but also includes sulfation and acetylation conjugations

Question 4

describe how urinary pH can affect drug excretion

Answer 4

many drugs, especially weak acids and weak bases are actively excreted into the renal tubule and therefore rapidly excreted; increasing the alkalinity of urine, however, will decrease the absorption of a weak acidic drug because the more alkaline the urine gets, the more that weak acidic drug is ionized and therefore unavailable to absorb and is cleared instead (as only nonionized drugs can cross membranes to get absorbed!)

SO if you have a patient that is overdosed on a weak acidic drug, you can increase the alkalinity of the pH to increase clearance of the weak acid treat the toxicity (and vice versa with increasing urine acidity to increase clearance of a weak basic drug)

Question 5

what is the relationship between lipophilicity, protein binding, and drug elimination?

Answer 5

more lipophilic drugs are more often protein bound, and therefore are primarily cleared by the liver, while more hydrophilic drugs are more often free and are therefore more often cleared by the kidneys

Question 6

what is clearance?

Answer 6

the rate at which an active drug is removed from the body; is specific to an individual!! you cannot change clearance!!

Question 7

how do you calculate clearance and why do you do that?

Answer 7

Cl(plasma) = Dose (IV)/AUC (plasma)

Question 8

describe how mathematical models can be used to produce what if scenarios and optimize therapeutic use

Answer 8

you can assume that the exposure-response relationship is not species specific, so the AUC of a man should equal the AUC of a rat, as long as you include the proper dose and clearance of that man and that rat, so you could calculate the exposure of a man to the same drug as a rat