Chapter 9. Pharmacokinetic and Toxicokinetic Principles Flashcards
Difference between pharmacokinetics and toxicokinetics?
Pharmacokinetics is study of absorption, distribution, metabolism, elimination of xenobiotics. Toxicokinetics is study of absorption, distribution, metabolism, elimination of xenobiotic producing toxicity
What is first-pass effect?
Metabolism before the xenobiotic reaches the blood.
How does membrane thickness effect simple diffusion?
Membrane thickness (h) is inversely proportional to rate of diffusion. (Fick’s Law of Diffusion)
When pH = pKa, what proportion of xenbiotic is charged/uncharged?
When pH = pKA then xenobiotic is in 1:1 ration charged/uncharged
If pH
Uncharged. Diffuses more readily across membranes.
Thallium and lead use active endogenous transport mechanisms by resembling which electrolytes?
Thallium - potassium
Lead - calcium
Inhibitors of P-glycoprotein
Amiodarone, ketoconazole, quinidine, verapamil
Inducers of P-glycoprotein
St. John’s Wort, rifampin
Substrates of P-glycoprotein
digoxin, protease inhibitors, vinca alkaloids, and paclitaxel
Site of accumulation of following: lead, DDT, carbon monoxide, and paraquat?
Lead - bone
DDT - fat
CO - hemoglobin
Paraquat - type ll alveolar cells
What is concern for phenytoin dosing in malnourished patient?
Phenytoin is 90% bound to albumin. If malnourished then decreased albumin available - results in greater free concentration of phenytoin.
In setting of salicylate overdose, how does saturation of protein binding effect Vd?
Volume of distribution will increase and salicylate levels will increase in CNS
CYP-2D6
Genetic variations - rapid or slow metabolizers. Codeine.
Difference between first order and zero order kinetics?
First order - constant percentage of drug
Zero order - constant level of drug
CYP associated with cancer?
CYP 1A2 & CYP 2E1
