RT Book, Section A1 Butterworth IV, John F. A1 Mackey, David C. A1 Wasnick, John D. SR Print(0) ID 1190603744 T1 Pharmacological Principles T2 Morgan & Mikhail’s Clinical Anesthesiology, 7e YR 2022 FD 2022 PB McGraw-Hill Education PP New York, NY SN 9781260473797 LK accessanesthesiology.mhmedical.com/content.aspx?aid=1190603744 RD 2024/10/08 AB KEY CONCEPTS Drug molecules obey the law of mass action. When the plasma concentration exceeds the tissue concentration, the drug moves from the plasma into tissue. When the plasma concentration is less than the tissue concentration, the drug moves from the tissue back to plasma. Most drugs that readily cross the blood–brain barrier (eg, lipophilic drugs like hypnotics and opioids) are avidly taken up in body fat. Biotransformation is the chemical process by which the drug molecule is altered in the body. The liver is the primary organ of metabolism for drugs. Small, unbound molecules freely pass from plasma into the glomerular filtrate. The nonionized (uncharged) fraction of drug is reabsorbed in the renal tubules, whereas the ionized (charged) portion is excreted in urine. Elimination half-life is the time required for the drug concentration to fall by 50%. For drugs described by multicompartment pharmacokinetics (eg, all drugs used in anesthesia), there are multiple elimination half-lives. The offset of a drug’s effect cannot be predicted from half-lives. The context-sensitive half-time is a clinically useful concept to describe the rate of decrease in drug concentration and should be used instead of half-lives to compare the pharmacokinetic properties of intravenous drugs used in anesthesia.