Direct Penetration Of The Membrane

Chapter 4 Pharmacokinetics Learning Objectives: 1. List the four main processes that make up pharmacokinetics. ● The four main processes that make up pharmacokinetics are absorption, distribution, metabolism, and excretion. Chapter 4 reading: Pharmacokinetics is the study of how drugs move throughout the body, including processes like absorption, distribution, metabolism, and excretion. Understanding pharmacokinetics is crucial in maximizing the benefits of drug therapy and minimizing harm. By applying this knowledge, healthcare professionals can make informed decisions regarding dosage, route of administration, and dosing schedule. Bullet points Direct penetration of the membrane ● ● ● Most drugs need to penetrate membranes directly to move throughout the body Many drugs are too large to pass through channels or pores Most drugs lack transport systems to help them cross membranes Ions ● ● Ions are molecules with a net electrical charge Except for small molecules, ions are unable to cross membranes Water molecule and electron distribution ● ● Water's electrons spend more time near the oxygen atom than near the hydrogen atoms This makes the area near the oxygen atom somewhat negative and the area near the hydrogen atoms more positive Gentamicin and its polarity ● ● Gentamicin is a polar drug The two -OH groups of gentamicin attract electrons, causing the area around these groups to be more negative than the rest of the molecule Quaternary ammonium compounds and their properties ● ● ● Quaternary ammonium compounds have atypical bonding to nitrogen and always carry a positive charge The nitrogen atoms of quaternary ammonium compounds have four chemical bonds, which results in the positive charge Due to their charge, these compounds are unable to cross most membranes Ionization of weak acids and bases ● ● ● The extent of ionization of weak acids and bases depends on the pH of their surroundings The ionized forms of acids and bases are not lipid soluble and do not readily cross membranes Acids ionize by giving up a proton, while bases ionize by accepting a proton pH-dependent ionization ● ● ● Many drugs, which can exist in charged and uncharged forms, undergo pH-dependent ionization Acids tend to ionize in basic (alkaline) media Bases tend to ionize in acidic media Ionization of aspirin ● Aspirin, an acid, tends to give up its proton (becomes negatively charged) in basic media The process of ion trapping using aspirin as an example: ● ● ● ● ● ● ● ● ● ● ● ● ● Aspirin is an acidic drug In acidic media (pH 1), aspirin is nonionized In alkaline media (pH 7.4), aspirin is ionized Ion trapping causes orally administered aspirin to move from the acidic environment of the stomach to the more alkaline environment of the plasma In the stomach, nonionized aspirin molecules dissolve and remain nonionized because the stomach is acidic Nonionized aspirin molecules can readily cross the membranes between the stomach and the plasma As nonionized aspirin molecules move into the alkaline plasma, most give up a proton (H+) and become negatively charged ions Ionized aspirin molecules cannot diffuse back into the stomach Nonionized aspirin molecules in the plasma become ionized as more nonionized molecules pass from the stomach to the plasma Equilibrium is established between the plasma and the stomach, with equal amounts of nonionized aspirin in both, but a much higher concentration of ionized aspirin in the plasma Aspirin molecules remain nonionized in acidic media and ionize in alkaline media Acidic drugs will accumulate on the alkaline side, while basic drugs will accumulate on the acidic side The process of a drug accumulating on the side of the membrane where the pH most favors its ionization is called ion trapping or pH partitioning Ion trapping and pH dependence ● ● ● The ionization of drugs is pH dependent When the pH of the fluid on one side of a membrane differs from the pH of the fluid on the other side, drug molecules tend to accumulate on the side where the pH most favors their ionization Ion trapping has practical clinical implications and can influence the movement of drugs throughout the body