Pharmacology

Absorption

The process of absorption begins at the point of administration to the organism (like the gut after swallowing a pill, or directly if injected) and enters the bloodstream. Absorption is affected by the solubility and concentration of the drug, the circulation at the site of absorption, the surface area for absorption and the route of ingestion.¹

The critical step of the process of absorption is the drug's passage across the cell membrane. A drug's ability to pass through this membrane relates to the intrinsic properties of the drug as well as those of the cell membrane itself. The molecular size and shape of the drug, the solubility of the drug at the site of absorption, and the relative lipid solubility of the drug's ionized and nonionized forms are all important factors.

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Drugs can cross the cell membrane by several routes;(See Membrane Transport)

some require energy and are therefore active processes. Others do not require energy and are termed passive. Drugs that are electrically charged and have difficulty entering into a cell are transported by carrier-mediated active membrane transport. Their passage across the membrane is linked to the passage of certain anions and cations [usually sodium (Na) and potassium (K)] and requires adenosine triphosphate (ATP). A variant of this type of transport occurs when the charged particles do not have to travel against the established intercellular electrochemical gradient and therefore the process does not require energy. This process of carrier-mediated transport is called facilitated diffusion.

Drugs crossing cell membranes by passive mechanisms do so by passive diffusion along concentration gradients according to their solubility in the lipid bilayer. This diffusion is proportional to the magnitude of the concentration gradient across the membrane as well as to the lipid/water coefficient of the drug. It follows that the greater the coefficient, the higher the concentration of the drug in the membrane, and therefore the faster the diffusion.

Passive diffusion differs for drugs that are electrolytes from those that are nonelectrolytes. For nonelectrolytes, after steady state is achieved, the concentration of that drug on either side of the membrane is equal. For electrolytes, the concentration of that drug relates to the differences of pH across the membrane as well as to the pKa. This is an important concept because most drugs are either weak acids or bases existing both in ionized and nonionized forms. The Pharmacological Basis of Therapeutics (Hardman et al, 2001) offers an excellent example of a drug that is a weak acid in the stomach where the gastric mucosa acts as a partition between the acidic environment in the stomach and the plasma itself. It is assumed for the purpose of this example that the mucosa acts as a lipid bilayer cell membrane.

In plasma, the ratio of the nonionized to ionized drug is 1:1000, whereas in the gastric contents the ratio is 1:0.001. An opposite result would be seen if the drug were a weak base. Understanding these concepts is extremely important because of the tremendous implications in terms of further absorption, and then upon excretion.

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1. Pharmacological Principles. In: Butterworth IV JF, Mackey DC, Wasnick JD. eds. Morgan & Mikhail’s Clinical Anesthesiology, 7e. McGraw-Hill Education; 2022. Accessed October 12, 2024. https://accessanesthesiology-mhmedical-com.usu01.idm.oclc.org/content.aspx?bookid=3194&sectionid=266517902

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