Pharmacology

Author: Chief Editor: Zhang Dalu
Publisher:
Publishing Date: 1998-08-01
Features: Summary This book is a specialized pharmacology teaching material organized by the National Medical and Pharmaceutical Administration under the commission of the National Education Commission. It is divided into eight parts. The first seven parts, consisting of 46 chapters, cover the pharmacology section. They focus on the fundamental theories and basic knowledge of modern pharmacology. The book emphasizes the pharmacological actions, mechanisms, pharmacokinetics, clinical uses, adverse reactions, precautions, and clinical application principles of commonly used drugs and some new drugs. It also appropriately incorporates basic pathological knowledge closely related to each chapter's pharmacological content. The eighth part, comprising seven chapters, is an introduction to clinical pharmacology, briefly introducing the fundamental and common content of clinical pharmacology. It provides a theoretical foundation for formulating rational, safe, and effective medication plans in clinical practice. The entire book emphasizes the "five characteristics" of teaching materials, highlighting practicality. It can serve as teaching material for pharmacy junior colleges, secondary vocational schools, vocational and technical education, or adult education. It is also suitable for self-study and improvement among clinical medical, pharmaceutical, and nursing personnel. Excerpt: The pKa value of acidic drugs becomes smaller as acidity increases, and the degree of dissociation increases with the increase of environmental pH. Conversely, for alkaline drugs, the pKa value becomes larger as alkalinity increases, and the degree of dissociation increases with the decrease of environmental pH. For example, aspirin has a pKa value of 3.5. It is only about 0.8% dissociated in gastric juice with a pH of 1.4, but about 99.99% dissociated in plasma with a pH of 7.4. Therefore, aspirin is easily absorbed from the gastric mucosa into the plasma. When antacid calcium carbonate is used to raise the gastric pH, aspirin dissociates almost completely, reducing its absorption in the stomach. Within the physiological range of pH changes, strong acids, strong bases, and highly polar quaternary ammonium salts are fully dissociated and do not easily penetrate biological membranes, making absorption difficult. Most weakly acidic or weakly alkaline drugs are non-dissociated and exhibit rapid passive diffusion. Weakly acidic drugs with a pKa of 3–7.5 and weakly alkaline drugs with a pKa of 7–10 are significantly affected by environmental pH. 2. Filtration (filtration) or aqueous diffusion (aqueous diffusion) refers to the transport of polar molecules with a molecular weight less than 100, such as water, ethanol, urea, lactic acid, and water-soluble small-molecule drugs, as well as gas molecules like O2 and CO2, through filtration pores by aqueous diffusion. The filtration rate is proportional to the concentration difference across the membrane and is promoted by external forces, such as the filtration pressure of the glomerulus. The pore sizes of various membranes in the body vary, and the filtration rates of substances also differ. 3. Facilitated diffusion (facilitated diffusion), also known as carrier transport, refers to the diffusion that requires the assistance of specific proteins in the membrane—permeases, such as the need for glucose permease for glucose to enter red blood cells or the use of transferrin for iron transport. In this case, molecules or ions complete the transport process along the concentration gradient or electrochemical gradient without energy consumption. There are also various ion channel proteins present in the membrane, each selectively binding to Na＋, K＋, or Ca2＋ to form channels, allowing the corresponding ions to rapidly transport along the concentration or electrochemical gradient difference. All channels can be inhibited by specific blockers, such as calcium channel blockers that selectively block the passage of Ca2＋. The transport rate of facilitated diffusion is much faster than simple diffusion, especially necessary for the transport of endogenous compounds. However, the transport capacity of permeases or ion channels is limited, and when drug concentrations are too high, saturation and rate-limiting phenomena may occur. Additionally, due to the structural specificity of enzymes and channels, the transport targets have certain selectivity, and when two drugs act on the same carrier, competitive inhibition may occur. In summary, passive transport involves the transport along the concentration (or potential) gradient without energy consumption; when drug concentrations on both sides of the membrane reach equilibrium, transport stops. Furthermore, except for facilitated diffusion, it generally does not require carriers and is not affected by saturation and competitive inhibition. (II) Active Transport Active transport (active transport) is a transport against the gradient, where drug molecules or ions are moved from one side with low concentration or low potential difference to the other side with higher concentration or potential difference by special carrier proteins on the cell membrane. Transport requires energy and relies on specific carrier proteins, such as Na＋, K＋-ATPase (sodium pump), Ca2＋, Mg2＋-ATPase (calcium pump), proton pump (hydrogen pump), and amine pumps in the process of catecholamine reuptake. The transport capacity of carrier proteins is limited, and saturation and rate-limiting phenomena may occur. When two drugs are transported by the same carrier, competitive inhibition may occur. Additionally, active transport may be inhibited if drug combinations affect oxygen or energy supply. (III) Membrane Movement Transport Membrane movement transport (cytosis) refers to the process by which drugs and other substances form small vesicles upon contact with the cell membrane to complete the transport into and out of cells. The transport of large-molecule substances, such as powder from the posterior lobe of the pituitary gland, glandular secretion, or neurotransmitter release, often involves membrane movement. Common methods include pinocytosis and exocytosis (also known as exocytosis). Section II: The In Vivo Processes of Drugs I. Absorption The process by which drugs enter the bloodstream from the site of administration is called absorption (absorption). Except for direct intravenous injection, the rate and extent of drug absorption are closely related to the physicochemical properties of the drug, the route of administration, and the absorption environment. 1. Absorption from the Digestive Tract Oral administration includes various dosage forms such as solutions, suspensions, tablets, and capsules. If the drug is not in a solution form, the absorption rate generally depends on the process of the drug forming a solution and its absorption process. These two processes are not only related to the ease of drug disintegration of the dosage form but also closely related to the physicochemical properties of the drug (such as pKa values) and the absorption environment (especially the pH of the digestive tract and the basic characteristics of the gastrointestinal mucosa). Drugs are mainly absorbed from the gastrointestinal mucosa through passive transport. Small-molecular, water-soluble drugs can be absorbed through filtration. Drugs with higher lipophilicity are more easily absorbed through simple diffusion. Gastric juice has a pH of 0.9–1.5, and weakly acidic drugs like salicylic acid and barbiturates can be absorbed from the stomach. However, the gastric absorption area is relatively small, and the residence time is short, resulting in less absorption. Weakly alkaline drugs such as ephedrine and quaternary ammonium salt drugs have a high degree of dissociation in the stomach and are rarely absorbed. When gastric juice is alkalized, the absorption of weakly acidic drugs may decrease, while the absorption of weakly alkaline drugs relatively increases.