Therapeutic Consequences of Drug Metabolism

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 Protein Binding ● ● ● ● ● Drugs can form reversible bonds with proteins in the body Plasma albumin is the most important protein for drug binding Drug molecules bind to albumin, which restricts their distribution Competition for binding sites can lead to drug interactions Increased levels of free drugs can cause toxicity Entering Cells ● ● ● Some drugs need to enter cells to reach their target sites All drugs need to enter cells for metabolism and excretion Factors determine a drug's ability to enter cells Therapeutic Consequences of Drug Metabolism ● ● ● ● ● Retention of protein-bound drugs in the bloodstream Accelerated renal excretion of drugs Drug inactivation Increased therapeutic action Activation of "prodrugs" ● Increased toxicity or decreased toxicity Protein binding of drugs ● ● ● Albumin is the most prevalent protein in plasma and important for drug binding Only unbound (free) drug molecules can leave the vascular system Bound molecules are too large to fit through the pores in the capillary wall Renal drug excretion ● ● ● Kidneys are the major organs of drug excretion Highly lipid-soluble drugs are difficult to excrete Metabolic conversion can accelerate renal excretion by converting drugs into more hydrophilic forms Metabolic transformations and drug excretion ● ● Addition of a hydroxyl group converts pentobarbital into a more polar form Glucuronidation attaches a hydrophilic glucose derivative to phenytoin, making it more water-soluble for rapid excretion Hepatic drug-metabolizing enzymes ● ● ● Most drug metabolism takes place in the liver by the hepatic microsomal enzyme system The system is composed of multiple forms of cytochrome P450 enzymes Cytochrome P450 families metabolize drugs, while other families metabolize endogenous compounds Drug inactivation ● ● Drug metabolism can convert pharmacologically active compounds into inactive forms Example: Conversion of procaine into para-aminobenzoic acid Increased therapeutic action ● ● Metabolism can increase the effectiveness of some drugs Example: Conversion of codeine into morphine Promotion of Renal Drug Excretion Inactivation of Drugs Increased Effectiveness of Drugs Activation of Prodrugs Increased Drug Toxicity First-Pass Effect Special Considerations in Drug Metabolism Drug interactions - competition for metabolism ● ● ● When two drugs are metabolized by the same metabolic pathway, they may compete with each other for metabolism This can decrease the rate at which one or both drugs are metabolized Accumulation of drugs can lead to dangerous levels and potential toxicity Induction and inhibition of drug-metabolizing enzymes ● ● Inducers are drugs that increase rates of drug metabolism by stimulating enzyme synthesis in the liver Inhibition occurs when drugs decrease rates of drug metabolism ● Both induction and inhibition can have therapeutic consequences and affect dosages of drugs