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 Enterohepatic recirculation ● ● ● ● Enterohepatic recirculation refers to a repeating cycle in which a drug is transported from the liver to the duodenum, and then back to the liver via the portal blood Drugs that undergo glucuronidation can be affected by drugs that act as enzyme inducers or inhibitors Glucuronidated drugs can undergo hydrolysis by intestinal beta-glucuronidase, leading to the release of free drug Free drug can be reabsorbed across the intestinal wall and undergo transport back to the liver Excretion of drugs ● ● ● ● ● Drug excretion is the removal of drugs from the body Drugs and their metabolites can be excreted in urine, bile, sweat, saliva, breast milk, and expired air The kidney is the most important organ for drug excretion Renal excretion involves glomerular filtration, passive tubular reabsorption, and active tubular secretion Lipid-soluble drugs can move back into the blood through passive reabsorption, while polar and ionized drugs remain in the urine The kidney tubule ● ● ● ● The glomerulus consists of a capillary network surrounded by Bowman's capsule Small pores in the capillary walls allow fluids and small molecules, including drugs, to move from blood to urine Blood cells and large molecules are too big to pass through and do not undergo filtration Passive tubular reabsorption allows lipid-soluble drugs to move back into the blood Manipulation of urinary pH ● ● Elevating urinary pH can promote the excretion of acidic drugs by causing them to become ionized and less likely to be reabsorbed Conversion of lipid-soluble drugs into more polar forms through metabolism also reduces passive reabsorption Competition for active tubular transport ● ● If two drugs compete for the same transport system, their excretion will be delayed as they wait their turn Factors like the number of molecules present can affect the rate of excretion Factors that modify renal drug excretion ● ● pH-dependent ionization can accelerate the renal excretion of drugs Penicillin, for example, is normally rapidly cleared from the blood through active tubular transport Excretion of penicillin and manipulation of urinary pH: ● ● ● Rugs that are ionized at the pH of tubular urine will remain in the tubule and be excreted The ionization of a drug can be promoted by manipulating urinary pH Concurrent administration of probenecid can delay the excretion of penicillin by occupying the same tubular transport system ● ● Probenecid is removed from the blood by the same tubular transport system that pumps penicillin Administering a large dose of probenecid can delay renal excretion of penicillin