Chapter 4 Pharmacokinetics Copyright © 2011 Delmar, Cengage Learning

Drug Movement Pharmacokinetics is the physiological movement of drugs Four steps: –Absorption –Distribution –Biotransformation (metabolism) –Excretion Copyright © 2011 Delmar, Cengage Learning

Drug Movement Pharmacokinetics includes the movement of substances across cell membranes Basic mechanisms: –Passive diffusion –Facilitated diffusion –Active transport –Pinocytosis/phagocytosis Copyright © 2011 Delmar, Cengage Learning

Passive Diffusion movement of particles from an area of high concentration to an area of low concentration –Good for small, lipophilic, nonionic particles –The drug must dissolve and pass through in the cell membrane Copyright © 2011 Delmar, Cengage Learning

Facilitated Diffusion passive diffusion that uses a special carrier molecule –Good for bigger molecules that are not lipid soluble –No energy is needed for a facilitated diffusion Copyright © 2011 Delmar, Cengage Learning

Active Transport molecules move against the concentration gradient from areas of low concentration of molecules to areas of high concentration of molecules; involves both a carrier molecule and energy –Good for accumulation of drugs within a part of the body Copyright © 2011 Delmar, Cengage Learning

Pinocytosis/Phagocytosis molecules are physically taken in or engulfed. Pinocytosis is engulfing liquid; phagocytosis is engulfing solid particles –Good for bigger molecules or liquids Copyright © 2011 Delmar, Cengage Learning

Movement of Substances Across the Cell Membrane Copyright © 2011 Delmar, Cengage Learning

Drug Absorption Drug absorption is the movement of a drug from the site of administration into the fluids of the body that will carry it to its site(s) of action Drug factors include drug solubility, pH, and molecular size Patient factors include the animal’s age, health, metabolic rate, genetic factors, sex, and species Copyright © 2011 Delmar, Cengage Learning

Drug Absorption Terms Bioavailability: percent of drug administered that actually enters the systemic circulation Ionization: the property of being charged –Hydrophilic = ionized –Lipophilic = nonionized Nature of the drug: pH of drug –Weakly acid drugs = hydrophilic form in alkaline environment –Weakly alkaline drugs = hydrophilic form in acid environment Ion trapping: when drugs change body compartments, they may become ionized and trapped in the new environment Drug form is important; oral drugs must have different properties than parenteral drugs Copyright © 2011 Delmar, Cengage Learning

Drug Absorption Age –Young animals may not have well developed gastrointestinal tracts and less active enzyme systems Health –Sickness will affect the rate of absorption of certain drugs Copyright © 2011 Delmar, Cengage Learning

Drug Absorption Metabolic rate –Animals with a high metabolic rate may eliminate drugs from their system quicker Genetic factors –Individual variation in response to drugs may occur because of genetic differences between animals Copyright © 2011 Delmar, Cengage Learning

Drug Absorption Sex –Male and females have different body compositions –These specific compositions may affect the action and distribution of the drug Species –Herbivores may have altered drug absorption due to food in the gastrointestinal tract Copyright © 2011 Delmar, Cengage Learning

Drug Distribution Drug distribution is the physiological movement of drugs from the systemic circulation to the tissues Goal of distribution is for the drug to reach the target tissue or intended site of action Factors affecting drug distribution: –Membrane permeability: large molecules cannot pass through fenestrations of blood capillaries –Tissue perfusion: relative amount of blood supply to an area or body system –Protein binding: drugs bound to proteins cannot leave the capillaries due to the size of the protein –Volume of distribution: how well a drug is distributed throughout the body based on the concentration of drug in the blood Copyright © 2011 Delmar, Cengage Learning

Biotransformation Biotransformation is also called drug metabolism, drug inactivation, and drug detoxification Biotransformation is the chemical alteration of drug molecules by the body cells of patients to a metabolite that is in an activated form, an inactivated form, and/or a toxic form Primary site of biotransformation is the liver Copyright © 2011 Delmar, Cengage Learning

Drug Interactions Affecting Drug Metabolism Drug interactions may affect metabolism: –Altered absorption: one drug may alter the absorption of other drugs –Competition for plasma proteins: drug A and drug B may both bind to plasma proteins; one may have a higher affinity than the other –Altered excretion: some drugs may act directly on the kidney and decrease the excretion of other drugs –Altered metabolism: the same enzymes may be needed for biotransformation of two drugs that are prescribed at the same time for an animal Copyright © 2011 Delmar, Cengage Learning

Drug Interactions Affecting Drug Metabolism Drug interactions may affect metabolism (cont.): –Inducing the enzyme system: some drugs alter metabolism by causing liver enzymes to become more efficient –Liver issues: the liver’s ability to metabolize drugs may be impaired –Tolerance: the animal may develop tolerance or decreased response to a drug Copyright © 2011 Delmar, Cengage Learning

Drug Interactions Affecting Drug Metabolism Tolerance –Decreased response to a drug because of repeated use –The two types of tolerance in animals are metabolic and cellular Metabolic tolerance –Drug is metabolized more quickly because of chronic use Cellular tolerance –Occurs when receptors adapt to the presence of the drug by either reducing the number of receptors, or reducing their sensitivity Copyright © 2011 Delmar, Cengage Learning

Drug Elimination Drug elimination is removal of a drug from the body (excretion) Renal elimination of drugs involves –Glomerular filtration –Tubular secretion –Tubular reabsorption Liver elimination of drugs is also important Other elimination routes include the intestine and through milk Copyright © 2011 Delmar, Cengage Learning

Drug Elimination Terms Withdrawal time: period of time after drug administration during which the animal cannot be sent to market for slaughter and the eggs or milk must be discarded because of the potential for drug residues Half-life: time required for the amount of drug in the body to be reduced by half of its original level Steady state: point at which drug accumulation and elimination are balanced Copyright © 2011 Delmar, Cengage Learning

Measuring Drug Action Graphic depiction of the plasma concentration of the drug vs. time –X axis represents time –Y axis represents drug concentration in plasma Onset of action occurs when the drug enters the plasma The peak plasma level of the drug is when the elimination rate of the drug is equivalent to its rate of absorption Copyright © 2011 Delmar, Cengage Learning

Measuring Drug Action The time elapsed from the time of administration to the time that the peak plasma level is reached is known as the time to peak –Important in making clinical judgments about the use of a drug From the peak plasma level the concentration declines since the amount of drug being eliminated exceeds the amount being absorbed Copyright © 2011 Delmar, Cengage Learning

How Do Drugs Work? Drugs work in a variety of ways: –Drugs alter existing cellular functions –Drugs alter the chemical composition of body fluids –Drugs can form a chemical bond with specific cell components on target cells within the animal’s body Copyright © 2011 Delmar, Cengage Learning

Receptors Receptors are three-dimensional proteins or glycoproteins –Located on the surface, in the cytoplasm, or within the nucleus of cells Affinity is the strength of binding between a drug and its receptor –High-affinity drugs bind more tightly to a receptor than do low-affinity drugs Copyright © 2011 Delmar, Cengage Learning

Receptors Copyright © 2011 Delmar, Cengage Learning

Agonist vs. Antagonist Agonist: drug that binds to a cell receptor and causes action Antagonist: drug that inhibits or blocks the response of a cell when the drug is bound to the receptors Copyright © 2011 Delmar, Cengage Learning

Agonist vs. Antagonist Copyright © 2011 Delmar, Cengage Learning