Pharmacokinetics and Factors of Individual Variation 2 Pharmacokinetics and Factors of Individual Variation

Learning Outcomes 2.1 List different forms of drug products and the routes by which they are administered. 2.2 Understand the pharmacokinetic factors that determine the absorption, distribution, metabolism, and excretion of drugs. 2.3 Identify how half-life, blood drug level, and bioavailability relate to drug response.

Learning Outcomes 2.4 List several factors of individual variation that can alter drug response. 2.5 Understand the drug factors that relate to pediatric drug administration. 2.6 Define the different types of drug interaction. 2.7 Explain the basic terminology of chronic drug administration and drug dependence.

Drug Forms Drugs come in various dosage forms: The physical and chemical properties of a drug usually determine what form will be most effective. Some common dosage forms include tablets, capsules, syrups, and injectables. Learning Outcomes 2.1 List different forms of drug products and the routes by which they are administered. Drugs are prepared in various forms. Some common drug forms include: tablets, capsules, lozenges, suppositories, ointments, creams, transdermal patches, and injections.

Routes of Administration Drugs can enter the body several different ways. Two common routes are orally and parenterally. Learning Outcomes 2.1 List different forms of drug products and the routes by which they are administered. Drugs can enter the body through several different routes. The most common routes of administration are oral (by mouth) and parenteral (by injection).

Pharmacokinetic Phases There are four pharmacokinetic phases: Absorption Distribution Metabolism Excretion Learning Outcomes 2.2 Understand the pharmacokinetic factors that determine the absorption, distribution, metabolism, and excretion of drugs. There are four kinetic phases for drug movement within the body. Absorption is the entrance of drug into the bloodstream. Absorption can happen through filtration, passive transport or active transport. Lipid solubility, drug ionization and drug formulation are properties that affect absorption. Distribution is the movement of drugs out to the various body tissues and organs. Several factors determine how much drug will reach a particular organ, including plasma protein binding, blood flow and specific tissue barriers. Metabolism is the biotransformation or chemical alteration of a drug in the body. The liver is the main organ involved in metabolism. The drug microsomal metabolizing system contains enzymes which convert drugs to their metabolites. Enzyme induction and inhibition can play a role in how fast or slow drugs are metabolized. Excretion is the removal of drugs from the body. The main routes of excretion are renal, GI, and respiratory. Drugs can also be excreted through sweat, saliva and breast milk.

Half-Life and Blood Drug Levels Half-life is the amount of time it takes for the blood concentration to drop by half of the original amount. Blood drug levels The intensity of a drug effect is determined mainly by the concentration of drug in the blood. Learning Outcomes 2.3 Identify how half-life, blood drug level, and bioavailability relate to drug response. The half-life of a drug is the time required for plasma concentration to fall to half of the original level. Drug metabolism and excretion are the major factors that affect half-life. The intensity of the drug effect is mainly determined by the concentration of drug in the blood or plasma. The plasma concentration is determined by all four pharmacokinetic phases and by pharmacodynamic factors. Loading doses are given to rapidly attain therapeutic drug levels and maintenance doses are smaller doses given to continue therapeutic levels.

Bioavailability Bioavailability is the percentage of drug that is actually absorbed into the bloodstream. There are several factors that influence bioavailability. Learning Outcomes 2.3 Identify how half-life, blood drug level, and bioavailability relate to drug response. Bioavailability is the amount of drug absorbed into the bloodstream. Differences in drug formulation, route of administration, and factors that affect GI absorption can influence bioavailability.

Factors of Individual Variation Age Weight Sex Genetic Variation Emotional State Placebo Effect Disease State Patient Compliance Learning Outcomes 2.4 List several factors of individual variation that can alter drug response. Several factors affect how drugs work in the body. These factors are called individual variation. Age, weight, sex, genetic variation, emotional state, placebo effect, the presences of disease and patient compliance all play a role in the variation of drug response seen in individual patients.

Pediatric Considerations Medications taken by pregnant women may pass to the fetus. Some drugs can cause birth defects. Drugs can also pass through breast milk to infants. Learning Outcomes 2.5 Understand the drug factors that relate to pediatric drug administration. Medications taken by a pregnant woman can pass on the fetus. Some drugs can cause birth defects in the unborn fetus. The FDA places drugs into pregnancy categories which determine the risk to the inborn fetus. Drugs can pass through breast milk of nursing mothers to their babies. These medications can produce undesired effects in the infant. Drug absorption is altered in infants due to their smaller size and limited movement. Administration of certain types of medications should be carefully considered and appropriate routes should be chosen. Because of the higher body water percentage and less fat, infants have a decrease in distribution of lipid soluble medications which causes an increase in blood drug levels. They also have an increase in distribution of water soluble drugs which leads to a decrease in blood drugs levels. Drug metabolism and excretion is slower in infants under one year of age which leads to slower elimination of drugs and prolonged drug effects. Drug dosages should be adjusted and calculated based on weight, body surface area, or patient age.

Pediatric Considerations FDA Pregnancy Categories Learning Outcomes 2.5 Understand the drug factors that relate to pediatric drug administration.

Drug Interactions Drug interaction refers to one drug affecting the actions of another drug. There are several types of drug interactions: Incompatibility Additive Effects Summation Synergism Antagonism Learning Outcomes 2.6 Define the different types of drug interaction. Drug interaction refers to one drug affecting the actions of another drug. There are several different ways in which drugs can interact with each other. Incompatibility, additive effects, summation, synergism, and antagonism are several different types of drug interactions. Refer to table 2:5

Chronic Drug Use and Abuse Tolerance Dependence Decreased drug effect with repeated administration Two main types are metabolic and pharmacodynamic. Reliance on drug becomes ever more vital to the well-being of the patient The two types are physical and psychological. Learning Outcomes 2.7 Explain the basic terminology of chronic drug administration and drug dependence. The chronic use of certain drugs results in a number of physiological and pharmacologic changes in drug response. Drug tolerance and drug dependence are two important phenomena associated with chronic use.