Onset and Duration of Drug Effects

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 Onset and duration of drug effects ● ● ● Responses to a drug can only occur when drug levels reach the MEC, leading to a latent period between drug administration and the onset of effects The duration of drug effects is influenced by the rate of absorption, as well as metabolism and excretion Therapeutic responses are maintained as long as drug levels remain above the MEC Drug accumulation and plateau ● ● ● ● If a drug is administered before the prior dose has been eliminated, total body stores of the drug will be higher after the second dose. As succeeding doses are administered, drug levels will continue to climb. The drug will continue to accumulate until a state is reached where the amount of drug eliminated between doses equals the amount administered. When the amount of drug eliminated between doses equals the dose administered, average drug levels will remain constant and plateau will have been reached. Time to reach plateau ● The time required to reach plateau is independent of dosage size. ● ● Reaching plateau when giving repeated large doses of a drug is similar to reaching plateau when giving repeated small doses of the same drug. The height of the plateau may be different with different dosage sizes, but the time required to reach plateau will remain unchanged. Fluctuations in drug levels ● ● ● ● When a drug is administered repeatedly, its levels will fluctuate between doses. The highest level is referred to as the peak concentration, and the lowest level is referred to as the trough concentration. The peaks must be kept below the toxic concentration, and the troughs must be kept above the minimum effective concentration (MEC). Three techniques can be employed to reduce fluctuations in drug levels. Three methods to maintain constant plasma levels of drugs: ● ● ● Continuous infusion: administers a constant flow of the drug to keep plasma levels stable Depot preparation: releases the drug slowly and steadily to maintain constant levels over time Reducing dose size and dosing interval: administering smaller doses more frequently to keep total daily dose constant Time to reach plateau: ● ● ● Plateau is reached when the amount lost between doses becomes as large as the amount administered Reaching plateau takes approximately four half-lives when the drug is administered repeatedly in the same dose Large initial dose (loading dose) followed by smaller doses (maintenance doses) can speed up achievement of plateau Drug elimination and consequences of overdose: ● ● ● When drug administration is discontinued, it takes about four half-lives for most of the drug to be eliminated Elimination time is important for assessing toxicity; toxic levels can persist if the drug has a long half-life Example: Digitoxin overdose can result in prolonged toxic levels as it has a half-life of 7 days Pharmacokinetics ● ● Pharmacokinetics consists of four basic processes: absorption, distribution, metabolism, and excretion These processes determine the concentration of a drug at its sites of action and the intensity and time course of responses Drug Administration ● ● ● ● ● ● ● Intramuscular administration has disadvantages of inconvenience and potential discomfort Subcutaneous administration has the same advantages and disadvantages as IM administration Oral administration has advantages of ease, convenience, economy, and safety Principal disadvantages of oral administration are high variability and possible inactivation by stomach acid and liver enzymes Enteric-coated oral formulations release contents in the small intestine, not in the stomach Sustained-release oral formulations release contents slowly, allowing longer intervals between doses Intravenous administration has advantages of rapid onset, precise control over drug amount, suitability for large fluid volumes, and suitability for irritant drugs