Drug Movement and Membrane Crossings

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 Drug Movement and Membrane Crossings ● ● ● ● To move around the body, drugs cross membranes by passing through pores, undergoing transport, or penetrating the membrane directly Lipid-soluble drugs can easily cross membranes, while polar or ionized drugs cannot Most drugs must dissolve into the lipid bilayer of the membrane to cross it P-glycoprotein in various organs can transport certain drugs out of cells Drug Distribution and Blood-Brain Barrier ● ● ● Distribution is the movement of drugs from the blood to the interstitial space of tissues, and from there into cells Drugs can easily leave the vasculature in most tissues through the spaces between capillary wall cells The blood-brain barrier (BBB) is the presence of tight junctions between capillary wall cells in the CNS, requiring drugs to pass through the cells rather than between them Absorption and Elimination ● Absorption is the movement of a drug from its site of administration into the blood ● ● ● Absorption is enhanced by rapid drug dissolution, high lipid solubility, a large surface area for absorption, and high blood flow at the administration site Elimination refers to the process of drug metabolism and excretion Some drugs are eliminated at a constant rate, while others are cleared within four halflives Intravenous administration disadvantages: ● ● ● ● High cost Difficulty Inconvenience Danger due to irreversibility, potential for fluid overload, infection, and embolism Intramuscular administration advantages: ● ● Suitability for insoluble drugs Suitability for depot preparations Drug metabolism (biotransformation): ● ● ● Chemical alteration of drug structure Takes place mainly in the liver Catalyzed by cytochrome P450 enzymes Consequences of drug metabolism: ● ● ● ● Promotion of renal drug excretion Conversion of drugs to less active or inactive forms Conversion of drugs to more active or toxic forms Conversion of prodrugs to their active forms Therapeutic range and minimum effective concentration (MEC): ● ● MEC is the plasma drug level below which therapeutic effects will not occur Therapeutic range lies between MEC and toxic concentration Factors affecting drug metabolism: ● ● P450 inducers increase metabolism rate P450 inhibitors decrease metabolism rate Half-life of a drug: ● ● Time required for the amount of drug in the body to decline by 50% Drugs with short half-life require more frequent administration Plateau and fluctuations in plasma drug levels: ● ● Plateau is reached after approximately four half-lives Fluctuations between doses can be reduced by adjusting dose size, using continuous infusion, or using depot preparations First-pass effect: ● Rapid inactivation of some oral drugs as they pass through the liver