Fundamentals of Pharmacology PK Principles PDF

Your Lecturer Hi, class! My name is Reysan S. Cosas, you call me Sir Reysan. I am a registered pharmacist. I started teaching in CEU School of Pharmacy last 2015 handling courses like Pharmacology, Therapeutics, Biopharmaceutics and Pharmacokinetics. I also handle General and Ocular Pharmacology in...

Your Lecturer Hi, class! My name is Reysan S. Cosas, you call me Sir Reysan. I am a registered pharmacist. I started teaching in CEU School of Pharmacy last 2015 handling courses like Pharmacology, Therapeutics, Biopharmaceutics and Pharmacokinetics. I also handle General and Ocular Pharmacology in the School of Optometry. I hope you will learn a lot in our course. See you virtually! Contact me: Email [email protected]  It is the study of substances that interact with living systems through chemical processes especially by binding and regulating molecules and activating or inhibiting normal body processes. What is a drug? u Any chemical substance, natural, semi-synthetic or synthetically acquired, when introduced into the body alter the normal body functions or inhibit or kills foreign bodies. u It may be defined as any substance that brings about a change in biologic function through its chemical actions. A drug may: u Interacts as an Agonist – activator of a specific molecule; or as an Antagonist –inhibitor of a specific molecule u Interacts with the Receptor – “the target molecule” for drug Two Main Divisions of Pharmacology Two Main Divisions of Pharmacology u (I) PHARMACOKINETICS u Is the study of how the body absorbs, distributes, metabolizes, and excretes drugs u What the body does to the drug u (II) PHARMACODYNAMICS u Describes the action of drugs u It includes the measurement of responses to drugs and how response relates to drug dose or concentration u What the drug does to the body Disciplines related to Pharmacology 1. PHARMACOTHERAPEUTICS (PHARMACOTHERAPY) – the study of the use of drugs to treat diseases. The use of drug treatment is to: u Cure a disease u Delay disease progression u Alleviate the signs and/or symptoms of the disease u Facilitate nonpharmacologic therapeutic intervention 2. PHARMACOGENETICS – is the study of the relationship of genetic factors to variations in drug response 3. PHARMACOECONOMICS – is the study of the cost effectiveness of drug treatments 4. PHARMACOEPIDEMIOLOGY – is the study of the effect of drugs on population Other related areas are: u TOXICOLOGY - study of drug’s adverse effects u POSOLOGY - study of doses u PHARMACY – study of drug’s manufacture, preparation and dispensing of drugs u PHARMACEUTICS – is the study of formulation, manufacture, stability, and effectiveness of pharmaceutical dosage forms u PHARMACOGNOSY – is the study of the identification and preparation of crude drugs from natural sources u CHEMOTHERAPY - drugs that are used to kill or inhibit the growth of cells that are considered foreign in the body. u “What the body does to the drug” u It describes the movement or transit of the drug throughout the body. u The science of the kinetics of drug absorption, distribution, and elimination. u ENTERAL ADMINISTRATION u PARENTERAL ADMINISTRATION u TOPICAL ADMINISTRATION u Alimentary route of administration u Administering a drug by mouth or by rectum u The safest and most common, convenient, and economical method of drug administration. u Peroral administration (by mouth) u Sublingual administration (under the tongue) u Buccal administration (between cheeks and gums) u Rectal administration u The diminished oral drug absorption may be due to: ü drug instability in the gastrointestinal tract, ü drug degradation by the digestive enzymes in the intestine, ü high hepatic clearance (first-pass effect), and ü efflux transporters such as P-glycoprotein resulting in poor and/or erratic systemic drug availability. u The parenteral route introduces drugs directly into the systemic circulation. u Parenteral administration is also used if a patient is unable to take oral medications (unconscious patients) and in circumstances that require a rapid onset of action. u have the highest bioavailability and are not subject to first-pass metabolism or the harsh GI environment.  MAIN TYPE OF PARENTERAL ADMINISTRATION u Intravenous (IV) administration u IV bolus/IV push u IV infusion u Intramuscular (IM) administration u absorbed rapidly, or in specialized depot preparations, which are absorbed slowly u Subcutaneous (SC) administration u provides absorption via simple diffusion and is slower than the IV route.  OTHER TYPES OF PARENTERAL ADMINISTRATION u Intradermal injection u Drug injected into surface area of skin u Intra-arterial injection u Used in chemotherapy to target drug to organ u Intrathecal Injection u Drug is directly injected into cerebrospinal fluid (CSF) for uptake into brain u Intraperitoneal injection u Used commonly in laboratory animals u Topical application u Inhalational administration u Oral inhalation u Nasal inhalation u Transdermal u Ocular and Otic routes u Intraurethral and Intravaginal Routes u Absorption is the transfer of a drug from the site of administration to the bloodstream. u The rate and extent of absorption depend on the environment where the drug is absorbed, chemical characteristics of the drug, and the route of administration (which influences bioavailability). u Routes of administration other than intravenous may result in partial absorption and lower bioavailability. 1. Effect of pH on drug absorption 2. Blood flow to the absorption site 3. Total surface area available for absorption 4. Contact time at the absorption surface 5. Expression of P-glycoprotein u Bioavailability is the rate and extent to which an administered drug reaches the systemic circulation. FACTORS THAT INFLUENCE BIOAVAILABILITY 1. First-pass hepatic metabolism 2. Solubility of the drug 3. Chemical instability 4. Nature of the drug formulation u particle size, salt form, crystal polymorphism, enteric coatings, and the presence of excipients u Drug distribution is the process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and the tissues. 1. Blood flow 2. Capillary permeability 3. Binding of drugs to plasma proteins and tissues 4. Lipophilicity 5. Volume of distribution u Drug elimination is described in terms of clearance from a hypothetical well-stirred compartment containing uniform drug distribution. u METABOLISM u EXCRETION u The term clearance describes the process of drug elimination from the body or from a single organ without identifying the individual processes involved. u Clearance may be defined as the volume of fluid removed of the drug from the body per unit of time. u First-order Elimination ü First order kinetics means that the rate of change of drug concentration by any process is directly proportional to the drug concentration remaining to undertake that process. ü The rate of drug metabolism and elimination is directly proportional to the concentration of free drug ü First-order kinetics is also referred to as linear kinetics. Zero-order Elimination ü Aspirin, ethanol, and phenytoin ü The amount of drug eliminated does not change with the amount or concentration of drug in the body, but the fraction removed varies. ü The enzyme is saturated by a high free drug concentration, and the rate of metabolism remains constant over time. ü Also called nonlinear or saturation kinetics u Biotransformation u Metabolism leads to production of products with increased polarity, which allows the drug to be eliminated. ü Prodrugs are inactive and must be biotransformed in the body to metabolites that have pharmacologic activity. u Clearance (CL) estimates the amount of drug cleared from the body per unit of time. u Pathways of drug biotransformation may be divided into two major groups of reactions, phase I and phase II reactions. ü PhaseI, or asynthetic reactions, include oxidation, reduction, and hydrolysis. ü Phase II, or synthetic reactions, include conjugations. u Phase I biotransformation reactions occur first and introduce or expose a functional group on the drug molecules. u Phase I reactions convert lipophilic drugs into more polar molecules by introducing or unmasking a polar functional group, such as –OH or – NH2. u Oxidation – catalyzed by monooxygenase (cytochrome P-450) u Reduction u Hydrolysis  Phase II consists of conjugation reactions. Many phase I metabolites are still too lipophilic to be excreted. A subsequent conjugation reaction with an endogenous substrates results in polar, usually more water-soluble compounds that are often therapeutically inactive. Conjugation reactions - combine the parent drug (or its metabolites) with certain endogenous constituents: glucuronic acid, glycine, glutamine, sulfate, glutathione, two-carbon acetyl fragment, or one-carbon methyl fragment u Drug excretion is the removal of the intact drug. u The kidney is the main excretory organ for the removal of metabolic waste products and plays a major role in maintaining the normal fluid volume and electrolyte composition in the body. u The processes by which a drug is excreted via the kidneys may include any combination of the following: ü Glomerular filtration ü Active tubular secretion ü Tubular reabsorption u Half-life ü The most useful in designing drug dosage regimens. ü The time required to change the amount of drug in the body by one-half during elimination u Maintenance dose ü Drugs are generally administered to maintain a steady state concentration (Css) within the therapeutic window. u Loading dose ü Drug is administered to achieve the desired plasma level rapidly, followed by a maintenance dose to maintain the steady state