Lecture 1 & 2 Overview 2023 PDF

Primary Textbook PHARMACEUTICS § Development (science) of drug products § Drug properties Physiologic/biologic properties § Drug targeting § § ADME § Absorption § Distribution § Metabolism § Excretion WHAT IS A DRUG? ¡ Any agent interacting with a living system for……. ¡ Diagnosis/...

Primary Textbook PHARMACEUTICS § Development (science) of drug products § Drug properties Physiologic/biologic properties § Drug targeting § § ADME § Absorption § Distribution § Metabolism § Excretion WHAT IS A DRUG? ¡ Any agent interacting with a living system for……. ¡ Diagnosis/treatment/ prevention/ management of a disease or condition ¡ Maintenance of physiological conditions ¡ Alter an existing physiological or biochemical process WHAT IS A MEDICINE? ¡ Formulation of a drug ¡ Therapeutic effect ¡ Prevention of toxicity ¡ Uniformity and reliability of the product KEY CONCEPT #1 To be effective a drug MUST ¡ Travel to its site of action ¡ Interact with its target ¡ Overcome potential barriers ¡ Anatomical ¡ Chemical ¡ Biochemical HOW DO DRUGS WORK? ¡ MUST reach the site of action ¡ Action maybe extracellular, intracellular or at/on the cell membrane ¡ Interacts with target molecules at the site of action ¡ Alters activity in a way that is beneficial to health ¡ Targets are usually biomolecules ¡ Temporarily bind (attach) to the target ¡ Drug-target binding stimulate the target or block the normal activity of the target ¡ Common drug target is a receptor KEY CONCEPT #2 The ideal drug is one that: • • • • Has pharmacological action Is free of side effects Reaches its target in right concentration Remains at site of action long enough to elicit a response • Is rapidly and completely removed from the body KEY CONCEPT #3 ¡ The Ideal Medication ¡ Has pharmacological action ¡ Reaches its target in right concentration ¡ Remains at site of action long enough to elicit a response ¡ Is rapidly and completely removed from the body ¡ Is free of side effects ¡ Patient friendly ¡ Affordable Header Yahoo Search Box Search query OVERVIEW OF DRUG DESIGN HOW ARE DRUGS DESIGNED? Two (2) Methods: Rational Drug Design and Random Screening Rational Drug Design 1. ¡ Systemic approach ¡ ¡ ¡ Understanding of the disease or condition Understanding of structure and function of the biological target molecule Chemical compounds are synthesized ¡ Compounds are refined to optimize binding ¡ Address possible barriers ¡ Address elimination and removal HOW ARE DRUGS DESIGNED (CONT’D)? 2. Random Screening ¡ Trial and error approach ¡ Search of natural sources or synthesis of compounds ¡ Random testing for biological activity ¡ Resulted in the discovery and development of important drugs ¡ Used by pharmaceutical companies to identify lead compounds KEY CONCEPTS #4 ¡ Most drugs are small organic molecules derived through chemical synthesis ¡ Biopharmaceutical drugs or biologics produced through biological processes are becoming increasingly more common HOW ARE DRUGS ADMINISTERED ¡ Usually administered at a site other than the site of action ¡ Almost always incorporated into dosage form or drug delivery system ¡ Oral: requires absorption from the GI tract ¡ Injection: reserved for drugs that have poor absorption via the GI tract ¡ Topical: local or systemic effect This Photo by Unknown Author is licensed under CC BY-SA KEY CONCEPT #5 ¡ Drug disposition is the distribution, metabolism and elimination (DME) of drugs after entering the bloodstream ¡ Inactive ingredients can affect the drug’s DM in the body and E from the body BENCHTOP TO MARKET Step 1 Discovery and Development: research for a new drug begins in the laboratory Step 2 Pre-clinical Research: Drugs undergo laboratory (in vitro) and animal testing (in vivo) to answer basic questions about safety Step 3 Clinical Research: Drugs are tested on people to make sure they are safe and effective. Studies how the drug will interact in the human body Step 4 FDA drug review: FDA review teams conduct a thorough examine of all submitted data related to the drug or device and decides whether to approve it or not Step 5 FDA Post-market safety monitoring: FDA monitors all drug and device safety once products are available for use by the public. NEW DRUG DEVELOPMENT, APPROVAL AND MARKETING PROCESS HOW ARE DRUGS CLASSIFIED? Drug entities are classified into three (3) groups Non-electrolytes Strong electrolytes Weak electrolytes DRUG CLASSIFICATION 1. Non-electrolytes: Do not ionize/dissociate when dissolved in water (ex. alcohols and sugars, ethers, esters, ketones, aldehydes, most amines) 2. Strong electrolytes: Ionizes/dissociates completely when dissolved in water 3. Weak electrolytes: Many drugs and pharmaceutically important compounds are weak electrolytes. Partially dissociates IMPORTANCE OF IONIZATION A drug must be in solution in order to exert physiologic effect Only ionized drugs will go into solution Physiologic pH ~ 7 – 8 A drug with pKa lower than 7 will ionize and go into solution IMPORTANCE OF IONIZATION • Ionization is an important physiochemical property of a drug • When dissolved in water , a strong electrolyte dissociates completely, a weak electrolyte dissociates partially, and a nonelectrolyte does not dissociate. • Many drugs are weak electrolytes (weak acids, weak bases or their salts) • Ionization is important when predicting the absorption, distribution, metabolism and excretion (ADME) of a drug or biologically active compound The charged and uncharged forms will be absorbed and distributed differently IMPORTANCE OF IONIZATION The ratio of ionized to unionized forms of the compound in the body is critical in determining its behavior Ionization of drug in the drug product influences the selected route(s) of administration and the shelf-life of the drug product REVIEW OF MOLECULAR EXPRESSIONS Solution Solute Number of particles Moles Solute dissolved in solvent Drug must be in solution to be dispersed at molecular level Quantified by number of particles (molecules/ions) Osm (osmole) mEq (milliequivalent) 6.0225 x 1023 molecules per mole REVIEW OF MOLECULAR EXPRESSIONS EQUIVALENTS — CONCENTRATION Expression of amount of substance in a preparation Molarity (M) • Moles per volume • mol/L or mmol/mL Molality (m) • Moles per weight • mmol/g Osmolarity (Osm) • Osmoles per volume • Osm/L or mOsm/mL OSMOLES Osmoles • Total number of particles in solution • Particles (ions) generated when molecules go into solution • i = number of ions per molecule CONCENTRATIONS CONCENTRATIONS Normality (N) Gram-equivalent weight per volume Expressed as Eq/L or mEq/mL Mole fraction (X) Moles of substance per total moles in preparation No units; fraction SUMMARY PERCENT CONCENTRATION —