Clinical Pharmacology

BASIC & CLINICAL PHARMACOLOGY: 

BASIC & CLINICAL PHARMACOLOGY SECTION 1 Basic Principles

INTRODUCTION: 

INTRODUCTION Study of substances that prevent, diagnose and treat disease Deals with undesirable effects of chemicals in the living systems PHARMACOLOGY Interaction of substances or chemicals in the living system which maybe administered within the body Medical Pharmacology Toxicology Branches

HISTORY: 

HISTORY 1500 years ago Prehistoric people undoubtedly recognized the beneficial or toxic effects of many plant and animal materials.

HISTORY: 

HISTORY 17th Century Materia medica was developed in the 17th Century as the precursor to pharmacology Contains all the science of drug preparation and the medical use of drugs

HISTORY: 

HISTORY 18th-19th century The development of Experimental Animal Physiology and Pharmacology began. Controlled clinical trial were introduced in medicine Information about drug action and drug receptors were accumulated

PHAMACOLOGY & GENETICS: 

PHAMACOLOGY & GENETICS

PHAMACOLOGY & GENETICS: 

PHAMACOLOGY & GENETICS Homozygous mice Heterozygous mice complete suppression partial suppression Pharmacogenomics Refers to the genetic variations that cause differences in drug response among individuals or populations.

The Nature of Drugs: 

The Nature of Drugs Receptor protein Drug Action Synthesized in the body Hormones Not synthesized in the body Xenobiotics DRUG MOLECULE

The Nature of Drugs: 

The Nature of Drugs harmful effects poisons of biologic origin synthesized by plants or animals POISONS TOXINS

REACTIVITY & DRUG-RECEPTOR BONDS: 

REACTIVITY & DRUG-RECEPTOR BONDS Three major types of Bonds Covalent Electrostatic Hydrophobic Strong Not reversible Weaker than Covalent bonds Weak Important in highly-lipid soluble drug interaction

REACTIVITY & DRUG-RECEPTOR BONDS: 

REACTIVITY & DRUG-RECEPTOR BONDS Three major types of Bonds Covalent Electrostatic Hydrophobic Strong Not reversible Weaker than Covalent bonds Weak Important in highly-lipid soluble drug interaction

REACTIVITY & DRUG-RECEPTOR BONDS: 

REACTIVITY & DRUG-RECEPTOR BONDS Three major types of Bonds Covalent Electrostatic Hydrophobic Strong Not reversible Weaker than Covalent bonds Weak Important in highly-lipid soluble drug interaction

DRUG-BODY INTERACTIONS: 

DRUG-BODY INTERACTIONS Two Classes Pharmacodynamic Pharmacokinetic Action of drug on the body Action of the body on the drug

PHARMACODYNAMIC PRINCIPLES: 

PHARMACODYNAMIC PRINCIPLES Types of Drug – receptor Interactions

PHARMACODYNAMIC PRINCIPLES: 

PHARMACODYNAMIC PRINCIPLES Agonist that Inhibit their Binding Molecules & Partial Agonist

DURATION OF DRUG ACTION: 

DURATION OF DRUG ACTION Short Acting drugs Long Acting drugs lasts only as long as the drug occupies the receptor the action may persist after the drug has dissociated due some coupling molecule that is still present in activated form

RECEPTORS & INERT BINDING SITES: 

RECEPTORS & INERT BINDING SITES A Receptor must : 1. Be selective 2. Change its function

PHARMACOKINETIC PRINCIPLES: 

PHARMACOKINETIC PRINCIPLES Clopidogrel is a pro drug. CYP2C19 helps change it to its active form in the liver.

PHARMACOKINETIC PRINCIPLES: 

PHARMACOKINETIC PRINCIPLES All forms of Administration ( except IV)

PHARMACOKINETIC PRINCIPLES: 

PHARMACOKINETIC PRINCIPLES Types of Membrane Transport A. PERMEATION B. FICK'S LAW OF DIFFUSION C. IONIZATION OF WEAK ACIDS AND WEAK BASES; THE HENDERSON-HASSELBALCH EQUATION

PHARMACOKINETIC PRINCIPLES: 

PHARMACOKINETIC PRINCIPLES Types of Membrane Transport A. PERMEATION 1. Aqueous diffusion 2. Lipid diffusion 3. Special carriers 4. Endocytosis and exocytosis occurs within the larger aqueous compartments, such as the interstitial space and cytosol

PHARMACOKINETIC PRINCIPLES: 

PHARMACOKINETIC PRINCIPLES Types of Membrane Transport A. PERMEATION 1. Aqueous diffusion 2. Lipid diffusion 3. Special carriers 4. Endocytosis and exocytosis Most barrirs that separates the membranes are lipids

PHARMACOKINETIC PRINCIPLES: 

PHARMACOKINETIC PRINCIPLES Types of Membrane Transport A. PERMEATION 1. Aqueous diffusion 2. Lipid diffusion 3. Special carriers 4. Endocytosis and exocytosis ABC (ATP-Binding casseette family) P-glycoprotein or multidrug-resistance type 1 (MDR1) transporter Multidrug resistance-associated protein (MRP1 through MRP5)

PHARMACOKINETIC PRINCIPLES: 

PHARMACOKINETIC PRINCIPLES Types of Membrane Transport A. PERMEATION 1. Aqueous diffusion 2. Lipid diffusion 3. Special carriers 4. Endocytosis and Exocytosis the substance is engulfed by the cell membrane the secretion of many substances from cells

PHARMACOKINETIC PRINCIPLES: 

PHARMACOKINETIC PRINCIPLES Types of Membrane Transport A. PERMEATION B. FICK'S LAW OF DIFFUSION C. IONIZATION OF WEAK ACIDS AND WEAK BASES; THE HENDERSON-HASSELBALCH EQUATION

PHARMACOKINETIC PRINCIPLES: 

Area X Permeability Coefficient Thickness PHARMACOKINETIC PRINCIPLES Types of Membrane Transport B. FICK'S LAW OF DIFFUSION The passive flux of molecules down a concentration gradient is given by Fick's law: Flux (molecules per unit time) = (C1-C2 ) X

PHARMACOKINETIC PRINCIPLES: 

PHARMACOKINETIC PRINCIPLES Types of Membrane Transport A. PERMEATION B. FICK'S LAW OF DIFFUSION C. IONIZATION OF WEAK ACIDS AND WEAK BASES; THE HENDERSON-HASSELBALCH EQUATION

PHARMACOKINETIC PRINCIPLES: 

PHARMACOKINETIC PRINCIPLES Types of Membrane Transport C. IONIZATION OF WEAK ACIDS AND WEAK BASES; THE HENDERSON-HASSELBALCH EQUATION C 8 H 7 O 2 COOH C 8 H 7 COO - + H + Nuetral Aspirin Aspirin anion Proton For drugs, a weak acid is best defined as a neutral molecule that can reversibly dissociate into an anion (a negatively charged molecule) and a proton (a hydrogen ion).

PHARMACOKINETIC PRINCIPLES: 

PHARMACOKINETIC PRINCIPLES Weak Bases Amine -containing molecules primary amine secondary amine tertiary amine R : N : : : H H R : N : : : H R R : N : : : R R

DRUG GROUPS: 

DRUG GROUPS Several thousand drugs currently available can be arranged in about 70 groups Drugs are grouped together according to the similarity of their action If a protype drug is identified, it permits classification of other important drugs in the group as variants of the prototype

SOURCES : 

SOURCES Pharmacology: Examination and Board Review , by Trevor, Katzung Masters (McGraw-Hill, 2005) or USMLE Road Map: Pharmacology , by Katzung and Trevor (McGraw-Hill, 2006).