* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download 3-1General Properties of Drugs
Survey
Document related concepts
Plateau principle wikipedia , lookup
Compounding wikipedia , lookup
Psychopharmacology wikipedia , lookup
Theralizumab wikipedia , lookup
Pharmaceutical industry wikipedia , lookup
Neuropsychopharmacology wikipedia , lookup
Pharmacognosy wikipedia , lookup
Drug design wikipedia , lookup
Prescription costs wikipedia , lookup
Prescription drug prices in the United States wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Drug discovery wikipedia , lookup
Neuropharmacology wikipedia , lookup
Transcript
Principles of Drug Action: Pharmacokinetics Pharmacodynamics Pharmacotherapeutics Copyright © 2006, 2001 by Mosby, Inc. Slide 1 General Properties of Drugs Drugs do not perform any new functions on a tissue or organ in the body; they only modify existing functions. Drugs in general exert multiple actions rather than a single effect. Drug action results from a physiochemical interaction between the drug and a molecule in the body. Copyright © 2006, 2001 by Mosby, Inc. Slide 2 Definitions Pharmaceutics—process of dissolution when drug becomes a solution so it can cross the biologic membrane Pharmacokinetics—processes by which drugs are distributed in the body Pharmacodynamics—processes by which drugs influence living tissue Pharmacotherapeutics—process of using drugs to treat disease Toxicology—the study of harmful effects of chemicals (toxins and poisons) on the body Copyright © 2006, 2001 by Mosby, Inc. Slide 3 Phases of Drug Activity Copyright © 2006, 2001 by Mosby, Inc. Slide 4 Pharmaceutical Phase Copyright © 2006, 2001 by Mosby, Inc. Slide 5 Pharmacokinetic Activities Absorption—the process of a drug moving from the entry site to the bloodstream Distribution—the process of moving from the bloodstream to target tissue or receptor site Metabolism (biotransformation)—process by which liver transforms drug from an active to an inactive form by liver enzymes Excretion—elimination of the drug from the body (kidneys) Copyright © 2006, 2001 by Mosby, Inc. Slide 6 Types of Absorption Passive transport. Molecules move across a membrane from a region of higher concentration to lower concentration. Copyright © 2006, 2001 by Mosby, Inc. Slide 7 Types of Absorption (cont’d) Active or carrier transport. In this example, adenosine triphosphate (ATP) moves a molecule across a membrane from an area of low concentration to high concentration. Copyright © 2006, 2001 by Mosby, Inc. Slide 8 Factors Affecting Absorption Route Condition of site and blood supply to site Patient age Peristalsis Concentration of drug Form of oral med Presence of food and amount of fluid taken (contact) Pain, stress, exercise Condition of liver (hepatic first pass) Whether drug is lipid soluble or nonionized (faster) The amount of drug actually absorbed is called the bioavailability. Copyright © 2006, 2001 by Mosby, Inc. Slide 9 A comparison of drug onsets and duration of action by route of administration. Copyright © 2006, 2001 by Mosby, Inc. Slide 10 Effect of pH on drug ionization and transport Copyright © 2006, 2001 by Mosby, Inc. Slide 11 Factors Affecting Distribution Condition of target site and amount of blood supply to target site Circulatory status of patient Concentration of drug Whether drug is protein-bound If drug can pass blood-brain or placental barrier Drugs affinity to tissue or receptor site Copyright © 2006, 2001 by Mosby, Inc. Slide 12 Factors Affecting Metabolism Genetic differences Age of patient Hormone levels (broken down by same method and may compete with drug) Condition of liver Concentration of drug (overdose) Nutritional status of patient (many enzymes are proteins) Stress, cigarette smoking (increases) Copyright © 2006, 2001 by Mosby, Inc. Slide 13 Factors Affecting Excretion Age of patient Condition of and blood supply to excreting organ (usually kidney) pH of urine—acid urine promotes elimination of weak basic drugs; alkaline urine promotes elimination of weak acidic drugs Half-life of drug—amount of time it takes for half of the drug to be eliminated from body. Most drugs have about 5 half-lives. Copyright © 2006, 2001 by Mosby, Inc. Slide 14 Biologic half-life (t½) Copyright © 2006, 2001 by Mosby, Inc. Slide 15 Time to steady-state drug concentration. Copyright © 2006, 2001 by Mosby, Inc. Slide 16 Half-life timing to steady-state drug concentration and elimination with discontinuation of the drug. Copyright © 2006, 2001 by Mosby, Inc. Slide 17 A loading dose is administered to reach a therapeutic response level rapidly. Maintenance doses are administered at prescribed intervals to maintain a therapeutic drug response. The amount of drug eliminated = amount absorbed is the ideal condition to maintain a constant level in the blood. Copyright © 2006, 2001 by Mosby, Inc. Slide 18 Pharmacodynamics: Study of the Mechanism of Drug Action on Living Tissue Mechanism of action Drug-receptor interaction Drug-enzyme interaction Nonspecific interaction Copyright © 2006, 2001 by Mosby, Inc. Slide 19 Mechanism of Action: Plasma level profile of a drug Copyright © 2006, 2001 by Mosby, Inc. Slide 20 Highest and Lowest Levels Trough: lowest level of drug in bloodstream (usually just before next dose is due) Peak: highest level of drug in bloodstream (depends on route as to when this level is achieved) Copyright © 2006, 2001 by Mosby, Inc. Slide 21 Therapeutic Index and Serum Concentration Therapeutic index—Range of safe treatment—a narrow index can make it easier for patient to become toxic Serum concentration—amount of drug in blood at a given testing time Therapeutic index represents the ratio between two factors: Lethal dose (LD50) Effective dose (ED50) TI = LD50/ED50 Copyright © 2006, 2001 by Mosby, Inc. Slide 22 Drug-Receptor Interactions: Once a drug binds to a receptor, a chemical or electrical signal is transmitted via a transducer to an intermediary effector resulting in a pharmacologic response. Copyright © 2006, 2001 by Mosby, Inc. Slide 23 Affinity is how well the drug fits and is attracted to the receptor site. This is a picture of agonist activity. Drug has an affinity and produces a response. Copyright © 2006, 2001 by Mosby, Inc. Slide 24 This depicts competitive antagonistic activity at the receptor site (B-blockers, antihistamines, ARBS). Has affinity but does not produce response—only blocks response. Copyright © 2006, 2001 by Mosby, Inc. Slide 25 This depicts noncompetitive antagonist activity at the receptor site. Usually inhibits activity at receptor site. Copyright © 2006, 2001 by Mosby, Inc. Slide 26 Drug-Enzyme Interactions Enzyme is a catalyst that accelerates, activates, or inactivates a chemical reaction. Some drugs are designed to inhibit enzyme activity. These drugs “look like” the chemical substance that the enzyme usually acts on and can “fool” the enzyme into combining to the drug instead of to the chemical. This inhibits the action of the enzyme on the real chemical. Example: ACEIs—inhibit acetylcholinesterase Copyright © 2006, 2001 by Mosby, Inc. Slide 27 Nonspecific Interactions Causing a change in cell membranes or DNA processes in the cell (antibiotics, antineoplastics) Causing a change in pH of body fluids (antacids, sodium bicarbonate) Detoxifying a poison (Mucomyst, activated charcoal) Altering body chemistry (potassium, Kayexalate) Copyright © 2006, 2001 by Mosby, Inc. Slide 28 Pharmacotherapeutics Types of Drug Therapy Patient Responses to Drug Therapy Copyright © 2006, 2001 by Mosby, Inc. Slide 29 Types of Drug Therapy Acute—short-term for acute condition Maintenance—long-term for chronic condition Supplemental—what the body can’t make or take in Palliative—keep patient comfortable Supportive—maintains body function while body is recovering Prophylactic—prevents a problem Adjuvant—a substance added to an Rx to assist in the action of the main ingredient Copyright © 2006, 2001 by Mosby, Inc. Slide 30 Patient Response to Drug Therapy Assessing patient condition Assessing effects Therapeutic effects Side effects Adverse effects Placebo effect Cumulative effects Toxic effects Teratogenic, mutagenic, carcinogenic Copyright © 2006, 2001 by Mosby, Inc. Slide 31 Patient Condition History Present condition Weight and/or height if needed Present drug tx Compliance How current illness may affect a chronic condition (i.e., diabetes) Copyright © 2006, 2001 by Mosby, Inc. Slide 32 Therapeutic Effect, Side Effect, and Adverse Effect Drug Responses Therapeutic effects—predictable, expected, desirable and helpful effects—measured by serum concentration (see drug profile slide) Side effects—predictable secondary effects such as anorexia, N/V/D, dizziness, drowsiness, dry mouth, abdominal gas or distress, constipation. Adverse effects (iatrogenic)—unintended, undesirable, and often unpredictable drug effects that range from mild to fatal. Copyright © 2006, 2001 by Mosby, Inc. Slide 33 Adverse Effects: Allergic Drug Reactions Type I: anaphylactic reaction—immediate, severe with respiratory and cardiac effects; less severe characterized by hives Type II: cytotoxic reaction—autoimmune response usually manifested by blood dyscrasias or autoimmune disease Type III: Arthus reaction—”serum sickness”—drugantibody complexes in vessels leading to angioedema, arthralgia, lymphadenopathy, splenomegaly Type IV: cell-mediated reaction—delayed response of 24-48h usually manifested as a rash Copyright © 2006, 2001 by Mosby, Inc. Slide 34 Other Adverse Effects Tachyphylaxis—AKA tolerance—a decreased response to repeated doses esp. with narcotics, barbs, laxatives, psychotropics Drug dependence Idiosyncratic—from genetic differences in enzyme production (pharmacogenetics and anthropology) Cumulative—ingestion > excretion Teratogenic—harmful to fetus 3 wk-3 mo Mutagenic—alters chromosomes Carcinogenic—causes cancer Toxic—poisonous from therapeutic or intentional overdosing or accumulation Copyright © 2006, 2001 by Mosby, Inc. Slide 35 Placebo Effect Psychologic benefit that is not related to chemical effect. Effective in about 1/3 of persons. Studied in drug research; seen in everyday drug therapy. Can be affected by the health practitioner’s and patient’s attitude. Copyright © 2006, 2001 by Mosby, Inc. Slide 36 Interactions Drug-drug: alters pharmacologic action when drugs are combined. Can either be in either of the pharmacokinetic phases or in pharmacodynamics at receptor sites. Can be beneficial or detrimental. Can alter serum concentration. Drug-food: can slow or enhance absorption or can cause unusual reaction (grapefruit or licorice) Alcohol, tobacco—usually interferes with absorption Copyright © 2006, 2001 by Mosby, Inc. Slide 37 Interactions: Drug-Drug Additive—smaller doses of similar drugs given together (1+1=2; BP drugs or Tylenol+codeine) Synergistic—2 drugs together potentiate each other (1+1=3; Demerol+Phenergan or PCN+probenecid) Antagonistic—combination of 2 is less than either given alone and may work against each other (1+1=1 or 1+1=0; Narcan) Incompatibility—mixing causes precipitate or a chemical or physical reaction (outside body) See inside of drug book. Copyright © 2006, 2001 by Mosby, Inc. Slide 38 Labs Associated with Drug Administration Serum concentration Peak and trough levels Body fluid analysis Complete blood count (CBC) Culture and sensitivity (C&S) Copyright © 2006, 2001 by Mosby, Inc. Slide 39