Transcript Drug abuse
Drug references American Hospital Formulary Service (AHFS) the most reliable source of information on medications and drugs. Physician's Desk Reference (PDR) Nursing Drug Reference (NDR) Handbook of injectable drugs Medication package inserts Electronic data bases FDA web page Medline PharmInfoNet web page MicroMedex Controlled substances Comprehensive Drug Abuse Prevention and Control Act, 1970 Drug abuse: the excessive use of any substance for nonmedical purposes Classified drugs into five categories (schedules) based on: Potential for abuse and physical and psychological dependence Defined terms drug dependency and drug addiction. Established education and treatment programs for drug abuse Drug Schedules Schedule I High abuse potential No accepted medical use (heroin) Schedule II High abuse potential Accepted medical uses (morphine) Schedule III Less abuse potential than drugs in schedules I and II Accepted medical uses; may lead to some physical dependence or high psychological dependence (paracetamol with codiene) Schedule IV Lower abuse potential than schedule III drugs Accepted medical uses; may lead to limited physical or psychological dependence (Diazepam) Schedule V Low abuse potential compared to schedule IV drugs Accepted medical uses; may lead to limited physical or psychological dependence (codiene containing cough syrup) Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Pharmaceutical Phase Pharmaceutics Science of dispensing drugs to achieve effective drug administration. Dosage Form of drug affects its activity, it should be able to deliver the drug. Drug must be in solution to cross cell membrane. Dissolution Rate at which a solid drug goes into solution after ingestion More rapid rate of dissolution = more quickly drug absorbed. Tablet drug disintegration dissolution absorption Pharmacokinetic phase Pharmacokinetics How the body handles a drug over a period of time Absorption Distribution Biotransformation Excretion Absorption : Movement of drug molecules from site of entry to general circulation Variables affecting drug absorption Absorbing surface area. Blood flow to the administration site. Acid-base properties of the drug. Drug lipophilicity. Drug concentration. Compatibility . Dosage form Membranes and Absorption Lipid Bilayer Hydrophilic Heads Hydrophobic Tails Small, uncharged H2O, urea, CO2, O2, N2 Swoosh! Large, uncharged Glucose Sucrose DENIED! Small charged ions H+, Na+, K+, Ca2+, Cl-, HCO3- DENIED! Oral absorption Rich blood supply, little absorption in mouth Nitroglycerin and some hormones administered by sublingual or buccal routes Rapidly dissolve in salivary secretions Gastric Absorption Length of time a drug remains in the stomach varies depending on: pH of the environment Gastric motility Food Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Absorption in the Small Intestine Rich blood supply Large absorption area Most drug absorption occurs in the upper portion of the small intestine Prolonged exposure allow more time for absorption. Dosage forms include tablets , capsules. Rectal Absorption Effective for some medications Vascular surface area capable of drug absorption Erratic absorption may occur from: Rectal contents Local drug irritation Uncertainty of drug retention No hepatic alteration on first pass through body Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Parenteral Administration Subcutaneous Intramuscular Intravenous Intradermal Intraosseous Endtoracheal Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Subcutaneous Administration An injection beneath skin into connective tissue or fat beneath dermis Used for small volumes of drugs (<0.5 mL) that do not irritate tissue Absorption rate is slow Can provide sustained effect Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Intramuscular Administration Injection given into skeletal muscle Absorption occurs more rapidly than SC injection Greater tissue blood flow Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Intravenous Administration An injection given directly into the bloodstream Bypasses absorption process Almost immediate effect Most IV drugs are administered slowly to help prevent adverse reactions Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Intradermal Administration Injection just below the epidermis Primarily used for allergy testing and to administer local anesthetics Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Intraosseous Administration An injection directly into the bone marrow cavity through an IO infusion system Agents circulate via bone’s medullary cavity Time from injection to onset of action similar to venous route Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Endotracheal Administration Generally through an ET tube Drug delivery into the pulmonary alveoli Systemic absorption via lung capillaries Absorption almost as rapid as IV route Usually reserved for situations in which an IV line cannot be established Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Endotracheal Administration Adult ET medications include: Lidocaine (Xylocaine) Epinephrine (Adrenalin) Atropine Naloxone (Narcan) Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Pulmonary Route Drugs given by gas or fine mist (aerosol) Absorption in blood is rapid due to: Large surface area Rich alveolar capillary network Produces primarily local effects (bronchodilators) Occasionally unwanted systemic effects Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Topical Route Drugs applied topically to skin and mucous membranes Usually rapidly absorbed to produce a local effect Only intact skin surfaces used to prevent systemic effects Massaging skin promotes drug absorption Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Topical Route Drugs applied topically to skin and mucous membranes Usually rapidly absorbed to produce a local effect Only intact skin surfaces used to prevent systemic effects Massaging skin promotes drug absorption Copyright © 2006, 2001, 1994 by Mosby, Inc. All rights reserved. Distribution: Transport of a drug through the bloodstream to body tissues and site of action. Affected by: Cardiac output: amount of blood pumped by the heart per minute. Regional blood flow: amount of blood supplied to a specific organ or tissue. Drug reservoirs: drug bound to specific sites.( tissue binding, plasma protein binding) Barriers to drug distribution: Blood –brain barrier A Single layer of capillary endothelial cells line blood vessels entering the CNS Permits only lipid-soluble drugs to be distributed into brain and CSF e.g., general anesthetics and barbiturates Drugs poorly soluble in fat have trouble passing this barrier Cannot enter the brain e.g., many antibiotics Placental barrier: Membrane layers separate blood vessels of mother and fetus Not permeable to many lipid-insoluble drugs Provides some protection to the fetus Allows passage of certain non-lipid-soluble drugs Steroids, narcotics, anesthetics, and some antibiotics Can affect developing embryo or neonate if given to pregnant mother Metabolism: Process by which the drug is chemically converted to a metabolite. Purpose is to "detoxify" a drug and render it less active. Liver is primary site of drug metabolism. If drug metabolism is delayed, drug accumulation and cumulative drug effects may occur Effect of liver diseases….. Hepatic ‘First-Pass’ Metabolism Affects orally administered drugs Metabolism of drug by liver before drug reaches systemic circulation Drug absorbed into portal circulation, must pass through liver to reach systemic circulation May reduce availability of drug Excretion: Elimination of toxic or inactive metabolites Organs of excretion Kidneys (main site) Intestine Lungs Sweat and salivary glands Mammary glands Effect of renal diseases Pharmacokinetic Phase of Drug Action Pharmacodynamics Study of how a drug acts on a living organism Pharmacologic response relative to the concentration of a drug at an active site in the organism Most drugs produce effects by: Drug-receptor interaction Agonists Antagonists Affinity Efficacy Types of receptors Drug-enzyme interaction Nonspecific drug interaction Agonists Drugs that bind to a receptor and cause a physiological response Antagonists Drugs that bind to a receptor and whose presence prevents a physiological response or other drugs from binding Affinity : the propensity of the drug to bind or attach itself to a given receptor site. Efficacy :also called intrinsic activity, the ability of a drug to initiate biological activity as a result of binding to a receptor site. Agonist have affinity and efficacy at the receptor site. Receptor Interactions Lock and key mechanism Agonist Receptor Agonist-Receptor Interaction Receptor Interactions Induced Fit Receptor Perfect Fit! Receptor Interactions Competitive Inhibition Antagonist Receptor DENIED! Antagonist-Receptor Complex Receptor Interactions Non-competitive Inhibition Agonist Antagonist Receptor DENIED! ‘Inhibited’-Receptor Non receptor interactions Action on enzymes :- some drugs produce their effect through inhibition of certain enzymes e.g. cholinesterase inhibitors ; mono amine oxidase inhibitors Action on cell membranes: - local anesthetic as procaine hydrochloride act by stabilization of the neuronal membrane renders it non-excitable. Physically Chemically Drug Response Assessment Assess by observing the physiological parameters e.g., BP, pain Effects of some drugs cannot be monitored solely by the patient's response. Drugs must reach certain concentration at the target site to achieve the desired effect. Plasma Level Profiles Relationship between plasma concentration and level of therapeutic effectiveness over time Depend on: Rate of absorption Distribution Biotransformation Excretion Plasma Level Profiles Therapeutic range Concentration (dose) that provides the desired response with the least risk of toxicity. Some patients fail to respond to therapeutic doses Others may develop toxicity Plasma Level Profile Biological half life Time needed to metabolize or eliminate half of total amount of drug in body A drug is considered gone from the body after five half-lives have passed Affected by renal and hepatic function. Determine the frequency of dug administration. Therapeutic index Measures relative safety of a drug Ratio between: Lethal dose 50 (LD 50) Dose of a drug lethal in 50% of laboratory animals tested Effectiveness dose (ED 50) Dose that produces a therapeutic effect in 50% of a similar population TI = LD 50/ED 50 The closer the ratio to 1, the greater the danger in administering the drug to humans (Digoxin)