Drug Action And Handling Chapter 2 PDF

Drug Action and Handling Chapter 2 Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 1  Characterization of Drug Action  Terms used to measure drug response or action  Dose-response curve Log dose effect curve...

Drug Action and Handling Chapter 2 Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 1  Characterization of Drug Action  Terms used to measure drug response or action  Dose-response curve Log dose effect curve  Potency  Efficacy Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 2 Dose-response curve  Simple model  “pinch your ear” harder you pinch more it hurts  Increase the dose increase the effect Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 3 Log Dose Effect Curve  More complicated model  Relationship between the actual dose of the drug and the actual response Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 4  Therapeutic Range: where the dose is increasing sharply  Maximum Response: where the curve plateaus; maximum response a drug can exhibit (ceiling effect) Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 5  Potency  Pharmacological activity of a drug, related to DOSE; amount of drug necessary to produce an effect  Potency is GREATER when dose is SMALLER Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 6  Potency (Cont.) Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 7  Efficacy  Maximum response of a drug, REGARDLESS OF THE DOSE  Administering more of a drug will not increase the efficacy of the drug probability of adverse reaction Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 8  Therapeutic Index  Ratio of the median lethal dose to the median effective dose and is expressed  TI = LD50/ED50  LD = dose that causes death in 50% of test animals  ED = dose required to produce the desired clinical effect in 50% of test animals  The greater the TI the safer the drug  Closer to 0 require careful monitoring Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 9  TI Examples  Drug A LD=200mg, ED = 20mg, TI = 10  Drug B LD=300mg, ED = 100mg, TI = 3 https://toxtutor.nlm.nih.gov/02-005.html Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 10  Mechanism of Action of Drugs  Pharmacologic effect – drugs do not impact a new function of the organism  Produce same action as endogenous agent  Block action of endogenous agent  Therapeutic effect  Desired effect of a drug - predictable  Must bind with the receptor site on the cell membrane  Adverse effect  Unwanted effects of a drug  Actions on nontarget organs – vomiting with antibiotics Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 11  Agonists and Antagonists  Agonist  Has affinity for a receptor  Combines with the receptor  Produces an effect  Antagonist  Counteracts the action of the agonist  Drugs with stronger affinity will bind to more receptors  More of a drug with weaker affinity will be required  Drugs with stronger affinity are more potent Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 12 Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 13  Pharmacokinetics ADME  Pharmacokinetics is the study of how a drug enters the body, circulates within the body, is changed by the body, and leaves the body  Absorption  Distribution  Metabolism  Excretion Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 14 Pharmacokinetics: Drug Absorption  Transfer of a drug from the site of administration to the blood stream  Factors that influence rate of drug absorption:  Physicochemical properties  Site of absorption  Solubility of drug  Dose form  Presence of infection  Blood flow at injection site  IV administered drugs bypass this step Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 15 Pharmacokinetics: Drug Distribution  Distribution is the passage of drugs into various body fluid compartments such as plasma, interstitial fluids, and intracellular fluids  Process by which a drug leaves the blood stream and enters the body systems  Distributed to organs with highest blood flow Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 16 Pharmacokinetics: Drug Distribution  Factors that determine distribution of drug:  Organ size  Blood flow to organ  Drug solubility  Plasma protein-binding capacity – drugs may bind to proteins in the blood  Presence of barriers – blood-brain and placenta Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 17 Pharmacokinetics: Drug Metabolism  Metabolism or biotransformation is the body’s way of changing a drug so that it can be more easily excreted  Also known as biotransformation  Liver is the most important site for metabolism Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 18  Pharmacokinetics: Drug Metabolism (Cont.)  Metabolism mechanisms:  Active to inactive (most drugs)  Inactive to active (acyclovir)  Active to active (diazepam) Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 19 Pharmacokinetics: Drug Metabolism  Factors that affect drug metabolism:  Impaired liver function  Hepatic portal circulation  Drugs and environmental substances Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 20  Pharmacokinetics: Drug Excretion  The removal of the drug from the body  Drug elimination terminates drug effects Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 21  Pharmacokinetics: Excretion  Renal (kidney)  Lungs  Saliva  Bile  Gastrointestinal tract  Sweat  Milk Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 22 Clinical Pharmacokinetics: Half-Life  Drug half-life: The time it takes for the concentration of a drug to fall to one-half (50%) of its original blood level  It takes 4-5 half-lives for a drug to be considered eliminated from the body  (ex. If half life is 1 hour then 4-5 hours drug will be gone; drug reference book)  azithromycin (Zithromax) half life 68 hours = 272 – 340 hours = 14 days Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 23 Half-Life First-Order Kinetics Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 24 Half-Life Zero-Order Kinetics aspirin and alcohol Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 25  Altering Drug Effects  Patient adherence  Gender  Psychological factors  Genetic variation  Pathologic state  Drug interactions  Time of administration  Age and weight  Route of  Environment administration  Other Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 26  Routes of Administration page 20-21  Affects  Onset: Time it takes for the drug to begin to have its effect  Duration: The length of time of a drug’s effect  Classified  Enteral: placed directly in the GI tract Oral or rectal  Parenteral: bypass the GI tract Various injection routes, inhalation, and topical Useful for emergencies, unconsciousness, lack of cooperation, nausea Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 27  Oral Route of Drug Administration  Advantages  Small intestine presents large absorbing area  Produces a slower onset of action  Safest, least expensive, most convenient  Disadvantage  Nausea, vomiting  Certain drugs are inactivated by GI tract acidity or enzymes  Drug interactions  Requires patient cooperation  First-pass effect: drug metabolized when first passes through the liver Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 28  Rectal Route of Administration  Advantages  Used if patient is vomiting or unconscious  Produces local or systemic effect  Disadvantages  Drugs are poorly and irregularly absorbed  Poor patient acceptance! Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 29  Intravenous Route of Drug Administration  Advantages  Produces most rapid drug response  More predictable blood levels  Use in emergency situations  Disadvantages  Phlebitis  Drug irretrievability  Allergy  Side effects related to high plasma concentrations Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 30  Intramuscular Route of Drug Administration  Advantages  Allows increased tolerance to irritating drugs  Allows injection of suspensions, which provides a sustained effect Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 31  Subcutaneous Route of Drug Administration  Injection of drugs into the subcutaneous areolar tissue (insulin and local anesthesia)  Disadvantage  Irritating solutions may cause sterile abscesses or hematoma Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 32 Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 33 Other Routes of Drug Administration  Intradermal  Injected into epidermis  Tuberculin test  Intrathecal  Spinal space  Intraperitoneal  Into body cavity Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 34  Inhalation Route of Drug Administration  Examples: Inhalers used to treat asthma, general anesthetics, nitrous oxide/oxygen  ProAir (albuterol) asthma inhaler  Advantages  Rapid onset of action  Lack of need for needles  Disadvantage  Popular route for abuse of drugs Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 35 Topical Route of Drug Administration  Advantages  Systemic side effects are rare  Disadvantages  Increased risk of systemic side effects if surfaces are large and/or abraded, inflamed, or sloughing  Intraorally spayed anesthetics may be absorbed into blood stream  Most effective in non-keratinized areas  Contraindicated in ulcerated, burned or abraded surfaces Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 36  Topical  Epicutaneous – cream, ointment, gel  Transdermal patch – fentanyl patch  Sublingual – tablets NTG  Buccal – tablets  Subgingival – atridox, periochip Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 37  Questions? Copyright © 2016 by Mosby, an imprint of Elsevier, Inc. All rights reserved. 38