Rau Chapter_1-3 2023.pptx

Pharmacology Terms, Principles, & Intro to Med Delivery Prof. McKenney Copyright © 2016, Elsevier Inc. All rights reserved. 1 Pharmacology and the Study of Drugs Drugs Respiratory care pharmacology Pharmacology  Pharmacy  Pharmacognosy  Pharmacogene...

Pharmacology Terms, Principles, & Intro to Med Delivery Prof. McKenney Copyright © 2016, Elsevier Inc. All rights reserved. 1 Pharmacology and the Study of Drugs Drugs Respiratory care pharmacology Pharmacology  Pharmacy  Pharmacognosy  Pharmacogenetics  Therapeutics  Toxicology Copyright © 2016, Elsevier Inc. All rights reserved. 2 Pharmacology and the art, practice, or the Study of Drugs profession of preparing, preserving, compounding, and dispensing medical Drugs drugs. 2a the branch of :knowledge a place concerned where Respiratory care pharmacology with medicines medicinal are drugscompounded obtained from or dispensed plants or other natural sources. Pharmacology the branch of pharmacology  Pharmacy  Pharmacognosy 1.concerned the branchwith the effect of genetic of medicine factors on with concerned reactions to drugs. of the treatment  Pharmacogenetics 1. the branch of science disease concerned and the action ofwith the nature,  Therapeutics effects, and remedial detection agents. of poisons.  Toxicology 2. the measurement and analysis of potential 2. a treatment, therapy, or drug.toxins, intoxicating"current or bannedtherapeutics substances, andfor prescription medicationsasthma" present in a person's body. "toxicology reports will determine if alcohol was a factor in the crash" Copyright © 2016, Elsevier Inc. All rights reserved. 3 Complimentary & Alternative Medicine With Instead Copyright © 2016, Elsevier Inc. All rights reserved. 4 Respiratory Care Pharmacology: An Overview Aerosolized agents given by inhalation Five advantages Smaller dose Fewer side effects Rapid onset Targets respiratory system Painless, relatively safe Goal? To use the smallest, effective dose! Copyright © 2016, Elsevier Inc. All rights reserved. 5 Respiratory Care Pharmacology: An Overview (Cont.) Related drug groups in respiratory care  Anti-infective agents (Pentamidine)  Neuromuscular blocking agents (NMBA)  Central nervous system agents (Pain/Anxiety/others)  Antiarrhythmic agents  Antihypertensive and antianginal agents  Anticoagulant and thrombolytic agents  Diuretics Copyright © 2016, Elsevier Inc. All rights reserved. 6  Chapter 2 Principles of Drug Action Copyright © 2016, Elsevier Inc. All rights reserved. 7 Principles of Drug Actions Three major topics Drug administration How it is made available to the body Pharmacokinetics What the body does to the drug Pharmacodynamics What the drug does to the body On Board! Copyright © 2016, Elsevier Inc. All rights reserved. 8 Pharmacokinetics vs. Pharmacodynamics ADME Copyright © 2016, Elsevier Inc. All rights reserved. 9 Phases of Drug Action Route determines dose! Figure 2-1 Conceptual scheme illustrating the major phases of drug action in sequence, from dose administration to effect in the body. (From Katzung BG, Masters SB, Trevor AJ, editors. Basic and clinical pharmacology, ed 11, New York, 2009, McGraw Hill Medical.) Copyright © 2016, Elsevier Inc. All rights reserved. 10 Drug Administration Phase Drug dosage forms  Drug formulations and additives  Tablets, capsules, solutions Drug formulations and additives  Active drug ingredient  Inactive ingredients Capsule material, preservatives, propellants, dispersants, carrier agents Copyright © 2016, Elsevier Inc. All rights reserved. 11 Routes of Administration Enteral Tablet, capsule, suppository, elixir, suspension Parenteral IV, IM, SC, IT, IO Transdermal Patch, paste Inhalation Gas, aerosol Topical Powder, lotion, ointment Copyright © 2016, Elsevier Inc. All rights reserved. 12 Pharmacokinetic Phases Absorption Distribution Metabolism Liver Elimination Kidneys Copyright © 2016, Elsevier Inc. All rights reserved. 13 Pharmacokinetic Phase: Absorption Absorption  Aqueous diffusion  Lipid diffusion  Carrier-mediated transport  Pinocytosis  Factors affecting absorption Bioavailability 14 Copyright © 2016, Elsevier Inc. All rights reserved. 14 Pharmacokinetic Phase: Distribution Distribution The process by which a drug is transported to its sites of action, eliminated, or stored Volume of distribution (VD) – relates the total amount of drug in the body to the plasma concentration VD = drug amount/plasma concentration Copyright © 2016, Elsevier Inc. All rights reserved. 15 Volumes of Major Body Compartments Copyright © 2016, Elsevier Inc. All rights reserved. 16 Pharmacokinetic Phase: Metabolism Metabolism Drug biotransformation Most important isoenzyme families are CYP1, CYP2, CYP3, CYP4  Enzyme induction and inhibition Chronic administration or abuse of drugs Enzyme induction can affect therapeutic dose Inhibitions of CYP enzymes First-pass effect Copyright © 2016, Elsevier Inc. All rights reserved. 17 Catecholamine s Copyright © 2016, Elsevier Inc. All rights reserved. 18  Catechol-O- methyltransferase Copyright © 2016, Elsevier Inc. All rights reserved. 19 Copyright © 2016, Elsevier Inc. All rights reserved. 20 Pharmacokinetics of Inhaled Aerosol Drugs Route and nature of drug determine absorption, distribution, metabolism, elimination of the aerosol drug Local versus systemic effect Inhaled aerosols in pulmonary disease Distribution of inhaled aerosols Oral portion (stomach) Inhaled portion Copyright © 2016, Elsevier Inc. All rights reserved. 21 Potency Figure 2-14 ​The potency of a drug is defined as the dose producing 50% of the drug’s maximal effect. Drug A is more potent than Drug B; however, Drugs B and C are equally potent, although Drug C has less maximal effect than Drug B. 22 Copyright © 2016, Elsevier Inc. All rights reserved. 22 Therapeutic Index Figure 2-15 Therapeutic index (TI), defined as the ratio of the dose that is lethal for 50% of test animals (LD50) to the dose causing improvement in 50% of test animals (ED50). 23 Copyright © 2016, Elsevier Inc. All rights reserved. 23 Pharmacogenetics Variations in patient response to drugs due to hereditary differences Examples:  Isoniazid  Succinylcholine  Isoflurane 24 Copyright © 2016, Elsevier Inc. All rights reserved. 24 Autonomic Nervous System Copyright © 2016, Elsevier Inc. All rights reserved. 25  Chapter 3 Administration of Aerosolized Agents Copyright Copyright© 2016, Elsevier © 2016, Inc. All Elsevier rights Inc. All reserved. rights reserved. 26 Three Main Uses of Aerosol Therapy Humidification of dry inspired gases Improved mobilization and clearance of respiratory secretions Delivery of aerosolized drugs to the respiratory tract 27 Copyright © 2016, Elsevier Inc. All rights reserved. 27 Advantages with Aerosol Delivery of Drugs Aerosol doses are smaller Onset of drug action is rapid Drug delivery is targeted to the respiratory system Fewer systemic side effects Relatively painless The lung provides a portal to the body for inhaled aerosol agents intended for system effect 28 Copyright © 2016, Elsevier Inc. All rights reserved. 28 Disadvantages with Aerosol Delivery of Drugs Numerous variables affect the dose Dose estimation and dose reproducibility are inconsistent Difficulty in coordination of hand action and breathing Physicians, nurses, and therapists lack knowledge of device use and administration protocols LOTS of device types Copyright © 2016, Elsevier Inc. All rights reserved. 29 Copyright © 2016, Elsevier Inc. All rights reserved. 29 Physical Principles of Inhaled Aerosol Drugs Aerosol particle size distributions Count mode Count median diameter (CMD) Mass median diameter (MMD) Mass median aerodynamic diameter (MMAD) Geometric standard deviation (GSD) Measurement of particle size distributions Aerodynamic diameter (MMAD) Copyright © 2016, Elsevier Inc. All rights reserved. 30 Copyright © 2016, Elsevier Inc. All rights reserved. 30 Physical Principles of Inhaled Aerosol Drugs (Cont.) Particle size and lung deposition Fine particle fraction Particle size and therapeutic effect Particles >10 μm Particles 5 to 10 μm Particles 2 to 5 μm Particles 0.8 to 3 μm Copyright © 2016, Elsevier Inc. All rights reserved. 31 Copyright © 2016, Elsevier Inc. All rights reserved. 31 Deposition within Airway Figure 3-2 Effect of aerosol particle size on area of preferential deposition within the airway. 32 Copyright © 2016, Elsevier Inc. All rights reserved. 32 Physical Principles of Inhaled Aerosol Drugs Mechanisms of deposition Inertial impaction Gravitational settling Diffusion (Brownian motion) Effect of temperature and humidity Hygroscopic increase in MMAD Copyright © 2016, Elsevier Inc. All rights reserved. 33 Copyright © 2016, Elsevier Inc. All rights reserved. 33 Particle Size for Common Aerosols Figure 3-4 Range of particle size for common aerosols in the environment and the influence of inertial impactions, sedimentation, and diffusion. (From Wilkins RL, Stoller JK, Kacmarek RM: Egan’s fundamentals of respiratory care, ed 9, St Louis, 2009, Mosby.) 34 Copyright © 2016, Elsevier Inc. All rights reserved. 34 Aerosol Devices for Drug Delivery Nebulizers Jet (pneumatic) nebulizers Mesh nebulizers Ultrasonic nebulizers (USNs) 35 Copyright © 2016, Elsevier Inc. All rights reserved. 35 Pneumatic Jet Nebulizers Jet nebulizer with reservoir tube Jet nebulizer with collection bag Breath-enhanced jet nebulizer Breath-actuated jet nebulizer Copyright © 2016, Elsevier Inc. All rights reserved. 36 Copyright © 2016, Elsevier Inc. All rights reserved. 36 Types of Jet Nebulizers Copyright © 2016, Elsevier Inc. All rights reserved. 37 Copyright © 2016, Elsevier Inc. All rights reserved. 37 Mesh Nebulizers Use a plate or mesh with multiple apertures to move liquid Do not require a gas source Electrically powered Active vibrating mesh nebulizers Passive mesh nebulizers Copyright © 2016, Elsevier Inc. All rights reserved. Copyright © 2016, Elsevier Inc. All rights reserved. 38 Factors Affecting Jet Nebulizer Performance Small volume nebulizers (SVNs) Dead volume Filling volume and treatment time Effect of flow rate Type of power gas Device interface Type of solution Copyright © 2016, Elsevier Inc. All rights reserved. 39 Copyright © 2016, Elsevier Inc. All rights reserved. 39 Aerosol Devices for Drug Delivery (Cont.) Metered dose inhalers (MDIs) Two categories Conventional pMDI Breath-actuated pMDI Technical description Canister, propellant, drug formulary, metering valve, actuator, dose counter Correct use Copyright © 2016, Elsevier Inc. All rights reserved. 40 Copyright © 2016, Elsevier Inc. All rights reserved. 40 Metered Dose Inhaler Figure 3-17 Major components of a metered dose inhaler, with an illustration of the function of the metering valve. Oral and nasal adapters are shown. 41 Copyright © 2016, Elsevier Inc. All rights reserved. 41 Aerosol Devices for Drug Delivery (Cont.)  Metered dose inhalers  Factors affecting MDI performance Loss of dose Shaking canister Timing of actuation intervals Open-mouth versus closed-mouth use Loss of prime Storage temperature Copyright © 2016, Elsevier Inc. All rights reserved. 42 Copyright © 2016, Elsevier Inc. All rights reserved. 42 Aerosol Devices for Drug Delivery (Cont.) Metered dose inhalers Breath-actuated inhalers Off the market Hydrofluoroalkane (HFA) propellants Equivalence and safety Improved drug delivery with HFA formulation Copyright © 2016, Elsevier Inc. All rights reserved. 43 Copyright © 2016, Elsevier Inc. All rights reserved. 43 Respimat Soft-Mist Inhaler Propellant free Utilizes mechanical energy in the form of a tension spring Combivent Respimat Copyright © 2016, Elsevier Inc. All rights reserved. 44 Copyright © 2016, Elsevier Inc. All rights reserved. 44 Copyright © 2016, Elsevier Inc. All rights reserved. 45 Aerosol Devices for Drug Delivery (Cont.) MDI reservoir devices Reservoir devices Design variables Size Other MDI auxiliary devices Copyright © 2016, Elsevier Inc. All rights reserved. 46 Copyright © 2016, Elsevier Inc. All rights reserved. 46  Metered-Dose Inhaler Accessories Figure 3-23 Pressurized metered dose inhaler (pMDI) and accessory devices consisting of spacer and holding chambers. All of the accessory devices reduce oropharyngeal deposition. Small volume spacers (OptiHaler and Myst Assist) offer no additional advantage, but large volume spacers (toilet paper roll and Ellipse) improve inhaled aerosol with delay between actuation and inspiration. Only the bag (InspirEase) and valved holding chambers (AeroChamber, OptiChamber, ACE, and MediSpacer) protect the patient from blowing the dose away when the pMDI is actuated during expiration. (From Wilkins RL, Stoller JK, Kacmarek RM: Egan’s fundamentals of respiratory care, ed 9, St Louis, 2009, Mosby.) 47 Copyright © 2016, Elsevier Inc. All rights reserved. 47 Aerosol Devices for Drug Delivery (Cont.) Dry powder inhalers (DPIs) Inspiratory flow rate Between 30 and 90 L/min Humidity 40 lpm Clinical efficacy Three categories After taste, nausea? Unit-dose DPIs Multiple unit-dose DPIs Multiple-dose DPIs Copyright © 2016, Elsevier Inc. All rights reserved. 48 Copyright © 2016, Elsevier Inc. All rights reserved. 48 Clinical Application of Aerosol Delivery Devices Recommendations based on clinical evidence Aerosol delivery of short-acting β2-agonists in ER Aerosol delivery of short-acting β2-agonists in hospital Intermittent versus continuous nebulizer delivery of β2-agonists Aerosol delivery of β2-agonists to patients receiving mechanical ventilation Aerosol delivery of short-acting β2-agonists for asthma in the outpatient setting Inhaled corticosteroids for asthma β2-Agonists and anticholinergic agents for COPD Copyright © 2016, Elsevier Inc. All rights reserved. 49 Copyright © 2016, Elsevier Inc. All rights reserved. 49 Clinical Application of Aerosol Delivery Devices (Cont.) Recommendations based on clinical evidence (Cont.) Device selection Patient or clinical preference Convenience of device Practicality of device Durability of device Cost and reimbursement Drug availability Ability of all prescribed drugs to be delivered by the same device Copyright © 2016, Elsevier Inc. All rights reserved. 50 Copyright © 2016, Elsevier Inc. All rights reserved. 50 Clinical Application of Aerosol Delivery Devices (Cont.) Lung deposition and loss patterns with traditional aerosol devices MDI (CFC) = 8.8% deposition MDI (HFA) = 53% deposition MDI (CFC) with spacer = 14.8% deposition SVN = 12.4% deposition DPI = 14.8 to 27.7% deposition Copyright © 2016, Elsevier Inc. All rights reserved. 51 Copyright © 2016, Elsevier Inc. All rights reserved. 51 Clinical Application of Aerosol Delivery Devices (Cont.) Equivalent doses among device types Lung deposition with newer aerosol devices Clinical equivalence of MDIs and SVNs Age guidelines for use of aerosol devices Copyright © 2016, Elsevier Inc. All rights reserved. 52 Copyright © 2016, Elsevier Inc. All rights reserved. 52 Clinical Application of Aerosol Delivery Devices (Cont.) Patient-device interface Administration by intermittent positive-pressure breathing Face mask administration Endotracheal tube administration Copyright © 2016, Elsevier Inc. All rights reserved. 53 Copyright © 2016, Elsevier Inc. All rights reserved. 53