Sedation in the GI Suite Curt Mardis, MD Staff Anesthesiologist St Mary’s Medical Center Evansville, Indiana

Objectives Review the pharmacodynamics of medications used for sedation –Mention common side effects Review the pharmacokinetics of these same medications Review the antidotes for medications Review fundamentals of airway management Review rescue medications

Basic nomenclature Pharmacodynamics –What a drug does to the body –Study of the biochemical and physiological effects of drugs on the body Pharmacokinetics –What the body does to a drug –Studying the fate of substances administered externally to a living organism –Include pharmaceutical agents, hormones, nutrients, and toxins

Midazolam (Versed) Benzodiazepine Enhances effect of GABA on GABA A receptors Used to treat acute seizures Induce sedation and amnesia before medical procedures

Midazolam (Versed) Potent anxiolytic and amnestic medication Anticonvulsant and sedative properties Most commonly used benzo for sedation, because of very fast recovery time Less commonly used for induction and maintenance of anesthesia

Midazolam drawbacks Tolerance Withdrawal syndrome Paradoxical effects can occur, especially at high doses –Children –Elderly

Midazolam and lethal injection Manufacturer of pentobarbital has disallowed its use for lethal injection Florida used midazolam to execute a prisoner in 2013 Ohio used midazolam in 2014

Flumazenil GABA A receptor antagonist Antidote to benzo overdose Antidote to overdose of non- benzodiazepine sleep enhancers –Zolpidem –Zaleplon –Zopiclone 200 mcg IV every 2 min, up to 3 mg/hour

Strong agonist at mu-opioid receptors Potent synthetic opioid analgesic with rapid onset, short duration of action Commonly used in procedures for analgesia x more potent than morphine Fentanyl

Side effects –Nausea –Constipation –Dry mouth Less nausea than morphine Less histamine-induced itching than morphine Responsible for many fatal overdoses, due to respiratory depression

Naloxone (Narcan) Opioid antagonist Antidote to opioid overdose –Fentanyl –Morphine –Heroin Naloxone can be administered IV, IM, SQ, or via nasal mucosa Start at 80 mcg, then 4 mcg/kg/hour gtt

Propofol (Diprivan) Potentiates GABA A receptor activity Acts as a sodium channel blocker Diprivan: diisopropyl IV anesthetic Anti-emetic Rapid onset and recovery

Propofol Adverse Effects Vasodilation Decreases SVR Hypotension Apnea

Propofol and lethal injection Missouri Supreme Court –Propofol for lethal injection is constitutional First execution was scheduled for October 2013, but halted European Union threatened to limit drug’s export to United States

Epinephrine Useful medication in emergency Non-specific agonism at adrenoreceptors Increases heart rate and blood pressure Increases coronary perfusion pressure

Atropine Competitive antagonist at muscarinic acetylcholine receptors Dilates pupils Increases heart rate Antidote to vagal responses