Anesthesia Pharmacology

CONTENTS © Jones & Bartlett■■ Pharmacology Learning, Pearls LLC © Jones & Bartlett Learning, LLC NOT FOR SALE■■ Volatile OR AnestheticsDISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ Sedation, Anxiolytic, Amnestic ■■ Alpha 2 Agonists ■■ Induction Agents ■■ Total Intravenous Anesthetic (TIVA) © Jones & Bartlett Learning,■■ Narcotic LLC Opioids © Jones & Bartlett Learning, LLC ■■ NOT FOR SALE OR DISTRIBUTIONNonopioid Analgesics NOT FOR SALE OR DISTRIBUTION ■■ Agonist–Antagonists (Partial Agonists) ■■ Antagonist Agents ■■ Muscle Relaxants ■■ Anticholinesterase ■■ Anticholinergic © Jones & Bartlett Learning, LLC ■■ Antiemetics—Receptor© Jones Specific & andBartlett Adjunct Learning, LLC NOT FOR SALE OR DISTRIBUTION ■■ Local AnestheticsNOT (LA) FOR SALE OR DISTRIBUTION ■■ Antibiotics ■■ Corticosteroids ■■ Drugs to Affect Heart Rate

■■ Beta-Blockers Pharm © Jones & Bartlett Learning, LLC 151 © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 151 27/10/16 2:40 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 152 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ Angiotensin Inhibitors (Ace inhibitors; ACEi; ARB) ■■ Calcium Channel Blockers (CCB) ■■ Vasopressors–Inotropes ■■ Vasodilators © Jones & Bartlett Learning, LLC ■■ Antiarrhythmic IV Agents© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION ■■ Herbals NOT FOR SALE OR DISTRIBUTION ■■ 5.1 Pharmacology Pearls The metabolic, cardiovascular, and pulmonary function differences between a patient with ideal body weight (IBW) and morbid obesity is clear. Because these © Jones & Bartlettdifferences affect Learning, the apparent LLC volume of distribution of © Jones & Bartlett Learning, LLC some drugs, there is increased risk of anesthesia in the NOT FOR SALEmorbidly OR obese. DISTRIBUTION As drug dosages based on total body NOT FOR SALE OR DISTRIBUTION weight (TBW) can result in overdose, conversely, administration of drugs based on IBW can result in subtherapeutic doses.

Drugs That Need to Be Given in Ideal Body Weight © Jones & Bartlett Learning,IBW is the LLC difference between TBW and fat mass.© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONPropofol—induction dose NOT FOR SALE OR DISTRIBUTION Rocuronium Vecuronium Remifentanil Morphine © Jones & Bartlett Learning, LLC Alfentanil © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Sufentanil—maintenanceNOT dose FOR SALE OR DISTRIBUTION Sugammadex (IBW + 40% excess weight)

Formula for IBW: Males: 50 kg + 2.3 kg for each inch above 5 feet Pharm Females: 45 kg + 2.3 kg for each inch above 5 feet © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 152 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 153 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Drugs That Need to Be Given in Total Body Weight TBW Propofol—maintenance dose © Jones & Bartlett Learning, LLC Succinylcholine © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Neostigmine NOT FOR SALE OR DISTRIBUTION TIVA anesthetic Midazolam Atracurium Cisatracurium © Jones & FentanylBartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALESufentanil—induction OR DISTRIBUTION dose NOT FOR SALE OR DISTRIBUTION Thiopental

■■ 5.2 Volatile Anesthetics Inhalational agent pharmacokinetics is divided into four © Jones & Bartlett Learning,phases: absorption, LLC distribution to the brain, metabolism,© Jones & Bartlett Learning, LLC and excretion. The ultimate goal is to establish a particular

NOT FOR SALE OR DISTRIBUTIONpartial pressure of an agent in the alveoli (PA), whichNOT will FOR SALE OR DISTRIBUTION equilibrate to attain a therapeutic tissue concentration with the brain to produce an anesthetized state. Uptake and Distribution Partial pressure of agent in alveoli (PA) is determined by © Jones & Bartlett Learning, LLC delivery minus loss. It is a ©reflection Jones of partial& Bartlett pressure of Learning, LLC agent in brain. NOT FOR SALE OR DISTRIBUTION • Delivery affected by: inspiredNOT partialFOR pressure, SALE alveolar OR DISTRIBUTION ventilation • Uptake affected by: solubility, cardiac output, alveolar-to-venous partial pressure difference • The relative solubilities of anesthetic in air, blood, and tissues are expressed as partition coefficients. The greater Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 153 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FOR SALE ORDISTRIBUTION © Jones &Bartlett Learning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALE ORDISTRIBUTION © Jones& BartlettLearning,LLC 9781284115147_CH05_151_242.indd 154

Pharm

154 TABLE 5-1 Alpha Beta Dopa Chart

© Jones & Bartlett Learning, LLC. NOTFOR SALEORDISTRIBUTION © Jones&BartlettLearning, Receptors Tissue Actions Agonist Antagonist Alpha 1 Smooth muscle constriction: α1: STIMULATORY RESPONSE Norepinephrine Treat HTN and vascular, iris, uterus, bladder *Vasoconstriction, inrecreased peripheral ++++ BPH: Selective sphincters, heart resistance Epinephrine +++ antagonists: Pupil *Increased BP Phenylephrine +++ Minipress Smooth *Inotrope (activation increases intracellular Dopamine ++ Hytrin muscle- gastrointestinal calcium ion → concentration muscle Ephedrine ++ Cardura NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC contraction) Flomax *Increase bladder sphincter Prazosin *Decrease splanchnic flow Nonselective *Mydrias is (dilates pupil) antagonists: *Pancreas-insulin inhibited Phentolamine = *Liver-hepatic glycogenesis Phenoxybenzamine * GI relaxation NOT FOR SALE ORDISTRIBUTION © Jones &Bartlett Learning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC Alpha 2 Platelets, Adrenergic & α2: INHIBITORY RESPONSE *alpha 2 Dexmedetomidine Yohimbe NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC Cholinergic pathways, NEGATIVE FEEDBACK LOOP — decr NE ++++

Vascular smooth muscle, release & SNS outflow

24/10/16 11:04 PM Coronary arteries, Kidney, Brain, Fat cells NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC

NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC

NOT FORSALE ORDISTRIBUTION © Jones& BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FOR SALE ORDISTRIBUTION © Jones &Bartlett Learning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALE ORDISTRIBUTION © Jones& BartlettLearning,LLC 9781284115147_CH05_151_242.indd 155

© Jones & Bartlett Learning, LLC. NOTFOR SALEORDISTRIBUTION © Jones&BartlettLearning, α2 presynaptic: inhibits NE (1600/1 of alpha2/ *Coronary artery vasodilation alpha 1) Clonidine *Centrally sedates; anxiolytic +++ (200/1 of α2 postsynaptic: alpha2/alpha1) Nor- *Coronary artery constriction epinephrine +++

*Promote excretion of Na+ & H2O Epinephrine + *Insulin inhibited (↑ BG) Dopamine + NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC *Platelet aggregation *Inhibition of lipolysis *Deer BP + catecholamine levels Beta 1 Myocardium, SA Node, Ven- β1: STIMULATORY RESPONSE Isoproterenol ++++ Atenolol tricular conduction, Coronary * Cardiac: positive inotrope (increases Dobutamine +++ Metoprolol arteries contraction) and BP Epinephrine +++ Esmolol *Chronotrope (increases HR) Norepinephrine ++ NOT FOR SALE ORDISTRIBUTION © Jones &Bartlett Learning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC *Increase myocardial demand Ephedrine ++ NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC *Dilates coronary arteries Dopamine ++ *Renin release Dopexamine + 155 continues

24/10/16 11:04 PM Pharm NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC

NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC

Pharm 156 Alpha Beta Dopa Chart, continued © Jones & Bartlett Learning, LLC. NOTFOR SALEORDISTRIBUTION © Jones&BartlettLearning, Receptors Tissue Actions Agonist Antagonist Beta 2 Myocardium, SA Node, β2: presynaptic NE release accelerated Isoproterenol Propranolol Smooth muscle Myocardial, *positive inotrope; chronotrope; some ++++ Esmolol Bronchial, Uterine and constriction Dopexamine +++ Timolol Vascular smooth muscle, β2: postsynaptic Epi sensitive Epinephrine ++ Nadolol Skeletal muscle, Renal *Reduces diastolic blood flow Norepinephrine Labetalol NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC *Relaxation of bronchial and vascular ++ (Increase airway smooth muscle Ephedrine ++ constriction) *Renal vessel relaxation Dopamine + Dobutamine + Terbutaline Dopa 1 Blood vessels: renal, *Dilates blood vessels Fenoldopam +++ Haloperidol coronary, mesenteric * Increased RBF, glomerular filtration, Dopamine +++ Droperidol NOT FOR SALE ORDISTRIBUTION © Jones &Bartlett Learning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC diuresis Dopexamine ++ Phenothiazine NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC Metoclopromide + Dopa 2 Renal & mesenteric vessels, *Modulates transmitter release – inhibits Dopexamine Domperidone

Sympathetic nerves by NEGATIVE FEEDBACK LOOP — decrease ++++

24/10/16 11:04 PM Dopamine +++ NE release & SNS outflow NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC

NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC

NOT FORSALE ORDISTRIBUTION © Jones& BartlettLearning,LLC © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 157 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION the Blood:Gas (B:G) coefficient, the greater the anesthetic solubility—the drug more easily leaves the alveoli and goes out to blood (pulmonary circulation) causing the alveolar partial pressure to rise more slowly and leading to a prolonged induction and emergence. © Jones & Bartlett Learning, LLC • Insoluble agents are taken© upJones by blood &less Bartlett avidly than a Learning, LLC soluble agent—the alveolar partial pressure rises more NOT FOR SALE OR DISTRIBUTION quickly and induction andNOT emergence FOR are SALE faster. OR DISTRIBUTION • What speeds induction: less solubility of inspired gas, increased concentration of volatile agent, high flows, increased minute ventilation, decreased cardiac output (the faster the rate of rise of alveolar concentration). • What slows induction: greater the solubility of inspired © Jones & Bartlettgas, increased Learning, cardiac output (slows LLC the rate of rise of © Jones & Bartlett Learning, LLC NOT FOR SALEalveolar ORconcentration). DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Fast Induction------Slow Induction Desflurane > Nitrous Oxide > Sevoflurane > Isoflurane > Enflurane > Halothane Decreased Solubility------Greater Solubility

© Jones & Bartlett Learning,Inhaled LLCAnesthetics © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONInhaled anesthetic agent: nitrous oxide NOT FOR SALE OR DISTRIBUTION Inhaled halogenated agents: desflurane, halothane, isoflurane, enflurane, and sevoflurane • produce immobility via actions on the spinal cord, enhance inhibitory channels, and attenuate excitatory channels (GABA, NMDA, glycine, acetylcholine, © Jones & Bartlett Learning, LLC serotonin); supraspinal ©mechanisms Jones produce & Bartlett sedation, Learning, LLC hypnosis, and amnesia. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Metabolism of Volatiles: ventilation is most important factor in elimination of all inhaled anesthetics though small amounts of metabolism occur via the kidneys and the cytochrome P-450 system in the liver. Inducing

enzyme systems in the liver are not associated with Pharm © Jones & increasedBartlett metabolism Learning, of volatile LLC anesthetics. © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 157 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 158 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-2 Volatile Chart HIESDN Odor — + — — ++ — © Jones & Bartlett Learning, LLC MAC in O2 ©0.75 Jones1.17 1.63 &1.8 Bartlett 6.6 104 Learning, LLC NOT FOR SALE OR DISTRIBUTION MAC w 70% N2O NOT0.29 0.56 FOR0.57 SALE0.66 2.4 OR — DISTRIBUTION MAC > 65 yrs old 0.64 1.0 1.55 1.45 5.17 — Oil:Gas Potency 224 91 97 47 19 1.4 Coefficient Blood:Gas Solubility 2.5 1.46 1.9 0.65 0.42 0.46 Coefficient © Jones & BartlettVapor Pressure Learning,VP 243 LLC238 172 157 669 38,770 © Jones & Bartlett Learning, LLC NOT FOR SALE@ 20°C OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION -Directly propor- tional to temp Vapor Pressure / VP/760 32 31 23 21 88 51.0 total ambient pressure © Jones & Bartlett Learning,Metabolism LLC Metab % 20 0.2 2–3 2–5 ©0.02 Jones0.004 & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION(kidneys, liver) NOT FOR SALE OR DISTRIBUTION

H: halothane I: isoflurane E: enflurane S: sevoflurane D: desflurane N: nitrous oxide Measures of Anesthetic Potency: Minimum Alveolar Concentration (MAC) MAC mirrors the brain partial pressure of an agent and is © Jones & Bartlett Learning, LLC an indicator of gas potency.© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION MAC—1 MAC is the end-expiratoryNOT FOR concentration SALE at OR DISTRIBUTION which 50% of patients will not show a motor response

to surgical incision (ED50).

MAC awake—volatile: 0.3–0.5; N2O: 0.6 MAC 95%—1.3 Pharm MAC BAR (Block Autonomic Response to noxious © Jones & Bartlettstimuli)— 1.5Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 158 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 159 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Note: MAC need is highest in 6-month-old child.

N2O and Diffusion Hypoxia: nitrous oxide is eliminated more rapidly than O2 and CO2—this results in the dilution of O2 and CO2 as N2O is escaping, resulting in © Jones & Bartlett Learning, LLC hypoxia. Give 100% O2 ©for Jones5 minutes after& Bartlett N2O is dis- Learning, LLC continued to prevent diffusion hypoxia. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ 5.3 Sedation, Anxiolytic, Amnestic Benzodiazepines (BZD): produce effects by stimulating receptors in CNS enhancing inhibitory effects of GABA (gamma aminobutyric acid).

© Jones & Pro:Bartlett decrease CBF/ICP/OLearning,2 consumption, LLC potent antegrade © Jones & Bartlett Learning, LLC amnesia, good preoperative anxiolytic, increases sei- NOT FOR SALEzure threshold—anticonvulsant, OR DISTRIBUTION unconsciousness at NOT FOR SALE OR DISTRIBUTION

TABLE 5-3 Influence on MAC Factors That Increase MAC Factors That Decrease MAC © Jones & Bartlett Learning,Hyperthermia LLC Hypothermia (MAC decreases 7%© forJones each & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION(> 42 degrees C) degree decrease in Celsius temperature)NOT FOR SALE OR DISTRIBUTION Hypernatremia Hypotension Incr. levels of CNS excitatory Hypercarbia transmitters i.e. (cocaine, CNS depressants; drugs that decrease amphetamines) - drug central catecholamines that increases central Anemia (Hgb < 5 g/dL) © Jones & Bartlett Learning, LLC catecholamines, i.e., Acute© Jonesalcohol intoxication & Bartlett Learning, LLC MAO inhibitors; Elderly (after age 40 yo, MAC decreases NOT FOR SALE OR DISTRIBUTION chronic alcohol abuse 6%/decadeNOT ofFOR age) SALE OR DISTRIBUTION Red hair, esp. females Pregnancy

Infant Hypoxia (PaO2 less than 40 mmHg) High cardiac output Hypotension

Benzodiazepines, clonidine, narcotics, Pharm © Jones & Bartlett Learning,lithium, ketamine,LLC lidocaine © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 159 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 160 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION s1. ↓ 0 0 0 0 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Desflurane Nitrous yes yes Sevoflurane ↑ ↑ ↑ no no no 0 ↓ ↓ ↑ or sl. © Jones & Bartlett Learning, LLC ↑ sl. © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ↑ ↑ ↑ ↑ 1% 0 3% ↑↑ yes ↑ ↑ ↓↓ ↓ ↓ ↓↓ sl. ↓sl. ↓↓ ↓ ↓ © Jones & Bartlett Learning, LLC © Jonesyes! & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Halothane Isoflurane Enflurane ↑↑ ↑↑ ↑ ↓↓ ↓↓↓ ↓ ↓↓ ↓↓↓ ↓ or ↑ ↓↓ ↓ ↓↓↓ ↓ ↓↓ ↓↓ ↓↓↓ ↓↓↓ ↓ ↓↓ 0 ↓ ↑ ↑ 0 ↓↓ yes ↓ ↓ ↓↓ ↓ ↓ ↓

Pharm TABLE 5-4 Cerebral (CBF) blood flow Cerebral Intracranial pressure (ICP) pressure Intracranial Cerebral metabolic rate (CMR) metabolic rate Cerebral Seizures or EEG changesSeizures no no Cardiovascular depression Contractility—myocardial BP HR SVR CO Coronary vasodilator Coronary © Jones & Bartlett Learning, LLC Respiratory volume Tidal © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 160 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 161 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 0 no © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION sl. ↓sl. ↓ potent no - © Jones & Bartlett Learning, LLC ↓sl. ↓ ↓ © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ↑↑ ↑↑ ↑↑ ↑ ↑↑ ↑↑ ↑ ↑↑ ↑ ↑ ↑ blunts blunts blunts - blunts blunts! yes yes yes potentiates potentiates! potentiates! potentiates potentiates! ↑ sl. relaxes relaxes relaxes relaxes varied 0 ↓ ↓ ↓↓ ↓ ↓ ↓↓ ↓ ↓ ↓ ↓↓ ↓ ↓ ↓ 0 0 0 0 0 mild yes yes yes yes yes

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 2 Pharm Respiratory rate Apneic threshold Apneic PaCO Bronchodilator Pulmonary resistance vascular 0 0 0 0 0 increase NEUROMUSCULAR NDMRelaxant Skeletal muscle Skeletal Renal Blood flow GFR Urinary output Analgesia Malignant hyperthermiaMalignant trigger © Jones & Bartlett Learning, LLC “-“=not known “0”=no change; © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 161 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Stage I Sedation stage - Respiratory: regular/voluntary getting sleepy. Will Muscle tone: normal respond to verbal Eye movement: normal stimuli. Tolerates Pupil size: normal © Jones & Bartlett Learning, LLC pain. ©Eye and Jones larynx reflexes: & Bartlettnormal Learning, LLC NOT FOR SALE OR DISTRIBUTION NOTnormal FOR SALE OR DISTRIBUTION Stage II Delirium Respiratory: irregular/ stage - want to spontaneous get through this Muscle tone: tense stage - patient can Eye movement: dysconjugate get agitated and Pupil size: dilated/gets bigger can hurt self or Eye and larynx reflexes: disconjugate dilated © Jones & Bartlettothers. Learning,tearing, swallowing, LLC © Jones & Bartlett Learning, LLC Loss of LARYNGOSPASM NOT FOR SALE ORconsciousness. DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Stage III Anesthesia Respiratory: regular/deep stage - Muscle tone: Ø desired depth for Eye movement: Ø general anesthesia. Pupil size: constricted/ “loss of lash” convergent constricted © Jones & Bartlett Learning, LLC Eye and larynx reflexes: Ø © Jones & Bartlett Learning, LLC Stage IV Overdose - Respiratory: apnea NOT FOR SALE OR DISTRIBUTIONdecrease Muscle tone: flaccid NOT FOR SALE OR DISTRIBUTION volatile agent Eye movement: Ø dose. Pupil size: fixed/dilated Eye and larynx reflexes: Ø fixed/dilated

higher doses. Wide therapeutic index with a low inci- © Jones & Bartlett Learning, LLC dence of toxicity. Not© analgesics. Jones & Bartlett Learning, LLC Con: no burst suppression, some circulatory depression NOT FOR SALE OR DISTRIBUTION and hypotension—canNOT cause significantFOR SALE hypotension OR DISTRIBUTION if patient hypovolemic, depresses ventilatory response

to CO2, small doses may cause apnea/respiratory arrest, produces upper airway reflex depression, nonanalgesic,

Pharm no muscle relaxation. © Jones & BartlettReversal: Flumazenil Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 162 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 0.075 mg/kg - shorter 1–3 min / USDOA than midazolam to metabolized rapidly by an inactive metabolite (organ tissue esterases independent) Remimazolam

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC PO: 0.5–1 mg IV 0.1 Max 4 mg/dose mg/kg, hrs IV 1–3 mins / 6-8 hrs LDOA inactive to Glucuronide metabolites NOT FOR SALE OR (Ativan) Lorazepam DISTRIBUTION NOT FOR SALE OR DISTRIBUTION (Versed)

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC IV: 0.1–0.2 mg/kg or 0.1–0.2 mg/kg IV: a time 1–3 mg at titrated hydroxylation; liver active metabolite. in urine. Excreted NOT FOR SALE OR DISTRIBUTION Midazolam NOT FOR SALE OR DISTRIBUTION e activ IM or IV: 2 to 5 mg or 2 to IM or IV: 10 mg × one dose to 1–2 mins / 20 hrs LDOA 0.5–2 min / 1–4 hrs PO 30–60 mins / 10-20 microsomal hepatic enzymes 2 to metabolites: desmethyldiazepam both and oxazepam with LDOA © Jones & Bartlett Learning, LLC (Valium) Diazepam © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Benzodiazepines

Pharm TABLE 5-6 © Jones & Bartlett Learning,Dose Onset / Elim ½-life LLCMetabolism Excretion © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 163 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

ance ance alpha

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Combines properties of Combines and midazolam remifentanil trials; In Phase III clinical procedural for developed anes- sedation & general on GABA thesia. Works flumazenil. Higher clear flumazenil. of distri- and smaller volume bution than midazolam. receptor; can be reversed with be reversed can receptor; Remimazolam

© Jones & Bartlett Learning, LLCt as diazepam. © Jones & Bartlett Learning, LLC ticonvulsant. ticonvulsant. Strong amnestic, amnestic, Strong An excessive have Can 5–10× as sedation. poten NOT FOR SALE OR DISTRIBUTION (Ativan) Lorazepam NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Water-soluble; does Water-soluble; not cause pain on injection. 2–3× as as diazepam. potent respiratory have Can depression. NOT FOR SALE OR DISTRIBUTION (Versed) Midazolam NOT FOR SALE OR DISTRIBUTION Burns on injection with mixed because it’s glycol propylene © Jones & Bartlett Learning, LLC (Valium) Diazepam © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Pharm Benzodiazepines, continued Benzodiazepines, © Jones & Bartlett Learning,Notes LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 164 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 165 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-7 Sedation–Other Droperidol Methohexital (Inapsine) (Brevital) © Jones & Bartlett Learning, LLC Action Dopamine© JonesBarbiturate & Bartlett Learning, LLC antagonist NOT FOR SALE OR DISTRIBUTION Dose 0.6–2.5 mgNOT FOR2 mg/kg dosesSALE to effect; OR DISTRIBUTION Sedation up induction: 50–120 mg, to 10 mg 20–40 mg q4–7 mins Rectal suppository: Onset / Duration 3 mins / 2–4 hrs – IV: immediate; rectal: 5–11 © Jones & Bartlett Learning,sedation up to LLCmins / USDOA 5–10 mins © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION12 hours NOT FOR SALE OR DISTRIBUTION Metabolism Liver and kidney Liver, kidney, brain Excretion Contraindicated Parkinsonism, Acute intermittent pheochromocytoma, porphyria (AIP), asthma, head Injury, long QT CV instability; caution with © Jones & Bartlett Learning, LLC on EKG. Give liver impairment.© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONcautiously in NOT FOR SALE OR DISTRIBUTION patients with liver or kidney disease. Notes Elongates QT with Amnestic; 2–3× more possible torsade de potent with faster onset and pointes, use as seda- recovery time as pentothal. © Jones & Bartlett Learning, LLC tive, neuroleptic,© Jones See excitatory & Bartlett phenomenon. Learning, LLC antiemetic. Not Can cause hypotension, NOT FOR SALE OR DISTRIBUTION amnestic. NOT FORseizures, vascularSALE collapse. OR DISTRIBUTION Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 165 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Higher affinity for alpha2 than clonidine; dose receptors effect- sympatholytic dependent bradycardia, cause hypotension, cardio-depression; respiratory discontinuation Abrupt sparing. infusions can cause of prolonged hypertension. dose in Decrease disease. or hepatic renal © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC

NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ↔ Liver almost Liver bio- complete via transformation glucuronidation and Cytochrome P450 in urine and Excrete feces. range: 0.2–0.7 mcg/kg/hr Maintenance (#1) = (#5) × ______kg 0.4 mcg/kg 4 mcg/ml = ml/hr ______mcg (#6) + by or 0.4 at run × 0.1 = ______ml/hr to in kg weight mcg/kg/hr Metabolism / Excretion Notes or nd

NOT FOR SALE OR DISTRIBUTIONt NOT FOR SALE OR DISTRIBUTION degree heart degree block. rd 7 min onset; elim half- 2–3 hr. life Do not give if Do not give patien hypotensiv 3 Contraindication / Contraindication / Onset-DOA

NOT FOR SALE OR DISTRIBUTION IM, IV, nasal, Oral, Oral: rectal routes. 2.6–4 mcg/kg 30–60 mins preop IN: 1–2 mcg/ NOT 1 mcg/ Load: kg 10 mins; over kg maintenance: FOR0.2–0.7 mcg/kg/hr. SALE OR DISTRIBUTION Pharm + sedation worksheet Dexmedetomidine 10 minutes over dose: 1 mcg/kg Loading + analgesia 1 mcg/kg: give to formula Example: =______(#2) ______(#1) × 1 mcg/kg in kg Pt weight + hypnotic______mcg (#2) ÷ 4 mcg/ mL = ______(#3) ______mL (#3) × 6 ______ml/hour (#4) #3 limit at #4 with volume at Set IV pump rate + anxiolysis amnesia not predictable © Jones & BartlettDrug Dexmedetomi- dine (Precedex) Learning, Dose LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 166 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 167 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION A tiva- Reduces Reduces © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT DO Prolongs FOR SALE OR DISTRIBUTION secretion by ac by secretion ering. ering. with local anesthetic in intrathe- block.cal or epidural Stimulates gastric acid Used to decrease blood pressure, blood pressure, decrease to Used and SVR; negative heart rate, effects. Decreases chronotropic anesthetic requirements. shiv postop tion of histamine 2 receptors. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC y

NOT FOR SALE OR DISTRIBUTION eted NOT FOR SALE OR DISTRIBUTION Excr eces eces Liver via Liver Cytochrome P450. unchanged b 20% in kidney; f

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Can exacerbate exacerbate Can & bradyarrhythmias need dose hypotension; with renal adjustment Caution impairment. with CAD, in patients PO Onset or CVA. PVD, 45 mins; IV Half-life 9–12 hr

NOT FOR SALE OR DISTRIBUTION 5mcg/ Premed: Oral 0.1 mg/hr kg BP controlled, until Trans- max 6 mg. NOTdermal 0.1–0.3 Intrathecal mg/day 150–450 mcg FOR 30 mcg/hr, Epidural max 40 mcg/hr SALE OR DISTRIBUTION Pharm © Jones & Bartlett Learning,Clonidine (Catapres) LLC + sedation + analgesia + hypnotic© + anxiolysis Jones no amnesia & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 167 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Barbiturate; acts on Barbiturate; activiating reticular system infusion IV 4 mg/kg; incr ICP: for 1.5–3.5 mg/kg Acute can precipitate Porphyria Intermittent asthma, COPD, (AIP); shock, hypotension Pentothal Pentothal (Thiopental)

NOT FOR SALE OR Etomidate (Amidate) DISTRIBUTION affinity Increased GABA receptor; for hypnotic IV bolus 0.3 mg/kg only disorder; seizure in pts with avoid porphyria. NOT FOR SALE OR DISTRIBUTION Increased affinity Increased GABA receptor; for hypnotic IV/IM 2 mg/kg infusion: 100–250 mcg/kg/min 30 secs3–10 mins shock hypotension, 30–60 sec EF < 50% states, 3–7 mins 30 secs 10–25 mins © Jones & Bartlett Learning, LLC Propofol (Diprivan) © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ts © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Ketamine (Ketolar) NOT FOR SALE OR DISTRIBUTION General Antagonist; NMDA Sedation, Anesthetic, Hallucinogenic NOTIV 1 mg/kg infusion: 0.1–0.5 IM 10 mg/kg mg/kg/hr FORIV 1 min IM 3–4 mins 12–25 mins SALE surgery, neuro ICP, increased heart disease, hypertension, aneurysms, an- ORgina, hyperthyroid DISTRIBUTION Induction Agen

Pharm TABLE 5-8 © Jones & BartlettInduction drugs Learning,Class Dose LLCOnset Duration Contraindicated © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 168 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © te when Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION redistributed Highly liophilic and can alkaline, precipita injected in acidic fluid no yes yes

NOT FOR SALE enzymes microsomal OR plama in liver; esterases DISTRIBUTION hemodynamically For unstable patients. no no no NOT FOR SALE OR DISTRIBUTION tes, tes, onide creted creted urine © Jones & Bartlett Learning, phase II LLC glucur conjuga ex CBF, CO, ↓ MAP, children CPP; ICP, higher dose require volume incr. due to of disribution and (opposite clearance elderly). for no ©yes Jonesno & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

NOT FOR SALE OR DISTRIBUTION CYP450; phase I demethylation to metabolite as norketamine-1/4 as potent ketamine when shock states For must depression cardiovascular NOT anticho- preop give be avoided; for (glycopyrrolate) linergic give antisialogogue; FOR help with to benzodiazepines effects. psychomimetic SALEye yes no OR DISTRIBUTION Pharm © Jones & BartlettMetabolism Learning,Notes LLC Anlalgesia Amnesia Histamine © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 169 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

soldilates; soldilates; sms , negative

NOT FOR SALE OR DISTRIBUTION NOT FORdiopulmonary SALE OR DISTRIBUTION Anticonvulsant; used Anticonvulsant; CMRO2 decrease to CPP main- and ICP, protec- brain tained, burst tion, and for suppression. analgesia. No + histamine; car depressant laryngospa inotrope, inotrope, cause can bronchospasm. Pentothal (Thiopental) elerates elerates acc © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC

NOT FOR SALE Etomidate (Amidate) OR or myocardial Least pulmonary depres- DISTRIBUTION inductionsion of any agent; good for unstable patients. analgesia. pain on No IV injection; myoclo- adrenocortical nus; increased suppresion; nausea and incidence vomiting; / can foci seizure seizure lower threshold. NOT FOR SALE OR DISTRIBUTION - tor;

eases - intraocu Antiemetic; bronchodila quick recovery; anticonvulsant; antipruritic, decr lar pressure. analgesia. Pain No on IV injection; (apnea) respiratory de & myocardial (negative pression SVR; decr. inotrope), in reativity cross patients with egg supportsallergy; bacterial growth. © Jones & Bartlett Learning, Propofol (Diprivan) LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION essure; essure;

/ intraocular pr / intraocular

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC - If pt catechol airway secretions. Ketamine Ketamine (Ketolar) increased CO/HR- negative effect on negative CO/HR- increased oxygen-demand ratio; myocardial ↑ NOT FOR SALE OR DISTRIBUTION patient; Good with uncooperative airway reflexes- preserve helps to minimally bronchodilator; potent cardiorespiratory depresses SNS-increases Stimulates system. NOT and heartBP rate. fom thalamus Dissociates FOR –> dysphoria and cerebrum ICP /hallucinations; increases cerebral and blood flow cerebral SALEmetabolism OR cause can ketamine amine depleted, depression. myocardial DISTRIBUTION Pharm Induction Agents, continued Induction Agents, © Jones & BartlettInduction drugs Pro Learning, LLCCon © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 170 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 171 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ 5.6 Total Intravenous Anesthetic (TIVA) No volatile (inhaled) anesthetics used. For a TIVA anesthetic, an IV-loading dose of the induction agent is given and a continuous infusion started immediately to © Jones & Bartlett Learning, LLC maintain the desired plasma© Jonesdrug concentration—it & Bartlett must Learning, LLC be reached quickly and maintained. A combination of IV NOT FOR SALE OR DISTRIBUTION infusions is required to provideNOT complete FOR anesthesia.SALE ORA DISTRIBUTION continuous infusion(s) requires less dose of each drug, creating synergy with less toxicity. TIVA achieves all 3 requirements for general anesthetic: • Amnesia • Analgesia © Jones & • BartlettAutonomic arLearning,eflexia LLC © Jones & Bartlett Learning, LLC NOT FOR SALE** TIVA does OR not allowDISTRIBUTION for muscle relaxation. NOT FOR SALE OR DISTRIBUTION TIVA Medications • Preoperative sedation recommended: Midazolam 1–5 mg IV • Propofol is often the hypnotic drug of choice in TIVA. © Jones & Bartlett Learning,If using LLCpropofol, a narcotic infusion must be© added. Jones & Bartlett Learning, LLC Propofol produces unconsciousness and amnesia but NOT FOR SALE OR DISTRIBUTIONdoes not possess analgesia properties. NOT FOR SALE OR DISTRIBUTION • Common Maintenance: propofol-opioid synergy. ▪▪ Propofol: bolus: 0.25–1.5 mg/kg ▪▪ Infusion: 100–200 mcg/kg/min ▪▪ Stop infusion 5–8 minutes before extubation with. . . © Jones & Bartlett Learning, LLC ▪▪ Remifentanil drip or © Jones & Bartlett Learning, LLC ▪▪ Fentanyl drip NOT FOR SALE OR DISTRIBUTION • Other induction drugs thaNOTt can beFOR used include:SALE OR DISTRIBUTION ketamine, etomidate, and methohexital. TIVA is associated with better hemodynamic stability, earlier recovery, and less postoperative nausea and vomiting. Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 171 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 172 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ 5.7 Narcotic Opioids Analgesia produced by opioid receptor agonism in the brain (periaqueductal gray matter) and spinal cord (substantia gelatinosa); reduces MAC of volatile © Jones & Bartlett Learning, LLC anesthetics. © Jones & Bartlett Learning, LLC Characteristics common to all opioids: NOT FOR SALE OR DISTRIBUTION • Dose dependent ventilatoryNOT depression: FOR SALE decreased OR RR DISTRIBUTION with increased VT; decreased response to increased carbon dioxide. • Causes sedation but not unconsciousness in normal doses; primary effect is analgesia. • May stimulate chemoreceptor trigger zone. © Jones & Bartlett• Spasm of sphincter Learning, of Oddi inLLC biliary tract: morphine © Jones & Bartlett Learning, LLC NOT FOR SALEmore thanOR other DISTRIBUTION opioids, meperidine the least. NOT FOR SALE OR DISTRIBUTION Treat spasm with glucagon, atropine, narcan, or nitroglycerin. • Increases ICP in head trauma patient. Reversal: naloxone (Narcan) Listed in order of potency: Sufentanil (750) > Remifentanil (250) > Fentanyl (100) > Alfentanil (10) > © Jones & Bartlett Learning,Hydromorphone LLC (7) > Morphine (1) = Methadone© Jones (1) > & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONMeperidine (0.1) NOT FOR SALE OR DISTRIBUTION Volume of Distribution: a drug with a smaller volume of distribution has a quicker onset and shorter duration of action. Larger to smaller: Meperidine > Fentanyl > Sufentanil > Morphine > © Jones & Bartlett Learning, LLC Alfentanil© >Jones Remifentanil & Bartlett Learning, LLC Opioid drugs mimic endogenous opioids: dynor- NOT FOR SALE OR DISTRIBUTION phins, enkephalins, endorphins,NOT FOR endomorphins, SALE and OR DISTRIBUTION nociceptin; receptors found distributed widely in the brain but are also found in the spinal cord and diges- tive tract. Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 172 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION IV Loading: 25-100 mcg/kg; 25-100 mcg/kg; IV Loading: min Infusion: 0.5-2 mcg/kg opioids) SDOA <10 min SDOA Hepatic metabolism; metab Hepatic inactive noralfentanil to (Alfenta) Alfentanil

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Give IV to Blunt DL: Blunt IV to Give 25–50 mcg 3 min before induction. 1–5 mcg/kg; General: 50–100 mcg/ Cardiac: Infusion: 2–10 mcg/ kg : 0.5–1.5 Postop kg/min IV mcg/kg onsetImmediate onset of all 1 min (fastest 30–60 min Hepatic metabolism; Hepatic inactive norfen-metab to Renal excretion tany. (Sublimzte) Fentanyl

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Mix 1 mg:20 mL for 50 Mix 1 mg:20 mL for 1 mcg/ mcg/mL Load: Infusion: 0.1–1.0 kg; Postop: mcg/kg/min; 0.025–0.3 mcg/kg/min 1–3 min USDOA 3–8 min, plasma USDOA decr 50% in 40 secs level Hydrolyzed by by Hydrolyzed erythrocyte & tissue nonspecific esterases NOT FOR SALE OR DISTRIBUTION (Ultiva) Remifentanil NOT FOR SALE OR DISTRIBUTION elated to dose to elated (Sufenta) tanil © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Sedation: Sedation: 0.25–2 mcg/kg 8–10 mcg/kg General: 10–30 meg/ Cardiac: Infusion: kg 0.5–1.5 mcg/kg/hr 1–3 min 20–40 min- SDOA duration r duration Hepatic metabolism; Hepatic blood crosses rapidly barrier brain NOT FOR SALE OR DISTRIBUTION Sufen NOT FOR SALE OR DISTRIBUTION Sufentanil–Alfentanil

/ Opioid

Pharm TABLE 5-9 Narcotic Dose Onset Duration © Jones & Bartlett Learning, LLC Metabolism Excretion © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 173 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC cardia, cardia, increased NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Causes profound profound Causes brady nausea and vomiting, Onset 4x muscle rigidity. than but 1/3 DOA faster potent 10x more fentanyl; than morphine. use as bolus for Good to brief; stimulation, intense head pinning, i.e., block Retrobulbar (Alfenta) Alfentanil , rigidity

© Jones & Bartlett Learning,, muscle LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION bradycardia. Releases bradycardia. histamine. Minimal Lipid soluble. Good to CV depression. with stimulation blunt laryngoscopy and incision Highly addictive 80x more potent than potent 80x more causesmorphine; &nausea vomiting (Sublimzte) Fentanyl

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Similar potency to use as Good to fentanyl. intense brief, bolus for head i.e., stimulations, retrobulbar pinning, block NOT FOR SALE OR DISTRIBUTION (Ultiva) Remifentanil NOT FOR SALE OR DISTRIBUTION (Sufenta) tanil © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Most potent opioid – Most potent potent 1000x more than morphine with depression. less resp muscle rigidity, Causes bradycardia, ICP incr. hypotension, NOT FOR SALE OR DISTRIBUTION Sufen NOT FOR SALE OR DISTRIBUTION / Opioid

Pharm Sufentanil–Alfentanil, continued Sufentanil–Alfentanil, © Jones & Bartlett Learning,Narcotic Notes LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 174 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Postop: IV/IM 25–100 mg Postop: 12.5–50 mg IV Shivering: 2–4 hr — active 90% liver — neurotoxic metabolite lowers - Normeperidine threshold. seizure Renally excreted Meperidine (Demerol)

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Single dose 20 mg, Single dose 20 mg, RR of 8, or for titrate 5 mg every 30– 40min post-op 1–24 min4–6 hrs 1–5 min IM 10 mins inactive form; to Liver in bile and cleared urine NOT FOR SALE Methadone OR(Dolophine) DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Morphine IV; Infusion: 0.1 mg/kg IV; 5–10 min peak time ~ 4–5 hr slow LDOA analgesia prolonged 90 mins, period postop into to glucuronidation Hepatic – active metabolites (6 morphine 3 & 6 glucuronide is active analgesic), excreted renally

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC IV 0.01–0.02 mg/kg 1–30 mg or 0.03–0.15 mg/kg 1.5 min 4–5 hr; peak effect in 20 mins with 2 active Liver can ac- metabolites; with renal cumulate failure NOT FOR SALE OR DISTRIBUTION Hydromorphone (Dilaudid) NOT FOR SALE OR DISTRIBUTION Dilaudid–Demerol

Pharm © Jones & Bartlett TABLE 5-10 Learning,Dose Onset LLCDuration Metabolism Excretion © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 175 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION + histamine - struc inhibitors; MAO Avoid atropine- to related turally 1/10th causes tachycardia. potency of morphine. Chemically incompatible be Can with barbiturates. post-op shiv treat used to Only opioid with localering. anesthetic properties Meperidine (Demerol) -

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC + histamine long- acting mu agonist. receptor NMDA proper antagonist be helpful May ties. with neuropathic used pain. Primarily of in the prevention opioid withdrawal and tx of symptoms pain chronic NOT FOR SALE ORMethadone DISTRIBUTION(Dolophine) NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Morphine + histamine don’t give with give + histamine don’t Stimulates asthma patient. depresses nausea & vomiting; Bradycardia. ventilation. soluble Water

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC - histamine Nausea & vomiting, 5–10x as potent Good as morphine. PCA for pump drug postoperatively. in Better tolerated than patients renal morphine NOT FOR SALE OR DISTRIBUTION Hydromorphone (Dilaudid) NOT FOR SALE OR DISTRIBUTION Pharm Dilaudid–Demerol, continued Dilaudid–Demerol, © Jones & Bartlett Learning,Notes LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 176 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 177 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-11 Opioid Receptors Opioid Effect Agonist Antagonist Receptor Mu-1 Analgesia: supraspinal/ morphine Naloxone © Jones & Bartlett Learning, LLC spinal © Jonesmeperidine & BartlettNalbuphine Learning, LLC NOT FOR SALE OR DISTRIBUTION Euphoria NOThydro FOR- SALE(partial OR DISTRIBUTION Low abuse potential morphone antagonist) Miosis, bradycardia, methadone Buprenorphine hypothermia, urinary fentanyl (partial retention; slow GI peri- sufentanil antagonist) stalsis; pruritus, skeletal © Jones & Bartlettmuscle Learning, rigidity LLC © Jones & Bartlett Learning, LLC Mu-2 Analgesia: primarily morphine Naloxone NOT FOR SALE ORspinal DISTRIBUTIONfentanyl NOT FOR SALE OR DISTRIBUTION Respiratory depression Physical dependence Marked constipation; bradycardia Kappa Spinal analgesia ketamine Naloxone © Jones & Bartlett Learning, LLCDysphoria, sedation Low morphine © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONabuse potential fentanyl NOT FOR SALE OR DISTRIBUTION Anticonvulsant effects; neuroprotection Miosis Delta Analgesia: supraspinal / fentanyl Naloxone mostly spinal © Jones & Bartlett Learning, LLC Antidepressant effects© Jones & Bartlett Learning, LLC Depression of ventilation NOT FOR SALE OR DISTRIBUTION Physical dependenceNOT FOR SALE OR DISTRIBUTION Epileptogenic Constipation minimal Sigma A nonopioid receptor. Ketamine Progesterone

Dysphoria, hallucinations, Haloperidol Pharm © Jones & Bartlettrespiratory Learning, stimulation LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 177 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 178 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ 5.8 Nonopioid Analgesics Multimodal Approach (Preemptive Analgesia) Multimodal approach—to minimize use of opioids. All of these agents have a ceiling effect in analgesia, and all © Jones & Bartlett Learning, LLC have potential for serious© adverse Jones effects. & Bartlett Learning, LLC Include: nonsteroidal anti-inflammatory drugs NOT FOR SALE OR DISTRIBUTION (NSAIDs—COX inhibitors),NOT acetaminophen, FOR SALE Pregabalin/ OR DISTRIBUTION gabapentin, ketamine, alpha 2 agonists, corticosteroids, and local anesthetics. NSAIDS—Cyclooxygenase (COX) Inhibitors Anti-inflammatory, analgesic, antipyretic. © Jones & BartlettProstaglandins Learning, are produced LLC by an enzyme in © Jones & Bartlett Learning, LLC the cyclooxygenase pathway; they are a family of NOT FOR SALEhormone-like OR substancesDISTRIBUTION that participate in a wide range NOT FOR SALE OR DISTRIBUTION of body functions: they promote inflammation needed in healing, fever, pain, support the blood clotting function of platelets, vasodilate and vasoconstrict, and protect the lining of the gastrointestinal tract. There are two COX enzymes: COX-1 and COX-2, which both produce © Jones & Bartlett Learning,prostaglandins. LLC COX-1 specifically supports platelet© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONfunction and protects the stomach. COX inhibitorsNOT work FOR SALE OR DISTRIBUTION through inhibition of the production of prostaglandins. All NSAIDs share the same significant adverse effects, though with differing frequency. These include effects in the following systems: • Gastrointestinal: anorexia, nausea, pain, gastritis, © Jones & Bartlett Learning, LLC ulcers, bleeding, and perforation.© Jones GI complications& Bartlett can Learning, LLC often be offset by also taking a proton pump inhibitor: NOT FOR SALE OR DISTRIBUTION esomeprazole (Nexium),NOT lansoprazole FOR (Prevacid),SALE OR DISTRIBUTION omeprazole (Prilosec), pantoprazole (Protonix), or rabeprazole (Aciphex). These problems tend to emerge only after long-term or heavy use. • Cardiovascular: including hypertension, myocardial Pharm infarction, stroke, and other thromboembolic events. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

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© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 179 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION • Renal: sodium and water retention, decreased GFR, and renal failure (especially worrisome in patients with CHF, CRF, cirrhosis, HTN, or hypovolemia); kidney failure can occur; though it occurs rarely. • Central nervous system: headache, dizziness, confusion, © Jones & Bartlett Learning, LLC depression, reduced seizure© Jones threshold. & Bartlett Learning, LLC • Platelets: aspirin causes an irreversible inhibition of NOT FOR SALE OR DISTRIBUTION platelet aggregation. PlateletNOT inhibition FOR lastsSALE 1 week OR (life DISTRIBUTION of exposed platelets) COX-2 is the enzyme produced in acute inflammation. COX-2 inhibitors were developed to relieve the pain but without all the gastrointestinal side effects. Only one COX-2 inhibitor, celecoxib (Celebrex), is still on the market. © Jones & OtherBartlett NSAID-type Learning, examples include: LLC © Jones & Bartlett Learning, LLC NOT FOR SALE• Aspirin (acORetylsalicylic DISTRIBUTION acid) NOT FOR SALE OR DISTRIBUTION • Celecoxib 400 mg—contraindicated with Sulfa allergy. • Ketorolac 30–60 mg IV; don’t give greater than 5 days Acetaminophen: acetaminophen eases pain and fever but does not affect inflammation. Excessive doses can cause serious, even fatal hepatic injury; reduced dose needed in © Jones & Bartlett Learning,renal impairment. LLC © Jones & Bartlett Learning, LLC ▪▪ PO max dose 4g/day (if < 50 kg—75 mg/kg/day); max NOT FOR SALE OR DISTRIBUTIONsafe dose: 3–4 grams per day, < 3 g/day forNOT elderly orFOR SALE OR DISTRIBUTION hepatic impairment. ▪▪ IV (Ofirmev) 1 gram over 15 mins Anti-neuropathic/GABA Analog/Anticonvulsant Used to treat certain types of nerve pain. Caution in © Jones & Bartlett Learning, LLC patients with renal impairment© Jones (Creatinine & >Bartlett 1.5) or Learning, LLC history of angioedema. NOT FOR SALE OR DISTRIBUTION ▪▪ Pregabalin: PO: 100 NOTmg FOR SALE OR DISTRIBUTION ▪▪ Gabapentin (Neurontin): PO: 100, 300 mg, 400 mg Ketamine—see Section 5 Induction agents for more information Works as sedative. Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 179 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 180 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Alpha 2 agonists—see Section 5.4 Alpha 2 agonists Centrally sedates, anxiolytic. Also, decreases blood pressure and catecholamine levels. Analgesic, sedates, hypnotic, anxiolysis without © Jones & Bartlett Learning, LLC amnesia, activates ©histamine Jones release. & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Corticosteroids—see SectionNOT 5.17 FOR Corticosteroids SALE OR DISTRIBUTION Anti-inflammatory effect. Local Anesthetics—see Section 5.15 Local Anesthetics (LA) Relieve pain by blocking the sodium channels from within the nerves, blocking the transmission of nociceptive impulses from reaching the dorsal horn © Jones & Bartlettof the spinothalamic Learning, tract. LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ 5.9 Agonist–Antagonists (Partial Agonists) Agonist–antagonists (Partial Agonists): drugs that possess properties of both full agonists and antagonists. Partial agonists bind to the receptors with varying affinity © Jones & Bartlett Learning,and activate LLC these receptors, but not to the full© degree. Jones & Bartlett Learning, LLC Because these drugs are partial agonists, higher doses can NOT FOR SALE OR DISTRIBUTIONbe given with fewer side effects than when highNOT doses FOR of SALE OR DISTRIBUTION full-agonist opioids are given. For example, low-dose buprenorphine is more potent than morphine but with less opioid-associated side effects such as respiratory depression, itching, constipation, etc. These drugs are less prone to abuse as they cause less euphoria. © Jones & Bartlett Learning, LLC When partial agonists© are Jones given at lower & Bartlett doses, in Learning, LLC patients who are not opioid-dependent, effects are the NOT FOR SALE OR DISTRIBUTION same as if they’ve receivedNOT a full FORagonist. SALEAs doses are OR DISTRIBUTION increased, partial agonists produce increasing effects but only to a certain, maximum level even if doses continue to increase; thus, agonist–antagonists have a ceiling effect. At the highest doses, agonist–antagonists actually Pharm begin to act like partial or full antagonists—occupying © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

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© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 181 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION receptors but only partially, or not at all, activating them while preventing a full agonist from attaching to the receptor. Of the agonist–antagonists, three of the most commonly given are: © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Butorphanol (Stadol) NOT FOR SALE OR DISTRIBUTION • Receptor: agonist at kappa,NOT partial FOR agonist SALE of mu; partial OR DISTRIBUTION agonist at sigma receptor, which is responsible for psychotomimetic effects • Supplied: vial 1 mg/mL, 2 mg/mL; aerosol 10 mg/mL spray • Dose 0.01–0.04 mg/kg or 1 mg IV q 3–4 hr PRN; 1–4 mg IM Q 3–4 hr PRN. Geriatric dosing should be decreased by 50% © Jones & Bartlett▪▪ Intranasal Learning,(IN): 1 mg spray in LLC 1 nostril; may repeat © Jones & Bartlett Learning, LLC NOT FOR SALEafter 60–90OR minsDISTRIBUTION up to 2 mg total dose. NOT FOR SALE OR DISTRIBUTION ▪▪ Preop: 2 mg IM 60–90 minutes preoperatively ▪▪ Anesthesia: 2 mg IV before induction and/or 0.5–1 mg increments during anesthesia (higher dose may be required, up to 0.06 mg/kg, or 4 mg/70 kg). Total cumulative dose varies; typically ranges between © Jones & Bartlett Learning,4–12.5 LLC mg (0.06–0.18 mg/kg) © Jones & Bartlett Learning, LLC • Onset: IV < 10 mins; IM 5–10 mins; IN < 15 mins NOT FOR SALE OR DISTRIBUTION• DOA: 3 hrs IV/IM, 4–5 hrs IN NOT FOR SALE OR DISTRIBUTION • Side effects: sedation, hypotension, nausea. In patients with cardiovascular disease, butorphanol causes increases in cardiac output and pulmonary artery pressures. Can cause acute biliary spasm. • 2 mg of Stadol produces analgesia similar to 10 mg of © Jones & Bartlett Learning, LLC morphine. © Jones & Bartlett Learning, LLC • Treats postoperative shivering more effectively than NOT FOR SALE OR DISTRIBUTION meperidine NOT FOR SALE OR DISTRIBUTION • Can produce withdrawal in opioid-dependent patients

Nalbuphine (Nubain) Semi-synthetic opioid used for moderate to severe pain. Pharm Can be used as treatment for morphine-induced pruritus. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 181 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 182 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION • Receptor: agonist at kappa, partial agonist of mu and delta • Supplied: 10 mg/mL • Dose in opiate-naive patient: 0.1–0.3 mg/kg or 10 mg/ 70 kg IV/IM/SQ—up to 20mg/dose or 160 mg/day • Dose in opioid-dependent patient: administer ¼ © Jones & Bartlett Learning, LLC anticipated dose and observe© Jones for withdrawal & Bartlett symptoms. Learning, LLC NOT FOR SALE OR DISTRIBUTION • Anesthesia: NOT FOR SALE OR DISTRIBUTION ▪▪ Induction: 0.3–3 mg/kg IV over 10–15 mins ▪▪ Maintenance: 0.25–0.5 mg/kg in single IV administrations • Onset: IV onset 2–3 mins, 15 mins IM • DOA: 3–6 hrs • Dosage adjustment: decrease dose for patients at high © Jones & Bartlettrisk for respiratory Learning, depression. LLC Use with caution in © Jones & Bartlett Learning, LLC NOT FOR SALEpatients OR with DISTRIBUTION liver or renal impairment. NOT FOR SALE OR DISTRIBUTION • Side effects: sedation, vertigo, bradycardia, spasm sphincter of Oddi, hypertension, anaphylaxis • Analgesia similar to morphine. • Giving IV can reverse the respiratory depressant effects of the narcotic but sustain the analgesia © Jones & Bartlett Learning,(better LLC to use than naloxone as it does not push© Jones opioid & Bartlett Learning, LLC off the receptor) NOT FOR SALE OR DISTRIBUTION• Also used to antagonize itching from epiduralNOT and FOR SALE OR DISTRIBUTION intrathecal MSO4 • Can produce withdrawal in opioid-dependent patients and cause spasm of the sphincter of Oddi

Buprenorphine (Buprenex, Suboxone) © Jones & Bartlett Learning, LLC • Receptor: partial agonist© atJones mu, antagonist & Bartlett at delta. Learning, LLC • Supplied: 0.3 mg/mL injection, 7.5—20 mcg/hr NOT FOR SALE OR DISTRIBUTION transdermal NOT FOR SALE OR DISTRIBUTION • Dose: 0.3 mg deep IM or slow IV, may repeat after 45 mins. Max dose IM 0.6 mg or 0.3 mg IV. Dose of 0.3 mg = morphine 10 mg.

Pharm • At low doses, buprenorphine is many times more © Jones & Bartlettpotent than Learning, morphine. LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

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© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 183 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION • Onset: 2 mins IV; 15 mins IM; peak effect 3 hours • DOA: 6 hrs; 4-10 hrs with IM • Dosage adjustment: decrease dose for patients at high risk for respiratory depression. • Side effects: sedation, hypotension, dizziness, © Jones & Bartlett Learning, LLC anaphylaxis © Jones & Bartlett Learning, LLC • Buprenorphine has a very slow dissociation from mu NOT FOR SALE OR DISTRIBUTION opioid receptors and resistantNOT to FOR reversal SALE by naloxone. OR DISTRIBUTION • Some preparations of buprenorphine contain naloxone to deter intravenous injection. • Can produce withdrawal in opioid-dependent patients

© Jones & Bartlett■■ 5.10 Antagonist Learning, Agents LLC © Jones & Bartlett Learning, LLC NOT FOR SALEFlumazenil OR (Romazicon) DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Benzodiazepine (BZD) antagonist: Vial: 0.1 mg/mL Dose: 0.2 mg IV, repeat q1 min up to 1.0 mg. Last < 1hr Onset: 1–3 mins, peak 6–10 mins © Jones & Bartlett Learning,DOA: 1 hour LLC to re-sedation (romazicon has very© short Jones & Bartlett Learning, LLC half-life)—the shortest half-life of a BZD is 2–3 hours and NOT FOR SALE OR DISTRIBUTIONthe half-life of Flumazenil is 1 hour. Patients shouldNOT be FOR SALE OR DISTRIBUTION closely monitored and repeated doses of Flumazenil may be necessary. Notes: Do not give to patient on BZD for life-threatening conditions (i.e., ICP, status epilepticus, cyclic antidepres- © Jones & Bartlett Learning, LLC sant overdose). © Jones & Bartlett Learning, LLC Contraindicated: seizure disorder NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Naloxone (Narcan) Opioid antagonist: competes and displaces narcotics at mu receptor sites. Including analgesia, naloxone can

reverse opioid-induced side effects (i.e., pruritus, biliary Pharm © Jones & Bartlettspasm, nausea Learning, and vomiting, LLCetc.) © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 183 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 184 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Vial: 0.4 mg/mL—dilute in 9 mL NS = 0.04 mg/mL. * Giving a full undiluted ampule (1 mL = 0.4 mg/mL) of naloxone in a patient who has received opioids, but is not in respiratory arrest, may cause ischemia, heart attack, hypertension, stroke, heart failure, and/or © Jones & Bartlett Learning, LLC pulmonary edema.© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Dose adults: 0.04–0.4 mgNOT IV, repeat FOR PRN up SALE to 10 mg. OR DISTRIBUTION Narcan can be administered IV, IM, SC, or intratrache- ally (ETT), with the most rapid onset of action achieved following IV administration Onset: 2 mins (ETT 2– 5 mins) © Jones & BartlettDOA: 20–60 minsLearning, (dose may need LLC to be repeated if © Jones & Bartlett Learning, LLC patient received narcotic with DOA > 1 hours. NOT FOR SALECaution: ORin patients DISTRIBUTION with known renal insufficiency as NOT FOR SALE OR DISTRIBUTION it may have a prolonged effect. When naloxone is given, there is a risk of acute withdrawal syndrome in opioid-habituated patients and infants of opioid-habituated mothers. © Jones & Bartlett Learning,Patients LLC with IV Access © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONPatients ≤ 20 kg: Dilute and give 0.02 mg (0.5 NOTmL) IV every FOR SALE OR DISTRIBUTION 3 minutes until desired respiratory rate is established NOT until return of desired sensorium. Patients > 20 kg: Dilute and give 0.08 mg (2 mL) IV every 3 minutes until desired respiratory rate is established NOT until return of desired sensorium. © Jones & Bartlett Learning, LLC Patients without IV ©Access Jones (IM, SC,& ETT)Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Patients ≤ 20 kg: Give undilutedNOT (0.4FOR mg/mL) SALE naloxone OR DISTRIBUTION 0.01 mg/kg SC/IM/ETT every 2 minutes until desired respiratory rate is established NOT until return of desired sensorium.

Pharm Patients > 20 kg: Give undiluted (0.4 mg/mL) naloxone at © Jones & Bartlett0.2 mg (0.5 Learning, mL) LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 184 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 185 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION SC/IM/ETT every 2 minutes until desired respiratory rate is established NOT until return of desired sensorium. Naltrexone © Jones & Bartlett Learning, LLC Used in alcoholics and opioid© Jones addicts, naltrexone & Bartlett is a mu, Learning, LLC delta, and kappa opioid receptor antagonist. It is taken in NOT FOR SALE OR DISTRIBUTION oral form and is longer actingNOT than FOR naloxone. SALE OR DISTRIBUTION ■■ 5.11 Muscle Relaxants

TABLE 5-12 Succinylcholine Description © Jones & BartlettDepolarizing Muscle Learning, Relaxant LLC © Jones & Bartlett Learning, LLC NOT FOR SALEDrug OR Succinylcholine DISTRIBUTION (Anectine) NOT FOR SALE OR DISTRIBUTION Dose Without pretx of defasciculating dose: 0.5–1 mg/kg With pretx: 1–2 mg/kg Infusion: 1 gram/500 mL, titrate to effect Onset 30–60 seconds © Jones & Bartlett Learning,Duration ofLLC ½ life: 47 seconds; USDOA < 10 mins © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONAction NOT FOR SALE OR DISTRIBUTION Metabolism Succinylcholine diffuses away from the neuromuscular junction (NWJ) and is rapidly hydrolyzed by pseudocholinesterase into succinylmonocholine. Don’t Give Hyperkalemia, eye injury, increased intraocular pressure, With burns and trauma > 24 hours old; known abnormal © Jones & Bartlett Learning, LLC pseudocholinesterase© Jones levels. Should ¬ beBartlett used routinely Learning, LLC NOT FOR SALE OR DISTRIBUTION in children. NOT FOR SALE OR DISTRIBUTION Notes + histamine Increased risk of problems with undiagnosed myopathies. Don’t use routinely in pediatrics—can cause profound bradycardia; if have to give, administer atropine pre-Suxx in children. Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 185 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 186 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Succinylcholine stimulates both muscarinic and nicotinic receptors. Nicotinic effect: mimics action of acetylcholine at the neuromuscular junction on skeletal muscles. Muscarinic effect: stimulation of the muscarinic recep- © Jones & Bartlett Learning, LLC tors in the SA node of© the Jones heart produces & Bartlett bradycardia Learning, LLC NOT FOR SALE OR DISTRIBUTION especially in patients NOT(e.g., children) FOR with SALE a high vagal OR DISTRIBUTION tone. Anticholinergic drugs (atropine) are effective in preventing or treating bradycardia. Succinylcholine Depolarizing Blocks— 2 Types Seen © Jones & BartlettPhase I block Learning, (depolarization LLC block): produced by © Jones & Bartlett Learning, LLC succinylcholine, often preceded by muscle fascicula- NOT FOR SALEtion. (OnlyOR depolarizing DISTRIBUTION agent produces fasciculations NOT FOR SALE OR DISTRIBUTION before onset of paralysis.) This is thought to be due to the prejunctional action of succinylcholine stimulating acetylcholine receptors on the motor nerve. Recovery from Phase 1 block occurs as succinylcholine quickly diffuses away from the NMJ. © Jones & Bartlett Learning,• Does notLLC exhibit fade during tetanus or TOF© monitoring Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION• No post-tetanic potentiation NOT FOR SALE OR DISTRIBUTION Phase II block: if enough succinylcholine is given (>4 mg/kg) or there is prolonged exposure (repeated boluses or continuous infusion) of the NMJ to succinylcholine, the quality of the block will change to resemble that of a nondepolarizing block. © Jones & Bartlett Learning, LLC • Fade of twitch response© in Jones TOF monitoring & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION • Has tetanic fade NOT FOR SALE OR DISTRIBUTION • Has post-tetanic potentiation (enhancement of synaptic strength following tetanus) • Acetylcholinesterase may reverse blockade but difficult to predict Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 186 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 187 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-13 Succinylcholine Complications Increased Normal muscle releases enough potassium to increase serum K+ normal serum potassium levels 0.5 mEq/L from succinylcholine-induced depolarization. Normally, this © Jones & Bartlett Learning, LLC would not affect© healthy Jones patients with& normalBartlett K+ levels, Learning, LLC but in patients with pre-existing hyperkalemia, it can be NOT FOR SALE OR DISTRIBUTION deadly. ExamplesNOT of diseases FOR where receiving SALE succinylcho- OR DISTRIBUTION line could elevate serum potassium levels: • burn injury • massive trauma • familial periodic paralysis © Jones & Bartlett • Learning,Guillain-Barré syndrome LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR• muscularDISTRIBUTION dystrophy (succinylcholine is a relative con- NOT FOR SALE OR DISTRIBUTION traindication in children because of the potential for undiagnosed myopathies) • muscular denervation—hemiplegia/spinal cord injury • prolonged immobilization © Jones & Bartlett Learning,Trigger for LLCAlong with volatiles. © Jones & Bartlett Learning, LLC Malignant NOT FOR SALE OR DISTRIBUTIONHyperthermia NOT FOR SALE OR DISTRIBUTION Anaphylaxis Succinylcholine accounts for ~50% of hypersensitivity reactions due to histamine release. Increased Normal IOP is 10–22 mmHg and generated by ocular intraocular muscle contraction. Succinylcholine increases IOP by © Jones & Bartlett Learning, LLC pressure 5–10 mmHg and© this Jones was thought to& be dueBartlett to increased Learning, LLC NOT FOR SALE OR DISTRIBUTION (IOP) muscle contractions,NOT though FOR this is not confirmed.SALE OR DISTRIBUTION Increased Muscle fasciculations can increase ICP but this effect can intracranial be offset with hyperventilation. In patients who already pressure (ICP) have an increased ICP, succinylcholine is NOT contraindicated because the harmful stimulation of intubation far

outweighs any increase of ICP by the drug. Pharm © Jones & Bartlett Learning, LLC continues © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 187 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 188 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Succinylcholine Complications, continued Increased Fasciculations may be responsible; however, there is a intragastric corresponding increase in lower esophageal sphincter pressure pressure. © Jones & Bartlett Learning, LLC Muscle pain Thought to be© due Jonesto fasciculations & but Bartlettthis relationship Learning, LLC is inconsistent. No preventative measure is effective in all NOT FOR SALE OR DISTRIBUTION cases; however,NOT a small dose FOR of a nondepolarizing SALE muscle OR DISTRIBUTION relaxant (1/10th the intubating dose; i.e.: rocuronium 5 mg IV) given before the administration of succinylcholine can help to minimize this discomfort. This technique, however, reduces the potency of succinylcholine and a © Jones & Bartlett Learning,larger dose must be given LLC to produce the same effect. © Jones & Bartlett Learning, LLC Abnormal After giving succinylcholine, make sure twitches have NOT FOR SALEplasma ORreturned DISTRIBUTION (test with a peripheral nerve stimulator) before NOT FOR SALE OR DISTRIBUTION pseudocho- giving nondepolarizing muscle relaxants. Done to confirm linesterase patient does not have a prolonged succinylcholine block levels due to abnormal plasma pseudocholinesterase levels

© Jones & Bartlett Learning,Nondepolarizing LLC Muscle Relaxants (NDMR)© Jones & Bartlett Learning, LLC Benzylisoquinolines NDMR NOT FOR SALE OR DISTRIBUTIONDrug names end in “urium” NOT FOR SALE OR DISTRIBUTION e.g., atracurium, cisatracurium (mivacurium no longer produced in United States) • metabolized by organ-independent degradation • atracurium releases histamine (increased risk of bronchospasm), not cisatracurium © Jones & Bartlett Learning, LLC • lack any vagolytic effect© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Aminosteroid NDMR NOT FOR SALE OR DISTRIBUTION Drug names end in “onium”: e.g., vecuronium, rocuronium, pancuronium • depend on organ function for metabolism and excretion (prolonged action in liver and renal disease)

Pharm • can have active metabolites © Jones & Bartlett• tend not to Learning, release histamine LLCT © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

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© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 189 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-14 NDMR Mivacurium–Vecuronium Mivacurium Rocuronium Vecuronium (Mivacron) (Zemuron) (Norcuron) Dose 0.2 mg/kg 0.8 mg/kg 0.1 mg/kg; Maint: 0.12 © Jones & Bartlett Learning, LLC Maint: 0.05 Maint:© Jones 0.15 mg/ mg/kg& Bartlett Infusion: 1–2 Learning, LLC NOT FOR SALE OR DISTRIBUTION mg/kg kgNOT Infusion: FORmcg/kg/min SALE OR DISTRIBUTION 9–12 mcg/kg/ min Onset 1–3 min 1.5–3 min 3–4 min Duration SDOA 15–20 IDOA 30–75 min IDOA 40–90 min © Jones & Bartlettof Action min Learning, LLC © Jones & Bartlett Learning, LLC Metabolism Enzymes predominantly Excretion- NOT FOR SALE ORpseudocho- DISTRIBUTIONhepatobiliary— hepatobiliary 80%, NOT FOR SALE OR DISTRIBUTION linesterase no active Renal 10–20% Active metabolite; metabolite: prolonged excreted renally NMB—sometimes neuropathy develops; caution with IV © Jones & Bartlett Learning, LLC infusion © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONDon’t Give No longer Prolonged Long actingNOT in neo- FOR SALE OR DISTRIBUTION With produced in elimination in nates & infants (due U.S. patients with to immature liver). hepatic disease Prolonged elimina- & renal failure tion in patients with hepatic disease & renal © Jones & Bartlett Learning, LLC © Jones failure& Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Notes + histamine noNOT histamine FOR no histamineSALE Recon- OR DISTRIBUTION Low risk for High risk for stitute to 1–2 mg/mL. anaphylaxis anaphylaxis Women 30% more sensitive than men. Intermediate risk of

anaphylaxis Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 189 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 190 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-15 NDMR Atracurium–Pancuronium Atracurium Cisatracurium Pancuronium (Tracrium) (Nimbex) (Pavulon) © Jones & Bartlett Learning, LLC Dose 0.5 mg/kg; ©0.2 Jones mg/kg Maint: & Bartlett0.1 mg/kg; Maint: Learning, LLC Maint: 0.1 mg/ 0.02 mg/kg Infu- 0.01 mg/kg NOT FOR SALE OR DISTRIBUTION kg Infusion: NOTsion: 1–2 FORmcg/ SALE OR DISTRIBUTION 5–12 mcg/kg/ kg/min min Onset 2–3 min 2–3 min 2–3 min Duration IDOA 30–45 min IDOA 40–75 min LDOA 60–120 min © Jones & Bartlettof Action Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALEMetabo- ORHoffman DISTRIBUTION Hoffman Elimina- 15–20% biliary/ NOT FOR SALE OR DISTRIBUTION lism Elimination tion (temp and pH hepatic 70–80% (temp and pH dependent) renal dependent) to → Laudanosine (metabolite) © Jones & Bartlett Learning, LLCcan cause © Jones & Bartlett Learning, LLC excitement and NOT FOR SALE OR DISTRIBUTIONseizure activity. NOT FOR SALE OR DISTRIBUTION Don’t Histamine Prolonged elimina- Give release may tion in patients With worsen cardio- with renal and vascular disease, hepatic disease. asthma. May be danger- © Jones & Bartlett Learning, LLC © Jones & Bartlettous with patients Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALEwho have CAD, OR DISTRIBUTION fixed outflow obstruction (aortic stenosis or HOCM); arrhythmogenic Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 190 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 191 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION NDMR Atracurium–Pancuronium, continued Notes + histamine no histamine 4x no histamine Intermediate more potent than Vagolytic: risk of Atracurium. Low risk tachycardia – © Jones & Bartlett Learning, LLC anaphylaxis. ©for anaphylaxis. Jones &ca Bartletttecholamine Learning, LLC release & NOT FOR SALE OR DISTRIBUTION NOT FOR SALEdecreased uptake. OR DISTRIBUTION Intermediate risk of anaphylaxis.

© Jones & BartlettTABLE 5-16 Conditions–Drugs Learning, Potentiate LLC NMB © Jones & Bartlett Learning, LLC NOT FOR SALEConditions andOR Drugs DISTRIBUTION • Aminoglycoside, gentamicin, streptomycin, NOT FOR SALE OR DISTRIBUTION That Potentiate clindamycin antibiotics Neuromuscular • Volatile (inhaled) anesthetics Blockade • Magnesium • High doses of local anesthetics © Jones & Bartlett Learning, LLC • Calcium channel blockers © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION• Quinidine NOT FOR SALE OR DISTRIBUTION • Acid-base balance disturbances (respiratory acidosis potentiates blockade and antagonizes its reversal) • Trimethaphan, alpha blocker • Hypermagnesemia, hypokalemia, hypocalcemia © Jones & Bartlett Learning, LLC • Elderly© hav Jonese decreased clearance & Bartlett and prolonged Learning, LLC NOT FOR SALE OR DISTRIBUTION durationNOT of neuromuscular FOR blockSALE OR DISTRIBUTION Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 191 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 192 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-17 States That Reduce NMB Metabolism States That Reduce Neuromuscular • Renal insufficiency — reduction in Block Metabolism and Prolong plasma clearance Effect • Hepatic disease © Jones & Bartlett Learning, LLC © Jones• Hypothermia & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT• Volume FOR status SALE OR DISTRIBUTION • Trimethaphan, alpha blocker

© Jones & Bartlett TABLE 5-18 Learning,Antagonists to NMB LLC © Jones & Bartlett Learning, LLC NOT FOR SALEConditions OR • SomeDISTRIBUTION neuromuscular diseases: resistance to NDMR below NOT FOR SALE OR DISTRIBUTION and Drugs the level of the lesion. That Antag- • In hemiplegia, monitoring the paralyzed side has a less onize Non- intense block and recovery is more rapid than on the depolarizing unaffected side. Blockade • Debilitating muscle diseases or denervated muscle is © Jones & Bartlett Learning, LLCresistant to nondepolarizing relaxants. © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION• Chronic administration of drugs receptors NOTsuch as Dilan- FOR SALE OR DISTRIBUTION tin, Tegretol, antipsychotic medications (thorazine, etc.) cause up regulation of receptors • Calcium • Patients who take steroids • Cord transection © Jones & Bartlett Learning, LLC • Stroke © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION • Nerve damageNOT FOR SALE OR DISTRIBUTION • Thermal burn injuries: increased protein binding and up regulation of receptors • Chronic alcohol dependence

Pharm • Hypermetabolic states © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 192 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 193 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Obese patients: dosing with neuromuscular block: 20% more than lean body weight. Onset to Maximum Block Ultra-rapid (< 1 min) Succinylcholine © Jones & Bartlett Learning, LLC Rapid (1–2 mins) Rocuronium© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Intermediate (2–4 mins) Atracurium,NOT FOR Mivacurium, SALE Pan- OR DISTRIBUTION curonium, Vecuronium Long (> 4 mins) Cisatracurium Duration to ¼ TOF Recovery Ultra-short (< 8 mins) Succinylcholine © Jones & ShortBartlett (8–20 mins) Learning, Mivacurium LLC © Jones & Bartlett Learning, LLC NOT FOR SALEIntermediate OR (20–25 DISTRIBUTION mins) Atracurium, Cisatracurium, NOT FOR SALE OR DISTRIBUTION Rocuronium, Vecuronium Long (> 50 mins) Pancuronium

■■ 5.12 Anticholinesterase © Jones & Bartlett Learning,(Cholinesterase LLC inhibitor) © Jones & Bartlett Learning, LLC Anticholinesterase drugs reverse nondepolarizing NOT FOR SALE OR DISTRIBUTIONmuscle relaxation by inhibiting the destructionNOT of FOR SALE OR DISTRIBUTION acetylcholine by acetylcholinesterase. This leads to increased acetylcholine at neuromuscular junction overcoming the neuromuscular blocking effect at the nicotinic receptor. The most prominent side effect of the anticholinester- © Jones & Bartlett Learning, LLC ase drugs, bradycardia, is ©due Jones to muscarinic & receptorBartlett acti- Learning, LLC NOT FOR SALE OR DISTRIBUTION vation, though salivation,NOT increased FOR bronchial SALE secretions, OR DISTRIBUTION and urinary and fecal incontinence also can occur. See list of muscarinic side effects in “Anticholinergics.” Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 193 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Anticholinesterase Dose Anticholinesterase 0.05 mg/kg 0.7 mg/kg TOF 3–4 4 0.04 mg/kg 3–4 4 0.5 mg/kg 2 0.07 mg/kg 2 1.0 mg/kg

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Most potent, given most commonly anticholinesterase; BBB does not cross BBB. Does not cross as Neostigmine 10% as potent effect as anticholinergic BUT—½ . Has less muscarinic Neostigmine only ½ dose of requires effects, ef- Less premedication. atropine profound antagonizing at fective blockade and is not recommended of long-acting muscle reversal for relaxants. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 3–5 m / 1–3 hrs IDOA 1– 2 min / 1–1.5 hrs onset and fastest SDOA

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Dose IV Onset / Duration Notes 0.04–0.07 mg/kg max = 5 mg 0.5–1.0 mg/kg 30–45 sec over q5–10 min Repeat max = 40 mg Cholinesterase Inhibitors Cholinesterase

Pharm TABLE 5-19 © Jones & BartlettDrug response until patient has at least should not be attempted 2 out of 4 TOF at reversal Attempt Learning, > 35°C and temperature Neostigmine (Prostigmin) (Bloxiverz) LLCEdrophonium (Enlon); (Tensilon) © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 194 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 0.25 mg/kg Anticholinergics not needed with sugammadex. at when given 2 mg/kg, At 2/4, TOF TOF produce will reliably >0.9 in 2 minutes. is recommended 2 mg/kg recovery if spontaneous the reap- has reached of the second pearance TOF to twitch in response stimulation. 3–4 4 0.2 mg/kg 2 0.3 mg/kg

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Recently approved by the FDA, Su- the FDA, by approved Recently is a modified gamma- gammadex it has cyclodextrin. Chemically, periphery and a a hydrophilic lipophilic core charged negatively exerts its effectsforming by that complexes water-soluble tight with aminosteroid in a 1:1 ratio > (rocuronium muscle relaxants >> pancuronium) vecuronium interacting it from preventing “encapsu- receptors; with nicotinic and inactivates”. lates and/or marked see: anaphylaxis Can pain, nausea, vomiting, bradycardia; and headache. hypotension, does not cross blood brain barrier. blood brain does not cross as Neostigmine. 20% as potent CNS effects reverse be used to Can ; of anticholinergic © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Readily recov- or ers shallow neuro- profound muscular blockade in consistently 2–3 minutes 10–20 mins / 2–3 onset, hr slowest of longest duration action

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 4–8 mg/kg single-4–8 mg/kg bolus injection; is 4 mg/kg recommended if spontaneous of the recovery twitch response 1 to has reached 2 post-tetanic and (PTC) counts no twitch are there to responses train-of-four (TOF) stimulation. 0.1–0.3 mg/kg, 0.1–0.3 mg/kg, max 2–4 mg/hr Pharm Sugamma- (Bridion) dex © Jones & BartlettPyridostig- mine (Mestinon) Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 195 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Listed for information only. information for Listed muscle reverse used to Not relaxants. only. information for Listed muscle reverse used to Not relaxants. Anticholinesterase Dose Anticholinesterase TOF

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Anticholinesterase eye drops used drops eye Anticholinesterase of glaucoma. in treatment Unlike other anticholinesterase other anticholinesterase Unlike has no action Sugammadex drugs, or effectat the neuromuscular junction. is no biotransformation There excre- renal is by and elimination tion only. Given barrier. blood brain Crosses of atropine/ overdose central for scopolamine; of CNS depression/delirium reversal benzodiaz- receiving secondary to shivering. postoperative epines, salivation, see excessive Can convulsions. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 30 mins— 5 hrs

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 0.01–0.03 mg/kg 3–8 mins / Dose IV Onset / Duration Notes Pharm Cholinesterase Inhibitors, continued Inhibitors, Cholinesterase Echothio- phate Physostig- mine © Jones & BartlettDrug Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 196 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 197 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Factors That Confound Reversal • Electrolyte disturbance: hypokalemia, hypocalcemia, hypermagnesemia ▪▪ Alkalosis (hyperventilation)—can induce hypokalemia/hypocalcemia © Jones & Bartlett Learning, LLC • Hypothermia © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION • Blood flow to muscle: sloNOTw blood FOR flow increases SALE onset OR DISTRIBUTION and duration of action • Acidosis (potentiates effects of nondepolarizing block agents)

■■ 5.13 Anticholinergic © Jones & (AntimuscarinicsBartlett Learning, or muscarinic antagonists)LLC © Jones & Bartlett Learning, LLC NOT FOR SALEUsed in association OR DISTRIBUTION with anticholinesterase agents (i.e., NOT FOR SALE OR DISTRIBUTION neostigmine) to prevent the side effects associated with their use The chosen anticholinergic should be given at the same time, or immediately before, giving the reversal dose of anticholinesterase to prevent muscarinic side © Jones & Bartlett Learning,effects. LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-20 Muscarinic Side Effects Organ System Muscarinic Side Effects Cardiovascular Bradycardia, bradyarrhythmias, hypotension © Jones & Bartlett Learning, LLC Pulmonary Bronchospasm,© bronchialJones secretions, & hypoxiaBartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Cerebral Diffuse excitationNOT (with FOR physostigmine) SALE OR DISTRIBUTION Ophthalmological Pupillary constriction (miosis) Gastrointestinal Intestinal spasm, increased salivation Genitourinary Increased bladder tone Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 197 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Pharm TABLE 5-21 Anticholinergics

© Jones & Bartlett Learning, LLC. NOTFOR SALEORDISTRIBUTION © Jones&BartlettLearning, Drug Dose Onset / Duration Contraindications S. E. Glycopyr- 0.007 mg/ 1–5 min / Narrow angle glaucoma, Prostatic Orthostatic hypotension, dry mouth, mydriasis, rolate kg or 0.2 2–7 hrs hypertrophy, Myasthenia Gravis blurred vision, urinary retention, slows peristalsis in (Robinul) mg for each Longer duration (anticholinesterase drugs used to the intestine. No sedation, does not cross BBB. 1 mg of of action than treat myasthenia gravis), Paralytic Neostigmine atropine ileus, Ulcerative colitis (severe) NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC Atropine IV or IMNOT FORSALEORDISTRIBUTION © Jones&BartlettLearning, LLC 1–4 min / Narrow angle glaucoma, Prostatic Constipation, dry mouth, mydriasis, blurred vision, 0.007– 20 mins hypertrophy, bladder-neck obstruc- urinary retention. Crosses the BBB, causes slight 0.014 mg tion. Reduces lower esophageal sedation, can cause delirium. If dose too small, can with edro- tone. cause bradycardia by acting directly on the SA Node or phonium; increasing vagal activity by affecting muscarinic re- up to usual ceptors. Cutaneous vessel dilation = Atropine Flush adult dose "red as a beet"; Inhibition of sweat glands lead to a 0.4–0.6 mg rise in body temperature = Atropine Fever. NOT FOR SALE ORDISTRIBUTION © Jones &Bartlett Learning, LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC Scopol- IV, IM 0.3–0.6 IV 30 mins before, Urinary bladder obstruction, narrow Crosses the BBB, causes sedation, poss. delirium. amine mg, SQ 0.6–1 IM 1 hr before, angle glaucoma, intestinal obstruc- Best antisialagogue, + amnestic

(Transderm mg, patch patch tion, elderly patients, impaired liver

24/10/16 11:04 PM Scop) 1.5 mg 4 hr before / long or renal function DOA NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC

NOT FORSALEORDISTRIBUTION © Jones&BartlettLearning,LLC

NOT FORSALE ORDISTRIBUTION © Jones& BartlettLearning,LLC © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 199 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-22 Common Combinations Most common combinations-share speed of speed of onset and duration of action © Jones & Bartlett Learning, LLC Anticholinesterase Dose © JonesAnticholinergic & BartlettDose Learning, LLC Neostigmine 0.04–0.07 mg/ Glycopyrrolate 0.2 mg per 1 mg NOT FOR SALE OR DISTRIBUTION (Prostigmin, kg max = NOT FOR SALENeostigmine OR DISTRIBUTION Bloxiverz) 5 mg Edrophonium 0.5–1.0 mg/kg Atropine 0.007–0.014 mg (Enlon) max = 40 mg Pyridostigmine 0.1–0.3 mg/ Glycopyrrolate 0.2 mg per 5 mg © Jones & Bartlett(Mestinon) Learning,kg max 2–4 LLC Pyridostigmine © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONmg/hr NOT FOR SALE OR DISTRIBUTION

TABLE 5-23 Compare Effects of Anticholinergics Glycopyrrolate Atropine Scopolamine © Jones & Bartlett Learning,Antisialagogue LLC moderate mild large© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONSedation/amnesia none mild largeNOT FOR SALE OR DISTRIBUTION CNS effect none mild moderate Heart rate mild increase moderate no to mild increase increase Bronchodilator moderate large moderate © Jones & Bartlett Learning, LLC Pupil dilation mild© Jones moderate & Bartlett large Learning, LLC NOT FOR SALE OR DISTRIBUTION (mydriasis) NOT FOR SALE OR DISTRIBUTION Lower esopha- moderate moderate moderate geal sphincter relaxation

PONV prophylaxis — — large Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 199 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 200 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Choosing which anticholinergic to give with a specific anticholinesterase is done based on equivalent onset and duration of action. For example, the reason to use atropine, and not glycopyrrolate, in conjunction with edrophonium to reverse nondepolarizing muscle relaxants: © Jones & Bartlett Learning, LLC atropine has an onset time© moreJones similar & to Bartlettedrophonium; Learning, LLC otherwise, the muscarinic effects of edrophonium occur NOT FOR SALE OR DISTRIBUTION before glycopyrrolate canNOT block them.FOR SALE OR DISTRIBUTION

■■ 5.14 Antiemetics—Receptor Specific and Adjunct See Chapter 1, Section 1.3, Postoperative Nausea and © Jones & BartlettVomiting (PONV) Learning, or Postoperative LLC Vomiting (POV) for more © Jones & Bartlett Learning, LLC information. NOT FOR SALEEven patientsOR DISTRIBUTION with zero known risk factors, and NOT FOR SALE OR DISTRIBUTION considered low risk for postoperative nausea and vomiting (PONV), carry a 10% risk of PONV and may benefit from prophylactic antiemetic therapy. Some providers believe, though, that not all patients should receive PONV prophylaxis. © Jones & Bartlett Learning,Adults LLC at moderate risk for PONV should receive© Jones com- & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONbination therapy with one or two prophylacticNOT drugs from FOR SALE OR DISTRIBUTION different classes. In general, combination therapy has superior efficacy compared with monotherapy for PONV prophylaxis because drugs with different mechanisms of action optimize efficacy. Combination drug antiemetic therapy of greater than 2 antiemetics is recommended for patients at high risk for PONV. © Jones & Bartlett Learning, LLC All drugs given below in© BOLD Jones are listed & in Bartlett charts Learning, LLC NOT FOR SALE OR DISTRIBUTION Serotonin (5-HT3) receptorNOT antagonists FOR SALE (cheat: drug OR DISTRIBUTION names end in “tron”)—more effective in preventing emesis than nausea. • ondansetron (Zofran)—DO NOT give to pediatric patients < 1 month. Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 200 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 201 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION • dolasetron (Anzemet)—prolongs QT interval the most; single dose only. • granisetron (Kytril) • tropisetron (Navoban) • palonosetron (Aloxi)—long acting © Jones & Bartlett Learning, LLC Dopamine 2 receptor antagonist© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION • Metoclopramide (Reglan)NOT FOR SALE OR DISTRIBUTION ▪▪ Increases LES tone and intestinal motility; promotes gastric emptying, thus reducing gastric volume; “prokinetic.” ▪▪ Can cause extrapyramidal symptoms, manifested primarily as acute dystonic reactions. © Jones & Bartlett▪▪ GI motility Learning, effects antagonized LLC by anticholinergics © Jones & Bartlett Learning, LLC NOT FOR SALE(glycopyrrolate) OR DISTRIBUTION and narcotics. NOT FOR SALE OR DISTRIBUTION ▪▪ Check with surgeon before giving for ANY GI case. ▪▪ Can cause methemoglobinemia; treat methemoglobinemia with methylene blue 1–2 mg/kg IV. ▫▫ Contraindications ○○ Bowel obstruction ○○ Pheochromocytoma: metoclopramide © Jones & Bartlett Learning,stimulates LLC secretion of catecholamines© from Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONpheochromocytoma causing hypertensiveNOT crisis FOR SALE OR DISTRIBUTION ○○ QT prolongation—can worsen prolongations and cause Torsades de pointes ○○ Parkinson’s disease: may experience exacerbation of parkinsonian symptoms ○○ Patients on antipsychotics © Jones & Bartlett Learning, LLC • Butyrophenone—Black© box Jones warning: & can Bartlett increase QT Learning, LLC prolongation, which can lead to Torsades de pointes NOT FOR SALE OR DISTRIBUTION ▪▪ droperidol (Inapsine,NOT Innovar) FOR SALE OR DISTRIBUTION ▫▫ Antiarrhythmic properties at higher doses ▫▫ Higher doses are used for sedation ▪▪ haloperidol (Haldol) ▫▫ Don’t use with Parkinson’s patients Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 201 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 202 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION • Phenothiazine—very sedating ▪▪ prochlorperazine (Compazine)—weak antihistamine, potent antidopaminergic, and antimuscarinic (anticholinergic) agent ▪▪ promethazine (Phenergan) © Jones & Bartlett Learning, LLC AChM1 Acetylcholine-muscarinic© Jones receptor & antagonistBartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Scopolamine (TransdermNOT Scop, FOR Scopace)-predomi- SALE OR DISTRIBUTION nantly motion sickness; long onset of action, not effective for rescue therapy Adjunctive Antiemetics Benzodiazepines: midazolam (Versed) © Jones & BartlettCorticosteroid: Learning, dexamethasone LLC (Decadron) © Jones & Bartlett Learning, LLC Antihistamine and Anticholinergic (acetylcholine NOT FOR SALEreceptor): OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION dimenhydrinate (Dramamine)—motion sickness

Antihistamine H1 blockers: diphenhydramine (Benadryl)

Antihistamine H2 blockers—partial inhibition of © Jones & Bartlett Learning,enterochromaffin-like LLC cells of gastric antrum—© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONreversible inhibition of H2 receptor-mediatedNOT secre- FOR SALE OR DISTRIBUTION tion of acidic gastric fluid; increases gastric pH. Famotidine, Cimetidine, Nizatidine, Ranitidine ANTACIDS—Must be nonparticulate Sodium Citrate (Bicitra): 15–30 mL PO 30 minutes before induction © Jones & Bartlett Learning, LLC NK-1 receptor—Substance-P© Jones antagonists & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION aprepitant (Emend):NOT long onsetFOR of action,SALE not OR DISTRIBUTION effective for rescue therapy. Usually given before chemotherapy treatment. Given in combination with corticosteroid and 5-HT3 antagonist.

Pharm Note: These recommendations are evidence-based and not © Jones & Bartlettall the drugs haveLearning, an FDA indication LLC to treat PONV. © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 202 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Dose Timing 30 mins before EOC 30 mins before 15 mins before EOC 15 mins before Just after inductionJust after NOT FOR SALE OR DISTRIBUTION NOT FOR EOC 30 mins before SALE OR DISTRIBUTION

Pharm TABLE 5-24 Drug (Zofran)ONDANSETRON antagonist 5-HT3 receptor 4–8 mg IV DOLASETRON (Anzemet) antagonist 5-HT3 receptor 12.5 mg IV GRANISETRON (Kytril) antagonist 5-HT3 receptor 0.35–1.5 mg IV TROPISETRON (Navoban)TROPISETRON antagonist 5-HT3 receptor 2 mg IV © Jones & Bartlett Learning, LLC METOCLOPRAMIDE (Reglan) (Inapsine)DROPERIDOL dopamine antagonist © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 203 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Dose and Route 1.5 mg transdermal patch1.5 mg transdermal surgery is ideal 4 hr before 0.5–2 mg IM/IV 12.5–25 mg IV/rectal

Class receptor antagonist receptor - Butyrophenone dopamine antagonist Phenothiazinedopamine antagonist 5–25 mg IM/IV/rectal EOC 30 mins before dopamine antagonist Phenothiazinedopamine antagonist 6.25 mg IM M1-

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Pharm Doses and Timing in Adults, continued in Adults, Timing Doses and Drug (Haldol)HALOPERIDOL dopamine antagonist PROCHLORPERAZINE PROCHLORPERAZINE (Compazine) PROMETHAZINE (Phenergan) © Jones & Bartlett Learning, LLC PROMETHAZINE SCOPOLAMINE © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 204 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION After combination therapy given and patient and patient given therapy combination After nauseous postoperatively inductionJust after unknown © Jones & Bartlett Learning, LLCPre-induction prior to PO 1 hour or IV 30 minutes Give chemotherapy © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 1 mg/kg IV 1 mg/kg 25-50 mg IV20 mg IV induction Just after 115–150 mg over 30 mins IV

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 1 2 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION tive Corticosteroid 4–5 mg IV and Antihistamine Anticholinergic H Antihistamine blockers blocker Substance-P antagonists

Pharm TABLE 5-25 (Versed)MIDAZOLAM Benzodiazepine DEXAMETHASONE (Decadron) 1-2 mg IV DIMENHYDRINATE (Dramamine) DIPHENHYDRAMINE (Benadryl) © Jones & Bartlett Learning, LLC (Pepcid)FAMOTADINE H Antihistamine (Emend)APREPITANT receptor - NK-1 © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 205 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 206 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Pharmacologic Combination Therapy Because the effects of interventions from different drug classes are additive, combining interventions has an additive effect in risk reduction. © Jones & Bartlett Learning, LLC Combinations in Adults© Jones & Bartlett Learning, LLC • droperidol (max dose 1 mg IV) + dexamethasone NOT FOR SALE OR DISTRIBUTION • 5-HT3 receptor antagonistNOT + dexamethasone FOR SALE OR DISTRIBUTION • 5-HT3 receptor antagonist + droperidol • 5-HT3 receptor antagonist + dexamethasone + droperidol • 5-HT3 antagonist + promethazine + dexamethasone • 5-HT3 antagonist + dexamethasone + scopolamine © Jones & Bartlettpatch + IM Learning,promethazine LLC © Jones & Bartlett Learning, LLC NOT FOR SALECombination OR DISTRIBUTION Therapy Pearls NOT FOR SALE OR DISTRIBUTION Corticosteroids given in combination with a serotonin receptor antagonist yield the greatest antiemetic protection. The 5-HT3 antagonists, which have strong antivomiting efficacy (but have headache as a common side effect), © Jones & Bartlett Learning,can be LLC used in combination with droperidol,© which Jones & Bartlett Learning, LLC works against nausea and helps to fight headache NOT FOR SALE OR DISTRIBUTION(droperidol IM is used to treat migraine headaches).NOT FOR SALE OR DISTRIBUTION When used in combination with another drug, ondansetron doses in adults typically should not exceed 4 mg and can be much lower.

■■ 5.15 Local Anesthetics (LA) © Jones & Bartlett Learning, LLC Provide anesthesia and analgesia© Jones by blocking & Bartlett voltage- Learning, LLC NOT FOR SALE OR DISTRIBUTION gated sodium channels, NOTdisrupting FOR the conduction SALE ofOR DISTRIBUTION impulses along nerve fibers. • Potency related to lipid solubility • Speed of onset related to pKa (degree of ionization) • Duration of action related to protein binding Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 206 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 207 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Lidocaine, prilocaine, or benzocaine/cetacaine local anesthetics may cause methemoglobinemia (Hgb can carry oxygen but can’t release it effectively); treat methemoglobinemia with methylene blue 1–2 mg/kg IV. © Jones & Bartlett Learning, LLC Ester LA © Jones & Bartlett Learning, LLC cheat: have one “i” in their name NOT FOR SALE OR DISTRIBUTION General: metabolized byNOT pseudocholinesterase FOR SALE into OR DISTRIBUTION “paba”; increased allergy risk—if there is an existing allergy to an Ester LA, choose an Amide LA instead. • Procaine (Novocaine)—0.5–1 % Max dose 12mg/kg Fast onset, short duration (<1hr) © Jones & BartlettUsed for spinal, Learning, infiltration, PNBsLLC © Jones & Bartlett Learning, LLC NOT FOR SALE• Chloroproc ORaine DISTRIBUTION—1–3 % NOT FOR SALE OR DISTRIBUTION Max dose 12mg/kg Very quickly metabolized so very high doses can be used to speed onset Fastest onset, short duration (<1hr) Used to convert labor epidurals to surgical blocks for © Jones & Bartlett Learning,STAT cesarean, LLC PNBs © Jones & Bartlett Learning, LLC • Tetracaine (Pontocaine)—0.5–1 % NOT FOR SALE OR DISTRIBUTIONMax dose 3mg/kg NOT FOR SALE OR DISTRIBUTION Slow onset, long duration (2–6hrs) Used for very long-acting spinals, topical Motor blockade may be denser than sensory block • Cocaine—blocks NE reuptake vasoconstrictor, topical use only, significant systemic absorption occurs. Solution © Jones & Bartlett Learning, LLC 4% (40 mg/mL) available,© max Jones dose 1.5 & mg/kg. Bartlett Often Learning, LLC NOT FOR SALE OR DISTRIBUTION used in awake airway managementNOT FOR for local SALE anesthetic OR DISTRIBUTION and to decrease bleeding; can produce cardiovascular toxicity. Do not give to patients with cardiovascular disease, severe HTN, or if taking MAO inhibitor. • Benzocaine (Hurricaine/Cetacaine)—spray

formulations for topical anesthesia Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 207 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 208 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Max dose—not available. Cetacaine is a combination of tetracaine & benzocaine. Amide LA cheat: have at least two “i’s” in their name © Jones & Bartlett Learning, LLC General: metabolized© by amidasesJones in & liver—CP450 Bartlett Learning, LLC system; may be safely used in patients with Ester LA allergy NOT FOR SALE OR DISTRIBUTION • Lidocaine (Xylocaine)—0.5–5NOT %FOR SALE OR DISTRIBUTION Max dose—4.5 mg/kg, 7 mg/kg with epi Fast onset, short duration (0.5–2hrs) Used for IV induction, IV regional, infiltration, PNB, epidural anesthesia Can be used as a continuous intravenous analgesic © Jones & Bartlett• Mepivacaine Learning,—1–2 % LLC © Jones & Bartlett Learning, LLC NOT FOR SALEMax dose—4.5 OR DISTRIBUTION mg/kg, 7 mg/kg with epi NOT FOR SALE OR DISTRIBUTION Fast onset, moderate duration (2–4hrs) Used for infiltration, PNB, epidural • Bupivacaine (Marcaine, Sensorcaine)—0.5–0.75 % Max dose—3mg/kg (Levobupivacaine is less cardiotoxic, but not avail in United States) © Jones & Bartlett Learning,Less motor LLC than sensory block © Jones & Bartlett Learning, LLC Slow onset, long duration, high cardiac toxicity NOT FOR SALE OR DISTRIBUTIONUsed for PNBs, epidural, spinal, infiltration NOT FOR SALE OR DISTRIBUTION • Prilocaine 4%—used for dental nerve block • Ropivacaine—0.2–1 % Max dose—3mg/kg Similar to bupivacaine with less cardiac toxicity • Dibucaine—used to diagnose atypical © Jones & Bartlett Learning, LLC plasmacholinesterase.© Dibucaine Jones will &depress Bartlett the Learning, LLC activity of normal pseudocholinesterase by 80%; NOT FOR SALE OR DISTRIBUTION Heterozygous 60–80%;NOT homozygous FOR 20%. SALE OR DISTRIBUTION Local Anesthetics—Absorption Rate Related to Tissue Vascularity

Pharm Affected by presence of use of a vasoconstrictor with local © Jones & Bartlettanesthetic Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 208 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 209 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Highest absorption to lowest: IV > tracheal > intercostal > paracervical > caudal > lumbar epidural > brachial plexus > sciatic > (topical) > subcutaneous Plasma Concentration of Local Anesthetic and © Jones & Bartlett Learning, LLC Effects © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION • 1–5 mcg/mL: analgesiaNOT FOR SALE OR DISTRIBUTION • 5–10: lightheaded, tongue numb, tinnitus, muscle twitch • 10–15: seizures, unconscious • 15–25: coma, respiratory arrest • >25: CV depression © Jones & ExBartlettcitatory precedes Learning, depression: LLCsigns/symptoms (s/s) © Jones & Bartlett Learning, LLC NOT FOR SALEAsleep ORpatient: DISTRIBUTION first s/s heart arrhythmia and collapse NOT FOR SALE OR DISTRIBUTION Awake patient: central nervous system s/s LA Toxicity Avoid intravascular injection, prevention is paramount (aspirate prior to injection, small test dose), use appropriate monitoring. © Jones & Bartlett Learning,• Treatment LLC if signs of toxicity occur: © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION▪▪ Stop local anesthetic NOT FOR SALE OR DISTRIBUTION ▪▪ Begin supportive care—ACLS: CPR, meds (may need decreased dose of epi), airway management as appropriate • Initiate early Intralipid (IL) therapy ▪▪ Bolus IL 20% 1.5 ml/kg over 1 minute © Jones & Bartlett Learning, LLC ▪▪ Follow by infusion of ©0.25 Jones ml/kg & Bartlett Learning, LLC ▪▪ May repeat boluses q3–5 min NOT FOR SALE OR DISTRIBUTION ▪▪ Total dose 12 ml/kg NOT FOR SALE OR DISTRIBUTION ▪▪ Consider early initiation of cardiopulmonary bypass

■■ 5.16 Antibiotics

Antibiotic therapy should be given within 60 minutes prior Pharm © Jones & toBartlett surgical incision Learning, for adequate LLCserum drug tissue levels at © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 209 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 210 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION incision. Exceptions to this include: 1) Vancomycin should be started 2 hours prior to incision; and 2) if a proximal (to incision) tourniquet is used, the entire antibiotic dose should be administered before the tourniquet is inflated. Considerations: © Jones & Bartlett Learning, LLC • Obesity has been linked© toJones an increased & riskBartlett for Learning, LLC NOT FOR SALE OR DISTRIBUTION surgical-site infection NOTand dosage FOR adjustments SALE may OR be DISTRIBUTION warranted. To be given via slow infusion • Vancomycin (Red Man Syndrome)—over 30–60 mins • Gentamicin (ototoxicity/nephrotoxicity)—over 30–60 min due to potential risk of oto-nephrotoxicity. © Jones & Bartlett• Metronidaz Learning,ole (low pH of 4.8–5.2)—over LLC 60 mins © Jones & Bartlett Learning, LLC • Ciprofloxacin (contains lactic acid)—over 60 mins to NOT FOR SALEreduce OR risk of DISTRIBUTION venous irritation. NOT FOR SALE OR DISTRIBUTION • Clindamycin (potential QT prolongation)—infusion rates should not exceed 30 mg/min Adult Dosing See your specific institution recommendations regarding dose and redose timing.

© Jones & Bartlett Learning,TABLE 5-26 LLC Common Prophylactic Antibiotics © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONAntibiotic Brand Name Normal DoseNOT FOR SALE OR DISTRIBUTION Ampicillin Omnipen 2 g Ampicillin-Sulbactam Unasyn 3 g Cefazolin Ancef 1 g < 80 kg © Jones & Bartlett Learning, LLC © Jones2 g& 80–120 Bartlett kg Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR3 g > SALE 120 kg OR DISTRIBUTION Cefotaxime Claforan 1 g Cefoxitin Mefoxin 2 g Ceftriaxone Rocephin 2 g Pharm © Jones & BartlettCefuroxime Learning, Ceftin, Zinacef LLC 1.5 g © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 210 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 211 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Common Prophylactic Antibiotics, continued Ciprofloxacin Cipro 400 mg Clindamycin Cleocin 900 mg © Jones & Bartlett Learning, LLC Ertapenem Invanz © Jones1 g & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Fluconazole DiflucanNOT FOR 400 SALEmg OR DISTRIBUTION Gentamicin Garamycin 5 mg/kg Levofloxacin Levaquin 500 mg Metronidozole Flagyl 500 mg Piperacillin- Zosyn 3.375 g © Jones & BartlettTazobactam Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALEVancomycin OR DISTRIBUTION Vancocin 15 mg/kg NOT FOR SALE OR DISTRIBUTION Adjust for renal insufficiency except for ceftriaxone and clindamycin

© Jones & Bartlett Learning,It is recommended LLC that the antibiotic be redosed© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONwhen two ½-lives have elapsed during a long surgicalNOT FOR SALE OR DISTRIBUTION procedure.

■■ 5.17 Corticosteroids Common IV Glucocorticoids include • dexamethasone (Decadron): long-acting © Jones & Bartlett Learning, LLC anti-inflammatory © Jones & Bartlett Learning, LLC • hydrocortisone (Cortisone, Solu-Cortef): short-acting NOT FOR SALE OR DISTRIBUTION anti-inflammatory NOT FOR SALE OR DISTRIBUTION • methylprednisolone (Solu-Medrol): intermediate-acting anti-inflammatory Produced by the adrenal cortex, corticosteroids work at

the cellular level to decrease the inflammatory response Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 211 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 212 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION by inhibiting phospholipase (preventing the formation of arachidonic acid), lymphocyte alterations, cytokine ex- pression; sodium ion channel blockade, and stabilization of the cell membrane with decreased capillary perme- ability. Steroids are used as an antiemetic and believed to © Jones & Bartlett Learning, LLC decrease edema, blood loss,© Jones and the formation & Bartlett of postop- Learning, LLC erative fibrosis and scarring. NOT FOR SALE OR DISTRIBUTION Antiemetic: DexamethasoneNOT FOR (Decadron) SALE at doses OR DISTRIBUTION of 4 mg, max dose 8 mg—is an effective antiemetic. It is believed to modulate the release of endorphins or inhibit prostaglandin synthesis. It has a delayed onset of action and should be given immediately after induction; it can cause genital burning in some awake patients. Caution in © Jones & Bartlettpatients with Learning, an active infection, LLC CHF, diabetes, or renal © Jones & Bartlett Learning, LLC NOT FOR SALEimpairment. OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Stress-dose steroids: Normal daily production of cortisol is 20 mg, but under stress the body will produce 300 mg. Perioperative stress is related to the degree of trauma and the depth of anesthetic. If patient on steroids for longer than 1 week in the last 6 months, cover with a © Jones & Bartlett Learning,stress dose LLC of Hydrocortisone 100 mg IV. This© stress Jones dose & Bartlett Learning, LLC potentiates catecholamines, epinephrine and norepineph- NOT FOR SALE OR DISTRIBUTIONrine, stabilizing hemodynamics. Acute adrenal NOTinsufficiency FOR SALE OR DISTRIBUTION rarely occurs, but it can be life threatening and giving steroid coverage with hydrocortisone has little risk. ■■ 5.18 Drugs to Affect Heart Rate These are agents that can be used specifically to increase © Jones & Bartlett Learning, LLC heart rate and a few others© thatJones are common & Bartlett drugs that Learning, LLC NOT FOR SALE OR DISTRIBUTION have the side effect of anNOT increased FOR heart SALE rate. OR DISTRIBUTION To Increase Anticholinergics ▪▪ glycopyrrolate (Robinul)

Pharm ▪▪ Atropine © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 212 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 213 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Sympathomimetic/catecholamine ▪▪ epinephrine (Adrenalin) ▪▪ isoproterenol (Isuprel) Dopamine © Jones & Bartlett Learning, LLC Dopexamine © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Ephedrine NOT FOR SALE OR DISTRIBUTION Alpha blockers Cardiac pacing To Decrease • beta-blockers © Jones & • Bartlettcalcium-channel Learning, blockers LLC © Jones & Bartlett Learning, LLC NOT FOR SALE• cardiac glycORoside: DISTRIBUTION digoxin (Lanoxin) NOT FOR SALE OR DISTRIBUTION

■■ 5.19 Beta-Blockers Beta-Blockers: block effect of endogenous catecholamines, norepinephrine, and epinephrine at Beta receptors © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC First generation B-blockers were non-selective: NOT FOR SALE OR DISTRIBUTIONB1 increases HR & BP, Beta blocking will decreaseNOT HR, FOR SALE OR DISTRIBUTION contraction, and BP B2 bronchodilates, Beta blocking will constrict bronchioles Second generation are relatively selective and more cardioselective for Beta 1 adrenoceptors. © Jones & Bartlett Learning, LLC B-Blocker Advantages: decrease© Jones HR and BP,& decreaseBartlett ven- Learning, LLC NOT FOR SALE OR DISTRIBUTION tricular contractility heartNOT rate (increasingFOR SALE diastolic ORtime DISTRIBUTION for coronary artery perfusion), MVO2; opposes effect of endogenous catecholamines at Beta receptors. B-Blocker Disadvantages/Contraindications: bronchospasm risk, asthma, cardiac failure, 2° and 3° heart

block, severe bradycardia Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 213 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 214 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-27 Atenolol–Labetalol Atenolol Brevibloc Labetalol (Tenormin) (Esmolol) (Trandate, Normodyne) © Jones & Bartlett Learning, LLC Receptors B1© B1 Jones B1 & and BartlettB2, alphl Learning, LLC NOT FOR SALE OR DISTRIBUTION Action Cardioselec- NOTCardiose- FORNonselective SALE B-blocker OR DISTRIBUTION tive B1 lective B selective alphl blocker blocker blocker - short acting. SA node blocker Dose 1.25–5 mg Bolus: 10–30 IV bolus: 2.5–10 mg/ © Jones & Bartlett Learning,mg IV or LLC2 min repeat q10 mins © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION0.25–0.5 mg/ until target BP reached, NOT FOR SALE OR DISTRIBUTION kg; Infusion: max 30 mg Infusion: 500 25–200 mcg/ mg/250 mL in D5W: kg/min 0.5–2 mg/min Onset / 5 mins / 6–7 1–5 min / 2 mins / 5 hrs Duration hrs 10-20 mins; © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Used for HTN, HTN, tachycar- HTN, tachycardia, eclamp- NOT FOR SALE OR DISTRIBUTIONtachycardia dia, SVT, intra/ sia, aortic aneurysmNOT or FOR SALE OR DISTRIBUTION post op HTN dissection; decr peripheral resistance Side Agranu- decreases CO, seizure, headache, coma, Effects locytosis, hypotension, bradycardia, hypotension, © Jones & Bartlett Learning, LLC fever, mental ©negative Jones CHF, & bradycardia, Bartlett (delta) Learning, LLC depression/ inotrope MS, bronchospasm, NOT FOR SALE OR DISTRIBUTION disorienta- NOT FORfatigue, SALE urinary retention, OR DISTRIBUTION tion, arterial hypo- and hyperglycemia thrombosis, bronchoconstriction Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 214 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 215 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Atenolol–Labetalol, continued Notes Dosage Increase SA Rapidly drops BP with decreased node recovery minimal change in HR. in renal time, least Alpha:Beta 1:7 IV (1:3 © Jones & Bartlett Learning, LLC disease; likely© toJones cause PO)—helps & Bartlett to maintain Learning, LLC short-term broncho- myocardial oxygen NOT FOR SALE OR DISTRIBUTION management constriction.NOT FORsupply/demand SALE ratio OR DISTRIBUTION Most rapid elimination of all B-blockers- degraded by esterases © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-28 Lopressor–Propranolol Lopressor Propranolol (Inderal) (Metoprolol) Receptors B1 blocker ++ Prototype B1 and B2 blocker © Jones & Bartlett Learning, LLCB2 blocker + © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONAction Cardioselective Nonselective B-blockerNOT FOR SALE OR DISTRIBUTION B1 blocker Dose IV 1.25–5 mg IV 0.5–1 mg q5 mins, max 5 mg increments Onset / 20 mins / 3–5 hrs 2 mins / 3–6 hrs Duration © Jones & Bartlett Learning, LLC Used for HTN, tachycardia© Jones Angina, arrhythmias, & Bartlett AMI, aortic Learning, LLC NOT FOR SALE OR DISTRIBUTION NOTstenosis, FOR pheochromocytoma SALE OR DISTRIBUTION Side Effects bronchoconstriction Opposes effect of endogenous catecholamines at beta receptors continues Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 215 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 216 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Lopressor–Propranolol, continued Lopressor Propranolol (Inderal) (Metoprolol) Notes Preferred B-blocker with thy- © Jones & Bartlett Learning, LLC © Jonesrotoxicosis & (blocks Bartlett adrenergic Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOReffect & peripheral SALE deiodination OR DISTRIBUTION of T4) and Pheochromocytoma. High first pass metabolism in liver, only 25% reaches systemic circulation. Highly protein bound © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALEAME—Atenolol OR DISTRIBUTION Metoprolol Esmolol—B1 cardio NOT FOR SALE OR DISTRIBUTION selective. . .cheat: ”AME for the heart” Continue preoperative beta-blocker if already taking. Discontinuation can lead to paradoxical hypertension, tachycardia, and angina pectoris secondary to receptor up regulation. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC ■■ 5.20 Angiotensin Inhibitors (Ace inhibitors; NOT FOR SALE OR DISTRIBUTIONACEi; ARB) NOT FOR SALE OR DISTRIBUTION

Renin-Angiotensin System (RAS) renal blood flow (low BP) causes renin to be released renin converts Angiotensinogen © Jones & Bartlett Learning, LLC © Jonesto & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION AngiotensinNOT FOR I SALE OR DISTRIBUTION Angiotensin I is then converted to Angiotensin II by Angiotensin-Converting Enzyme

Figure 5-1 Angiotensinogen Renin Pathway Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 216 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 217 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Cheat: generic name ends in “pril” Angiotensin II is the active hormone. It has two main effects: ▪▪ potent vasoconstrictor © Jones & Bartlett Learning, LLC ▪▪ releases aldosterone© from Jones adrenal cortex & Bartlett causing Learning, LLC water reabsorption by the kidneys NOT FOR SALE OR DISTRIBUTION Used to: treat congestiveNOT heart failure, FOR essential SALE and ma-OR DISTRIBUTION lignant HTN, kidney complications from diabetes mel- litus, and for treatment after myocardial infarction. Action: • inhibit angiotensin converting enzyme (ACE), © Jones & Bartlettpreventing angiotensinLearning, I from LLC becoming angiotensin II © Jones & Bartlett Learning, LLC in the lung NOT FOR SALE• decrease OR blood DISTRIBUTION pressure by relaxing blood vessels, NOT FOR SALE OR DISTRIBUTION decreasing myocardial oxygen demand • decreases peripheral vascular resistance • decreases aldosterone secretion and decreases Na+ and water retention by reducing water reabsorbed by the kidneys, lowering blood volume (helps with CHF) © Jones & Bartlett Learning,• decreases LLC potassium loss; ACEi should not be© given Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONwith potassium-sparing diuretic. NOT FOR SALE OR DISTRIBUTION ACEi Advantages: highly effective in renovascular hypertension ACEi Disadvantages and Side Effects: cough, angioedema, hyperkalemia, ACEi Precautions: aortic stenosis, hypovolemia © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Notes: NOT FOR SALE OR DISTRIBUTION Dosages of all ACE inhibitorsNOT (except FOR fosinopril) SALE should OR DISTRIBUTION be reduced with renal dysfunction as ACEi’s can decrease glomerular filtration rate. Fosinopril has substantial biliary excretion, and renal insufficiency does not alter its

metabolism. Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 217 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 218 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-29 ACEi Name and Dose Generic Name Brand Name Dose IV Dose PO benazepril Lotensin — 10 mg/day © Jones & Bartlett Learning, LLC captopril Capoten© Jones — & 6.25 Bartlett to 25 mg Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR 2–3SALE x/day OR DISTRIBUTION enalapril Vasotec 1.25 mg IV start 2.5 to 5 mg/day slowly every 6 hours (max 5 mg IV q 6 hrs) © Jones & Bartlettfosinopril Learning, Monopril — LLC 10 to max 80 mg/day © Jones & Bartlett Learning, LLC NOT FOR SALElisinopril OR DISTRIBUTION Prinivil, Zestril — 10 to max 80 mg NOT FOR SALE OR DISTRIBUTION moexipril Univasc — 7.5 mg to max 30 mg perindopril Aceon — 4 to 8 mg/day quinapril Accupril — 5–10 to max 80 mg/day © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC ramipril Altace — 2.5 to max 20 mg/day NOT FOR SALE OR DISTRIBUTIONtrandolopril Mavik — 1 to maxNOT 8 mg/day FOR SALE OR DISTRIBUTION

Angiotensin-Receptor Blockers (ARBs): also modify the renin–angiotensin system by directly inhibiting the © Jones & Bartlett Learning, LLC effects of angiotensin© II, Jonesbut they do & not Bartlett inhibit the Learning, LLC breakdown of bradykinin and patients do not have the NOT FOR SALE OR DISTRIBUTION associated dry cough,NOT angioedema, FOR and SALE renal compli- OR DISTRIBUTION cations that can occur with ACEi’s. Used to treat the same conditions as ACEi. Examples of ARBs: irbesartan (Avapro), losartan (Cozaar),

Pharm olmesartan (Benicar), telmisartan (Micardis), valsartan © Jones & Bartlett(Diovan) Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 218 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 219 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ 5.21 Calcium Channel Blockers (CCB) Inhibits Ca++ ion influx across heart and smooth muscle cells. General Advantages: decreasing myocardial contractility © Jones & Bartlett Learning, LLC and oxygen demand; dilates© Jones coronary & arteries, Bartlett periph- Learning, LLC eral vasodilation with decreased afterload, decreased NOT FOR SALE OR DISTRIBUTION BP. Good with asthmatics,NOT instead FOR of B-blockers. SALE OR DISTRIBUTION Disadvantages: severe bradycardia, heart failure, peripheral edema Decrease dosing with myocardial ischemia or instability. Should be continued throughout the preoperative period for © Jones & Bartlettpatients going Learning, for surgery.T LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-30 CCB-Clevidipine–Diltiazem Clevidipine Diltiazem (Cleviprex) (Cardizem) Mix Provided in 50 or 100 mL 125 mg/100 mL D5W, NS © Jones & Bartlett Learning, LLCvials, 0.5 mg/mL; do not © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONdilute. NOT FOR SALE OR DISTRIBUTION Dose Infusion only: 1–2 mg/hr, Loading Dose: 0.25 mg/kg adjust dose q 5–10 mins; IVP over 2 minutes; may max dose 16 mg/hr repeat bolus in 15 minutes if necessary with 0.35 mg/ kg over 2 minutes. © Jones & Bartlett Learning, LLC © JonesInfusion: & 5–15Bartlett mg/hr Learning, LLC NOT FOR SALE OR DISTRIBUTION Onset/ 2–4 mins / endNOT of FOR2–5 mins SALE / 3–5 hrs OR DISTRIBUTION Duration infusion Used for HTN HTN, rapid ventricular response with A Fib. or A

Flutter; PSVT Pharm © Jones & Bartlett Learning, LLC continues © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 219 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 220 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION CCB-Clevidipine–Diltiazem, continued Clevidipine Diltiazem (Cleviprex) (Cardizem) Contraindica- Allergy to soy or eggs, sick sinus syndrome, VT, tions severe aortic stenosis second- or third-degree © Jones & Bartlett Learning, LLC © Jonesheat & block, Bartlett WPW, hypoten- Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FORsion, shock,SALE concurrent OR use DISTRIBUTION with IV beta-blocker Notes Does not protect against IV diltiazem has less nega- effects of abrupt tive inotropic action than B-blocker withdrawal. verapamil and preferred CCB in patients with LV failure © Jones & BartlettNegative Learning,+ LLC0 © Jones & Bartlett Learning, LLC inotrope NOT FOR SALENegative OR DISTRIBUTION+ 0 NOT FOR SALE OR DISTRIBUTION chronotrope Coronary + +++ vasodilator Systemic + ++ © Jones & Bartlett Learning,vasodilator LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-31 CCB-Nicardipine–Verapamil Nicardipine Nifedipine Verapamil (Cardene) (Procardia) (Calan, Isoptin) Mix 25 mg/240 mL —— D5W, NS © Jones & Bartlett Learning, LLC Dose Initiate: 5 mg/hr© Jones10–30 mg PO & BartlettIV: 2.5–10 mg Learning, LLC (50 mL/hr). Incr. or sublingual, over 2 mins, 2nd NOT FOR SALE OR DISTRIBUTION by 2.5 mg/hr NOTMax FOR 180 mg/ SALEdose 5–10 OR mg DISTRIBUTION (25 mL/hr) q5–15 day after 30 mins; mins to max of 15 not given IV max total dose mg/hr (150 mL/hr) 20 mg Onset/ 5–15 mins / 50 hrs 5–10 min / 1–5 min / 3 hrs Pharm Duration 6–8 hrs © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 220 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 221 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION CCB-Nicardipine–Verapamil, continued Used for HTN; arterial vaso- HTN, antianginal, SVT (antiarrhyth- dilator, antianginal, direct vascular mic), HTN, anti- significantly decr. smooth muscle anginal, increase SVR. relaxation; coro- CO, decrease SVR; © Jones & Bartlett Learning, LLC © Jonesnary vasodilator; & Bartlettno increase in ICP. Learning, LLC NOT FOR SALE OR DISTRIBUTION NOTused forFOR rate SALEDiltiazem pre -OR DISTRIBUTION control in SVT. ferred in patients with severe LV dysfunction. Contrain- Severe aortic Sick sinus syn- Sick sinus syn- dications stenosis, sick sinus drome, second- drome, second- © Jones & Bartlettsyndrome, Learning, second- or LLCthird-degree or third-degree © Jones & Bartlett Learning, LLC or third-degree heart block. heart block. NOT FOR SALE ORheart DISTRIBUTION block Not dose adjust- Dose adjust- NOT FOR SALE OR DISTRIBUTION compatible with ment in renal ment in hepatic NaHCO3 (5%) or or hepatic impairment. Can lactated ringers. impairment, cause ventricular Dose adjustment porphyria. Can arrhythmias. in renal or hepatic cause ventricu- © Jones & Bartlett Learning, LLCimpairment lar arrhythmias. © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONNegative 0 0 + NOT FOR SALE OR DISTRIBUTION inotrope Negative + 0 0 chronotrope Coronary + ++++ ++ © Jones & Bartlett Learning, LLC vasodilator © Jones & Bartlett Learning, LLC Systemic + ++++ ++ NOT FOR SALE OR DISTRIBUTION vasodilator NOT FOR SALE OR DISTRIBUTION

■■ 5.22 Vasopressors–Inotropes

All vasoconstrictors can cause tissue necrosis with Pharm © Jones & extravasationBartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 221 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Noncatecholamine Noncatecholamine sympathomimetic, NE Direct stimulates and indirect agonists B1-2 Alpha 1, chronotrope Inotrope, or D5W 0.2 mg/mL NOT FOR SALE OR DISTRIBUTION Ephedrine NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Dopexamine (Dopacard) Dopexamine Potent agonists B2 & D2, weak B1, agonists B2 & D2, weak Potent D1; no effect on alpha moderate receptors. 800 mcg/mLMix in D5W or NS to 50 mg in 250 mL NS

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Dopamine (Intropin) Endogenous sympathetic sympathetic Endogenous Direct & catecholamine. indirect agonists mod A1, B1, D1; vasoconstrictorInotrope, stimulant Cardiac 400 mg/250 mL NS, LR or D5W

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Dobutamine-Ephedrine Dobutamine (Dobutrex) Direct acting synthetic catecholamine—strong beta 2 beta 1, weak agonists Inotrope 500 mg/250 mL D5W or NS 2000 mcg/mL 1600 mcg/mL

Pharm TABLE 5-32 © Jones & Bartlett Learning,Receptors LLCAction Mix Concentr. © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 222 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

NOT FOR SALE OR DISTRIBUTION Bolus: 2.5–10 mg Infu- sion: 2–20 mcg/min; max 150 mg/24 hrs / 10–60 mins Immediate NOT myocardial CO, Increase if hy- give contractility, FOR HR with slow potensive HTN, tachycardia, SALEbronchodilator OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION POSSIBLE APPROVAL IN USA SOON . APPROVAL POSSIBLE IV infusion 0.5–1 mcg/kg/min Max 6 mcg/kg/min arte- & chronotrope; Mild inotrope decr SVR and to rial vasodilation pulmonary resistance vasc nausea and vomiting, Causes angina arrhythmias, 1

© Jones & Bartlett Learning, LLCor): 10–20 © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION dopa1 (inodilator): beta1 0.5–3 mcg/kg/min alpha 3-10 mcg/kg/min (inoconstrict min mcg/kg to CO; low Hypotension, & mesenteric incr renal shock blood flow, arrhythmias, Angina, PAP increases

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 2–20 mcg/kg/min; Max 2–20 mcg/kg/min; 40 mcg/kg 1–4 mins / 10–20 2–3 mins / 10–15 / 11 mins unknown without much incr CO To in HR; heart failure, incr. output states cardiac low HTN, arrhythmias, coronary tachycardia, artery vasodilator, improved hypokalemia, urinary output Pharm © Jones & BartlettDose Learning,Onset / Duration for Used LLC Side Effects © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 223 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC No effect No on uterine give Don’t blood flow. with hyper- in patients other sensitivities to sympathomimetics; angle-closure glaucoma, thyrotoxicosis increase increase decrease increase NOT FOR SALE OR DISTRIBUTION Ephedrine NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Dopexamine (Dopacard) Dopexamine Contraindications: thrombocy- Contraindications: aortic HOCM, topenia, stenosis, Dopaminer-pheochromocytoma. over gic agonist—has advantages & dopamine -less arrhythmogenic effectsalpha vasoconstrictor increase decrease slight

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Dopamine (Intropin) Contraindicated in Contraindicated pheochromocytoma, tachyarrhythmias; of stored release induces with Use norepinephrine; cause may inhibitors MAO HTN crisis increase no effectto increased no effectto increased decrease effect no

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Dobutamine (Dobutrex) in Contraindicated hypertrophic idiopathic subaortic Does stenosis. endog- not cause release enous norepinephrine minimal minimal increasedecreased decreased increase Pharm Dobutamine-Ephedrine, continued © Jones & Bartlett Learning,Notes LLC HR BP SVR PVR © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 224 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 225 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-33 Epinephrine–Norepi Epinephrine Isoproterenol Norepinephrine (Adrenalin) (Isuprel) (Levophed) Receptors Endogenous Synthetic Endogenous sympa- © Jones & Bartlett Learning, LLC sympathetic cat- ©catecholamine Jones &thetic Bartlett catecholamine. Learning, LLC echolamine. Direct pure Beta 1 & 2 Direct acting, potent NOT FOR SALE OR DISTRIBUTION acting agonists, NOTagonists FORalpha SALE 1, moderate OR B DISTRIBUTION Alpha 1, beta 1–2 1 & 2 agonists Action Inotrope, Chemical pace- Inotrope, vasoconstrictor maker, has inotro- vasoconstrictor pic & chronotropic © Jones & Bartlett Learning,properties LLC © Jones & Bartlett Learning, LLC Mix 4 mg/250 mL NS 2 mg / 250 mL 4 mg/250 mL NOT FOR SALE ORor D5W DISTRIBUTIOND5W or NS D5W or D5NS NOT FOR SALE OR DISTRIBUTION Concentr. 16 mcg/mL 8 mcg/mL 16 mcg/mL Dose ACLS IV push: 1 mg Bolus IV: dilute Initial infusion: 0.5–1 q 3 mins Beta2: 0.2 mg mcg/min Maint 1–2 mcg/min; Isuprel in 9 mL of infusion; 2–12 mcg/ Beta 1: 2-5 mcg/ NS - 0.02–0.06 mg min or 0.01–0.2 mcg/ © Jones & Bartlett Learning, LLCmin Alpha 1: 5–10 IV infusion kg/min © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONmcg/min Alpha & 0.5–5 mcg/min NOT FOR SALE OR DISTRIBUTION Beta: 10–20 mcg/ min or 0.01–0.2 mcg/kg/min Onset / 30 secs / 20–30 Immediate / 30 secs / 3 mins Duration mins < 1 hr © Jones & Bartlett Learning, LLC Used for To increase CO & ©Use withJones CHF with &Refractory Bartlett hypoten- Learning, LLC increase BP; bradycardia; drug sion, shock; increases NOT FOR SALE OR DISTRIBUTION bradycardia, for NOTof choice for FOR treat- SVR SALE OR DISTRIBUTION bronchospasm, ment of bradycar- asthma, shock dia in patient with complete heart block. Asthma or pulmonary HTN Pharm © Jones & Bartlett Learning, LLC continues © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 225 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 226 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Epinephrine–Norepi, continued Epinephrine Isoproterenol Norepinephrine (Adrenalin) (Isuprel) (Levophed) Side Vent. ectopy, Increased con- Variable CO, decr © Jones & Bartlett Learning, LLC Effects HTN, angina, ©tractility Jones & CO, &renal Bartlett blood flow, Learning, LLC NOT FOR SALE OR DISTRIBUTION bronchodilation. NOTbronchodilator, FOR SALEhyperglycemia; OR DISTRIBUTION hyperglycemia hypotension, angina, due to anti- myocardial tachyarrhythmias insulin effect. ischemia, SVR may be supraventricular decreased, arrhythmias © Jones & Bartlettmaintained, Learning, or LLC © Jones & Bartlett Learning, LLC increased de- NOT FOR SALE ORpending DISTRIBUTION on dose NOT FOR SALE OR DISTRIBUTION Notes Significant Increases myo- Increases myocardial increase in myocardial demand oxygen demand. cardial oxygen with increased Intense constriction demand. Proto- heart rate. Do in all vasc beds; give © Jones & Bartlett Learning, LLCtype adrenergic not use as a through© central Jones line & Bartlett Learning, LLC agonist; activated vasopressor if possible. Avoid NOT FOR SALE OR DISTRIBUTIONvia adrenal MAO NOTinhibitors FOR SALE OR DISTRIBUTION medulla Use with MAO inhibitors may cause HTN HR increase increase reflex brady © Jones & Bartlett Learning, LLC BP increase ©sl. Jones incr or no effect &increase Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION SVR increaseNOT decrease FOR SALE increase OR DISTRIBUTION PVR increase decrease increase Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 226 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 227 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-34 Phenylephrine–Vasopressin Phenylephrine Vasopressin (Neosynephrine) (Pitressin) Direct acting, Alpha 1 agonist endogenous antidiuretic hormone; © Jones & Bartlett Learning, LLC ©V1: bloodJones vessels; V2: & collecting Bartlett tubule Learning, LLC NOT FOR SALE OR DISTRIBUTION NOTin kidney FOR SALE OR DISTRIBUTION Direct vasoconstrictor direct arterial, mesenteric vasoconstriction through activation of smooth muscle receptors 20 mg/250 mL D5W or NS 40 u in 100 mL © Jones & Bartlett80 mcg/mL Learning,0.4 u/mL LLC © Jones & Bartlett Learning, LLC Bolus: 40–160 mcg infusion: IV bolus: 40 u Infusion: 0.20.4 u/min to NOT FOR SALE10–200 mcg/min OR or DISTRIBUTION0.01–0.2 max 0.9 u/min NOT FOR SALE OR DISTRIBUTION mcg/kg/min Immediate / 5–15 mins 1–3 mins / 45 mins Use in vasodilated state with Alternative to epinephrine in treating tachycardia, to slow HR in SVT countershock-refractory vent fibrillation © Jones & Bartlett Learning,with hypotension; LLC low SVR (VF), maintaining adequate ©SVR sepsis.Jones & Bartlett Learning, LLC Diabetes insipidus insufficient ADH. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Arrhythmias, HTN Avoid with vascular disease; H2O reabsorption in renal tubules; decr urine, decr in splanchnic blood flow & in platelet concentration No effect on myocardial oxygen no actions on β-adrenergic receptors, demand. Decr renal, splanchnic & so it may produce less tachycardia than © Jones & Bartlett Learning, LLC cutaneous flow, decr coronary ©epinephrine; Jones metabolic & acidosisBartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION flow. Avoid MAO inhibitors. NOT FOR SALE OR DISTRIBUTION reflex brady no change increase increase marked increase marked increase

minimal increase unknown Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 227 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 228 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ 5.23 Vasodilators Vasodilator-Alpha Blockers Beta-blockade may be instituted when alpha blockers are initiated to attenuate tachycardia. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION TABLE 5-35 PhentolamineNOT FOR SALE OR DISTRIBUTION Alpha Blockers Phentolamine (Regitine)

Class Competitive antagonist at alpha1-2, histamine and serotonin receptors Action Primarily arterial vasodilation with little venodilation. © Jones & BartlettMix Learning,10 mg in 500 mL D5W LLC © Jones & Bartlett Learning, LLC NOT FOR SALEConcentr. OR DISTRIBUTION20 mcg/mL NOT FOR SALE OR DISTRIBUTION Dose Bolus: 1 to 5 mg or 30–70 mcg/kg IV infusion: 1 to 20 μg/kg/min or 0.5–1 mg/min Onset / Immediate / 10–30 mins Duration © Jones & Bartlett Learning,Used for LLCGood for high norepinephrine states, i.e.,© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONpheochromocytoma or clonidine withdrawalNOT FOR SALE OR DISTRIBUTION Side effects Hypoglycemia, hypotension, AMI, arrhythmias, histamine release, increased gastric acid, cerebrovascular spasm Notes α2 stimulation decreases NE release. Used if vasopressors infiltrated into tissue from peripheral IV. See unopposed beta effects. © Jones & Bartlett Learning, LLC HR reflex increase© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Contractility increased NOT FOR SALE OR DISTRIBUTION BP decreased SVR large decrease PVR decreased slightly Pharm Preload decreased © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 228 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

TABLE 5-36 Ganglionic Blocker Ganglionic Blocker Trimethaphan (Arfonad) © Jones & Bartlett Learning, LLC Used for HTN emergencies© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Action PeripheralNOT vasodilation, FOR reflexive SALE tachycar- OR DISTRIBUTION dia, competes with nicotinic acetylcholine transmission Dose 10–20 mcg/kg/min Side effects prolonged neuromuscular blockade and © Jones & Bartlett Learning,potentiation of LLC neuromuscular blocking © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONagents, hypotension, urinary retention; NOT FOR SALE OR DISTRIBUTION pupillary mydriasis, histamine release; rapid onset tachyphylaxis Notes Ganglionic blockers interfere with neurotransmis- sion at ANS ganglia without inducing nicotinic neuromuscular blockade © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Vasodilator-Phosphodiesterase Inhibitors Do not stimulate either alpha or beta receptors; they act as an inotrope and vasodilator by inhibiting phosphodiesterase. Blocking the phosphodiesterase enzyme prevents the breakdown of cAMP and cGMP (intracellular second © Jones & Bartlett Learning, LLC messengers), which can have© Jones many effects, & Bartlettincluding Learning, LLC smooth muscle relaxation. These drugs are also used to NOT FOR SALE OR DISTRIBUTION inhibit platelet aggregation.NOT FOR SALE OR DISTRIBUTION Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 229 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 230 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-37 Phosphodiesterase Inhibitors Enoximone Inocor (Amrinone or Milrinone (Perfan) Inamrinone) (Primacor) Class imidazole phos- Pyridine phosphodiesterase inhibitors © Jones & Bartlett Learning, LLC phodiesterase © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION inhibitor NOT FOR SALE OR DISTRIBUTION Action vasodilator, Inotrope, vasodilator; does not act via weak inotrope & beta receptors chronotrope. Mix Unknown, new 400 mg in 250 mL in 50 mg/200 mL to U.S. 0.9% NS Do not mix in in D5W or NS © Jones & Bartlett Learning,dextrose LLC solutions © Jones & Bartlett Learning, LLC NOT FOR SALEConcentr OR DISTRIBUTION1.6 mg/mL 200 mcg/mL NOT FOR SALE OR DISTRIBUTION Dose Loading: 0.25–1 0.75 mg/kg over 2–3 Load: 50 mcg/ mg/kg slow IV mins, repeat in 30 mins kg over 10 Infusion: 1.25–7.5 if needed. Infusion: mins Infusion: mcg/kg/min; max 5–20 mcg/kg/min, 0.375–0.75 © Jones & Bartlett Learning, LLC24 mg/kg/24 hrs max 10 mg/kg daily ©mcg/kg Jones min & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONOnset / Rapid onset / 2–5 mins / 0.5–2 hrsNOT 5–15 mins FOR / SALE OR DISTRIBUTION Duration elim half-life is 3–6 hrs about 3–4 hours in normal subjects but about 7 hours in patients with cardiac failure © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Used for CHF Treats decreased CO Treats de- NOT FOR SALE OR DISTRIBUTION NOTand CHF; FOR to decrease SALE creased ORCO and DISTRIBUTION SVR/preload; pulmo- CHF, pulmonary HTN nary HTN, RV failure; given to decrease Pharm SVR/preload © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 230 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 231 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Phosphodiesterase Inhibitors, continued Side Decreases CO and Decreases preload; hypotension, Effects reduces ventricu- decreases SVR and PVR lar preload in car- © Jones & Bartlett Learning, LLC diogenic shock © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Does not increase NOTTachycardia FOR at higher SALETachyarrhyth- OR DISTRIBUTION myocardial oxy- dosing, arrhythmias, mias (SVT), gen consumption hepatotoxicity ventricular arrhythmias, hypotension, angina, © Jones & Bartlett Learning, LLC hypokalemia, © Jones & Bartlett Learning, LLC thrombocyto- NOT FOR SALE OR DISTRIBUTION penia NOT FOR SALE OR DISTRIBUTION Notes abnormal LFTs, Dose adjust- thrombocytope- ment needed nia. 1/10th as po- in renal tent as milrinone disease © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONNatural Vasodilators: bradykinin, histamine, serotonin,NOT FOR SALE OR DISTRIBUTION prostaglandins, ↑ K, ↑ H, ↑ CO2, ↑ Mg, ↑ Na In treating hypertension, before vasoactive medications are given, other pharmacologic interventions include giving or increasing: volatile anesthetics, opioids, propofol, etc. © Jones & Bartlett Learning, LLC Controlled Hypotensive© Technique Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION General antihypertensivesNOT include: FOR alpha SALE and beta OR DISTRIBUTION blockers, calcium channel blockers, angiotensin II antagonist, ace inhibitors, phosphodiesterase inhibitors, ganglionic blockers; diuretics.

Pharmacologically lowering blood pressure can be Pharm © Jones & Bartlettdone to aLearning, predetermined levelLLC to minimize blood © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 231 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 232 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION loss, improve surgical visibility, and decrease transfu- sion requirements. Done in all types of surgical cases but especially neurosurgery, orthopedics, and in patients who choose not to receive blood products (Jehovah’s Witness) or who may be difficult to cross- © Jones & Bartlett Learning, LLC match. Use caution© in patientsJones with & cardiac/renal/ Bartlett Learning, LLC cerebrovascular/peripheral vascular disease, chronic NOT FOR SALE OR DISTRIBUTION hypertension, fixedNOT cardiac FOR output, SALEand/or anemia. OR DISTRIBUTION Meticulous attention to mean blood pressure is important, especially in cases where the patient is in the prone or sitting (beach-chair) positions. Correlating to lower limit of cerebral perfusion pressure © Jones & Bartlett(CPP) will Learning, help to maintain LLC adequate perfusion to © Jones & Bartlett Learning, LLC vital organs. CPP = MAP—CVP (or ICP). NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION A gradual decrease in BP is much preferred to a rapid decrease. Complications Related to Reduced Tissue Perfusion: delayed recovery, renal disturbances, reflex tachycardia, cerebral thrombosis, hepatic necrosis, MI and/or © Jones & Bartlett Learning,cardiac LLC arrest, blindness © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION TABLE 5-38 Fenoldopam–Nisiritide Fenoldopam Hydralazine Nisiritide (Corlopam) (Apresoline) (Natrcor) Action Vasodilator- D1 Direct arterial B-type natri- © Jones & Bartlett Learning, LLC agonist—stimulates© Jonesvasodilator & Bartletturetic peptide Learning, LLC cAMP (BNP)—venous NOT FOR SALE OR DISTRIBUTION NOT FOR SALE& arterial OR DISTRIBUTION vasodilator Mix 20 mg/500 mL 1.5NS — 1.5 mg in 250 mL or D5W D5W, NS Pharm Concentr. 40 mcg/mL 20 mg/mL 6 mcg/mL © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 232 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 233 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Fenoldopam–Nisiritide, continued Dose Start infusion at 0.01 2.5–40 mg, dose Bolus: 2 mcg/kg mcg/kg/min, double over 1 min, re- IV; Infusion: 0.01 dose at 5–10 min peat as needed. mcg/kg/min © Jones & Bartlett Learning, LLC intervals until BP © Jones & BartlettMax dose 0.03 Learning, LLC controlled—max dose mcg/kg/min NOT FOR SALE OR DISTRIBUTION of 1.6 mcg/kg/min. NOT FOR SALE OR DISTRIBUTION

Onset / < 2 mins / 1–4 hrs 5–20 mins / 15 mins / Duration 2–6 hrs > 60 mins Used for Rapid decr in BP. HTN with slow CHF with © Jones & BartlettGood Learning, in manage- heart LLC rate, CHF dyspnea at rest, © Jones & Bartlett Learning, LLC ment of perioperative unresponsive Decreases R NOT FOR SALE ORhypertension DISTRIBUTION or in to digoxin and atrial pressure, NOT FOR SALE OR DISTRIBUTION patients with renal diuretics PCWP, SVR; dysfunction-decr re- improves CO nal vasc resistance & stimulates diuresis. © Jones & Bartlett Learning,Side LLCHypokalemia, hypo- Sodium Hypotension,© Jones & Bartlett Learning, LLC Effects tension, tachycardia, retention, can fever, lethargy, NOT FOR SALE OR DISTRIBUTIONperipheral edema increase CO syncope,NOT chest FOR SALE OR DISTRIBUTION pain; renal dysfunction Notes Use < 48 hours. Smooth muscle Endogenous hor- Has no alpha or relaxation; use mone released © Jones & Bartlett Learning, LLC beta activity with © Jonescautiously in CV & Bartlettby ventricles in Learning, LLC no effect on HR or or cerebrovascu- volume overload. NOT FOR SALE OR DISTRIBUTION contractility NOTlar disease FOR SALEDo not shake OR DISTRIBUTION vial of drug, rock gently. Caution in renal dysfunction Pharm continues © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 233 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 234 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Fenoldopam–Nisiritide, continued Fenoldopam Hydralazine Nisiritide (Corlopam) (Apresoline) (Natrcor) © Jones & Bartlett Learning, LLC HR reflex tachycardia© Jones can cause & Bartlett0 Learning, LLC tachycardia NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION BP decrease decrease decrease SVR decrease decrease decrease PVR 0 0 decrease © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALETABLE 5-39 OR Nitroglyc DISTRIBUTIONerin–Nitroprusside NOT FOR SALE OR DISTRIBUTION Nitroglycerin Sodium Nitroprusside (Tridil) (SNP, Nipride) Vasodilator: venous > arterial; Release of nitric oxide causing vaso- decreases preload dilation: arterial > venous; decreases © Jones & Bartlett Learning, LLC preload & afterload © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION50/250 premix 100 mg/250 mL D5W NOT FOR SALE OR DISTRIBUTION 200 mcg/mL 400 mcg/mL 5–400 mcg/min 1 mL/hr = 3 Infusion: 10–280 mcg/min or 2–4 mcg/ mcg/min, max 200 mcg/min or kg/min Max: 10 mcg/kg/min 0.2–4 mcg/kg/min © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 1–2 mins / 3–5 mins 30 secs / 1–10 mins NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Angina, coronary artery spasm, Rapid decr in BP; HTN, to decrease acute MI, increased preload; to SVR (afterload), aortic dissection, LV decrease preload/CVP, CHF; decr dysfunction LVEDP & LVEDV, decr myocardial

Pharm O2 consumption © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 234 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 235 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Nitroglycerin–Nitroprusside , continued Hypotension, increased cere- Hypotension, palpitations, increased bral blood flow; headaches, cerebral blood flow, methemoglobinemia methemoglobinemia © Jones & Bartlett Learning, LLC Marked reduction in preload, ©Can Jones cause cyanide & and Bartlett thiocyanate Learning, LLC some reduction in afterload; can toxicity. Contraindicated in pregnancy NOT FOR SALE OR DISTRIBUTION cause methemoglobinemia. In- NOTand renal FOR disease. Degraded SALE by light; OR DISTRIBUTION creases cerebral blood flow. Use cover infusion bag glass bottle and special tubing for infusion reflex tachycardia increase © Jones & Bartlettdecrease Learning,decrease LLC © Jones & Bartlett Learning, LLC NOT FOR SALEdecrease OR DISTRIBUTIONdecrease NOT FOR SALE OR DISTRIBUTION decrease decrease

© Jones & Bartlett Learning,■■ 5.24 Antiarrhythmic LLC IV Agents © Jones & Bartlett Learning, LLC All antiarrhythmic drugs are used cautiously in patients NOT FOR SALE OR DISTRIBUTIONwith renal or hepatic disease. When renal or hepaticNOT FOR SALE OR DISTRIBUTION dysfunction is present, a dosage reduction may be necessary.

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 235 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 236 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION t - (Cardizem) © Jones & Bartlett Learning, LLC © Jones & Bartlett (calcium tensive Learning, LLC 15 mg/hr for up to up to 15 mg/hr for tihyper

NOT FOR SALE OR DISTRIBUTION NOT FOR– SALE OR DISTRIBUTION follow with infusion a follow 0.25 mg/kg over 2 mins, 2 mins, over 0.25 mg/kg in 15 mins repeat may May with 0.35 mg/kg. 5 Diltiazem channel blocker) 125 mg in mL NS or D5W 1 mg/mL 24 hrs. Antianginals, antiar Antianginals, ven- rapid (SVT, rhythmic or Aflutter), tricular AFib an - - ophylaxis ophylaxis

2 mg/min – aine, pr aine,

© Jones & Bartlett Learning, as repeat 30 sec, LLC © Jones & Bartlett Learning, LLC – (Bretylol) 2 Gm in 500 mL D5W premix over IV bolus: 5 mg/kg 15 & other VTach Treat arrhyth ventricular to mias resistant lidoc Bretylium against VFib NOT FOR SALE OR DISTRIBUTIONnecessary max 30 to Infu in 24 hrs. mg/kg sion: 1 NOT FOR SALE OR DISTRIBUTION e med

, giv © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC u filter: Load 150 mg u filter: Amiodarone (Cordarone) only 1800 mcg/mL 10 mins, in 100 mL over 4 mg/mL then, 1 mg/min (360 mg) then next 6 hours, over 0.5 mg/min to decrease next 18 hrs (540 mg) over Suppression of VFib, Prolongs pulseless VTach. action and potential refractory period NOT FOR SALE OR DISTRIBUTION Infusion only thr NOT FOR SALE OR DISTRIBUTION

entrant pathway in pathway entrant © Jones & Bartlett Learning, LLC © Jones with 2 min later & Bartlett Learning, LLC – (Adenocard) Adenosine not diluted3 mg/mL IV bolus, rapid 6 mg by 900 mg in 500 mL D5W repeat if no results, PSVT to Converts N SR—interrupts re- Node AV 1 NOT FOR SALE OR DISTRIBUTION NOT FOR bolus. 12 mg rapid SALE OR DISTRIBUTION Adenosine–Diltiazem

Pharm TABLE 5-40 © Jones & Bartlett Learning,Mix Concentration Dose LLC Action Use © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 236 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

NOT FOR SALE OR DISTRIBUTION – NOT FOR SALE OR DISTRIBUTION Hives, flushing, AV block, flushing, Hives, hypo CHF, arrhythmias, Stevens-Johnson tension, syndrome duration unknown duration Contraindicated in SSS or Contraindicated AV - or third-degree second MI, systolic block, recent BP < 90 mmHg 24 hrs 2 – y © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 10 mins / 6 – 5 Dose timing in- Hypotension, angina, Hypotension, bradycardia No specific No contraindications NOT FOR SALE OR DISTRIBUTION with renal creased insufficienc NOT FOR SALE OR DISTRIBUTION - - second , 7 hrs / – ervals,

© Jones & Bartlett Learning, LLC block, d-degree AV © Jones & Bartlett Learning, LLC unknown duration unknown Decrease FIO2 to < 80% FIO2 to Decrease when on Cordarone decreases pulmonarydecreases resistance vascular or thir Hypotension, CHF, ARDS, CHF, Hypotension, pul pulmonary fibrosis, increases monary toxicity, int PR and QT in Contraindicated SSS NOT FOR SALE OR DISTRIBUTION shock cardiogenic NOT FOR SALE OR DISTRIBUTION 2 mins 2 hrs / peak 3 –

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION / 1 Immediate asthma, Flushing, chest discomfort NOT FOR in SSS Contraindicated or third- or second- block AV degree SALE OR DISTRIBUTION Pharm © Jones & BartlettOnset / Duration Learning,Side Effects LLCContraindication Notes © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 237 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

suppressed, suppressed,

© Jones & Bartlett Learning, LLC © Jonesension, bradycardia & Bartlett Learning, LLC in 50 mL D5W 16 mg/mL rate 200–400 mg at ≤ 10 mg/min until arrhythmia hypot widened or QRS complex prevention AFib/AFlutter, ventricular of recurrent decrease arrhythmias, excitability, myocardial conductionslow velocity NOT FOR SALE OR DISTRIBUTION Quinidine NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION (Pronestyl) 50 mg/min (or IV push: 10 to 100 mg every 2–5 mins) up to arrhythmia or until 17 mg/kg or hypotension suppressed, QRS widened > 50%. If ar- start disappears, rhythmia IV infusion: 1–4 mg/min arrhyth- and atrial Ventricular mainte- CO, decreased mias, conversion of NSR after nance AFib/AFlutter from Procainamide

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Lidocaine (Xylocaine) 2 gm in 250 mL D5W 2 g/250 mL of 0.9% NS8. mg/mLIV push: 1–1.5 mg/ 800 mg quinidine (10 mL) doses repeat may kg; q of 0.5–0.75 mg/kg 8 mg/mL a total 5–10 min up to may dose of 3 mg/kg; then start continuous fusion of 1–4 mg/min. stable VFib, VTach, vent wide complex ectopy

NOT FOR SALE OR DISTRIBUTION Ibutilide (Corvert) 0.1 mg/mL Undiluted: 1 mL/min Give 0.1 mg/mL NOT 1 mg over > 60 kg: be repeated may 10 mins, end of dose 10 mins after FOR over 0.01 mg/kg < 60 kg: be repeated may 10 mins, end of dose 10 mins after SALE onset recent Conversion to NSR AFib/Aflutter OR DISTRIBUTION Ibutilide-Q

Pharm © Jones & Bartlett TABLE 5-41 Learning,Mix Concentration Dose LLC Action Use © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 238 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

NOT FOR SALE OR DISTRIBUTION de torsades Hypotension, agranulocytosis pointes, NOT FOR of a pacemaker), absence gravis myasthenia excit- myocardial Decrease SALE conduction slows ability, velocity OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION immediate / 3–4 hrsimmediate heart asystole, block, Seizures, arrhythmias, ventricular 1–5 min / 6–8 hrs hypotension, arrest, cardiac Rapid IVpush agranulocytosis, or asystole. VFib can cause gravis block, myasthenia AV defects Conduction (in the or Dose in renal adjustment disease cardiac

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 10–20 min cardiac Seizures, anaphylaxis, arrest, AV CNS depression, block, hypotension, paresthesia block with liver Caution disease and all heart blocks

NOT FOR SALE OR DISTRIBUTION 45 mins / ≤ 24 hrsarrhythmias / immediate NOThypersensitivity FOR cur- inward slow heartActivates Third-degree SALE of sodium in cardiac rent in delayed resulting tissue, prolonged repolarization, action duration potential OR DISTRIBUTION Pharm © Jones & BartlettOnset / Duration Learning,Side Effects Contraindica- LLCtion Notes © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 239 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 240 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ 5.25 Herbals All herbal supplements should be discontinued 2 weeks before surgery. © Jones & Bartlett Learning, LLC TABLE 5-42 Herbals © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Risk with NOT FOR SALE OR DISTRIBUTION anesthesia / surgery Herbal Used for: Increased Black Used to decrease BP; can cause bleeding risk cohosh bleeding Gingko Taken to improve memory, biloba enhances antiplatelet and anti- © Jones & Bartlett Learning, LLCthrombotic; can cause bleeding © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONGarlic Used to lower BP and choles- NOT FOR SALE OR DISTRIBUTION terol, inhibits platelet aggregation. Can increase effects of blood thinners with increased bleeding Ginseng Inhibits clotting; interferes with © Jones & Bartlett Learning, LLC warfarin © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Ginger Increased risk of bleeding,NOT esp. FOR if SALE OR DISTRIBUTION taken with aspirin and ginkgo Fish oil Promotes blood thinning; can increase bleeding Dong quai Used for menopausal/menstrual symptoms, shown to affect © Jones & Bartlett Learning, LLC © Jonesestrogen & and Bartlettother hormones; Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FORmight slow SALEblood clotting OR DISTRIBUTION Feverfew Used to treat migraine headaches, arthritis, menstrual cramps, to reduce inflammation Hoodia Appetite suppressant; can Pharm increase bleeding © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 240 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Chapter 5 Anesthesia Pharmacology 241 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Herbals, continued Cardiovascular risk Ephedra Used for weight loss and (ma-huang) asthma. Can cause HTN, tachycardia, arrhythmias, and stroke © Jones & Bartlett Learning, LLC Garlic© Jones Can drop BP& Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION GinsengNOT EnergyFOR boost; SALE can cause HTN OR and DISTRIBUTION tachycardia Hoodia Can increase or decrease BP depending on other meds patient taking Guarana Caffeine active ingredient; can © Jones & Bartlett Learning, LLCincrease BP, cause cerebral © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONvasoconstriction NOT FOR SALE OR DISTRIBUTION Sedating risk Kava Decreases anxiety, CNS depress/sedative—potentiate barbiturates/benzodiazepines/ muscle relaxants St. John’s Relieves depression and anxiety; © Jones & Bartlett Learning, LLC wort can cause sedation.© Inhibit Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION serotonin neurotransmittersNOT FOR SALE OR DISTRIBUTION reuptake (similar to SSRI Prozac) Valerian Relieves anxiety; can cause sedation. May increase GABA levels Gingko Improves memory; can cause © Jones & Bartlett Learning, LLC biloba© Jonesincreased sedation& Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION GingerNOT Antiemetic,FOR anti-inflammatory;SALE OR DISTRIBUTION can increase sedation continues Pharm © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 241 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 242 Chapter 5 Anesthesia Pharmacology NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Herbals, continued Risk with anesthesia / surgery Herbal Used for: Interact with other Echinacea Increase immunity to fight colds, © Jones & Bartlett Learning, LLC medications © Jonesinfections; & can Bartlett lead to liver Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FORinflammation/damage SALE withOR DISTRIBUTION anesthesia. Contraindicated in autoimmune diseases Kava Calms anxiety; can cause liver damage Licorice Used to treat heartburn; can © Jones & Bartlett Learning, LLCcause hypokalemia; can cause © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONexcess mineralocorticoid activity NOT FOR SALE OR DISTRIBUTION manifested by sodium/water retention, hypervolemia, HTN, and edema St. John’s Alters metabolisms of other wort drugs (cyclosporine, warfarin, © Jones & Bartlett Learning, LLC steroids) © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Valerian Relieves anxiety; NOTcan cause ir-FOR SALE OR DISTRIBUTION regular heart rhythm Hoodia Appetite suppressant; can injure liver cells Photosensitivity St. John’s Photosensitivity rarely occurs © Jones & Bartlett Learning, LLC (skin laser procedure) wart© Joneswith very & high Bartlett doses Learning, LLC NOT FOR SALE OR DISTRIBUTION DongNOT quai FOR Increased photosensitivitySALE OR DISTRIBUTION Hypoglycemia Ginseng Energy boost; can lower blood sugar Hoodia Shown to affect hormones; can make brain see blood glucose lev- Pharm els greater than they really are © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE© Jones OR & Bartlett DISTRIBUTION Learning, LLC. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

9781284115147_CH05_151_242.indd 242 24/10/16 11:04 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION