Chapter 3 Anesthetic Agents and Adjuncts PDF

Chapter 3 Anesthetic Agents and Adjuncts Anesthesia and Analgesia for Veterinary Technicians and Nurses, 6th ed. Thomas and Lerche Learning Objectives—Lesson 3.1 (1 of 2) 1. Classify anesthetic agents and adjuncts based on route of administration, tim...

Chapter 3 Anesthetic Agents and Adjuncts Anesthesia and Analgesia for Veterinary Technicians and Nurses, 6th ed. Thomas and Lerche Learning Objectives—Lesson 3.1 (1 of 2) 1. Classify anesthetic agents and adjuncts based on route of administration, time of administration, principal effect, or chemistry. 2. Differentiate agonists, partial agonists, agonist– antagonists, and antagonists based on their action and effect. List anesthetics and adjuncts that can be reversed. 3. Describe the effect of protein binding, lipid solubility, and redistribution on the pharmacokinetics and pharmacodynamics of injectable anesthetics. Learning Objectives—Lesson 3.1 (2 of 2) 4. Apply principles of safe administration of anesthetic agents and adjuncts. 5. List anesthetic agents and adjuncts commonly used as preanesthetic medications, and describe their indications, mode of action, effects, adverse effects, and use.  Anesthetic Agents and Adjuncts  Anesthetic agent  Any drug used to induce a loss of sensation with or without unconsciousness  Adjunct  A drug that is not a true anesthetic, but that is used during anesthesia to produce other desired effects such as anxiolysis, sedation, muscle relaxation, analgesia, reversal, neuromuscular blockade, or parasympathetic blockade  Classification of Anesthetic Agents and Adjuncts  Route of administration  Time of administration  Principal effect  Chemistry Clinically Important Properties of Anesthetic Agents  Pharmacokinetics  Pharmacodynamics  Drug distribution  Target tissues and stimulation  Central nervous system—depression or stimulation Agonists, Partial Agonists, Mixed Agonist- Antagonists, and Antagonists  Agonists  Bind to and stimulate target tissue  Include most anesthetic agents and adjuncts  Partial Agonists and Mixed Agonist- Antagonists  Opioids  Antagonists  Bind to target tissue but don’t stimulate  Used as reversal agents  Analgesia  Most general anesthetics are not analgesics  Must provide analgesic before and after the procedure  No pain perception while anesthetized  True analgesics don’t provide general anesthesia  Route of Administration  Inhalant  Injectable  Intravenous  Intramuscular  Subcutaneous  Oral  Topical  Drug Combinations  Don’t mix drugs in a single syringe unless they are compatible  Don’t administer a drug combination if a precipitate develops when the drugs are mixed  Most anesthetic agents and adjuncts are water soluble  Diazepam is not water-soluble  Controlled Substances Regulations  Governmentally regulated drugs  Five drug schedules: I, II, III, IV, V  Dispensed Enforced  CSA in the U.S. -- DEA in the U.S.  CDSA in Canada -- RCMP in Canada  Controlled Substances Recordkeeping  Enforced by the DEA  Inventory every 2 years in a veterinary practice  Use of a controlled substance log Ordering Controlled Substances  Schedule II drugs – only by DEA Form 222  Allows careful tracking  Schedule III and IV – no special order form needed  Storing Controlled Substances  Schedule II through V drugs  Securely locked, substantially constructed cabinet  Not left on countertops or other public areas  Opioid agonist and antagonist drugs  Stored in a safe or steel cabinet  Unexpected, significant loss or suspected theft must be reported to the DEA and local police within 1 business day  Prescribing Controlled Substances  Take precautions to prevent abuse  Keep Rx pads in a secure location  Prevent illegal alteration of the prescription  Preanesthetic Medications (1 of 2)  Anxiolytics  Anticholinergics  Tranquilizers and sedatives  Phenothiazines  Benzodiazepines  Alpha2-adrenoceptor agonists (alpha2-agonists)  Opioids  Antiemetics  Preanesthetic Medications (2 of 2)  Calm or sedate excited animal  Minimize adverse drug effects  Reduce dose of concurrent drugs  Smoother anesthetic induction and recovery  Analgesia  Muscle relaxation  Anxiolytics  Used to minimize stress, anxiety, and fear  Gabapentin (mostly cats)  Analgesic properties, especially for neuropathic pain  Anxiolysis similar to tranquilizers (dogs and cats)  Anticonvulsant  Trazodone (mostly dogs)  Reduces stress, fear, and anxiety  Preanesthetic Anticholinergics  Parasympatholytic drugs—block acetylcholine  Prevent and treat bradycardia  Decrease salivary secretions  Atropine and glycopyrrolate (dogs and cats)  Intravenous, intramuscular, subcutaneous, or intratracheal  Atropine—faster onset, shorter peak, shorter duration  Glycopyrrolate—slower onset, longer peak, longer duration  Anticholinergic Effects  Central nervous system—limited effect  Cardiovascular—prevent bradycardia  Decrease in respiratory and salivary secretions  Bronchodilation  Eye—mydriasis and corneal drying  Decrease in gastrointestinal and lacrimal secretions  Anticholinergic Adverse Effects  Cardiac arrhythmia  Contraindicated in animals with elevated heart rates or cardiac diseases  Temporary bradycardia—atropine  Thickened respiratory and salivary secretions  May lead to airway blockage—cats and ruminants  Intestinal peristalsis inhibition  May lead to colic (horses) or bloat (ruminants)  Tranquilizers and Sedatives  Tranquilizer  Reduces anxiety but not awareness or wakefulness  Sedative  Reduces mental activity, causes sleepiness  Three classes used in veterinary medicine  Phenothiazines  Benzodiazepines  Alpha2-adrenoceptor agonists  Tranquilizers and Sedatives – General Risks  Patient should not be left unattended  Fall risk  Sedatives – can cause respiratory distress  Animals can exhibit unusual behavior when sedated including aggression  Phenothiazines: Acepromazine Maleate  Also known as acepromazine or “ace”  Only drug in class typically used as an anesthetic adjunct  Usually IV or IM route  Effects and Adverse Effects of Phenothiazines  Calming/sedation  Tachycardia or bradycardia  Antiarrhythmic effects  Peripheral vasodilation  Hypotension  Antiemetic  Hypothermia  Penile prolapse in large animals  Decreased PCV  Use of Acepromazine  Dose and needle placement  Increased potency and duration  Geriatrics, neonates, debilitated animals  Breed considerations  Australian shepherds, Collies: use low dose  Giant breeds, Boxers, Greyhounds: increased sensitivity  Terriers and cats: resistance  Overdose treatment  Benzodiazepines  Minor tranquilizers—controlled substances  Diazepam  Zolazepam  Midazolam  Rapid onset of action  Short duration of action  May produce the opposite effect in young, healthy animals  Effects and Adverse Effects of Benzodiazepines  Calming and antianxiety in old or ill patients  Anticonvulsant  Disorientation and excitement in young dogs  Dysphoria/aggression in cats  Muscle fasciculations in horses  Ataxia or recumbency in large animals  Few cardiopulmonary effects  Skeletal muscle relaxation  Pain on IM injection of diazepam  Alpha2-Adrenoceptor Agonists  Also written alpha2-agonists or 2-agonists  Noncontrolled agents  Sedation, analgesia, and muscle relaxation  Large and small animals—intramuscular or intravenous route  Administered before minor procedures  Readily reversed with alpha2-antagonist  Effects and Adverse Effects of Alpha2-Agonists (1 of 2)  Dose-dependent sedation  Analgesia  Agitation or Aggression  Reaction to loud noises  Muscle tremors in horses  Cattle may lie down  Initial hypertension, bradycardia, pale mucous membranes; then hypotension, decreased output, decreased heart rate  Effects and Adverse Effects of Alpha2-Agonists (2 of 2)  Severely decreased heart rate, blood pressure, cardiac output, tissue perfusion  Respiratory depression (can be severe)  Muscle relaxation  Vomiting (in cats and dogs)  Adverse GI effects (bloat, colic)  Hyperglycemia  Hypothermia  Increased urination  Premature parturition (cattle)  Sweating (horses)  Use of Alpha2-Agonists  Use with caution; monitor patients closely  Avoid use in geriatric, diabetic, pregnant, pediatric, or ill patients  Administer anticholinergics 10 to 20 minutes before  Alpha2-Antagonists  Reverse all effects of alpha2-agonists  Beneficial effects—for example, analgesia and sedation  Detrimental effects—for example, bradycardia  Wide margin of safety  Effects of overdose  Neurological—excitement and muscle tremors  Cardiovascular—hypotension and tachycardia  Gastrointestinal—salivation and diarrhea  Opioids  Produce analgesia and sedation  Anesthetic induction when combined with other drugs  Classified as agonists, partial agonists, agonist-antagonists, or antagonists  Most are controlled substances  Administered via intravenous, intramuscular, subcutaneous, oral, rectal, transdermal, subarachnoid, and epidural routes  Wide margin of safety  Commonly Used Opioids  Agonists  Morphine, hydromorphone, methadone, oxymorphone, fentanyl, and meperidine  Partial agonist  Buprenorphine  Agonist-antagonists  Butorphanol and nalbuphine  Antagonists  Naloxone  Opioids: Pharmacodynamics (1 of 2)  Mimic endogenous opioid peptides  β-Endorphins, dynorphins, enkephalins  Analgesia and sedative effects  Result of action on the receptors in the brain and spinal cord  Types of receptors Mu (μ), kappa (κ), and delta (δ), plus many subtypes Each opioid has a different action at each receptor  Opioids: Pharmacodynamics (2 of 2)  Agonists  Bind to and stimulate mu and kappa receptors  Best for moderate to severe pain  Partial agonists  Bind to and partially stimulate receptors  Agonist-antagonists  Bind to mu and kappa receptors, but stimulate only kappa receptors  Antagonists  Bind to but don’t stimulate mu and kappa receptors  Effects and Adverse Effects of Opioids (1 of 2)  CNS depression or excitement depending on dose, route, agent used, species, temperament, pain level  Excellent somatic and visceral analgesia  Dose-dependent bradycardia and respiratory depression  Panting (dogs)  Hypothermia (dogs) or hyperthermia (cats)  Salivation/vomiting (small animals)  Effects and Adverse Effects of Opioids (2 of 2)  Initial vomiting, diarrhea and flatulence, then constipation  Colic and sweating (horses)  Increased responsiveness to noise  Miosis (dogs); mydriasis (cats and large animals)  Decreased urine production and urine retention  Use of Opioids  Preanesthetic  Agonists, partial agonists, or agonist-antagonist  May be used alone or in combination with Tranquilizers Anticholinergics  Analgesia  Prevent and treat postoperative pain  Used with tranquilizer to produce neuroleptanalgesia  Neuroleptanalgesia  A profound state of sedation and analgesia induced by simultaneous administration of an opioid and a tranquilizer  Wide margin of safety when properly administered  Sedation for minor procedures  Induction of general anesthesia—dogs  Not in young, healthy dogs  Not in cats  Opioid Antagonists  Undesirable effects of opioids can be reversed  Central nervous system and respiratory depression  Wake up patient following sedation  Naloxone hydrochloride  Intramuscular or slow intravenous administration  Dogs, horses, cats, exotic mammals  Naltrexone  Used in wild animals  Longer-lasting  Effects of Opioid Antagonists  Reversal of effects of opioid agonists, partial agonists, and agonists-antagonists  Reversal can be complete in a few minutes  Adverse effects are rare  Sudden analgesia loss can cause excitement, anxiety, and sympathetic nervous system stimulation  Prevent by using an agonist-antagonist  Use of Opioid Antagonists  Emergencies  Overdose  Reverse neuroleptanalgesia  Reviving neonates delivered by C-section  If dam received opioids  One drop placed under the tongue Learning Objectives—Lesson 3.2 (1 of 2) 6. List injectable anesthetic drugs in common use, and describe their indications, mode of action, effects, adverse effects, and use. 7. Define dissociative anesthesia; describe the actions and effects of dissociative anesthetics, and explain ways in which these drugs differ from other injectable anesthetics. 8. List the inhalation anesthetic agents in common use, and describe their indications, mode of action, effects, adverse effects, and use. Learning Objectives—Lesson 3.2 (2 of 2) 9. Define vapor pressure, partition coefficient, minimum alveolar concentration (MAC), and rubber solubility; explain the ways in which these properties affect the action and use of inhalant anesthetic agents. 10. Describe the uptake, distribution, and elimination of the commonly used inhalation anesthetic agents.  Injectable Anesthetics  Can produce unconsciousness  Don’t provide analgesia or muscle relaxation  Must be used with other agents to produce complete effects of general anesthesia  Administered intravenously “to effect”  Propofol, etomidate, alfaxalone, and barbiturates  Propofol  Ultra–short-acting, nonbarbiturate anesthetic  Schedule IV for anesthetic induction and short-term maintenance  Small animals, small ruminants, exotic animals, neonates of all species  Other use  Intravenous bolus and CRI to treat status epilepticus in dogs and cats  Effects and Adverse Effects of Propofol  Dose-dependent CNS depression from sedation to general anesthesia  Transient excitement and muscle tremors (induction)  Bradycardia, decreased cardiac output, hypotension  Respiratory depression including apnea  Prolonged apnea, decreased oxygen saturation, cyanosis  Muscle relaxation  Antiemetic effect  Decreased intracranial and intraocular pressure  Pain on IV injection  Propofol Handling and Storage  Shake thoroughly before use  Poor storage characteristics  Egg lecithin, glycerol, and soybean oil support bacterial growth  Use aseptic technique  Discard unused drug within 6 hours of opening  3-year shelf life if unopened  Alfaxalone  Short duration of action  Wide margin of safety  Use intravenously for induction anesthesia and maintenance  Use intramuscularly in cats for deep sedation/light anesthesia  Schedule IV controlled substance (U.S.)  Steroid molecule  Works similar to other hypnotics  Effects and Adverse Effects of Alfaxalone  Dose-dependent CNS depression  Minimal cardiovascular depression  Tachycardia  Hypotension  Respiratory depression including apnea  Muscle relaxation  Excitement during recovery  Etomidate  Administered only intravenously  Begin with ¼ to ½ calculated dose  Adverse effects  Vomiting  Muscle contractions minimized by premedication  Can be administered in repeated boluses for short-term anesthesia  Barbiturates  Large class of controlled drugs  Use as a general anesthetic declined due to new drug development  Specific uses  Short-acting pentobarbital sodium Induce and maintain general anesthesia in lab animals Treat status epilepticus in small animals Euthanasia agent  Long-acting phenobarbital Seizure control Occasionally, sedative in dogs and cats  Dissociative Anesthetics (1 of 2)  Only ketamine is used in veterinary medicine  Used alone  Cats—for minor procedures or to facilitate restraint  Used with other drugs  Tranquilizers and opioids to induce general anesthesia  Subanesthetic dose  CRI for analgesia  Dissociative Anesthetics (2 of 2)  Disrupts nerve transmission in some brain sections  Selective stimulation in parts of the brain  Decreases windup through NMDA inhibition  Trancelike state  Animal appears awake  Immobile and unaware of surroundings  All dissociatives are either metabolized in the liver or excreted unchanged in the urine  Avoid use in animals with liver or kidney disease  Effects and Adverse Effects of Dissociatives (1 of 2)  Cataleptoid state  Intact reflexes  Eyes open, pupils central and dilated  Normal or increased muscle tone  Analgesia (somatic)  Sensitivity to stimuli  Nystagmus  Increased heart rate, cardiac output, mean arterial pressure  Effects and Adverse Effects of Dissociatives (2 of 2)  Decreased inotropy  Apneustic respiration at higher doses  Increased salivary and respiratory tract secretions  Pain after IM injection  Use of Dissociative Anesthetics  Administration: intramuscular or intravenous  Wide margin of safety  Useful in cats and horses  Used in combination with tranquilizers  Short procedures  Anesthetic induction for intubation  Chemical restraint—cats  Immobilization—large and exotic animals  Pain control  No effective reversal agent  Dissociative Anesthetic: Use of Guaifenesin (1 of 2)  Used with ketamine in anesthetic induction protocol  Premedicate with alpha2-agonist or acepromazine  Triple drip: GG, ketamine, xylazine  Used in horses  Maintain anesthesia for less than an hour  Administered IV rapidly until animal is ataxic  Following premedication  Induce when patient is ataxic  Smooth recovery  Dissociative Anesthetic: Use of Guaifenesin (2 of 2)  Part of an anesthetic induction protocol in combination with ketamine  Must premedicate  May cause excitement if there is no premedication  Increased risk of side effects if there is no premedication  Not used as a sole agent  Sedation and analgesia inadequate for surgery  Inhalation Anesthetics  Isoflurane and sevoflurane (halogenated compounds)  Nitrous oxide and desflurane  Enflurane (not used in veterinary medicine)  Halothane (no longer available)  Methoxyflurane (no longer available)  Inhalation Anesthetics: Halogenated Organic Compounds  Isoflurane and sevoflurane are the most commonly used agents in this class  Liquid at room temperature  Stored in a vaporizer on an anesthetic machine  Vaporized in oxygen that flows through the vaporizer  Halogenated Organic Compounds: Mode of Action and Pharmacology (1 of 2)  Liquid anesthetic is vaporized and mixed with oxygen gas  Mixture is delivered to the patient via a mask or endotracheal tube  Mixture travels to lungs (alveoli) and diffuses into the bloodstream  Diffusion rate is dependent on concentration gradient (alveoli/capillary) and lipid solubility  Concentration gradient is greatest during initial induction  Halogenated Organic Compounds: Mode of Action and Pharmacology (2 of 2)  Distribution to tissues is dependent on blood supply  Lipid solubility determines entry into tissues through cell walls  Depth of anesthesia is dependent on partial pressure of anesthetic in the brain  Partial pressure in the brain is dependent on partial pressure of the anesthetic in blood and alveoli  Maintenance of anesthesia is dependent on sufficient quantities of anesthetic delivered to the lungs  Effects and Adverse Effects of Halogenated Inhalation Anesthetics (1 of 2)  Dose-related CNS depression  Hypothermia  Paddling, excitement, and muscle fasciculations during recovery  Variable effect on heart rate  Vasodilation and hypotension  Decreased cardiac output and tissue perfusion  Effects and Adverse Effects of Halogenated Inhalation Anesthetics (2 of 2)  Dose-related respiratory depression  Hypoventilation, retention of carbon dioxide, and respiratory arrest  Adequate to good muscle relaxation  Depression of respiration in neonates  Production of carbon monoxide when exposed to desiccated CO2 absorbent  Inhalant Anesthetics: Physical and Chemical Properties  Important properties to consider  Vapor pressure  Partition coefficient  Minimum alveolar concentration (MAC)  Rubber solubility  Vapor Pressure (1 of 2)  The tendency of an inhalation anesthetic to vaporize to its gaseous state  Determines how readily an inhalation anesthetic will evaporate in the anesthetic machine vaporizer  Dependent on the temperature and on the anesthetic agent  Vapor Pressure (2 of 2)  Volatile agents  High vapor pressure  Isoflurane, sevoflurane, desflurane, and halothane  Delivered from a precision vaporizer to control the delivery concentration  All precision vaporizers are made to deliver only one specific halogenated agent  Nonvolatile agents  Low vapor pressure  Delivered from a nonprecision vaporizer  Blood-Gas Partition Coefficient (1 of 3)  The measure of the solubility of an inhalation anesthetic in blood as compared to alveolar gas (air)  Indicates the speed of induction and recovery for an inhalation anesthetic agent  Low blood-gas partition coefficient  Agent is more soluble in alveolar gas than in blood at equilibrium  Agent is less soluble in blood  Faster expected induction and recovery  Blood-Gas Partition Coefficient (2 of 3)  High blood-gas partition coefficient  Agent is more soluble in blood than in alveolar gas at equilibrium  Agent is less soluble in alveolar gas  Agent is absorbed into blood and tissues (sponge effect)  Slower expected induction and recovery  Blood-Gas Partition Coefficient (3 of 3)  Blood-gas partition coefficient determines the clinical use of the anesthetic agent  Induction: Can a mask be used?  Maintenance: How fast will the anesthetic depth change in response to changes in the vaporizer setting?  Recovery: How long will the patient sleep after anesthesia? Minimum Alveolar Concentration (MAC)  The measure of the potency of a drug  Used to determine the average setting on the vaporizer that will produce surgical anesthesia  The lower the MAC, the more potent the anesthetic agent and the lower the vaporizer setting  MAC may be altered by age, metabolic activity, body temperature, disease, pregnancy, obesity, and other agents present  Every patient must be monitored as an individual  Halogenated Organic Compounds: Isoflurane  Approved for use in dogs and horses; commonly used in other species  Most commonly used inhalant agent in North America  Halogenated Organic Compounds: Physical and Chemical Properties of Isoflurane (1 of 2)  Properties  High vapor pressure: need a precision vaporizer  Low blood: gas partition coefficient: rapid induction and recovery  Good for induction with mask or chamber  MAC = 1.30% to 1.63%: helps determine initial vaporizer setting  Low rubber solubility  Stable at room temperature; no preservatives needed  Halogenated Organic Compounds: Physical and Chemical Properties of Isoflurane (2 of 2)  Maintains cardiac output, heart rate, and rhythm  Fewest adverse cardiovascular effects  Depresses the respiratory system  Maintains cerebral blood flow  Almost completely eliminated through the lungs  Induces adequate to good muscle relaxation  Provides little or no analgesia after anesthesia  Can produce carbon monoxide when exposed to a desiccated carbon dioxide absorbent  Halogenated Organic Compounds: Sevoflurane  High vapor pressure: precision vaporizer required  Blood-gas partition coefficient: rapid induction and recovery  Good for induction with a mask or chamber  High controllability of depth of anesthesia  MAC = 2.34% to 2.58%  Halogenated Organic Compounds: Desflurane  Closely related to isoflurane  Expensive  Lowest blood-gas partition coefficient: very rapid induction and recovery  Used with a special precision vaporizer  MAC = 7.2% and 9.8%  Least-potent inhalant agent  Eliminated by the lungs  Halogenated Inhalation Agents: Nitrous Oxide  Used some in veterinary medicine  Gas is at room temperature; no vaporizer required  Used with a flowmeter and mixed with O2  Reduces MAC by 20% to 30%  Miscellaneous Anesthetic Adjuncts  Doxapram  Analeptic agent  Non-controlled substance  Stimulates respiration and speeds recovery  Used in neonate puppies and kittens after C-section  Intravenous administration or sublingual drops (neonates)  Mode of action: stimulates the central nervous system, including respiratory centers in the brain  Effects and Adverse Effects of Doxapram  Wide margin of safety  Can cause hyperventilation, hypertension, arrhythmia  Lowers seizure threshold  Must be used in presence of adequate oxygen levels in the brain  Can cause central nervous system damage  Use of Doxapram  Repeat injections may be necessary  Reverses respiratory depression from inhalant agents and barbiturates