Drugs Acting on the Central Nervous System (CNS) Lecture Notes PDF

DRUGS Acting on the Central Nervous System (CNS) Date: 10/01/2024 Lecture 15: Anesthesia / Pre-Anesthetics Anait S. Levenson, M.D., Ph.D. Office Hours: By Appointment (send me an email) Email: [email protected] Anesthesia and Pre-Anesthetic Drugs Learning Objectives:...

DRUGS Acting on the Central Nervous System (CNS) Date: 10/01/2024 Lecture 15: Anesthesia / Pre-Anesthetics Anait S. Levenson, M.D., Ph.D. Office Hours: By Appointment (send me an email) Email: [email protected] Anesthesia and Pre-Anesthetic Drugs Learning Objectives: ▪ Anesthesia ✓ Different types ✓ Four Major Stages of Anesthesia ▪ Pre-Anesthetic Drugs ✓ Anesthetics versus Adjunct Drugs ✓ Pre-Anesthetic Drugs: various categories ✓ Analgesics: Opioids ✓ Tranquilizers: Acepromazine ✓ Neuroleptanalgesia ✓ Benzodiazepines (BDZs): Diazepam Zolazepam Midazolam Clonazepam  Anesthesia Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical purposes “Loss of sensation” It is used daily in most veterinary practices to provide ❖ Sedation ❖ Tranquilization ❖ Immobility ❖ Muscle relaxation ❖ Unconsciousness ❖ Pain control For diverse range of indications including ❖ Surgery ❖ Dentistry ❖ Grooming ❖ Diagnostic imaging ❖ Wound care ❖ Capture/transport of wild animals  Conscious vs Unconscious Fully conscious AWAKE Light Moderate Sedation Deep Border between Hypnosis consciousness and Narcosis unconsciousness Unconscious Light surgical Moderate surgical General Deep surgical Anesthesia Anesthetic overdose  Anesthesia: Different Levels Local anesthesia: numbs a small section of the body. Examples: cataract surgery, a dental procedure or skin biopsy. Patient is awake during the procedure. Regional anesthesia: blocks pain in a larger part of the body. Examples: an epidural, a spinal for hip or knee surgery, or an arm block for hand surgery. Patient can be conscious during the procedure or have sedation. General anesthesia: makes animal unconscious and insensitive to pain or other stimuli. General anesthesia is used for more invasive surgical procedures, or procedures of the head, chest, or abdomen. Sedation: relaxes to the point where patient can be easily aroused or awakened. Disorientation in humans, in pets – sometimes not obvious Goal is to move through this stage as rapidly as possible Muscle relaxation, complete loss of pain sensation Too deep, essentially an overdose (anesthetic crisis)  Anesthetic and Adjunct Drugs An Anesthetic is a drug used to induce a loss of sensation with or without unconsciousness Adjunct is a drug that is not a true anesthetic, but that is used during anesthesia to produce other desired effects such as sedation, muscle relaxation, analgesia, reversal, neuromuscular blockade, or parasympathetic blockade Policy: The anesthetic protocol, dose, and route are chosen by the Veterinarian Many clinics have a routine protocol, but it is important to consider all aspects of the patient’s minimum database  Pre-Anesthetic Medications Used prior to the administration of an anesthetic agent to make anesthesia safe and more agreeable to the patient. Used: For sedation, to reduce anxiety and apprehension To obtain an additive or synergistic effect so that induction could be smooth and rapid To counteract certain adverse effects of anesthetic drug To relieve from pain Routes of administration: SC: slowest onset, longest duration IM: faster onset, shorter duration IV: fastest onset, shortest duration Pre-Anesthetic Medications and Adjuncts Effects: Calm and sedate excited animal Minimize adverse drug effects Reduce dose of concurrent drugs Smoother anesthetic induction and recovery Analgesia Muscle relaxation  Pre-Anesthetic Medications and Adjuncts ❑ Opioids provide analgesia ❑ Tranquilizers provide pre-operative sedation and amnesia and help to prevent or counteract the CNS stimulation caused by some anesthetics ❑ Central muscle relaxants provide muscle relaxation during anesthesia ❑ Anticholinergic agents prevent profuse salivation and bradycardia  Pre-Anesthetic Medications and Adjuncts Pre-anesthetic medications generally include combinations of drugs from multiple categories: ❖ Opioids (Morphine) ❖ Phenothiazine tranquilizers (Acepromazine) ❖ Benzodiazepines (Diazepam) ❖ α2-Agonists (Xylazine) ❖ Anticholinergics (Atropine) ❖ Muscle relaxants (Baclofen)  Analgesics used in General Anesthesia Most general anesthetics are not analgesics Must provide analgesic pre- and post operatively (no pain perception when anesthetized) True analgesics don’t provide general anesthesia Patient will feel pain after surgery if we don’t give anesthetics with analgesics  Pre-Anesthetic Opioids Opioids are commonly used for premedication and perioperative analgesia Morphine is safe, effective analgesic for most small animal patients Effective for mild and severe pain Added benefit of being a good sedative for dogs Butorphanol: partial agonist (μ), +++ (k) Keep analgesia, reversal of sedation and respiratory depression Pre-anesthetic agonists, partial agonists, or mix agonist-antagonists May be used alone or in combination with - Tranquilizers - Anticholinergics  Pre-Anesthetic Tranquilizers Reduce anxiety, produce calming, enhance CNS depressant and analgesic effects of other anesthetic drugs Phenothiazine: Acepromazine (ACE) An oral sedative before stressful events (such as thunderstorms) To treat motion sickness and nausea associated with car or plain rides Pre-anesthetic sedation Decrease dose of general anesthetic Not a pain reliever May be used with opioids for minor procedures Approved for horses, dogs, and cats Administered IV or IM Easy induction and recovery No reversal agent Metabolized by liver Will slowly cross the placenta FDA approved  Use of Acepromazine (ACE) Increased potency and long duration (10-20 times more potent than chlorpromazine) Caution: geriatrics, neonates, debilitated animals Breed considerations : may have increased risk of side effects Australian shepherds (MDR1 mutation) (less dose) Giant breeds, boxers, greyhounds, bulldogs (less dose) Terriers and cats (may require more dose of ACE) Overdose treatment: Norepinephrine In Australian shepherds without checking for MDR1  Acepromazine (ACE) Pharmacological Effects: CNS Cardiovascular Calming, reluctant to move, decreased Peripheral vasodilation that leads to hypotension, interest to surroundings decreased heart rate (bradycardia), and hypothermia Sedation less pronounced in cats Protects against arrhythmias Not an analgesic Respiratory system GI system Without significant respiratory depression Antiemetic  Acepromazine (ACE) Adverse Effects: CNS: reduced seizures threshold may produce aggression or excitement Cardiovascular system: hypotension (dose-dependent) Penile prolapse seen in horses and other large animals may lead to permanent injury Decreased packed cell volume (PCV) up to 30% ( anemia )  Pre-Anesthetic Benzodiazepines (BDZs) Produce anxiolytic, anticonvulsant, and muscle relaxant effects, potentiate general anesthetics Diazepam (Valium R ) Zolazepam Midazolam Clonazepam  Benzodiazepines (BDZs) Pharmacological Effects: Calming and antianxiety (old or ill patients) CNS Not an effective sedative or analgesic Anticonvulsant Appetite stimulation (cats and ruminants) Cardiovascular Respiratory Minimal effect with a high margin of safety Skeletal muscle relaxation  Benzodiazepines (BDZs) Diazepam (Valium R ) Lipid- soluble Don’t mix with water-soluble drugs and don’t store in plastic Store in dark Commonly use with ketamine to induce anesthesia in small animals and horses (not as much now) Slow IV administration Adverse Effects: Disorientation and excitement: young, healthy dogs (paradox) Dysphoria and aggression: cats Muscle fasciculations (eyelid twitch or leg spasm): horses Ataxia and recumbence: any large animal Diazepam must be given slowly (IV) Oral diazepam in cats can cause liver damage  Benzodiazepines (BDZs) Midozalam Water soluble Administration: IM or SC Excellent sedative for swine, rabbits, and birds Used in combination with ketamine to induce anesthesia in dogs, small mammals, and birds Zolazepam Available only as a component of Telazol R A powdered product reconstituted with sterile water Used in cats TelazolR: Zolazepam + Tiletamine  Neuroleptanalgesia A profound state of analgesia and sedation induced by simultaneous administration of a narcotic analgesic (opioid) and a tranquilizer Great sedation, animal does not care, no pain Characterized by profound sedation, immobilization, intense analgesia without loss of consciousness Advantages: Cardiovascular stability Excellent psychomotor sedation Patient co-operation  Neuroleptanalgesia Opioids: Tranquilizers: Morphine [+++ (μ); + (k)] Acepromazine Buprenorphine [partial (μ); -- (k)] Diazepam Butorphanol (partial (μ); +++ (k) Midazolam Hydromorphone (5 times > potent) Xylazine Dexmedetomidine Hydromorphone + Dexmedetomidine Hydromorphone + Acepromazine Uses: when you don’t want to do General Anesthesia (GA) Sedation for minor procedures Induction of general anesthesia: in dogs (not used often)  Pre-Anesthetic Medications and Adjuncts ❑ Opioids Provide analgesia Morphine Butorphanol ❑ Tranquilizers Provide pre-operative sedation and amnesia Phenothiazine: Acepromazine and help to prevent or counteract the CNS Benzodiazepines: Diazepam stimulation caused by some anesthetics Neuroleptanalgesia: analgesic + tranquilizer