Chapter 7 Drugs Affecting the Nervous System Copyright © 2011 Delmar, Cengage Learning

Basic Anatomy and Physiology Basic unit of the nervous system = neuron Sensory Associative Motor Parts of the neuron Cell body Dendrite Axon Two parts of the nervous system CNS (central): brain and spinal cord PNS (peripheral): cranial nerves, spinal nerves, autonomic nervous system Copyright © 2011 Delmar, Cengage Learning

Autonomic Nervous System Sympathetic (Adrenergic): “fight or flight” Increases heart rate, respiration rate, and blood flow to muscles; decreases GI function; causes pupillary dilation Preganglionic synapse: ACh; postganglionic synapse: epi or norepi Copyright © 2011 Delmar, Cengage Learning

Autonomic Nervous System Parasympathetic (Cholinergic): “homeostatic” Brings heart rate, respiration rate, and blood flow to muscles back to normal levels; returns GI function to normal; constricts pupils to normal size Pre- and postganglionic synapse: ACh Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Anticonvulsants help prevent seizures by suppressing the spread of abnormal electric impulses from the seizure focus to other areas of the cerebral cortex All anticonvulsants are CNS depressants and may cause ataxia, drowsiness, and hepatotoxicity Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Anticonvulsants Barbiturates CNS depressant Grouped by duration of action Phenobarbital, pentobarbital, primidone Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Anticonvulsants Benzodiazepines Potentiate effects of GABA, cause muscle relaxation, relieve anxiety Diazepam, lorazepam, clorazepate Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Anticonvulsants Potassium bromide Adjunct to anticonvulsant therapy Depressive effect on neuron excitability Long half life; given as a loading dose Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Anticonvulsants Add-ons: used for refractory seizures Levetiracetam Dogs and cats Side effects include sedation, ataxia, and anorexia Zonisamide Works by blocking calcium and sodium channels in the brain Side effects include ataxia and sedation Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Anticonvulsants Add-ons: used for refractory seizures Gabapentin Works by inhibiting calcium channels resulting in decreased excitatory neurotransmission Side effects include sedation, ataxia, and the potential for hepatotoxicity Felbamate Used in dogs that to control seizures Side effects include hepatotoxicity, reversible blood dyscrasias, and keratoconjunctivitis sicca Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Calming Agents Tranquilizers: used to calm animals; reduce anxiety and aggression Sedatives: used to quiet excited animals; decrease irritability and excitement Anti-anxiety drugs: lessen anxiousness, but do not make animals drowsy Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Calming Agents Phenothiazine derivatives Unknown mechanism, believed to block dopamine and alpha-1 receptors Causes sedation, relieves fear and anxiety Doesn’t produce analgesia Side effects: hypotension, lower seizure threshold, protrusion of nictitating membrane, paraphimosis Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Calming Agents Butyrophenones Similar to phenothiazines Side effects: salivation, panting, shivering Benzodiazepines Anti-anxiety, produce muscle relaxation, reduce anxiousness Alpha-2 agonists Some analgesia, some muscle relaxation, decreased response to stimuli Side effects: bradycardia and heart block Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Analgesics Pain is classified as: Physiologic: the bodies protective mechanism to avoid tissue injury Pathologic: arises from tissue injury and inflammation or from damage to nervous system Can be furthered divided into nociceptive (peripheral tissue injury) or neuropathic (damage to the peripheral nerves or central nervous system) Acute: arising from a sudden stimulus such as surgery Chronic: persisting beyond the time normally associated with tissue injury Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Analgesics Signs of pain in animals Change in personality Abnormal vocalization Licking, biting, scratching pain area Change in appearance of hair coat Change in posture/ambulation Change in activity level Change in appetite Change in facial expression Excessive sweating or salivation Oculonasal discharge Teeth grinding Change in bowel movement or urination Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Analgesics Analgesics: drugs that relieve pain Analgesics are categorized as non-narcotic (Chapter 16) or narcotic Narcotic analgesics are used for moderate to severe pain Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Analgesics Narcotics refers to opiate (natural from opium poppy seeds) or opioid-like (synthetic) Opioids produce analgesia and sedation and relieve anxiety Side effects of opioids include respiratory depression and excitement if given rapidly Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Opioids Do not produce anesthesia; patients still respond to sound and sensation Produce analgesia and sedation, and relieve anxiety Side effects: respiratory depression, excitement if given too rapidly Produce their effects by the action of opioid receptors Mu = found in the brain Kappa = found in the cerebral cortex and spinal cord Sigma = found in the brain Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Opioids Opium Morphine sulfate Meperidine Hydromorphone Butorphanol Hydrocodone Fentanyl Etorphine Buprenorphine Pentazocine Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Opioid Antagonist Block the binding of opioids to their receptors Used to treat respiratory and CNS depression of opioid use Examples include naloxone and naltrexone Naloxone is a opioid antagonist used to reverse respiratory depression following narcotic overdose Relatively free of side effects Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Neuroleptanalgesics Combination of an opioid and a tranquilizer or sedative Can cause a state of CNS depression and analgesia and may or may not produce unconsciousness Combination products may be prepared by veterinarian Examples include acepromazine and morphine; xylazine and butorphanol Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Anesthetics Anesthesia means without sensation Anesthetics interfere with the conduction of nerve impulses Anesthetics produce loss of sensation and muscle relaxation, and may cause loss of consciousness General anesthetics affect the CNS, produce loss of sensation with partial or complete loss of consciousness Local anesthetics block nerve transmission in the area of application with no loss of consciousness Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Local Anesthetics Block pain at the site of administration or application in the PNS and spinal cord May be used as nerve blocks, aid in endotracheal tube placement, and ease skin irritation Applied topically to mucous membranes and the cornea by infiltration of a wound or joint, by IV, and around nervous tissue Examples include lidocaine, proparacaine, tetracaine, mepivacaine, bupivacaine Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning General Anesthetics Injectable general anesthetics: Barbiturates: CNS depressants derived from barbituric acid. Used mainly as anticonvulsants, anesthetics, and euthanasia solutions Side effects: potent cardiovascular and respiratory depression May be long-acting, short-acting, or ultra-short acting May vary in structure and be classified as an oxybarbiturate or thiobarbiturate Examples: phenobarbital, pentobarbital, thiopental, methohexital Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning General Anesthetics Injectable general anesthetics (cont.): Dissociatives: belong to the cyclohexamine family Cause muscle rigidity (catalepsy), amnesia, and mild analgesia Work by altering neurotransmitter activity Used for restraint, diagnostic procedures, and minor surgical procedures Side effects: cardiac stimulation, respiratory depression, and exaggerated reflexes Examples include ketamine and tiletamine Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning General Anesthetics Injectable general anesthetics (cont.): Miscellaneous: Guaifenesin: skeletal muscle relaxant used in combination with an anesthetic drug to induce general anesthesia in horses Propofol: short-acting injectable anesthetic agent that produces rapid and smooth induction when given IV (lasts 2–5 minutes) Side effects include cardiac arrhythmias and apnea Copyright © 2011 Delmar, Cengage Learning

General Anesthetics/Analgesics Inhalant general anesthetics: inhalant anesthetics are halogenated hydrocarbons Halothane: Nonflammatory, inhalant anesthetic administered via a precision vaporizer Can cause hepatic problems, malignant hyperthermia, cardiac problems, and tachypnea Contraindicated in cases of gastric dilatation, pneumothorax, and twisted intestines Leave animals on 100% oxygen following surgery to prevent diffusion hypoxia Copyright © 2011 Delmar, Cengage Learning

General Anesthetics/Analgesics Inhalant general anesthetics (cont.): Isoflurane: Nonflammatory, inhalant anesthetic administered via a precision vaporizer Causes rapid induction of anesthesia and short recoveries following anesthetic procedures Does not cause the cardiac arrhythmia problems of halothane Vigilant monitoring is needed because the animal can change anesthetic planes quickly Masking of animals with isoflurane is difficult because it irritates the respiratory system Side effects include respiratory depression and malignant hyperthermia Copyright © 2011 Delmar, Cengage Learning

General Anesthetics/Analgesics Inhalant general anesthetics (cont.): Isomers of isoflurane: Nonflammable and have fewer cardiovascular side effects than other inhalants Quickly enter the bloodstream and escape to the brain, making them good for mask inductions Examples: Enflurane: increases intracranial pressure (do not use if animal has seizure history) Desflurane: cannot be delivered by standard vaporizers and can reduce blood pressure Sevoflurane: profound respiratory depressant; close monitoring is needed Copyright © 2011 Delmar, Cengage Learning

General Anesthetics/Analgesics Inhalant general anesthetics (cont.): Sevoflurane: A non-flammable inhalant anesthetic The main isomer of isoflurane Produces rapid induction and rapid recoveries Produces fewer cardiovascular side effects than the other inhalant anesthetics Quickly enters the bloodstream and escapes to the brain, also is eliminated quickly from the body Has low tissue solubility, resulting in rapid elimination of the drug by the body Copyright © 2011 Delmar, Cengage Learning

General Anesthetics/Analgesics Inhalant general analgesics (cont.): Nitrous oxide: Inhalant analgesic that diffuses rapidly throughout the body Can enter gas-filled body compartments (increases pressure in these compartments) Contraindicated in cases of gastric dilatation, pneumothorax, and twisted intestines Leave animals on 100% oxygen following surgery to prevent diffusion hypoxia Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning CNS Stimulants Reverse CNS depression caused by CNS depressants Doxapram: stimulates brainstem to increase respiration in animals with apnea or bradypnea; commonly used when animals have C-sections Methylxanthines: bronchodilators that have adverse effect of CNS stimulation; include caffeine, theophylline, and aminophylline; side effects include gastrointestinal irritation and bronchodilation Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Euthanasia Solutions Used to humanely end an animal’s life Usually contain pentobarbital When pentobarbital is the only narcotic agent present, it is a C-II controlled substance When pentobarbital is in combination with other agents, it is a C-III controlled substance Copyright © 2011 Delmar, Cengage Learning

Autonomic Nervous System Drugs Autonomic nervous system drugs work either by acting like neurotransmitters or by interfering with neurotransmitter release Two groups of drugs affect the parasympathetic nervous system Two groups of drugs affect the sympathetic nervous system Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Cholinergic Drugs Mimic the action of the parasympathetic nervous system (refer to Table 7-5 in your textbook) Examples include bethanechol, metoclopramide, pilocarpine, edrophonium, neostigmine, demecarium, and organophosphates Copyright © 2011 Delmar, Cengage Learning

Anticholinergic Drugs Inhibit the actions of acetylcholine by occupying the acetylcholine receptors (refer to Table 7-6 in your textbook) Examples include atropine, glycopyrrolate, aminopentamide, and propantheline Copyright © 2011 Delmar, Cengage Learning

Copyright © 2011 Delmar, Cengage Learning Adrenergic Drugs Simulate the action of the sympathetic nervous system (refer to Table 7-7 in your textbook) Side effects include tachycardia, hypertension, and cardiac arrhythmias Examples include epinephrine, norepinephrine, isoproterenol, dopamine, dobutamine, phenylpropanolamine, isoetharine, albuterol, terbutaline, ephedrine, and xylazine Copyright © 2011 Delmar, Cengage Learning

Adrenergic Blocking Agents Block the effects of the adrenergic neurotransmitters (refer to Table 7-7 in your textbook) Examples of alpha-blockers include phenoxybenzamine, prazosin, and yohimbine Examples of beta-blockers include propranolol, metoprolol, and timolol Copyright © 2011 Delmar, Cengage Learning