VEM027 Lecture 2.1 PDF - Drugs Acting on the Nervous System

Drugs acting on the: Nervous System DEAN SIDNEY S. LEYSON, DVM Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Divisions of the NS https:/...

Drugs acting on the: Nervous System DEAN SIDNEY S. LEYSON, DVM Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Divisions of the NS https://old-ib.bioninja.com.au/standard-level/topic-6-human-physiology/65-neurons-and-synapses/nervous-system.html Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Drugs acting on the: Central Nervous System DEAN SIDNEY S. LEYSON, DVM Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. CNS Drugs Organs: Brain & Spinal Cord Goals: ✓ develop/use drugs as probe compounds to both elucidate and manipulate the normal CNS ✓ to develop drugs to correct pathophysiological changes in the abnormal CNS Functions: ▪ Anticonvulsive effects ▪ Tranquilization ▪ Analgesia ▪ Anesthesia Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. CNS Drugs Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Drug classifications Anticonvulsants Tranquilizers, Ataractics, Neuroleptics, & Sedatives Opioids Anxiolytics/Anti-depressants Anesthetics CNS Stimulants Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved.  Convulsions Seizures vs Convulsions A seizure is a sudden, A convulsion is a specific uncontrolled electrical type of seizure characterized by disturbance in the brain. involuntary muscle contractions. “ALL CONVULSIONS are SEIZURES, but NOT ALL SEIZURES are CONVULSIONS.” Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anticonvulsants MOA: Stabilization of neuronal membranes. 1. Hyperpolarization of neuronal membranes through ion channels. Blocks sodium channels Activates potassium channels Regulates calcium channels 2. Hyperpolarization of neuronal membranes through GABA- gated Cl− channels. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anticonvulsants Indications: ✓ reduce the incidence, severity, or duration of seizures. Adverse Effects: Withdrawal symptoms, seizures, or status epilepticus may follow rapid cessation of administration of these drugs. Lowered seizure threshold when administered with other drugs. Phenothiazines (e.g., Acepromazine) Anthelminthics (e.g., Pyrantel, Levamisole) Metoclopramide Enzyme induction (Cytochrome P450) Hepatotoxicity Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anticonvulsants Barbiturates Adjuncts Phenobarbital Levetiracetam Primidone Zonisamide Pentobarbital Gabapentin Felbamate Benzodiazepines Diazepam Phenytoin Midazolam Lorazepam Zolazepam Bromides Potassium bromide (KBr) Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Barbiturates Difference in duration of action: Ultra short-acting Short-acting Long-acting Thiopental *Pentobarbital *Phenobarbital Thiamylal Secobarbital *Primidone Pharmacologic Effects Low Dose Moderate Dose High Dose Sedation General Anesthesia CNS Depression Hyperalgesia No Analgesia Poor Analgesia Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Barbiturates Phenobarbital Unique Characteristics: MOA - #2 Elevates seizure threshold & produces effect at lower doses and with no sedation. Does not prevent spread of seizure activity. DOC for long-term seizures. It should be used first in all cases but not for ongoing seizures. Increase cytochrome P450 activity. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Barbiturates Primidone Unique Characteristics: MOA - #1 An analog of phenobarbital (deoxybarbiturate). Commonly used as antiepileptic but rarely to control seizures. It has no hypnotic effects. Potency is only 1/30 of phenobarbital but is usually effective when phenobarbital fails. Metabolized into PEMA & phenobarbital in the liver. DO NOT USE IN CATS. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Barbiturates Pentobarbital Unique Characteristics: MOA - #2 Widely used as general anesthetic in small animals. Antidote to strychnine & atropine overdose. Major active ingredient to euthanasia solutions. Causes significant cardiopulmonary depression. Rapid onset, short duration of action. Mostly given IV due to risk of irritation if given SC or IM. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anticonvulsants Barbiturates Adjuncts Phenobarbital Levetiracetam Primidone Zonisamide Pentobarbital Gabapentin Felbamate Benzodiazepines Diazepam Phenytoin Midazolam Lorazepam Zolazepam Bromides Potassium bromide (KBr) Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Benzodiazepines Diazepam Unique Characteristics: MOA - #2 Most widely used anticonvulsant, also has sedative, hypnotic, and tranquilizing effects. Tx/Mgt of seizures of any origin, behavioral problems, and restlessness. Used as maintenance anticonvulsant, appetite stimulant, urine marking control, and anxiolytic for cats, but not in dogs. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Benzodiazepines Midazolam Unique Characteristics: MOA - #2 More potent that diazepam but DOA is shorter. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Benzodiazepines Lorazepam Unique Characteristics: MOA - #2 Very long acting with slow onset of action. 4 times more potent than diazepam and is not painful during injection. Safely used in individuals with compromised liver function as it does not produce active metabolites. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Benzodiazepines Zolazepam Unique Characteristics: MOA - #2 Available in combination with a dissociative drug – Tiletamine, forming ____. Most widely used anesthetic in small animal practice in combination with Xylazine. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Benzodiazepines REVERSAL AGENT: Flumenazil a specific competitive antagonist for benzodiazepine receptors and has minimal agonist activity. Remember: FaceBook (FB) Flumenazil vs Benzodiazepines Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anticonvulsants Barbiturates Adjuncts Phenobarbital Levetiracetam Primidone Zonisamide Pentobarbital Gabapentin Felbamate Benzodiazepines Diazepam Phenytoin Midazolam Lorazepam Zolazepam Bromides Potassium bromide (KBr) Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Bromides Potassium Bromide (KBr-) MOA: Hyperpolarization of neuronal membranes due to influx through chloride channels. Unique Characteristics: Used alone or in adjunct to barbiturates & benzodiazepines. Tx/Mgt for refractory seizures in dogs. DO NOT USE in cats (severe asthma). Eliminated unchanged in the urine. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anticonvulsants Barbiturates Adjuncts Phenobarbital Levetiracetam Primidone Zonisamide Pentobarbital Gabapentin Felbamate Benzodiazepines Diazepam Phenytoin Midazolam Lorazepam Zolazepam Bromides Potassium bromide (KBr) Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Adjuncts Levetiracetam MOA: Inhibits spread of seizure activity by binding to synaptic vesicle protein 2A (SV2A). Unique Characteristics: 100% bioavailability in oral administration. Minimal side effects (drowsiness and GI disturbances) if withdrawal is slow. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Adjuncts Zonisamide Unique Characteristics: MOA - #1 & stimulates dopamine synthesis and serotonin turn-over. Sulfonamide-based anticonvulsant used solely or adjunctively to control refractory epilepsy in dogs. High safety margin. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Adjuncts Gabapentin Unique Characteristics: MOA - #1 Synthetic GABA analog that can cross the BBB. Tx/Mgt of refractory or complex partial seizures and chronic pain in dogs and cats. Abrupt discontinuation may cause withdrawal symptoms. Caution on patients with liver and kidney problems Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Adjuncts Felbamate Unique Characteristics: MOA - #1, #2, and blockade of NMDA receptor- mediated neuronal excitation. Does not induce sedation. Tx/Mgt of refractory epilepsy in patients with obtunded mental status. Rare side effects include liver dysfunction, bone marrow depression, & keratoconjunctivitis sicca. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anticonvulsants Barbiturates Adjuncts Phenobarbital Levetiracetam Primidone Zonisamide Pentobarbital Gabapentin Felbamate Benzodiazepines Diazepam Phenytoin Midazolam Lorazepam Zolazepam Bromides Potassium bromide (KBr) Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenytoin MOA: ↓ Na+ influx during action potential, ↓ Ca2+ influx during depolarization, delayed K+ efflux during action potential. Unique Characteristics: Not recommended anti-convulsant due to its short half-life. Tx/Mgt for digitalis-induced ventricular arrhythmias due to its lidocaine-like effects. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anticonvulsants Barbiturates Adjuncts Phenobarbital Levetiracetam Primidone Zonisamide Pentobarbital Gabapentin Felbamate Benzodiazepines Diazepam Phenytoin Midazolam Lorazepam Zolazepam Bromides Potassium bromide (KBr) Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anticonvulsants Barbiturates Adjuncts Phenobarbital Levetiracetam Primidone Zonisamide Pentobarbital Gabapentin Felbamate Benzodiazepines Diazepam Phenytoin Midazolam Lorazepam Zolazepam Bromides Potassium bromide (KBr) Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Tranquilizers, Ataractics, Neuroleptics, & Sedatives “Drugs that calm the animal and promote sleep but do not necessarily induce sleep.” Typically used as pre-anesthetic medications Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TANS Phenothiazines α-adrenergic Agonists Acepromazine Xylazine Chlorpromazine Detomidine Promazine Medetomidine Fluphenazine Romifidine Butyrophenone Chloral Hydrate Droperidol Azaperone Benzodiazepines Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenothiazines MOA: Blocks dopamine, α-1, histamine, acetylcholine, and serotonergic receptors, leading to a calming effect. Pharmacologic Effects: Tranquilization due to blockade of dopamine and 5-HT receptors. Hypotension due to blockade of α-1-adrenergic receptor. Epinephrine reversal Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenothiazines Pharmacologic Effects: Respiratory depression Hyper- prolactinemia Anti-emesis PHENO- THIAZINE Decreased GIT Hyperglycemia motility Impaired thermoregulation Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenothiazines Pharmacologic Effects: RECEPTOR EFFECTS BLOCKED Dopamine Antipsychotic effects, Extrapyramidal side effects, Hyperprolactinemia α-adrenergic Hypotension, Dizziness, Reflex tachycardia, Sedation Histamine Sedation, Weight gain, Dry mouth Muscarinic Dry mouth, Blurred vision, Constipation, Acetylcholine Urinary retention Serotonin Sedation, Anti-emetic effects Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenothiazines Extrapyramidal Symptoms: Clinical Signs Parkinsonism Muscle tremors, rigidity, bradykinesia (slow movement), and postural instability. Dystonia Involuntary muscle contractions that cause abnormal postures, such as twisting of the neck or limbs. Dyskinesia Involuntary, repetitive movements of the face, tongue, limbs, or trunk. Akathisia A state of motor restlessness, often manifesting as an inability to sit still or pacing. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenothiazines Indications: Tranquilization, but with no analgesic effect. Anti-emetic Pre-anesthetic Contraindications: Epileptic animals or those susceptible to seizures. Hypovolemic & hypotensive patients. Patients with liver dysfunction. Cases of anti-ChE poisoning or patients under anti- ChE antiparasitic drug. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenothiazines NO REVERSAL AGENT AVAILABLE Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenothiazines Acepromazine Unique Characteristics: Slow onset, but long duration of action (nonreversible). Use cautiously in aggressive dogs, as it may increase sensitivity to stimuli. Giant breeds, greyhounds, and dogs with MDR-1 gene mutation (Collies) are extremely sensitive. Avoid in cases of tetanus or strychnine poisoning. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenothiazines Acepromazine Unique Characteristics: Not recommended for stallions due to risk of paraphimosis and hyperexcitability. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Paraphimosis NORMAL PARAPHIMOSIS Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenothiazines Chlorpromazine Unique Characteristics: Less potent than acepromazine but with longer duration of action. May cause extrapyramidal symptoms in cats when used at high dosages. Avoid IM chlorpromazine in rabbits (only IV) due to severe muscle irritation. Can be used during c-sections. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenothiazines Promazine Unique Characteristics: Approved for use in dogs, cats, and horses, but veterinary labeled products may no longer be available. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Phenothiazines Fluphenazine Unique Characteristics: A highly potent phenothiazine neuroleptic used in human medicine for the treatment of schizophrenia. Was used as performance-enhancing drug in racehorses (but is banned). Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TANS Phenothiazines α-adrenergic Agonists Acepromazine Xylazine Chlorpromazine Detomidine Promethazine Medetomidine Fluphenazine Romifidine Butyrophenone Chloral Hydrate Droperidol Azaperone Benzodiazepines Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Butyrophenone Azaperone Unique Characteristics: Same MOA with Phenothiazines. Mostly indicated in swine(should not be given IV) and avoided in horses. Prevent the development of halothane-induced malignant hyperthermia. Leave pigs undisturbed for 20 minutes after injection to avoid triggering excitement. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Butyrophenone Droperidol Unique Characteristics: Same MOA with Phenothiazines. 400x more potent in dogs than chlorpromazine. 1000x more potent anti-emetic than chlorpromazine. Droperidol is used in combination with Fentanyl (an opioid analgesic) to produce a state called neuroleptanalgesia. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TANS Phenothiazines α-adrenergic Agonists Acepromazine Xylazine Chlorpromazine Detomidine Promethazine Medetomidine Fluphenazine Romifidine Butyrophenone Chloral Hydrate Droperidol Azaperone Benzodiazepines Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. α-adrenergic Agonists MOA: Activates α-2 receptors and α-1 receptors (in high doses) reducing neurotransmitter release at nerve terminals α-1 VS α-2 Receptors Receptors Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. α-adrenergic Agonists Pharmacologic Effects: Sedation and analgesia Muscle relaxation Emesis ↓ GIT Motility and secretions Mild hypertension to hypotension Diuresis Hypoxemia (in ruminants). Inhibition of NE & EP release, insulin release, and increase growth hormone release. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. α-adrenergic Agonists Therapeutic Uses: Sedative, analgesic, immobilizing agents. Induce epidural anesthesia. Pre-anesthetic and as part of anesthetic combination (xylazine-ketamine, xylazine-zoletil). Reversal Agents: α-2 Receptor Blockers Yohimbine & Tolazoline (for nonruminants, ruminants). Atipamezole (all species). Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. α-adrenergic Agonists Xylazine Unique Characteristics: Non-selective adrenergic agonist Used in cats as potent emetic agent and as analgesic sedative in horses. DO NOT USE in ruminants DO NOT USE in diabetic patients DO NOT USE in pregnant patients DO NOT USE in in dehydrated or urinary obstructed animals. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. α-adrenergic Agonists Xylazine Unique Characteristics: Use cautiously as it can severely lower heart rate and impair thermoregulation. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. α-adrenergic Agonists Detomidine Unique Characteristics: Selective adrenergic agonist typically used in horses. Indicated for colic and short procedures like trimming of foot abscesses and suturing skin lacerations NOT APPROVED IN CATTLE Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. α-adrenergic Agonists Medetomidine Unique Characteristics: The most potent and selective α2-adrenergic agonist. Mainly used in wildlife and exotic animals. Similar effects with xylazine. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. α-adrenergic Agonists Romifidine Unique Characteristics: For IV use in horses Causes less ataraxia compared to xylazine and detomidine. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TANS Phenothiazines α-adrenergic Agonists Acepromazine Xylazine Chlorpromazine Detomidine Promethazine Medetomidine Fluphenazine Romifidine Butyrophenone Chloral Hydrate Droperidol Azaperone Benzodiazepines Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Chloral Hydrate MOA: In the body, chloral hydrate is reduced to trichloroethanol that is believe to be responsible for the pharmacological effects Pharmacologic Effects: Marked hypnotic effect, free of excitatory properties. Cerebral and respiratory depression General anesthesia at high doses Poor analgesic capability Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Chloral Hydrate Indications: Used mainly in horses For basal necrosis For anesthesia Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TANS Phenothiazines α-adrenergic Agonists Acepromazine Xylazine Chlorpromazine Detomidine Promethazine Medetomidine Fluphenazine Romifidine Butyrophenone Chloral Hydrate Droperidol Azaperone Benzodiazepines Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TANS Phenothiazines α-adrenergic Agonists Acepromazine Xylazine Chlorpromazine Detomidine Promazine Medetomidine Fluphenazine Romifidine Butyrophenone Chloral Hydrate Droperidol Azaperone Benzodiazepines Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved.  Opioids Terminologies Opioids Drugs that bind to all or part of a subtype of opioid receptors. It can be synthetic, semisynthetic, or naturally occurring. Either an agonist or antagonist. Opiates Drugs derived from opium (poppy plant). Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved.  Opioids Terminologies Opium Poppy (Papaver somniferum) https://images.app.goo.gl/LfZ9e9PZHyW9nPMP8 https://images.app.goo.gl/VY6xDaUSrorJWXdw9 Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved.  Opioids Terminologies Narcotics Refer to opioid analgesics. In law enforcement, it is used to indicate any drug that causes dependence. Endogenous Opioids Endorphins & Enkaphalins Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved.  Opioids Opioid Receptors Receptor Location Activation Effects Mu (μ) brain Analgesia, sedation, respiratory laminae I and II of the depression, inhibition of dopamine dorsal horn of the release, GI motility reduction due to spinal cord inhibition of ACh, and chemical dependence. Kapa (κ) cerebral cortex Spinal/supraspinal analgesia, mild spinal cord sedation, dysphoria, diuresis, and miosis. hypothalamus Delta (δ) limbic system Spinal/supraspinal analgesia, reduced cerebral cortex dopamine release, cardiovascular spinal cord depression. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved.  Opioids Opioid-Receptor Relationship Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioids MOA: Opioids bind to their receptors and produce their effects. Pharmacologic Effects: Analgesia without loss of consciousness. Drowsiness and mental clouding. Nausea and emesis. Respiratory depression. No direct effect on the cardiovascular system. Anti-diarrheal and constipation. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioids Therapeutic Uses: Pain relief Sedation and induction of sleep Relief of pulmonary edema Cough suppression Tx/Mgt of secretory diarrhea Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioids Opioid Agonist Opioid Agonist-Antagonist Morphine Buprenorphine Tramadol Nalbuphine Methadone Oxymorphone Hydromorphone Fentanyl Opioid Antagonist Alfentanil Naloxone Sufentanil Naltrexone Carfentanil Opioid Partial Agonist Butorphanol Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Agonist Morphine Unique Characteristics: Synthetic μ-agonist and a less potent κ-agonist. Tx of acute pain in dogs, cats (low doses), and horses (in combination with xylazine/diazepam). Morphine may be used as an anesthetic premedication in dogs. Used in canine heart failure therapy. Antitussive effect in dogs is quite good. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Agonist Tramadol Unique Characteristics: μ-receptor agonist that also inhibits reuptake of serotonin and norepinephrine. It may be useful as an analgesic or antitussive. It is given orally. Metabolized into desmethyltramadol (6x more analgesic, 20x more binding potency). Well tolerated in dogs and cats. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Agonist Methadone Unique Characteristics: Synthetic μ-receptor agonist that may be used as an alternative to morphine. Causes less sedation and vomiting than morphine. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Agonist Oxymorphone Unique Characteristics: Synthetic μ-receptor agonist that is a dihydroxy derivative of morphine. 10x more analgesic potency than morphine. Oxymorphone + Acepromazine is frequently used in dogs. Oxymorphone + Xylazine + Ketamine is used in swine for IV anesthesia. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Agonist Hydromorphone Unique Characteristics: Synthetic μ-receptor agonist that is similar to oxymorphone. Less expensive than oxymorphone, but has shorter duration of action. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Agonist Fentanyl Unique Characteristics: Very potent synthetic μ-receptor agonist. Part of an anesthetic induction in dogs and cats. Available in transdermal patches, used to control chronic pain. Rapid onset of action but shorter duration of action than morphine. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Agonist Alfentanil, Sufentanil, Carfentanil Unique Characteristics: Derivatives of fentanyl Order of potency: Carfentanil > Sufentanil > Fentanyl > Alfentanil Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Agonist Order of Potency: Fentanyl > Oxymorphone > Hydromorphone > Morphine Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioids Opioid Agonist Opioid Agonist-Antagonist Morphine Buprenorphine Tramadol Nalbuphine Methadone Oxymorphone Hydromorphone Fentanyl Opioid Antagonist Alfentanil Naloxone Sufentanil Naltrexone Carfentanil Opioid Partial Agonist Butorphanol Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Partial Agonist Butorphanol Unique Characteristics: Partial agonist for μ-receptors, but a full agonist for κ-receptors. Can be used to reverse the μ effects of other opioids. Has an analgesic potency 4–7 times that of morphine. Have antitussive and anti-emetic effect in dogs. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioids Opioid Agonist Opioid Agonist-Antagonist Morphine Buprenorphine Tramadol Nalbuphine Methadone Oxymorphone Hydromorphone Fentanyl Opioid Antagonist Alfentanil Naloxone Sufentanil Naltrexone Carfentanil Opioid Partial Agonist Butorphanol Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Agonist-Antagonist Buprenorphine Unique Characteristics: Partial agonist for μ-receptors (50x more affinity than morphine), but antagonist for κ-receptors. 30 times the analgesic potency that of morphine. Resistant to antagonism by naloxone. Used as an analgesic for small animals. Longest half-life of all opioids in humans (high plasma binding and receptor affinity). Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Agonist-Antagonist Nalbuphine Unique Characteristics: Antagonist for μ-receptors, but an agonist for κ- receptors. Potency equal to morphine. Used to control mild to moderate pain only (short duration of action). Used topically to control pain associated with corneal ulcer. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioids Opioid Agonist Opioid Agonist-Antagonist Morphine Buprenorphine Tramadol Nalbuphine Methadone Oxymorphone Hydromorphone Fentanyl Opioid Antagonist Alfentanil Naloxone Sufentanil Naltrexone Carfentanil Opioid Partial Agonist Butorphanol Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Antagonist Naloxone Unique Characteristics: High affinity for μ-receptors and lower affinity for κ- and δ-receptors. Used as reversal for respiratory depression (but buprenorphine and nalbuphine is more recommended and useful). Used in tx of shock. In itself has no adverse effects. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioid Antagonist Naltrexone Unique Characteristics: Naltrexone is a long-acting μ-, κ-, and δ-receptor antagonist. Used to counteract carfentanil. Given orally to treat behavioral problems in dogs (e.g., constant licking, tail chasing). Relatively free of adverse effects in animals. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioids Opioid Agonist Opioid Agonist-Antagonist Morphine Buprenorphine Tramadol Nalbuphine Methadone Oxymorphone Hydromorphone Fentanyl Opioid Antagonist Alfentanil Naloxone Sufentanil Naltrexone Carfentanil Opioid Partial Agonist Butorphanol Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Opioids Opioid Agonist Opioid Agonist-Antagonist Morphine Buprenorphine Tramadol Nalbuphine Methadone Oxymorphone Hydromorphone Fentanyl Opioid Antagonist Alfentanil Naloxone Sufentanil Naltrexone Carfentanil Opioid Partial Agonist Butorphanol Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anxiolytics/Anti-depressants Anxiolytics Benzodiazepines Buspirone Anti-depressants Tricyclic Anti-depressants Serotonin Selective Reuptake Inhibitors (SSRIs) Monoamine Oxidase Inhibitors (MAOIs) Progestins Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anxiolytics Buspirone MOA: 5-HT1A partial agonist, moderate dopamine affinity Unique Characteristics: Buspirone is the first nonsedating anxiolytic drug to be developed and marketed. Used for the management of generalized anxiety in dogs. Used for modulating urine spraying behavior and inappropriate urination in cats. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anxiolytics Buspirone Unique Characteristics: Used to reduce anxiety in cases involving inter-cat aggression within the same household. Adjunct to SSRIs Very low risk of side effects. Long-term use is not associated with withdrawal symptoms. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anxiolytics/Anti-depressants Anxiolytics Benzodiazepines Buspirone Anti-depressants Tricyclic Anti-depressants Serotonin Selective Reuptake Inhibitors (SSRIs) Monoamine Oxidase Inhibitors (MAOIs) Progestins Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anti-depressants Tricyclic Anti-depressants MAOIs Amitriptyline Selegiline Clomipramine Imipramine Doxepin SSRIs Progestins Fluoxetin Medroxyprogesterone Paroxetine acetate (MPA) Sertraline Megestrol acetate (MA) Fluvoxamine Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anti-depressants MOA: Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TCAs Therapeutic Uses: Reduction of anxiety and arousal. Mgt of mild aggression, compulsive behaviors, and anxious states in dogs. Used to treat urinary issues, excessive grooming, anxiety, and vocalization in cats. Contraindications: Narrow-angle glaucoma, KCS Px with cardiovascular problems Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TCAs Amitriptyline Unique Characteristics: Relatively inexpensive and is popular among veterinarians. Tx of aggression, self-induced mutilation, and separation anxiety in dogs. Tx of psychogenic alopecia, excessive, vocalization, urine marking, and inappropriate urination in cats. TX of severe recurring FIC. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TCAs Amitriptyline Unique Characteristics: DO NOT GIVE to pregnant animals. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TCAs Clomipramine Unique Characteristics: FDA approved tx for sepanx in dogs. DO NOT GIVE to pregnant and nursing animals. DO NOT USE in combination with MAOIs Contraindicated in patients with a history of epilepsy, cardiac arrhythmias, glaucoma, or urine and stool retention. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TCAs Imipramine Unique Characteristics: Tx cataplexy and urinary incontinence in dogs and cats. Tx ejaculatory dysfunction in stallions. DO NOT USE in combination with MAOIs. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. TCAs Doxepin Unique Characteristics: Has potent H1 and H2 inhibitory effects possibly accounting for its antipruritic effects. Adjunctive therapy to psychogenic dermatitis. Banned in race horses as performance-enhancer. DO NOT USE in combination with MAOIs. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anti-depressants Tricyclic Anti-depressants MAOIs Amitriptyline Selegiline Clomipramine Imipramine Doxepin SSRIs Progestins Fluoxetin Medroxyprogesterone Paroxetine acetate (MPA) Sertraline Megestrol acetate (MA) Fluvoxamine Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. SSRIs Therapeutic Uses: Same with TCAs Tx of generalized anxiety disorders in humans. Adverse Effects/Contraindications: Excellent safety profile. 5-HT Syndrome (rare) DO NOT USE in combination with other anti- depressants. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. SSRIs Fluoxetine Unique Characteristics: Causes changes in sleep pattern in cats. May cause hypoglycemia due to increasing insulin receptor sensitivity in diabetic patients. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. SSRIs Paroxetine Unique Characteristics: Transient anorexia is common side affect in dogs and constipation in cats. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. SSRIs Sertraline Unique Characteristics: Should be used with caution in animals with compromised liver function. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. SSRIs Fluvoxamine Unique Characteristics: Used to treat maternal aggression in dogs and cats. May decrease the clearance of BZDs when given concomitantly. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anti-depressants Tricyclic Anti-depressants MAOIs Amitriptyline Selegiline Clomipramine Imipramine Doxepin SSRIs Progestins Fluoxetin Medroxyprogesterone Paroxetine acetate (MPA) Sertraline Megestrol acetate (MA) Fluvoxamine Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. MAOIs MOA: Inhibits both isoforms of MAO (MAO-A & MAO-B). MAO-A Primarily metabolizes serotonin, norepinephrine, and dopamine. MAO-B Primarily metabolizes dopamine, phenethylamine, and certain other trace amines. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. MAOIs Selegeline MOA: Selegiline is an irreversible and selective inhibitor of MAO-B. Inhibits the presynaptic D2 receptors, thereby promoting DA release. Free radical scavenger of DA-derived oxidative species in the CNS. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. MAOIs Selegeline Unique Characteristics Tx of “rage syndrome” in Cocker Spaniels Tx of Canine Cognitive Dysfunction (CCD) May suppress cataplexy in canine narcolepsy. Metabolites include amphetamine and methamphetamine. Tx of progressive irreversible neurodegeneration. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anti-depressants Tricyclic Anti-depressants MAOIs Amitriptyline Selegiline Clomipramine Imipramine Doxepin SSRIs Progestins Fluoxetin Medroxyprogesterone Paroxetine acetate (MPA) Sertraline Megestrol acetate (MA) Fluvoxamine Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Progestins MOA: Anti-androgenic and calming effect on the limbic system. Inhibition of gonadotropin and sex steroid production, GABAA receptor activation. Therapeutic Uses: Mgt of sexually dimorphic behavior. Tx of feather-picking in parrots. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Progestins Adverse Effects: Profound adrenocortical suppression due to glucocorticoid activity. Uterine and mammary pathologies can occur in dogs and cats with long-term drug use. Transient DM and iatrogenic Addison’s Disease Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Progestins Contraindications: DO NOT USE in diabetic patients. DO NOT USE in patients with endometrial hyperplasia. Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Progestins Medroxyprogesterone acetate (MPA) Unique Characteristics DO NOT USE in prepubescent cats, especially intact females due to increased risk of mammary hypertrophy. Long duration of action (30 days in cats). Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Progestins Megestrol acetate (MA) Unique Characteristics Rapid onset of action. Shorter duration than MPA (1 week). Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anti-depressants Tricyclic Anti-depressants MAOIs Amitriptyline Selegiline Clomipramine Imipramine Doxepin SSRIs Progestins Fluoxetin Medroxyprogesterone Paroxetine acetate (MPA) Sertraline Megestrol acetate (MA) Fluvoxamine Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved. Anti-depressants Tricyclic Anti-depressants MAOIs Amitriptyline Selegiline Clomipramine Imipramine Doxepin SSRIs Progestins Fluoxetin Medroxyprogesterone Paroxetine acetate (MPA) Sertraline Megestrol acetate (MA) Fluvoxamine Any unauthorized reproduction and/or distribution of this document is punishable by law. Ⓒ 2024 D.S. Leyson. All Rights Reserved.