PHARM CH4.pptx

Chapter 4: DRUGS USED IN NERVOUS SYSTEM DISORDERS INTRODUCTION  Communication and control center  Functions of the nervous system • • • Sensory Integrative Motor ANATOMY AND PHYSIOLOGY  Central nervous system • Anatomical divisions • • •  Brain Spinal cord Control center Peripheral nervous system • Anatomic divisions • • Cranial nerves Spinal nerves PERIPHERAL NERVOUS SYSTEM  Functional divisions • • Afferent portion - composed of nerve cells that carry info from receptors in the periphery of the body to the CNS Efferent portion - consists of nerve cells that carry impulses from the CNS to muscles & glands • • Somatic nervous system - consists of efferent nn. that carry impulses from CNS to skeletal m. tissue Autonomic nervous system (ANS) - consists of efferent nn. cells that carry info from CNS to cardiac m., glands & smooth m. • • Sympathetic nervous system Parasympathetic nervous system NEURON   Fundamental unit of all branches & divisions of the nervous system Transmit info from point to point IMPULSE TRANSMISSION Transmission of messages occurs through a wave of charge reversal that moves down the fiber  Resting (polarized) fiber has + charges lined up on the outside of its membrane & - charges on the inside  NEUROTRANSMITTER RELEASE AND ACTIVITY Neurotransmitter release Neurotransmitt er activity REFLEX ARC   Most basic impulse conduction Components • • • • •  Receptor Sensory neuron Center in the CNS for a synapse Motor neuron Effector Spinal reflex – impulse travels around the arc w/o going to the brain THE BRAIN      Cerebrum – higher functions of the brain Thalamus – relay center Hypothalamus – controls the pituitary gland & controls and regulates the ANS Medulla – carries sensory & motor impulses b/w the spinal cord & brain; ctrls vital physiological activities Reticular activating system –functions to arouse the cerebral cortex & is responsible for consciousness, sleep & wakefulness AUTONOMIC NERVOUS SYSTEM  Parasympathetic (cholinergic) nervous system  Regulates energy-conserving activities  “Rest and digest”  Sympathetic (adrenergic) nervous system  Regulates energy-expending activities  “Fight or flight” AUTONOMIC NERVOUS SYSTEM Sympathetic Parasympathetic PARASYMPATHETIC NERVOUS SYSTEM  Receptors •  • Nicotinic – all autonomic ganglia & in adrenal medulla Muscarinic – synapse of postganglionic fibers • • • Neurotransmitters • Acetylcholine Receptors • Cholinergic receptors •  SYMPATHETIC NERVOUS SYSTEM •  alpha-1 – stimulatory (except in GI tract) alpha-2 – stimulatory (except in GI tract) beta-1 – inhibitory (except in heart) beta-2 – inhibitory (except in heart) Dopaminergic Neurotransmitters • • • Norepinephrine (alpha & beta) Epinephrine (alpha & beta) Dopamine (& acetylcholine) AUTONOMIC NERVOUS SYSTEM HOW DRUGS AFFECT THE ANS  Mimicking neurotransmitters  Interfering w/ neurotransmitter release  Blocking the attachment of neurotransmitters to receptors  Interfering w/ the breakdown or reuptake of neurotransmitters at the synapse CLASSES OF ANS AGENTS  Cholinergic agents  Cholinergic blocking agents  Adrenergic agents  Adrenergic blocking agents CHOLINERGIC AGENTS  Stimulate receptor sites mediated by acetylcholine by mimicking the action of acetylcholine (direct acting) or inhibiting its breakdown (indirect acting)  Aka parasympathomimetic  Clinical uses • • • • • • aid in diagnosis of myasthenia gravis reduce intraocular pressure of glaucoma stimulate GI motility tx urinary retention ctrl vomiting act as an antidote for neuromuscular blockers DIRECT-ACTING CHOLINERGICS  Carbamylcholine – tx atony of the GI tract & to stimulate uterine contractions in swine  Bethanecol – tx GI & urinary tract atony  Pilocarpine – reduces IOP  Metoclopramide (Reglan) – ctrl vomiting & promote gastric emptying INDIRECT- ACTING CHOLINERGIC AGENTS  Edrophonium (Tensilon)* – used to diagnose myasthenia gravis  Neostigmine – tx urinary retension & GI atony, diag. & tx myasthenia gravis & an antidote to neuromuscular blocking agents  Physostigmine – tx of glaucoma  Organophoshate compounds – insecticide dips  Demecarium –tx of glaucoma  Pyridostigmine – tx of myasthenia gravis CHOLINERGIC AGENTS  Adverse • • • • • • • side effects Bradycardia Hypotension Heart block Lacrimation Diarrhea/Vomiting ↑ Intestinal activity &/or rupture ↑ Bronchial secretions CHOLINERGIC BLOCKING AGENTS  Block the action of acetylcholine at muscarinic receptors of the PNS  Aka anticholinergic or parasympatholytic  Clinical uses • • • • • tx of diarrhea & vomiting by ↓ GI motility pre-an to dry secretions & prevent bradycardia dilate pupils for ophthalmic examination relieve ciliary spasm of the eye tx sinus bradycardia CHOLINERGIC BLOCKING AGENTS  Agents • • • • • Atropine – pre-an, antidote to organophosphate poisoning, ctrl ciliary spasms of the eye, tx sinus bradycardia, slow a hypermotile gut Scopolamine – antidiarrheal Glycopyrrolate – similar to atropine w/ longer DOA Propantheline – diarrhea, urinary incontinence, bradycardia & reduce colonic peristalsis in horses Pralidoxime (2-PAM) – tx organophosphate intoxication CHOLINERGIC BLOCKING AGENTS  Adverse • • side effects Dose related Drowsiness, disorientation, tachycardia, photophobia, constipation, anxiety & burning at injection site ADRENERGIC (SYMPATHOMIMETIC) AGENTS  Bring about action at receptors mediated by epinephrine or norepinephrine  Classified as catecholamines or noncatecholamines &/or according to specific receptor type activated ADRENERGIC (SYMPATHOMIMETIC) AGENTS  Clinical • • • • • • • • • uses Stimulate heart to beat during cardiac arrest Reverse hypotension & bronchoconstriction of anaphylactic shock Strengthen heart during CHF Correct hypotension Reduce capillary bleeding Tx urinary incontinence Reduce mucous membrane congestion Prolong the effects of local anesthetic agents Tx glaucoma ADRENERGIC (SYMPATHOMIMETIC) AGENTS  Agents • • • • • • • Epinephrine – stimulates all receptors Norepinephrine – mostly an alpha stimulator w/ some beta stimulation; 1° influence is that of a vasopressor (↑ BP) Isoproterenol – beta stimulator used for bronchodilation Dopamine – tx shock & CHF & ↑ renal perfusion Dobutamine – beta agonist used for short term tx of heart failure Ephedrine – beta agonists used for bronchodilation Phenylephrine – alpha stimulator used as a nasal vasoconstrictor Phenylpropanolamine* – tx urinary incontinence ADRENERGIC (SYMPATHOMIMETIC) AGENTS  Adverse • • side effects Tachycardia, hypertension, nervousness & cardiac arrhythmias Hypertension, arrhythmias & pulmonary edema may occur w/ an overdose ADRENERGIC BLOCKING AGENTS  Used to disrupt the activity of the sympathetic nervous system  Classes • • • Alpha blockers Beta blockers Ganglionic blockers ALPHA BLOCKERS Clinical uses limited  Agents  • • • • •  Phenoxybenzamine – hypotensive (vasodilator) agent Acepromazine (Promace) – tranquilizer & vasodilator Prazosin – hypotensive agent Yohimbine – antidote for xylazine toxicity Atipamezole (Antisedan) – reversal agent for medetomidine Adverse side effects • • • • Hypotension (phenoxybenzamine, acepromazine, prazosin) Tachycardia (phenoxybenzamine) Muscle tremors (yohimbine) Seizures (acepromazine) BETA BLOCKERS  Clinical • uses Tx glaucoma, arrhythmias & hypertrophic cardiomyopathy  Agents • • • Propanolol – cardiac arrhythmias & hypertrophic cardiomyopathy Timolol – ophthalmic prep used to tx glaucoma Atenolol – cardiac arrhythmias & hypertrophic cardiomyopathy  Adverse • side effects Bradycardia, hypotension, worsening heart failure, bronchoconstriction, heart block & syncope CENTRAL NERVOUS SYSTEM  Classes • • • • • • • • • • Tranquilizers/Neuroleptics Barbiturates Dissociates Opioid agonists/antagonists Neuroletanalgesics Anticonvulsants Inhalants Misc CNS drugs CNS stimulants Euthanasia agents TRANQUILIZERS/NEUROLEPTICS  Phenothiazine • • • dopamine blockers (?) alpha-adrenergic blockade depress chemoreceptor trigger zone in the brain  Clinical • • • derivatives uses prevention or tx of vomiting relief of mild pruritis sedation/tranquilization TRANQUILIZERS/NEUROLEPTICS  Agents • • • • acepromazine maleate chlorpromazine hydrochloride promazine prochlorperazine  Adverse side effects - hypotension, hypothermia & induce seizures in epileptic animals BENZODIAZEPINE DERIVATIVES  Depresses thalamic & hypothalamic areas of the brain  Clinical uses • • • • • Sedation Relief of anxiety & behavioral disorders Tx of seizures Appetite stimulant (cats) Induction cocktails BENZODIAZEPINE DERIVATIVES  Agents • • • diazepam (Valium) midazolam (Versed) alprazolam (Xanax)  Adverse • • side effects excitement (dogs) excessive CNS depression w/ overdose XYLAZINE HYDROCHLORIDE (ROMPUN)  Alpha-2 agonist  Clinical uses – sedation, analgesia, short-term anesthesia  Adverse side effects – bradycardia, hypotension, respiratory depression & ↑ sensitivity to epinephrine resulting in cardiac arrhythmias  Antagonized by yohimbine DETOMIDINE HYDROCHLORIDE (DORMOSEDAN)  Alpha-2 agonist  Clinical uses • sedation & analgesia in horses  Adverse • • • • side effects sweating muscle tremors penile prolapse bradycardia & heart block MEDETOMIDINE (DOMITOR) Alpha-2 agonist  Dexmedetomidine (Dexdomitor)  Clinical uses – facilitating clinical exam, minor surgical procedures & minor dental procedures that do not require intubation  Adverse side effects - bradycardia, AV heart block, ↓ respirations, hypothermia, urination, vomiting, hyperglycemia & pain at the injection site  Reversed by atipamezole (Antisedan)  ROMIFIDINE (SEDIVET)  Alpha-2 agonist  Clinical uses • • equine sedative used to facilitate handling, examination & tx pre-anesthetic BARBITURATES  Clinical • • • • uses sedatives anticonvulsants general anesthetics euthanasia agents  Adverse • side effects potent depressing effects on the cardiac & pulmonary systems (especially cats) BARBITURATES  Long-acting barbiturates (8-12 hours) • • •  Short-acting barbiturates (45 mins. to 1.5 hours) • • •  Agents – phenobarbital Clinical uses – anticonvulsant to prevent epileptic seizures Class IV controlled drug Agents – pentobarbital sodium Clinical uses – euthanasia Class II controlled drug Ultra-short barbiturates (5 to 30 mins.) • • • Agents – thiopental Clinical uses – anesthesia Adverse side effects – tissue necrosis when administered perivascularly due to alkalinity, CNS depression w/ rapid administration, CNS excitement w/ slow administration & cardiovascular depression DISSOCIATIVES Alter neurotransmitter activity resulting in depression of the thalamus & cerebral cortex & activating the limbic system  Characteristics – involuntary muscle rigidity (catalepsy), amnesia, analgesia (not for deep abdominal pain), pharyngeal/laryngeal reflexes maintained, muscle tone increased & minor cardiac stimulation  Clinical uses – sedation, restraint & anesthesia  DISSOCIATIVES  Agents • • •  ketamine (Ketaset) – good somatic but poor visceral analgesia tiletamine (Telazol, when combined w/ zolazepam) Class III controlled drugs Adverse side effects – spastic jerking movement, convulsions, resp. depression, burning at the intramuscular injection site, hallucinations (cats) OPIOID AGONISTS Characteristics – produce analgesia & sedation while reducing anxiety & fear  Receptor classes  • • • • mu – found in pain-regulating areas of the brain; contribute to analgesia, euphoria, resp. depression, physical dependence & hypothermic actions kappa – found in the cerebral cortex & spinal cord; contribute to analgesia, sedation & miosis sigma – may be responsible for struggling, whining, hallucinations & mydriatic effects delta – modify mu receptor activity OPIOID AGONISTS  Class II controlled drugs (most)  Clinical uses • • • Pre-anesthetics or post-anesthetics for sedation & analgesia Antitussive (depression of cough ctr) Antidiarrheal (reduce peristalsis or segmental contractions) OPIOID AGONISTS  Adverse • • • • • • • • • side effects Resp. depression Panting Defecation Flatulence Vomiting Sound sensitivity Excitement (dogs) w/ rapid administration Excitement (cats & horses) w/ high doses Convulsions OPIOID AGONISTS  Naturally occurring narcotics  Opium, paregoric – tx diarrhea primarily in calves & foals  Morphine sulfate (Duramorph)  Synthetic  Meperidine narcotics (Demerol) – 1/8 as potent as morphine  Butorphanol tartrate (Torbutrol, Torbugesic) – partial agonist, Class IV controlled drug, 4-7x analgesic properties of morphine, antitussive  Buprenorphine (Buprenex) – partial mu agonist-antagonist  Oxymorphone – 10x more potent than morphine  Fentanyl – 100x analgesic properties of morphine, transdermal patch available  Etorphine (M-99) – 1000x analgesic properties of morphine, zoo & exotic species  Carfentanil – 10,000x more potent than morphine, wildlife anesthesia OPOID AGONISTS  Synthetic narcotics (continued)  Diphenoxylate (Lomotil) - used in combination w/ atropine as an antidiarrheal, Class V controlled drug  Apomorphine – used to induce vomiting by stimulating the chemoreceptor trigger zone, conjunctival sac administration  Codeine – antitussive  Hydrocodone bitartrate (Hycodan, Tussigon) – antitussive OPIOID ANTAGONISTS  Block effects of opioids by binding w/ opiate receptors, displacing narcotic molecules already present & preventing further narcotic binding at the sites  Clinical uses – antagonize the effects of opioid agonists  Agents • • naloxone (Narcan) diprenorphine NEUROLEPTANALGESICS  Consists of an opioid & a tranquilizer  Clinical uses – sedation, restraint & anesthesia  Agents • • • • fentanyl & droperidol (Innovar-Vet) acepromazine & morphine acepromazine & oxymorphone xylazine & butorphanol NEUROLEPTANALGESICS  Adverse • • • • • • side effects Panting Flatulence Personality changes ↑ Sound sensitivity Bradycardia Overdose may cause severe depression of the CNS, resp. system & cardiovascular system DRUGS TO PREVENT OR CTRL SEIZURES  Agents • • • • • •  diazepam (Valium) phenobarbital* primidone phenytoin sodium potassium bromide clorazepate Adverse side effects – drowsiness, CNS depression, anxiety, agitation, PU/PD & hepatotoxicity INHALANTS  Converted from liquid to gas by an anesthetic vaporizer & delivered to lungs w/ the use of an oxygen source & patient breathing circuit  Alveoli → bloodstream →CNS  Produce unconsciousness, analgesia & muscle relaxation  Rapid induction & recovery INHALANTS  Agents • • • • • isoflurane (Forane, Isoflo) – rapid induction & recovery, stable heart rhythm & does not ↓ cardiac output, <0.2% metabolized sevoflurane (Sevoflo) – very rapid induction & recovery, used in high-risk small animal patients, 3% metabolized, $$ $ halothane – sensitizes heart to catecholamines which may result in cardiac dysrhythmias, 25% metabolized methoxyflurane –slow induction & recovery, 50% metabolized nitrous oxide – cannot produce general anesthesia as a sole agent MISCELLANEOUS CNS DRUGS  Propofol • (Rapinovet, PropoFlo) Adverse side effects – apnea w/ rapid administration, occasional seizure-like activity & prolonged recovery &/or Heinz body production in cats w/ repeated use  Glyceryl guaiacolate or Guaifenesin (Guailaxin, Gecolate) • • Skeletal muscle relaxant that exerts its effects on the connecting neurons of the spinal cord & brain stem Adverse side effects – hemolysis w/ use of >5% solutions CNS STIMULANTS  Clinical uses – tx of resp. depression or arrest  Agents • doxapram (Dopram-V)  Adverse • side effects hypertension, seizures & hyperventilation NEUROMUSCULAR BLOCKING DRUGS  Muscle relaxants; interfere w/ neuromuscular transmission of impulses  Clinical uses – adjunct to general anesthesia & to facilitate intubation  Agents • • Depolarizing – succinylcholine chloride Nondepolarizing – tubocurarine, gallamine, pancuronium, vecuronium, atracurium BEHAVIORAL PHARMACOTHERAPY  Behavioral • problems separation anxiety, fears & phobias, unruliness, hyperactivity, compulsive disorders, cognitive dysfunction (older dogs) & inappropriate elimination (cats)  Agents • anxiolytics, antidepressants, misc. ANTIANXIETY MEDICATIONS  Benzodiazepines • • • Clinical uses – tx of fears & phobias, separation anxiety, aggression, anxiety-induced stereotypes, urine marking (cats) & appetite stimulation Agents – diazepam, alprazolam & lorazepam Adverse side effects – lethargy, ataxia, PU/PD, hyperexcitability & hepatic necrosis (cats)  Azapirones • • Clinical uses – ctrl of urine spraying/marking & ctrl of fearfulness & anxiety Agents – buspirone (BuSpar) ANTIDEPRESSANTS  Tricyclics  Clinical • • uses – separation anxiety, obsessive disorders, fearful aggression, hyperactivity, hypervocalization & urine marking Agents – amitriptyline (Elavil), clomipramine (Clomicalm) Adverse effects – sedation, tachycardia, heart block, mydriasis, dry mouth, reduced tear production, urine retension & constipation ANTIDEPRESSANTS  Serotonin • • • reuptake inhibitors Clinical uses – obsessive disorders, phobias, aggression & separation anxiety Agents – fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil) Adverse side effects – anorexia, nausea, lethargy, anxiety & diarrhea ANTIDEPRESSANTS  Monoamine • • • oxidase-b inhibitors Clinical uses – old-dog dementia & canine Cushing’s disease Agents – selegiline (Anipryl) Adverse side effects – vomiting/diarrhea, anorexia, restlessness, lethargy, salivation, shaking & deafness MISCELLANEOUS BEHAVIOR MODIFIERS  Synthetic • • • progestins Clinical uses – urine spaying/marking, intermale aggression & dominance aggression Agents – megestrol acetate (Ovaban), medroxyprogesterone (Depo-Provera) Adverse side effects – transient DM (cats), PU/PD, wt. gain, personality changes, endometritis, endometrial hyperplasia, mammary hypertrophy, mammary tumors, adrenal atrophy & EUTHANASIA AGENTS  Agents • • • pentobarbital sodium (Sleepaway, Euthanasia6, Fatal-Plus) – Class II pentobarbital sodium w/ phenytoin (Beuthanasia-D, Euthasol) – Class III T-61 – nonnarcotic, nonbarbiturate that contains a general anesthetic, a local anesthetic & a muscle paralyzer  Adverse side effects – muscle twitching, agonal breathing, vocalization

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