Drugs Affecting the Nervous System Lecture 3 PDF

Drugs that Affect the Nervous System 😘 Neurons Basic unit of NS Message carriers 3 types: Sensory “message” Carry impulses ___ To __ the CNS Associative “around” Carry impulses _____Between___ neurons Motor “action” Carry impulses _...

Drugs that Affect the Nervous System 😘 Neurons Basic unit of NS Message carriers 3 types: Sensory “message” Carry impulses ___ To __ the CNS Associative “around” Carry impulses _____Between___ neurons Motor “action” Carry impulses __Away __ from the CNS How the Nervous System Functions Choices: Between Away To Direction of Message (“Action Potential”) Dendrites - receive & conduct impulses to the cell body Cell body - contains nucleus, which maintains life of neuron Axon - conduct away from cell body toward muscle cells, organs/glands or other nerves Myelin sheath - speeds up conduction Terminal end fibres - takes message to synapse Synapse Space between: 2 neurons OR Neuron & muscle/gland Requires neurotransmitter (NT) (carries the message)  Has a specific receptor Specific for the function Transmits message over the synapse Review Drugs alongside naturally occurring NTs…some are agonists, some antagonists… Physiology & Function Purpose of the Nervous System To receive stimuli & transmit information to initiate an appropriate response Components: Central Nervous System (CNS) Brain Spinal cord Peripheral Nervous System (PNS) Cranial nerves (originate from brain) Spinal nerves (originate from spinal cord) Sensory and Motor nerves (voluntary) Somatic Nervous System (SoNS) Voluntary muscle response Autonomic Nervous System (ANS) Involuntary responses to stimuli from muscle (smooth & cardiac) & glands 2 divisions Sympathetic (SNS) Parasympathetic (PSNS) CNS Encased in connective tissue known as meninges 3 layers > DAP Cerebral Spinal Fluid (CSF) Cushions & nourishes CNS Clear, colourless fluid  Interprets impulses from PNS & initiate response(s) Stimulation affects nerve cell activity ↑ or block Peripheral NS Cranial nerves How many? Sensory & motor functions Spinal nerves (paired) Dorsal: sensory impulses from periphery to ____ Spinal Cord______ Ventral: motor impulses from spinal cord to _____ Muscle , gland , Neuron ____ Choices: Spinal cord Muscle/gland/neuron Autonomic Nervous System Sympathetic Nervous System Sympathetic trunk b/w T1-T3 Pathway: NT > Ganglion (short) > Next NT > Effector organ/gland (long) Key Neurotransmitters (NT) 1. Preganglionic: ACETYLCHOLINE 2. Postganglionic: NOREPINEPHRINE, EPINEPHRINE Sympathetic Nervous System Fight/flight/freeze/fret response or “Adrenalin________ system” (think of “adrenalin”) When stimulated we see: 1. Eyes 2. Lungs  3. Heart 4. Blood flow where required 5. Digestion 6. Urinary bladder 7. Reproductive organs NT Act on Following Receptors on the Target Tissue CAUSING: Alpha-1 in smooth muscle of blood vessels, eyes, urethra Alpha-2 skeletal muscle Beta-1 in the heart Beta-2 in smooth muscle of the lung Dopaminergic in renal, mesenteric, & cerebral arteries Action of Drugs at Receptors (General) Effect of a drug is determined by: Number of receptors Strength of affinity (strength of binding between a drug & its receptor) Alpha 1 agonists = ↑ blood pressure due to constricting arterioles Alpha 2 agonists = sedation (plus some other roles). See slide 36… Beta 1 agonists = ↑ heart rate, conduction, & contractility Beta 2 agonists = bronchodilation & dilation of skeletal blood vessels Dopaminergic agonists = dilation of coronary vessels, renal & mesenteric blood vessels Q: Then what will antagonists do? Parasympathetic Nervous System Cranial-Sacral origins Pathway: NT > Ganglion (long) > Next NT > Effector organ/gland (short) Key Neurotransmitter (NT)?  Only 1 at PreG & PostG synapse!!!! Parasympathetic Nervous System Homeostatic system or “CHOLINERGIC system” Based on main NT: Acetylcholine When stimulated we see: 1. Eyes 2. Lungs 3. Heart 4. Blood flow where required 5. Digestion 6. Urinary bladder 7. Salivary gland Parasympathetic Responses Receptors & Targets THINKER: Acetylcholine is also found in the Somatic NS & ANS! How does it elicit a different response? Autonomic Nervous System Drugs ANS Drugs Sympathomimetics (_____Adrenergic _____ drugs) Sympatholytics (___Adrenergic______ blocking drugs) Parasympathomimetics (_____Cholinergic___ drugs) Parasympatholytics (anti_______Cholinergic____ drugs) How? Some examples: mimic NT, interfere w/ NT release, block NT breakdown, block NT at receptor, etc… Choices: CHOLINERGIC OR ADRENERGIC Sympathomimetics  Adrenergic drugs (catecholamines or noncatecholamines) Act on epinephrine & norepinephrine receptors (other NTs/SNS receptors too) Classified according to receptor class Alpha 1 agonists ↑ force of heart contraction ↑ BP Pupil dilation Beta 1 agonists ↑ HR & force of heart contraction Beta 2 agonists Dilates bronchioles Relaxes GI tract Uses: Stimulate heart to beat during cardiac arrest Reverse hypotension & bronchoconstriction Promote vasoconstriction Treat urinary incontinence Not an exhaustive list of affects at receptors/uses Drugs: Epinephrine – ↑ heart rate & cardiac output; vasoconstriction in skin; vasodilation in muscle; dilate bronchioles; ↑ metabolism Norepinephrine – ↑ blood pressure by vasoconstriction (vasopressor) Phenylephrine – nasal vasoconstrictor Dopamine – Tx hypotension; ↑ renal perfusion Phenylpropanolamine – Tx urinary incontinence Dobutamine – Tx hypotension; ↑ force of heart muscle contraction Ephedrine - bronchodilation Terbutaline - bronchodilation Albuterol - bronchodilation Sympatholytics A_r_n_r_i_ blocking agents  Occupy receptor or inhibit NT release Drugs & Use Alpha blockers vasodilation & ↓ blood pressure Phenoxybenzamine – vasodilator (Tx hypertension) Prazosin – vasodilator; Tx heart failure & hypertension Acepromazine - vasodilator Droperidol – vasodilator Yohimbine – reversal for xylazine (alpha 2 agonist) Atipamezole – reversal for medetomidine, detomidine, dexmedetomidine (alpha 2 agonist) Beta blockers ↓ heart rate & blood pressure Propranolol – Tx cardiac arrhythmias & Dz Atenolol - Tx cardiac arrhythmias & Dz Timolol – Tx glaucoma Adverse Side Effects Adrenergics/ Sympathomimetics Tachycardia Hypertension Nervousness Cardiac arrhythmia Pulmonary edema Adrenergic Blocking/ Sympatholytics Bradycardia Hypotension Worsening heart failure Bronchoconstriction Heart block Syncope Parasympathomimetics Cholinergic drugs Direct acting = mimic action of acetylcholine Indirect acting = block acetylcholine breakdown Drugs that Mimic… Reduce intraocular pressure from glaucoma Pilocarpine (IsoptoCarpine®) Stimulate GI motility & locally control vomiting Metoclopramide (Reglan®) Treat urinary retention Bethanechol (Urecholine®) Parasympatholytics Anticholinergics, antispasmodics*, antimuscarinics* Inhibit action of _______ACh______ by occupying muscarinic receptors Uses: Decrease GI motility (Tx: vomiting & diarrhea) Dry secretions (pre-anesthetic) Prevent & treat sinus bradycardia (pre-anesthetic) Dilate pupils Drugs: Atropine – all of the above + Tx organophosphate toxicity Glycopyrrolate – same as atropine; longer onset & duration; pre-anesthetic (less arrhythmias) Aminopentamide – control vomiting & diarrhea (discontinued) Pralidoxime – Tx organophosphate toxicity Adverse Side Effects Anticholinergics/ Parasympatholytics Drowsiness Disorientation Tachycardia Photophobia Constipation Anxiety Burning at injection site Cholinergics/ Parasympathomimetics Bradycardia Hypotension Heart block Lacrimation Diarrhea Vomiting Increased GI activity Intestinal rupture Increased bronchial secretions CNS Drug Classes in this Course: Anticonvulsants (AKA: Antiepileptic drugs or AEDs) Tranquilizers, Sedatives, & Anti-anxiety Tranquilizer = calming, reduce anxiety & aggression Sedative = decrease irritability & excitement Anti-anxiety = reduce anxiety Stimulants Euthanasia drugs Anticonvulsants (AKA: AEDs) To reduce frequency & severity of seizures Seizure = periods of altered brain function due to recurrent abnormal electrical impulses Classification = CNS depressant Long term (PO) or rapid (IV/PR) – status epilepticus Cannot be stopped “cold turkey” WHY? Blood work monitored: Phenobarbital: Drug blood levels 3-4 weeks post start or dose ∆ then ~ q 6 mos Lower margin of safety than other AEDs; can affect liver health Liver function ~ q 6 mos (e.g.: liver enzymes, proteins) Potassium bromide: Drug blood levels ~8 weeks post start or dose ∆; ~ 6 mos  Lower margin of safety than other AEDs; can affect mention, motor ability, appetite Common Anticonvulsants Diazepam (Valium®, benzodiazepine) Short acting IV/PR/CRI admin for status epilepticus; PO for control-OLD; pulse therapy Increases GABA (gamma-aminobutyric acid) > inhibits nerve impulse transmission GABA is an inhibitory neurotransmitter Noteworthy potential side effect: ↑ appetite, muscle relaxation, CNS excitement (paradoxical) Zonisamide PO Adjunct usually (refractory) Potassium Bromide (AKA: KBr) Adjunct PO (liquid or powder; compounded) Loading dose may be used Narrow therapeutic range NOT FOR USE IN CATS: ASTHMA LIKE LUNG CONDITION 1/3 OF PATIENTS Side effects: sedation (ataxia, weakness), PU/PD, gastritis (give with...?) Pentobarbital (Nembutal®, barbiturate) Short acting; IV (highly irritating IM or SQ) Treat toxin induced seizures & euthanasia (high dose) Tranquilizers, Sedatives, & Anti-anxiety Phenothiazine Derivatives Drugs: Acepromazine maleate Use: Sedation; anti-emetic Effects may be delayed or reduced in excited animal Sudden painful stimuli can arouse the patient NO analgesia  Side effects: Hypotension & hypothermia (vasodilation) Controversy- lower seizure threshold in epileptics? Raise nictitating membrane Paraphimosis in horses (caution!) Benzodiazepine Derivatives Use: anti-anxiety, anticonvulsant, muscle relaxation, appetite stimulant (cats-OLD) Animal remains alert (unless ill) NO analgesia Minimal CV and respiratory depression Combine with ketamine = short term anesthesia Side Effects: weakness, potential CNS excitement REVERSAL is available: flumazenil Drugs Diazepam (Valium®) Zolazepam (Telazol®) Midazolam (Versed®) Alpha-2 Agonists Detomidine (Dormosedan®) Better analgesia than Xylazine Severe CV & respiratory side effects Horse sedation Dexmedetomidine (Dexdomitor®) In dogs [dosage via BSA]/cats for sedative & analgesia Side effects: bradycardia, ↓ RR, muscle twitching, heart block, hypertension Medetomidine (Domitor®) Same as Dexmedetomidine Reversal = atipamezole Euthanasia Agents Controlled drug (Except T-61®, see below) Effects: Unconsciousness without struggling, vocalization, or excessive voluntary movement Death due to cessation of all vital functions Tip: Add colour – distinguish when in syringe Drugs: Pentobarbital sodium (Sleep-Away®, Fatal-Plus®) Pentobarbital sodium + blue dye + additives (Beuthanasia-D®, Euthansol C®) T-61® – general & local anesthetics + muscle paralyzer Non-narcotic, non-controlled, non-barbiturate CNS Stimulants Primarily to treat respiratory depression or arrest Doxapram – stimulates respiratory center in medulla Use – stimulate respiration IV, sublingual, umbilical Side effects – rare & usually associated with overdose; hypertension, seizures, hyperventilation