Nervous System Drugs & Neurons

• Drugs that affect the nervous system notes

Neurons

• Neurons serve as the basic unit of the nervous system
• Neurons act as message carriers
• There are 3 types of neurons: sensory, associative and motor
• Sensory neurons carry message impulses to the central nervous system, CNS
• Associative neurons carry "around" impulses between neurons
• Motor neurons carry action impulses away from the CNS

Neuron Anatomy

• The direction of a message is the action potential
• Dendrites receive and conduct impulses to the cell body
• The cell body contains the nucleus, which maintains the neuron's life
• The axon conducts impulses away from cell body toward muscle cells, organs/glands, and other nerves
• Myelin sheath speeds up conduction

Synapse

• A synapse includes the space between two neurons, or between a neuron and a muscle/gland
• Neurotransmitters (NT) are required to carry messages across a synapse
• Synapses have a specific receptor for the neurotransmitter
• Synapses are specific for the function of transmitting messages

Nervous System Function

• The purpose of the nervous system is to receive stimuli and transmit information to initiate an appropriate response
• Components and organization of the nervous system:
  • Central Nervous System (CNS)
    • Brain
    • Spinal cord -Peripheral Nervous System (PNS)
    • Cranial nerves which originate from the brain
    • Spinal nerves which originate from the spinal cord
    • Sensory and Motor nerves that are voluntary -Somatic Nervous System (SoNS)
    • Voluntary muscle response -Autonomic Nervous System (ANS)
    • Involuntary responses to stimuli from muscle (smooth/cardiac) and glands
    • 2 divisions
      • Sympathetic (SNS)
      • Parasympathetic (PSNS)

Central Nervous System (CNS)

• Encased in connective tissue, also known as meninges
• Meninges have 3 layers (DAP)
• Cerebral Spinal Fluid (CSF) cushions and nourishes the CNS
• CSF is a clear, colorless fluid
• It interprets impulses from the PNS and initiates a response(s)
• Stimulation affects nerve cell activity and either increases it or blocks it

Peripheral Nervous System (PNS)

• Consists of cranial and spinal nerves
• Cranial nerves functions include sensory and motor
• Spinal nerves come in pairs
  • Dorsal spinal nerves transmit sensory impulses from periphery to the spinal cord
  • Ventral spinal nerves transmit motor impulses from the spinal cord to muscle/gland/neuron

Autonomic Nervous System

• The Sympathetic Nervous System (SNS) triggers "Fight or Flight" responses
• The Sympathetic Nervous System also triggers freeze and fret responses too
• The SNS expends energy
• The Parasympathetic Nervous System (PSNS) creates a homeostatic system and saves energy

Sympathetic Nervous System Details

• The Sympathetic trunk runs between T1 and T3
• Pathway of SNS: NT > ganglion (short) > next NT > effector organ/gland (long)
• Key Neurotransmitters include:
  • One preganglionic: Acetylcholine
  • Two postganglionic: Norepinephrine and Epinephrine
• Fight/flight/freeze/fret response, also referred to as the adrenaline system
• When the SNS system is stimulated:
  • Eyes: Pupils dilate
  • Lungs: Bronchioles dilate
  • Heart Activity Increases
  • Increased blood flow where required
  • Digestion is inhibited
  • Urinary Bladder activity decreases
  • Reproductive organs activity decreases

Sympathetic Nervous System Receptors

• Neurotransmitters act on the following receptors on the target tissue
• Alpha-1 receptors are for smooth muscle of blood vessels, eyes, and the urethra
• Alpha-2 receptors are for skeletal muscle
• Beta-1 receptors are for the heart
• Beta-2 receptors are for smooth muscle of the lung
• Dopaminergic receptors are renal, mesenteric, and cerebral arteries

Action of Drugs at Receptors

• Is determined by the number of receptors, as well as the strength of affinity, and the binding between a drug and its receptor
  • Alpha 1 agonists increase blood pressure due to constricting arterioles
  • Alpha 2 agonists cause sedation
  • Beta 1 agonists increase heart rate, conduction, and contractility
  • Beta 2 agonists cause bronchodilation and dilation of skeletal blood vessels
  • Dopaminergic agonists cause dilation of coronary vessels, renal, and mesenteric blood vessels

Parasympathetic Nervous System

• Cranial-Sacral origins
• Pathway: NT > ganglion (long) > next NT > effector organ/gland (short)
• Key Neurotransmitter (NT): Acetylcholine
  • Only 1 at PreG and PostG synapse
• Is a homeostatic or "Cholinergic" system based on the neurotransmitter Acetylcholine
• When stimulated:
  • Eyes: Pupils constrict
  • Lungs: Bronchioles constrict and secretions increase
  • Heart rate decreases
  • Blood flow is restricted (to what's required)
  • Digestion is stimulated
  • Urinary bladder activity increases
  • Salivary gland activity increases

Efferent Nervous System & Receptor Details

• Sympathetic neurotransmitters include Norepinephrine and Acetylcholine
• Parasympathetic neurotransmitters include Acetylcholine
• Somatic neurotransmitters include Acetylcholine
• Nicotinic and muscarinic receptors = cholinergic receptors

Autonomic Nervous System Drugs

• Sympathomimetics mimic sympathetic responses
• Sympatholytics block sympathetic responses
• Parasympathomimetics mimic parasympathetic responses
• Parasympatholytics block parasympathetic responses
• The drugs mimic neurotransmitters, interfere with neurotransmitter release, block neurotransmitter breakdown, and/or block neurotransmitters at the receptor itself.

Sympathomimetics Details

• Adrenergic drugs such as catecholamines and noncatecholamines
• Act on epinephrine and norepinephrine receptors, as well as other neurotransmitters and SNS receptors Classified by receptor class:
  • Alpha 1 agonists increase force of heart contraction, increase Blood Pressure, and cause pupil dilation
  • Beta 1 agonists increase Heart Rate and force of heart contraction
  • Beta 2 agonists dilate bronchioles and relax the GI tract
• Uses: Stimulate the heart to beat during cardiac arrest Reverse hypotension and contraction bronchus Promote vasoconstriction Treat urinary incontinence

Sympathomimetics Drug List

• Epinephrine: Increases heart rate & cardiac output; vasoconstriction in the skin; vasodilation in muscle; dilate bronchioles; increase metabolism
• Norepinephrine: Increases blood pressure by vasoconstriction a vasopressor
• Phenylephrine: Nasal vasoconstrictor
• Dopamine: Treats hypotension and increase renal perfusion
• Phenylpropanolamine: Treats urinary incontinence
• Dobutamine: Treats hypotension and increases the force of heart muscle contraction
• Ephedrine, Terbutaline, and Albuterol are all bronchodilators

Sympatholytics (Alpha-adrenergic blocking agents)

• Sympatholytics occupy receptor or inhibit the release of neurotransmitters
• Alpha blockers cause vasodilation and lowers blood pressure:
  • Phenoxybenzamine is a vasodilator to treat hypertension
  • Prazosin is a vasodilator used to treat heart failure and hypertension
  • Acepromazine is a vasodilator
  • Droperidol is a vasodilator
  • Yohimbine reverses Xylazine (alpha 2 agonist)
  • Atipamezole reverses for medetomidine, detomidine, dexmedetomidine (alpha 2 agonist)
• Beta blockers lower heart rate and blood pressure
  • Propranolol treats cardiac arrhythmias and Dz
  • Atenolol treats cardiac arrhythmias and Dz
  • Timolol treats glaucoma

Adverse 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 mimics action of acetycholine
  • Indirect acting blocks the breakdown of acetylcholine

Parasympathomimetic Drugs

• Reduce intraocular pressure from glaucoma
  • Pilocarpine (IsoptoCarpine)
• Stimulate GI motility and locally controls vomiting
  • Metoclopramide (Reglan)
• Treats urinary retention
  • Bethanechol (Urecholine)

Parasympatholytics

• Include anticholinergics, antispasmodics and antimuscarinics, which inhibit the action by occupying muscarinic receptors
• Uses decrease GI motility to treat vomiting and diarrhea
• Dries secretions as a pre-anesthetic
• Prevents and treats sinus bradycardia as a pre-anesthesia
• Dilates pupils
• Drugs
  • Atropine has all the same effects + Treats organophosphate toxicity
  • Glycopyrrolate is the same as atropine but has a longer onset and duration, and pre-anesthetic with fewer arrhythmias
  • Aminopentamide controls vomiting and diarrhea but is discontinued
  • Pralidoxime treats organophosphate toxicity

Cholinergics/Parasympathomimetic Adverse Affects

 - Bradycardia
 - Hypotension
 - Heart block
 - Lacrimation
 - Diarrhea
 - Vomiting
 - Increased GI activity
 - Intestinal Rupture
 - Increased Bronchial Secretions

Anticholinergics/Parasympatholytic Adverse Affects

 - Drowsiness
 - Disorientation
 - Tachycardia
 - Photophobia
 - Constipation
 - Anxiety
 - Burning at Injection Site

CNS Drug Classes

• Drug classes and examples included in this course
• Anticonvulsants (AKA: Antiepileptic drugs or AEDs)
• Tranquilizers, Sedatives, & Anti-anxiety
  • Tranquilizer = calming, reduces anxiety & aggression
  • Sedative = decrease irritability & excitement
  • Anti-anxiety = reduce anxiety
• Stimulates
• Euthanasia Drugs

Anticonvulsants Info

• Anticonvulsants reduce the frequency & severity of seizures
• Seizures are periods of altered rain function caused by recurrent abnormal electrical impulses
  • This is a CNS depressant
  • Can be long term (PO) or rapid (IV/PR) use to treat status epilepticus
  • Can not be stopped “cold turkey"
• Blood work is monitored Phenobarbital:
  • Drug blood levels are evaluted 3-4 weeks post start and then every 6 months
  • Lower margin of safety than other AEDs; which can affect liver health
  • Liver function is evaluated every 6 months for liver enzymes and proteins
• Potassium bromide:
  • Drug blood levels are evaluted 8 weeks post start and then every 6 months
  • Lower margin of safety than other AEDs; can affect mention, motor ability, appetite
• Benzodiazepine Derivatives:
  • Use for anti-anxiety, as anti-convulsant, muscle relaxation, and an appetite stimulant for cats
  • Contains Diazepam (Valium)
  • Short Acting and administered with IV/PR/CRI for status epilepticus; can be administered with PO for long term control with pulse therapy
  • Increases GABA (gamma-aminobutyric acid) > inhibits nerve impulse transmission
  • GABA is an inhibitory neurotransmitter
  • Can cause increased appetite, muscle relaxation
  • Can cause CNS Excitement paradoxically
  • Adheres to plastic and should not be drawn up in advance for storage

Common Anticonvulsant Drugs

• Phenobarbital
  • Long acting barbiturate; PO or IV administration
  • Depresses motor center of cerebral cortex by impairing transmission of impulses across the synapse
  • Side effects include sedation (ataxia, weakness), PU/PD, as well as hepatotoxicity
  • Animals can develop a tolerance as a result of liver enzyme induction
• Levetiracetam
  • Administered PO or IV
  • May be the DVMs first choice and is used as treatment for refractory epilepsy
• Zonisamide
  • PO administration
  • Is an adjunct usually for refractory
• Potassium bromide
  • Adjunct
  • PO administration
  • Loading dose is used
  • Not for cats with asthma like lung condition
  • Causes sedation (ataxia, weakness, PU/PD and gastritis
• Pentobarbital (Nembutal®, barbiturate)
  • Short acting, administered IV (highly irritating IM or SQ)
  • Treats toxin induced seizures and euthanasia

Tranquilizers

• Are Sedatives, and Anti-Anxiety medications
• Phenothiazine derivatives
  • Acepromazine maleate
  • Is used for Sedation as an anti-emetic
  • May be delayed or reduced for excited animals
  • Sudden painful stimulus can arouse patients
  • There is no analgesia
    • Hypotension & Hypothermia via Vasodilation is an effect
    • Controversially lowers seizure threshold in epileptics
    • Causes Raise of the nictitating membrane in horses
    • Caution must be used during use in horses

Benzodiazepine derivatives

• Diazepam (Valium)
• Zolazepam (Telazol)
• Midazolam (Versed)
• Are used for anti-anxiety, anti-convulsant, muscle relaxation, and as a appetite stimulant
• Animals usually remain alert (unless ill)
• There is minimal cardiovascular and respitory depression Combining with ketamine equals short term amnesia
  • Weak Potential CNS excitement

_ Alpha-2 Agonists which: - are used for Sedation, and are emetic - cause release of neurotransmitter, norepinephrine - that remains the alert - cause a bind to alpha-2 receptors that inhibit alertness - therefore: absence equals Sedation Drugs: - Xylazine (Rompun®, AnaSed®) Profound cardiovascular effects are respiratory May be used the 6.1 in horses Reversals yohimbine

• Detomidine Domasa The Better than to

• Dexmedetomidine Side effects: Bradycardia heart block hypertension Medetermite

• the Medela reversa to

Euthanasia Agents

• A controlled drug
• Anesthesia without struggling, vocalization, or excessive voluntary movement
• Cause death due to cessation of all vital functions
  • drugs include the pentobarbital so then with all the blue,
• T with so that the animals will not.

CNS Stimulants

• Used primarily to treat respiratory depression or arrest
  • Doxapram stimulates the respiratory center in the medulla
  • Stimulates Respiration
  • Can be administered IV or sublingually through the umbilical cord
  • The side effects are rare and usually associated with Overdose and include hypertension sales and hypertension