Pharmacology PNS

• Functions of the nervous system:

  • Receive information from the external environment
  • Receive information from the tissues and organs of the animal
  • Interpret information received from both environment and animal
  • Send nervous impulses throughout the body of the animal to stimulate action
• The nervous system functions to control bodily functions and respond to the demands of the environment in a coordinated fashion
• The Peripheral Nervous System includes all of the nerves that branch out from the brain and spinal cord and extend to other parts of the body including muscles and organs
• The Somatic Nervous System is responsible for carrying sensory and motor information to and from the central nervous system
• The Autonomic Nervous System is responsible for regulating involuntary body functions such as blood flow, heartbeat, digestion, and breathing

  • Divided into:
  • Parasympathetic system: helps maintain normal body functions and acts to slow the heart rate, slow breathing, and constrict the pupils
  • Sympathetic system: regulates fight or flight responses by accelerating heart rate, increasing breathing rate, boosting blood flow to muscles, activating sweat secretion, and dilating the pupils
• PNS Neurotransmitters and Receptors:

  • Cholinergic neurons release Acetylcholine (ACh)
  • ACh binds to two types of cholinergic receptors:

  1. Nicotinic receptors

  2. Muscarinic receptors

  • Adrenergic neurons release noradrenaline (norepinephrine) and adrenaline (epinephrine)
  • Noradrenaline and adrenaline bind to adrenergic receptors (adrenoceptors)
  • Two main types of adrenergic receptors:

  1. 𝜶-adrenoreceptors

  2. 𝜷-adrenoreceptors
• Comparison of Autonomic and Somatic Motor Systems:

  • Somatic motor system:
  • One motor neuron extends from the CNS to skeletal muscle
  • Axons are well myelinated, conduct impulses rapidly
• Nicotinic Acetylcholine receptors:

  • Nicotinic acetylcholine receptors are a type of ligand-gated ion channel
  • Acetylcholine is the natural ligand, but they are named nicotinic receptors because the substance nicotine is an agonist of these receptors
  • When acetylcholine binds to these receptors they open and allow influx of Na+ into the muscle cell, exciting and 'depolarising' the muscle membrane
• Myasthenia Gravis, a disease caused by defective signaling at the Neuromuscular Junction:

  • Chronic autoimmune neuromuscular disease characterized by weakness of the skeletal (voluntary) muscles of the body
  • Common in mature dogs, rare in cats
  • Caused by production of antibodies which target the nicotinic receptor, causing the nicotinic receptors to be internalised and destroyed
• • Therapeutic effects: 1) To treat glaucoma, 2) to reverse effects of anticholinergic drugs, 3) treatment of myasthenia gravis. Lasts 3-6 hours
  • Neostigmine:
  • Similar to pyridostigmine, but is also used to treat conditions such as paralytic ileus (absence of normal peristaltic intestinal contractions), flaccid bladder, and myasthenia gravis
  • Edrophonium chloride (Tensilon®):
  • Also used as a diagnostic tool for myasthenia gravis
• Anti cholinesterase Agents:

  • Act by preventing the hydrolysis of ACh by acetylcholinesterase
  • Increase the concentration of acetylcholine (ACh) and activate more cholinergic receptors
  • Sometimes referred to as 'indirect agonists'
  • Examples:
  • Pyridostigmine (Mestinon®):
  • Pharmacologic effects: Mimics ACh, causes salivation, miosis (pupil constriction), increases GI motility. In large doses, it can cause twitching of skeletal muscle (fasciculations) and even paralysis of the muscle (due to effects at the neuromuscular junction)
• Neuromuscular Blocking Drugs:

  • Two main types of drugs that affect nicotinic receptors and the NMJ:

  1. Competitive Blocking Drugs

  • Examples: Tubocurarine, Pancuronium, Vecuronium

  2. Depolarising Drugs

  • Example: Succinylcholine (Anectine)
• Acetylcholinesterase Inhibitors
• Competitive Blocking (non-depolarizing) Drugs:

  • Example: Tubocurarine
  • In general, nondepolarizing muscle relaxants are not absorbed
• Nondepolarizing muscle relaxants like Tubocurarine are usually administered intravenously
• After IV administration, skeletal muscles become totally flaccid and nonresponsive to neuronal stimulation
• Muscles capable of rapid movement, such as those of the eye, are paralyzed first, followed by larger muscles of the head and neck, then limbs and body, and finally the diaphragm leading to cessation of respiration
• Animals with myasthenia gravis are more susceptible to the action of muscle relaxants
• Neuromuscular blocking drugs are used for skeletal muscle relaxation in various situations such as delicate surgery, tracheal intubation, cesarean section, convulsions, tetanus, and capture of exotic species
• Adverse effects of neuromuscular blocking drugs include reduced blood pressure, should not be used in animals with liver or kidney disease, and careful monitoring is essential with ventilation support
• Competitive relaxants' effects can be reversed by anticholinesterase drugs like neostigmine
• Succinylcholine is a depolarizing drug widely used for endotracheal intubation due to its rapid onset and short duration
• Depolarizing drugs initially behave like nicotinic receptor agonists, causing muscle contraction, but continued application leads to muscle paralysis
• Neuromuscular blocking drugs produce muscle relaxation but do not induce sedation, hypnosis, or analgesia
• Residual paralysis from these drugs can result in respiratory depression and muscle weakness
• Acetylcholinesterase inhibitor-related side effects can be minimized by administering anticholinergic drugs
• Neuromuscular blocking drugs should be used with caution or avoided in sick, depressed, dehydrated, obese, or aged horses, or those with a history of myasthenic syndromes