• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
351"a
 

351"a

on

  • 670 views

 

Statistics

Views

Total Views
670
Views on SlideShare
670
Embed Views
0

Actions

Likes
0
Downloads
10
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

351"a 351"a Presentation Transcript

  • Pharmacology-1 PHL 351, Parasympathetic Nervous System Abdelkader Ashour, Ph.D. 5 th Lecture
  • Muscarinic agonists None - - ++ Oxotremorine Glaucoma - - ++ Pilocarpine None † - - +++ Muscarine Bladder* and Gl hypotonia - - +++ Bethanechol None ++ + +++ Methacholine None - +++ ++ Carbachol None +++ +++ +++ Acetylcholine     Nic Musc     Clinical uses Hydrolysis by AChE Receptor specificity Structure Drug
  • Nicotinic Agonists
    • Nicotine is the most commonly encountered nicotinic agonist.
    • It is a tertiary amine found in the leaves of the tobacco plant.
    • It is sufficiently lipid-soluble to be absorbed across the skin.
    • It is responsible for the addicting properties of tobacco.
    • Nicotine has a greater affinity for neuronal than for skeletal muscle nicotinic receptors
    • Nicotine's actions are complex.
      • At low dosages it stimulates ganglionic nicotinic receptors (cause marked activation of these nicotinic receptors and initiate action potentials in postganglionic neurons) thus enhancing both sympathetic and parasympathetic neurotransmission
        • The initial response therefore often resembles simultaneous discharge of both the parasympathetic and the sympathetic nervous systems.
        • In the case of the cardiovascular system, the effects of nicotine are chiefly sympathomimetic on blood vessels, and parasympathomimetic on the heart
        • In the GI and urinary tracts, the effects are largely parasympathomimetic
      • As nicotine dosages increase, there is stimulation of nicotinic receptors in many other sites
      • At high dosages, nicotine possesses some antagonist effect at nicotinic receptors
        • Prolonged exposure results in depolarizing blockade of the ganglia
  • Nicotinic Agonists, Ganglion Stimulants
    • The mild alerting action of nicotine absorbed from inhaled tobacco smoke is the best-known of these effects.
    • In larger concentrations, nicotine induces tremor, emesis, and stimulation of the respiratory center. At still higher levels, nicotine causes convulsions, which may terminate in fatal coma.
    • Most nicotinic receptor agonists affect both ganglionic and motor end plate receptors, but nicotine and lobeline (a plant derivative similar to nicotine) affect ganglia preferentially
    • In spite of the smaller ratio of nicotinic to muscarinic receptors in the brain, nicotine and lobeline have important effects on the brainstem and cortex.
    • The lethal effects on the central nervous system, and the fact that nicotine is readily absorbed, form the basis for the use of nicotine as an insecticide.
    • These drugs are not used clinically, but only as experimental tools. They cause complex peripheral responses associated with generalized stimulation of ALL autonomic ganglia (sympathetic & parasympathetic)
  • Nicotinic Antagonists, Ganglionic Blockers
    • The primary receptors at ganglia are cholinergic receptors of the nicotinic (N N ) type.
    • Nearly all effects are predictable from the knowledge that ganglionic blockers reduce transmission in all autonomic ganglia, both sympathetic and parasympathetic.
    • In some sites, sympathetic activation seems to predominate over parasympathetic, while in other sites, the opposite is true.
    • Ganglionic blockade thus "uncovers" the predominant system. This class of drugs is now rarely used.
    • Example: trimetaphan
    • Mediators and Effects of Ganglionic Blockade on Organ Systems
      • Tissue Predominant System/Ganglionic Blockade Effect
      • Arterioles Sympathetic/(Vasodilation
      • Veins Sympathetic/Vasodilation
      • Heart Parasympathetic/Tachycardia
      • Iris Parasympathetic/Mydriasis
      • Ciliary muscle Parasympathetic/Cycloplegia
      • Gastrointestinal tract Parasympathetic/Hypomotility
      • Urinary bladder Parasympathetic/Urinary retention
      • Salivary glands Parasympathetic/Xerostomia
      • Sweat glands Sympathetic cholinergic /Anhidrosis
  • Nicotinic Antagonists, Skeletal Muscle Relaxants (drugs that block neuromuscular transmission)
    • Since skeletal muscle contraction is elicited by nicotinic (Nm) cholinergic mechanisms, it has similarities to nicotinic neurotransmission at the autonomic ganglia.
    • Two different kinds of functional blockade may occur at the neuromuscular endplate, and hence clinically used drugs fall into two categories:
      • Non-depolarizing blocking agents: antagonists at the nAChR (i.e. they act by blocking nAChR
      • Depolarizing blocking agents: agonists at the nAChR (i.e., they act by stimulating the nAChR)
    • Non-depolarizing neuromuscular blocking drugs:
      • They act as competitive antagonists at the ACh receptors of the endplate
      • Tubocurarine is a prototype for this class of drugs.
      • Blockade by these agents (such as tubocurarine, pancuronium, and doxacurium) can be reversed by increasing the amount of ACh in the synaptic cleft, for example, by the administration of a cholinesterase inhibitor
    • Depolarizing neuromuscular blocking drugs:
      • They stimulate the nicotinic endplate receptor to depolarize the neuromuscular endplate
      • This initial depolarization is accompanied by transient twitching of the skeletal muscle (fasciculation).
      • With continued agonist effect, the skeletal muscle tone cannot be maintained, and, therefore, this continuous depolarization results in a functional muscle paralysis (flaccid paralysis; muscles are weak and have little or no tone).
      • Thus, the effects of a depolarizing neuromuscular blocking agent move from a continuous depolarization (phase I) to a gradual repolarization (as the sodium channel closes) with resistance to depolarization (phase II)
    Nicotinic Antagonists, Skeletal Muscle Relaxants (drugs that block neuromuscular transmission)
      • Succinylcholine (suxamethonium ) is a prototype for this class of drug. It has a shorter half-life (5-10 minutes) and must be given by continuous infusion if prolonged paralysis is required.
      • An important aspect of succinylcholine is its hydrolysis by pseudocholinesterase
        • In patients with pseudocholinesterase deficiency, succinylcholine half-life is greatly prolonged, and such patients may suffer from prolonged apnoea and they may regain control of their skeletal muscles slowly after a surgical procedure. This is the most serious complication of pseudocholinesterase deficiency