Parasympathetic Nervous System
Parasympathetic Nervous System
Parasympathetic Nervous System
3) Involuntary regulation
by means of visceral reflexes.
Except:
the local axon reflexes
Parasympathetic Division of ANS:
(Cranio-Sacral Outflow)
a) Mechanoreceptor information
b) Chemosensory information
Parasympathetic Visceral Sensory System,
is transmitted by 4 Cranial Nerves:
1) Trigeminal (V)
internal face and head
2) Facial (VII)
tongue (taste)
3) Glossopharyngeal (IX)
hard palate, upper oropharynx
4) Vagus ( X )
carotid body, lower part of oropharynx, larynx,
trachea, esophagus, thoracic & abdominal organs.
Exception:
Spinal nerves S1 to S4
which innervate the Pelvic viscera
Distribution PNS:
= PNS fibers in CN 111
pupillary sphincter and ciliary muscle of eyes.
= Fibers from CN V11
pass to lacrimal, nasal, and
submandibular glands.
= Fibers from CN 1X
to parotid gland .
= Vagus (CN X)
contains 75 % of all PNS nerve fibers
pass to entire thoracic and abdominal regions
PNS (Cranio-Sacral Outflow):
Atropine:
= does not block all excitatory neurotransmissions,
because Neurokinin A and substance P
= As a result of activation
of Gq-PLC pathway,
seen in several Ca++ -mediated responses.
Stimulation of M2 and M4 Receptors:
decreased cAMP
A small dose IV of Acetylcholine:
transient fall in BP;
= due to generalized vasodilation
= mediated by vascular endothelial NO,
causes reflex tachycardia
= In Endothelial Damaged:
> ACh acts on M3 Receptors on VSMCs
causing vasoconstriction.
Baroreceptor or Chemoreceptor Reflexes:
or direct stimulation of the Vagus nerve, (CN X)
Causing Vasodilatation
CVS Pharmacologic Effects of Ach:
the physiological basis for the therapeutic uses of,
Muscarinic Receptor Agonists and Antagonists.
Reflex Bradycardia
Cardiac Function of Acetylcholine:
A. Is direct and indirect;
thro’ inhibition of adrenergic stimulation to the heart.
1) Causes hyperpolarization,
a) Slows conduction.
b) Increases refractory period.
by inhibiting the L-type of Ca++ channels.
c) Decreased AV conduction
responsible for complete heart block
in large doses of systemic Cholinergic agonists.
It is important to note that:
Cholinergic (Vagal) innervation to the:
a) His-Purkinje system
and
b) Ventricular myocardium
is sparse.
Increasing Parasympathetic (vagal) Tone,
as produced by Digitalis glycosides:
= M3 Muscarinic Receptors
mediate cholinergic control of GI motility.
• Features of the PNS, Cont’d :
A. Choline Esters:
a) Acetylcholine
1. Methacholine (acetyl-methylcholine)
differs from Ach by its:
1) stimulates peristalsis
2) increases motility
1. Muscarine:
= acts exclusively at muscarinic receptor sites
= has toxicological significance.
2. Arecoline:
the same principal sites of action as choline esters.
3. Pilocarpine:
Major Natural Alkaloid Muscarinic Agonists:
3. Pilocarpine:
has a dominant muscarinic action,
a partial rather than a full agonist.
= Pilocarpine clearance;
is decreased in patients with renal impairment,
natural alkaloids are eliminated by the kidneys.
2) In ophthalmology:
a) as miotic agents
b) for the treatment of Glaucoma.
Acetylcholine (Miochol-e):
for topical application as 1% solution by instillation.
to induce mydriasis during:
a) Ophthalmic examinations
b) Ophthalmic Surgery
Synthetic Choline Derivatives:
influence the naturally mediated release
of the neurotransmitters.
a) Adenosine
b) Dopamine (DA)
c) Glutamate- aminobutyric acid (GABA)
d) Prostaglandins
e) Enkephalins
= Donepezil:
binds with higher affinity to AchE active center.
= At the NMJ:
accumulation of Ach;
produces depolarization of end plates,
causing flaccid paralysis.
= At postganglionic muscarinic effector sites;
the response is either:
1) excessive stimulation,
results in contraction and secretion,
= At ganglia;
depolarization and enhanced transmission.
Drugs Acting at NMJ and Autonomic Ganglia:
Structure of Nicotinic Receptor:
1) Depolarizing:
Succinylcholine (ANECTINE, QUELICIN)
the only NMJ blocking agent used clinically so far.
2) Competitive/non-depolarizing:
Curare: localized paralysis
= Site of action of D-tubocurarine, and
other competitive blocking agents;
the motor end plate, (post-junctional membrane).
= Competitive antagonists
bind with Nicotinic ACh receptor at the end plate,
competitively block the binding of Ach, so that
so that the muscle cell becomes insensitive to the
motor-nerve impulses.
Galantamine:
An AChE inhibitor recently approved by the FDA.