Download Autonomic Nervous System

Autonomic Nervous System
Trachte
[email protected]
Autonomic Nervous System
• Autonomic Nervous System defined as nerves
outside of the central nervous system (outside bony
encasement of nervous system) with two efferent
fibers (must have a synapse prior to the final
junction with the end organ)
Parasympathetic Nervous System
• Nicotinic Receptor- Comprised of five proteins to
form a cation pore; agonists & antagonists not
typically used clinically (exception is Nicotine)
• Muscarinic Receptor- protein coupled to GTPbinding proteins to influence adenylyl cyclase,
potassium channels or phospholipase C
– Bethanecol is agonist; Atropine is antagonist
• Anticholinesterases- potentiate activity of system
– Example is neostigmine
Nicotinic Receptor
• Because it consists of 5 distinct proteins,
there are multiple isoforms
• Ganglionic nicotinic receptors typically are
composed of 2 alpha (acetylcholine binding
proteins) and 3 ß proteins
Muscarinic Receptors
• Actually five different clones exist
• M1, M3 & M5 couple to Phospholipase C
(stimulate it)
• M2 & M4 couple to adenylyl cyclase
(inhibit it)
Muscarinic Receptors
• [Muscarinic Receptors on eye (constrict pupil),
lacrimal glands (increase secretions), salivary
glands (increase secretions), gut (increase
secretions & motility), urinary bladder (relax
sphincter & contract detrusor to promote
urination), lung (contract bronchioles & increase
secretions), heart (decrease rate).]
Parasympathetic Nervous System
Can produce the following influences with the
agent indicated:
– augment peristalsis with bethanecol or neostigmine
(promotes defecation)
– contract urinary bladder with bethanecol or
neostigmine
– promote erection with a vasodilator (sildenafil (Viagra)
preserves cGMP)
– prevent urination caused by overactive bladder (usually
detrusor overactivity) with Tolterodine (muscarinic
antagonist- others include oxybutynin,
Trospium, propantheline, hyoscyamine)
Q1. If you want to induce urination,
which of the following strategies is best?
1.
2.
3.
4.
5.
nicotinic agonist
nicotinic antagonist
muscarinic agonist
muscarinic antagonist
Anticholinesterase
Sympathetic Nervous System
Nicotinic Receptor- receptor consists of 5 proteins forming a cation pore when
activated by acetylcholine agonists & antagonists not used much except in
anesthesia or smoking cessation
Beta2 Receptor- protein coupled to GTP-binding protein to activate adenylyl
cyclase; chief effects are to relax smooth muscle (bronchiole, uterine,
intestinal etc) and to promote glycogenolysis
– agonist is Albuterol; no specific ß2 antagonists used clinically
(Propranolol is nonselective ß antagonist)
Alpha1 Receptor- protein coupled to GTP-binding protein to activate phosholipase
C; chief effects are to constrict smooth muscle (vascular, pupillary dilator
muscle, sphincters)
• agonist is phenylephrine; antagonist is terazosin
Can prevent urination with agents potentiating the sympathetic nervous system
(imipramine)
Sympathetic Nervous System
After Norepinephrine (NE) exocytosis, it can do one of the following:
interact with receptors (1)
be reaccumulated into the nerve via the axoplasmic pump
be degraded by monoamine oxidase (actually occurs inside the nerve)
Drugs can affect these processes
Imipramine blocks the axoplasmic pump (as does cocaine)
Pargyline blocks monoamine oxidase
Potentiate sympathetic effects by one of the following:
add  receptor agonist
block the axoplasmic pump (imipramine)
block monoamine oxidase (pargyline)
Inhibit sympathetic effects by antagonizing  receptor
Genitourinary Applications
Contract Urinary Bladder by:
• Muscarinic agonists (Bethanecol is
example)
• Anticholinesterases (Neostigmine is
example)
Genitourinary Applications
• Prevent Urination by:
– blocking muscarinic receptors with Tolterodine (Detrol;
1-2 mg bid; $103/month) (others include oxybutynin
(Ditropan), Trospium (Sanctura), propantheline,
hyoscyamine)- Med. Let. 46: 64, 2004
– stimulating sympathetic nervous system (imipramine)
(Tofranil)
• used to help children with bedwetting problems
• a little dangerous- can cause lethal cardiac arrhythmias, even in
children
• bedwetting more commonly treated with antidiuretic hormone
currently
– In theory, could combine phenylephrine and albuterol
but not done in practice
Genitourinary Applications
• No sympathetic nervous system agents are
used to induce urination but 1 receptor
blockers are used to ease urination in benign
prostatic hyperplasia
– Drugs include Terazosin (Hytrin); Doxazosin
(cardura); Alfuzosin (uroxatral) and Tamsulosin
(Flomax)
Q2: If a patient cannot control urination because of excessive
activity of the parasympathetic nervous system, which of the
following is the best strategy for treatment:
1) block sympathetic receptor (Terazosin)
2) activate sympathetics (Imipramine)
3) inhibit parasympathetic receptors (Atropine)
4) stimulate parasympathetic receptors
(Bethanecol)
5) Use an anticholinesterase (Neostigmine)
Erectile Dysfunction treatment
• Induce erection (in males) by vasodilating
– Actual agents used most frequently are
Sildenafil (Viagra), Tadalafil (Cialis) and
Verdenafil (Levitra)
– they prevent degradation of cGMP by blocking
Phosphodiesterase 5
Erectile Dysfunction treatment
• Physiologically, erections are caused by nitric
oxide
– Nitric Oxide (NO) interacts with soluble guanylyl
cyclase to produce cGMP
– cGMP interacts with protein kinase G to phosphorylate
proteins
– opens potassium channel to hyperpolarize smooth
muscle
– net effect is relaxation of smooth muscle
– phosphodiesterase breaks down cGMP (this step
blocked by Sildenafil)