1. Drugs Affecting the Autonomic
Nervous System
Pharmacology 49.222
Bill Diehl-Jones RN, PhD
Faculty of Nursing and Department of Zoology
2. Agenda
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A Zen Review
Overview of CNS and ANS
Neurotransmitters and 2nd Messengers
Cholinergic Agonists and Antagonists
Adrenergic Agonists and Antagonists
Movement Disorder Drugs
4. Organization of the Nervous System:
Reticular Activating System
• Key Regulatory Functions:
Radiation Fibres
– CV, respiratory systems
– Wakefulness
• Clinical Link:
Thalamus
– Disturbances in the RAS are
linked to sleep-wake Visual Inputs
Reticular Formation
disturbances
Ascending Sensory Tracts
5. Organization of the Peripheral
Nervous System
• Three major divisions:
– Efferent
• Somatic (motor)
• Autonomic
– Sympathetic and Parasympathetic
– Afferent
• Sensory
6. Some Basic Plumbing:
The Peripheral Nervous System
Parasympathetic
Sensory
Sympathetic
Motor
Parasympathetic
9. What Happens at the Effectors?
• NE from postganglionic sympathetics binds to
Adrenergic Receptors
• ACh from postganglionic parasympathetics binds to
Muscarinic Receptors
NE
ACh
Adrenergic
Receptor
Muscarinic
Receptor
Sympathetic
Parasympathetic
11. Cholinergic Receptors
• Muscarinic receptors come in 5 flavours
– M1, M2, M3, M4, M5
– Found in different locations
– Research is on-going to identify specific
agonists and antagonists
• Nicotinic receptors come in 1 flavour
16. Atropine
(a cholinergic antagonist)
• Comes from Belladonna
– High affinity for muscarinic
receptors
– Causes “mydriasis” (dilation of
the pupil) and “cycloplegia”
• Useful for eye exams, tmt of
organophosphate poisoning,
antisecretory effects
• Side effects?
17. Scopalamine
(also a cholinergic antagonist)
• Also from Belladonna
• Peripheral effects
similar to atropine
• More CNS effects:
– Anti-motion sickness
– amnesiac
19. Neuromuscular Blockers
• Look like acetylcholine
• Either work as antagonists or agonists
• Two flavours:
– Non-depolarizing (antagonist)
• Eg: tubocurarine
• Block ion channels at motor end plate
– Depolarizing (agonist)
• Eg: succinylcholine
• Activates receptor
20. Turbocurarine
• Used during surgery to
relax muscles
– Increase safety of
anaesthetics
ACh
Curare
• Do not cross bloodNicotinic Receptor
brain barrier
Na+
Na+ Channel
21. Succinylcholine
• Uses:
– endotracheal intubations
• What is this?
• Why?
Na+
- - -
- - -
+ ++ +
+ + +
Phase I
– electroconvulsive shock
therapy
Na+
• Problem: can cause apnea
++ +
++ +
- - -
- - Phase II
27. Adrenergic Angonists
• Direct acting:
– Epinephrine: interacts with both alpha and beta
• Low dose: mainly beta effects (vasodilation)
• High dose: alpha effects (vasoconstriction)
• Therapeutic uses: emerg tmt of asthma, glaucoma,
anaphyslaxis
– (what about terbutaline?)
28. Adrenergic Agonists
• Indirect:
– Cause NE release only
– Example:
• Amphetamine
– CNS stimulant
– Increases BP by alpha effect on vasculature, beta effect on heart
29. Mixed-Action
• Causes NE release AND stimulates receptor
• Example:
– Ephedrine:
•
•
•
•
What type of drug?
Alpha and beta stimulant
Use: asthma, nasal sprays
slower action
39. BASAL GANGLIA cont’d
• Role of basal ganglia:
1. Inhibit muscle tone throughout the body
2. Select & maintain purposeful motor activity
while suppressing useless/unwanted patterns
of movement
3. Coordination of slow, sustained movements
(especially those related to posture & support)
4. Help regulate activity of the cerebral cortex
40. BASAL GANGLIA SYSTEM
Feedback loops - complex
- form direct & indirect pathways
- balance excitatory & inhibitory
activities
Neurotransimitters:
Excitatory - ACh
glutamate
Inhibitory - dopamine
GABA
41. DOPAMINE
• major NT regulating subconscious movements of skeletal
muscles
• majority located in the terminals of pathway stretching
from the neuronal cell bodies in SNc to the striatum
• generally inhibits the function of striatal neurons & striatal
outputs
• when dopamine production is , a chemical imbalance
occurs affecting movement, balance and gait
42. PATHOPHYSIOLOGY OF PARKINSON’S
DISEASE
• Major pathological features:
1. Death of dopamine producing cells in the SNc
leads to overactivation of the indirect pathway
2. Presence of Lewy bodies –small eosinophilic
inclusions found in the neurons of SNc
Results in:- degeneration of the nigrostriatal
pathway
- decreased thalamic excitation of the
motor cortex
43. 4. Drug of Choice: LEVODOPA
Why is it used?
- virtually all pt’s with PD show a response to
levodopa
- improves quality of life
- in use since 1960’s
- easy to administer (non-invasive)
- relatively inexpensive
- useful in diagnosing PD
• Mechanism of action: is a precursor to dopamine helps
restore the balance of dopamine in striatum
–most effective in combo with Carbidopa ( ’s levodopa’s
peripheral conversion to dopamine)
44. 5. OTHER APPROACHES TO TREATMENT
• Pharmacological:
– Dopamine agonists: ie. Bromocriptine or pergolide
mesylate
– Selective inhibitor of type B monoamine
oxidase: ie.Selegiline
– Antivirals: ie. Amantadine
– Anticholinergics: ie. Trihexyphenidyl
– COMT inhibitors: ie. Entacapone
45. APPROACHES cont’d
• Surgical:
• Pallidotomy & Thalotomy:
– microelectrode destruction of specific site in the basal
ganglia
• Deep brain stimulation:
– electrode implantation with external pacemaker
• Fetal nigral transplantation:
– Implantation of embryonic dopaminergic neurons into
the substantia nigra for growth and supply of dopamine
