REVIEW OF AUTONOMIC SYSTEMS AND DRUGS

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REVIEW OF AUTONOMIC SYSTEMS AND DRUGS SYLLABUS
PAGES 48-112
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Neurotransmitters
Adrenergic
Cholinergic
Acetyl choline
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Innervation
HR
Transmitter(s)
Contractility
Sympathetic
Norepinephrine Epinephrine
Parasympathetic
Acetyl Choline
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Important Exception
Vascular smooth muscle
Sympathetic only (or nearly so)
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Catecholamine Biosynthesis
Synthesized from
Tyrosine
Tyrosine hydroxylase
Rate limiting reaction
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Catecholamine Degradation
COMT - catechol-O-methyltransferase MAO -
monoamine oxidase
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Norepinephrine Inactivation
Reuptake into the nerve ending by an active
transport system
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Drugs Acting Presynaptically
Reserpine ?-Methyldopa Guanethidine Amphetamine Im
ipramine Fluoxetine
Inhibits storage in vesicles
False transmitter
Inhibits NE release
Stimulates NE release
Inhibits NE reuptake
Inhibits serotonin reuptake
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Postsynaptic Receptors(Adrenergic)
Alpha Beta
Generally excitatory Exception intestinal smooth
muscle
Generally inhibitory Exception beta1 in the heart
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Postsynaptic Receptors(Cholinergic)
Muscarinic Nicotinic
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Acetyl Choline Inactivation
Acetylcholinesterase
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Cholinergics

• Cholinergic agonists
• Bethanechol
• Pilocarpine
• Carbachol
• Antimuscarinics
• Atropine
• Scopolamine
• Anticholinesterases
• Neostigmine
• Organophosphates (e.g. DFP)
• Neuromuscular blockers
• Tubocurarine
• Pancuronium
• Succinyl Choline

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Cholinergic Agonists

• Parasympathomimetics limited uses
• Glaucoma
• Pupillary constriction (meiosis)
• Not used for
• Bronchial Asthma
• Coronary Insufficiency
• Peptic Ulcer
• Hyperthyroidism

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Antimuscarinics
Atropine Scopalamine

• Therapeutic uses
• Motion sickness
• Pupillary dilation
• Parkinsons Disease
• Side effects
• Dry mouth
• Blurred vision
• Tachycardia
• Urinary retention
• Constipation

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Anticholinesterases
Reversible Irreversible
Neostigmine Physostigmine
Organophosphates (e.g. DFP)

• Predict effects on
• Eye
• GI tract
• Urinary tract
• Skeletal muscle

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Organophosphate Toxicity
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Reversal of organophosphate poisoning

• Atropine
• Pralodoxime

Reversal of atropine poisoning

• Physostigmine

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Therapeutic Uses of Anticholinesterases

• Glaucoma
• Paralytic ileus
• Mysathenia gravis

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Neuromuscular Blockers
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Pancuronium
Succinylcholine
Mechanism
Competitive
Depolarizing
Onset
1-2 min
20-40 sec
Duration
30-60 min
2-5 min
Side Effects
Cardiac arrhythmia Prolonged apnea Malignant
hyperthermia
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Adrenergics
Autonomic reflexes modulate drug responses
SNS
PSNS
SNS
PSNS
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b1b2
a1a2b1b2
a1a2b1
Reflex (muscarinic)
b1
b1
b2 a1
a1
b2
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What is the treatment of choice for anaphylactic
shock?
Epinephrine
Why?

• It is the only drug that addresses the most
  serious manifestations
• b1 increases cardiac output
• b2 relaxes constricted bronchioles
• ?1 constricts capillaries

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?2-Selective Adrenergic Agonists

• Albuterol
• Terbutaline

Bronchial dilators Uterine relaxant (ritodrine)
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?1 Adrenergic Agonists

• Phenylephrine
• Ephedrine

Therapeutic uses

• Nasal decongestants
• Used with local anesthetics
• Local hemostasis
• Mydriatic
• Glaucoma
• Vasopressor
• Appetite suppressant

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Adrenergic Antagonists

• Alpha blockers
• Prazosin (?1)
• Phenoxybenzamine (?1?2)
• Phentolamine (?1?2)

Hypertension
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Adrenergic Antagonists

• Beta blockers
• Propranolol (?1 ?2)
• Metoprolol (?1 )
• Atenolol (?1 )
• Timolol (?1 ?2)

• Therapeutic uses
• Arrhythmia
• Angina pectoris
• Hypertension

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Adverse Effects

• Alpha blockers
• Postural hypotension
• Tachycardia
• First dose (prazosin)
• Beta blockers
• Cardiac depression
• Asthma attack
• Nightmares, lassitude, depression
• Angina pectoris (abrupt withdrawal)

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Anti-Parkinsons Drugs
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Carbidopa
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Adverse Effects
GI - nausea and vomiting Hypotension Dyskinesias P
sychiatric reactions
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Drugs to Know
Levodopa Carbidopa Amantidine Bromocryptine Selegi
line Tolcapone
used in combination
DA reuptake inhibitor (?)
DA receptor agonist
MAO-B inhibitor
COMT inhibitor