Drugs Affecting the

Autonomic Nervous
System
Learning Outcomes

•Identify important divisions of the peripheral

nervous system.
•Compare and contrast the actions of the
sympathetic and parasympathetic divisions of
the autonomic nervous system.
•Explain the process of synaptic transmission
and the neurotransmitters important to the
autonomic nervous system.
•Compare and contrast the types of responses
that occur when drugs activate alpha1-, alpha2-,
beta1-, or beta2-adrenergic receptors, and
nicotinic or muscarinic receptors.
 •Discuss the classification and naming of
autonomic drugs based on four possible actions.
•Describe the clinician’s role in the
pharmacological management of clients
receiving drugs affecting the autonomic nervous
system.
•For each of the drug classes listed explain the
mechanism of drug action, primary actions, and
important adverse effects.
 Overview of the ANS
• Consists of the sympathetic and parasympathetic
nervous system.
• Drugs that stimulate the sympathetic nervous
system are called adrenergics
• Adrenergics are also called adrenergic agonists or
sympathomimetics - mimic the effects of the SNS
neurotransmitters norepinephrine and epinephrine
(catecholamines).
 Overview of the ANS

• Drugs that stimulate the parasympathetic nervous

system are called parasympathomimetics
• = Cholinergics
• Cholinergic agonists - mimic the effects of the
PSNS neurotransmitter acetylcholine
 Summary of sympathetic neurons
and synapses
Preganglionic neurons
• Short
• Synapse with postganglionic neurons near spinal cord
• Release acetylcholine (ACH) to activate nicotinic
receptors on postganglionic neurons
Postganglionic neurons
• Long
• Synapse on the target organ
• Release norepinephrine to activate adrenergic
receptors on target organs
 Summary of parasympathetic neurons
and synapses
Preganglionic neurons
• Long
• Synapse with postganglionic neurons at or near
organ
• Release acetylcholine (ACH) to activate nicotinic
receptors on postganglionic neurons
Postganglionic neurons
• Short
• Synapse on the target organ
• Release acetylcholine (ACH) to activate
muscarinic receptors on the target organ
10
 Adrenergic Receptors
• Adrenergic receptors are the sites where
adrenergic drugs bind and produce their
effects.
• Adrenergic receptors are divided into
alpha-adrenergic and beta-adrenergic
receptors
• Both alpha- and beta-adrenergic receptors
have subtypes designated 1 and 2.
 Alpha Receptors
• Alpha1-adrenergic receptors are located on
the postsynaptic effector cells.
• Alpha2-adrenergic receptors are located on
the presynaptic nerve terminals.
 Beta Receptors
• Both types of beta-adrenergic receptors are
located on the postsynaptic effector cells.
• Beta1-adrenergic receptors are primarily
located in the heart.
• Beta2-adrenergic receptors are primarily
located in the smooth muscle of bronchioles,
arterioles, and visceral organs.
 Dopaminergic Receptors
• Dopaminergic receptors are only stimulated
by dopamine which causes the vessels of;
• Renal
• Mesenteric
• coronary, and
• Cerebral arteries
• to dilate and the flow of blood to increase.
 Adrenergic Receptor Specificity
Drug α1 α2 β1 β2
Dopaminergic
Epinephrine

Ephedrine

Norepinephrine

Phenylephrine

Isoproterenol

Dopamine

Dobutamine

terbutaline
 Adrenergic Blockers
• Adrenergic blockers, also called adrenergic
antagonists or sympatholytics, have the
opposite effect of adrenergics.
• Alpha-blockers and beta-blockers bind to the
receptor sites for norepinephrine and
epinephrine blocking the stimulation of the
SNS.
 Cholinergics
• Drugs that stimulate the parasympathetic
nervous system are called cholinergics.
• Sometimes called cholinergic agonists or
parasympathomimetics, these drugs mimic
the effect of acetylcholine, which is the
neurotransmitter responsible for the
transmission of nerve impulses to effector
cells in the PSNS.
 Cholinergic Receptors
• The receptors that bind the acetylcholine and
mediate its actions are called cholinergic
receptors.
• These receptors consist of nicotinic receptors
and muscarinic receptors.
• Nicotinic receptors are located in the ganglia
of the PSNS and SNS and are stimulated by
nicotine.
 Muscarinic Receptors
• Muscarinic receptors are located
postsynaptically in the smooth muscle, cardiac
muscle, and glands.
• These receptors are stimulated by muscarine
(found in mushrooms).
 Cholinergic Drugs
• Cholinergic drugs can be direct-acting (bind to
and activate cholinergic receptors) or indirect-
acting (inhibit cholinesterase which is the
enzyme responsible for breaking down
acetylcholine).
 Cholinergic Blockers
• Cholinergic blockers, anticholinergics,
parasympatholytics, and antimuscarinic
agents are all terms for the class of drugs that
block the actions of acetylcholine in the PSNS.
• Cholinergic blockers allow the SNS to
dominate and, therefore, have many of the
same effects as the adrenergics.
 Cholinergic Blockers
• Cholinergic blockers are competitive
antagonists that compete with acetylcholine
for binding at the muscarinic receptors of the
PSNS, inhibiting nerve transmission.
• This effect occurs at the neuroeffector
junctions of smooth muscle, cardiac muscle,
and exocrine glands.
• Have little effect at the nicotinic receptors.
 Autonomic Nervous System
Medications
• Drugs Affecting the Sympathetic System:
– Adrenergic Receptors
Adrenergic Agonists
Adrenergic Antagonists
 Adrenergic Drugs
• Also called sympathomimetics because they
produce effects similar to those produced by the
sympathetic nervous system.
 Adrenergic agonists
• Classified into two groups
- Chemical Structure
Catecholamines and Non-catecholamines
- Mode of Action
- direct-acting
- indirect-acting
- dual-acting.
Catecholamines Non-catecholamines
• Not used orally • Can be used orally
• Short half life • Longer half life –
• Polar metabolised slowly
• Do not cross BBB by MAO
• Less polar
• Cross the BBB
Catecholamines Non-catecholamines
• Dobutamine • Phenylephrine
• Dopamine • Salbutamol
• Epinephrine • Terbutaline
• Norepinephrine • Ritodrine
• Isoproterenol
 Adrenergic Antagonists
• Alpha blockers
• Beta blockers
 Autonomic Nervous System
Medications

• Drugs Affecting the Parasympathetic

System:
– Cholinergics
– Anticholinergics
Drugs affecting the cholinergic system
• Agonists
• Antagonists
 Cholinergic Drugs
• Cholinergic drugs can be:
• direct-acting (bind to and activate cholinergic
receptors) or
• indirect-acting (inhibit cholinesterase which is
the enzyme responsible for breaking down
acetylcholine).
 Cholinergic Blockers
• Cholinergic blockers, anticholinergics,
parasympatholytics, and antimuscarinic
agents are all terms for the class of drugs that
block the actions of acetylcholine in the PSNS.
• Cholinergic blockers allow the SNS to
dominate and, therefore, have many of the
same effects as the adrenergics.
Commonly used ANS Drugs
Adrenergic Agonists
 Examples
• Adrenaline/Epinephrine
• Noradrenaline
• Ephedrine
• Dopamine
• Dobutamine
• Phenylephrine
• Clonidine
 Adrenaline/Epinephrine
• Direct acting adrenergic agonist
• Stimulates all alpha & beta receptors
• A potent cardiac stimulant
• Stimulates contractility & heart rate by beta1
receptor stimulation
• Leads to dose related increase in systolic BP
• Causes contraction of vascular smooth
muscle- activation of alpha 1 receptors
• Stimulates beta2 receptors leading to
relaxation of respiratory smooth muscle
• relaxation of uterine smooth muscle
 Indications
• Bronchospasm in asthma & COPD
• Severe acute anaphylactic reactions
• Shock
• Cardiac arrest – promotes return of circulation
• Added to local anesthetics to reduce the rate
of systemic absorption –
vasoconstriction/prolongs desired anesthetic
effect/reduces risk of systemic toxicity
 Adverse effects
• Anxiety • Hypertension
• Headache • Tachycardia
• Tremors • Cardiac arrythmias
• Pallor • Cardiac ischemia
• Sweating • Intracranial hemorhage
• Nausea • Chest pain in patients
• Vomiting with ischemic heart
• Uterine relaxation- delay disease
2nd stage of labor • Urinary retention in
males with enlarged
prostate
 Noradrenaline
• INDICATIONS:
• Acute hypotensive states to restore BP
• Shock
 EPHEDRINE
• Asthma
• Upper respiratory congestion
• *stimulates release of norepinephrine from
nerve terminals
• Mild stimulation of the CNS
• Narcolepsy & Depression
• Nasal decongestion as pseudoephedrine
• Hypotension during anesthesia
 Dopamine
• Indications
– Shock
– Low cardiac output syndromes
– Hypotension
– Acute renal failure to support renal
perfusion at low doses
 Dobutamine
• Synthetic
• Beta 1 selective agonist
• Indications;
• Depressed cardiac contractility
• Cardiac surgical interventions
• Acute myocardial infarction
• Low cardiac output states following cardiac
arrest
 Phenylephrine
• Potent synthetic vasopressor
• Acts mainly on alpha 1 receptors
• Indications:
– Hypotension
– Shock
– Nasal congestion – topical
– Treatment of upper respiratory symptoms
– Hemorrhoids
 Clonidine
• Selective alpha2 adrenergic agonist
• Antihypertensive
• Central analgesic
• Stimulates alpha2 adrenergic receptors in the
CNS
• Inhibits the sympathetic vasomotor centers
• This causes reduction in peripheral SNS
activity
• Reduces peripheral vascular resistance & BP
• reduces heart rate by reducing the cardio-
accelerator activity in the brain
• Activates central pain suppression pathways
producing analgesia
• inhibits transmission of pain signals to the
brain through the spinal cord (useful in
chronic pain)
 Clonidine other indications
• Vascular headaches
• Dysmenorrhea
• Vasomotor symptoms associated with
menopause
• Smoking cessation therapy
• Opiate & alcohol depedency
• ADHD
Adrenergic antagonists
 Examples
• Phenoxybenzamine
• Phentolamine
• Prazosin
 Phenoxybenzamine
• Non reversible Alpha adrenergic antagonist
• Blocks alpha receptor effects
• Decreases peripheral vascular resistance
• Decreases blood pressure
• But heart rate increases due to reflex &
increased circulating noradrenaline
 Indications: Phenoxybenzamine
• Mgt of hypertension in pheochromocytoma
before surgical excision
 Phentolamine
• Reversible alpha antagonist
• Used to treat hypertension
 Prazosin
• Selective alpha 1 antagonist
• Decreases peripheral vascular resistance
• Increases venous capacity
• Decreases BP with little change in heart rate
• Rx of hypertension
• Analogs = terazosin, doxazosin, tamsulosin
• Terazosin/Tamsulosin = BPH
• Doxazosin = BPH & Hypertension
•Beta Adrenergic
Antagonists
 Block beta 1 &2 receptors
Nonselective or Cardio-selective
Beta 1 effects Beta 2 effect
• Inhibits pulmonary
• decreased heart rate bronchiole dilation
• Decreased
myocardial
contractility
 Indications of beta antagonists
• Hypertension
• Ischaemic heart disease
• Arrythmia
• Glaucoma
• Migraine
• Thyrotoxicosis
• Chronic heart failure
 Side effects
• Bronchospasm
• Bradycardia
• Fatigue
• Sleep distubances
• Impotence
 Beta blockers
• Selective • Non-selective
– Atenolol – Propranolol
– Esmolol – Labetalol
– Metoprolol – Sotalol
 Examples
• Propranolol – nonselective
• Not commonly used for HTN nowadays
• Remains useful in Thyroid storm, migraine
prophylaxis, pheocromocytoma
 Metoprolol indications;
• Hypertension
• Effective in limiting heart rate increases during
exercise in patients with ischaemic heart
disease
• Angina
• Acute myocardial infarction
• Chronic heart failure
• Migraine headaches
• Using the given reference materials, note the
Dosages of all drugs discussed above
 Cholinergic Drugs
• Classes
• Cholinergic antagonists
• Cholinergic agonists
 Cholinergic agonists
• Bethanecol/urecholine
• Stimulates muscarinic receptors on the
bladder
• Causing contraction & urination
• Stimulates peristalsis of the urethra & relaxes
external sphincter
• Indicated in unobstructed urinary retention
• Acetylcholinesterase
inhibitors/Anticholinesterases

• General Indications:
– Mgt of Alzeimer’s disease
– Treatment of Delilium
– Diagnosis & Rx of myasthenia gravis
 EXAMPLES
• Neostigmine
• Physostigmine
• Edrophonium
• Pyridostigmine
• Donepezil
 Neostigmine
• Treatment of;
– Myasthenia gravis
– Urine retention
– Paralytic ileus
– Antidote for nondepolarizing skeletal
muscle relaxants used in surgery
 Physostigmine
• Indications
– Myasthenia gravis
– Glaucoma
– Impaired gastric motility
– Antidote to CNS effects of atropine and
hyoscine (crosses BBB)
– Delilium associated with anesthesia
 Edrophonium
• Short acting cholinergic
• Ideal for diagnosis of myasthenia gravis
 Pyridostigmine
• As neostigmine
• Drug of choice for maintenance dosing in
myathenia gravis
• Has a long duration of action
• Available is SR form
• Given at bedtime – effective for 8-12hrs
 Donepezil
• Alzeimer’s disease – loss of neurons that
secrete acetylcholine
• improves attention, memory, reason,
language & ability to perform simple tasks
• Cholinergic Antagonists
•Anticholinergic Drugs
•Antimuscarinic Drugs
 Indications
• Decrease respiratory & intestinal secretions
• To prevent a drop in the heart rate caused by
stimulation of the vagus nerve during
intubation
• Examination of the eye/ocular surgical
procedures
• Rx of parkinson’s disease
• Decrease salivation/spasticity/tremors
• Treatment of asthma & COPD
• Bradycardia
 EXAMPLES
• Atropine
• Glycopyrrolate
• Hyoscine
• Ipratropium
• Tiotropium
• Benztropine
• Oxybutynin
 Atropine
• Used to treat excessive cholinergic stimulation
caused by anticholinesterase toxicity
• e.g – mushroom poisoning
- nerve gases used in chemical warfare
- Organophosphate pesticide poisoning
 Hyoscine
• Rx of disorders characterised by smooth
muscle spasm;
- gastro-intestinal
- genito-urinary
- excessive respiratory secretions
 Ipratropium
• Inhalation treatment for COPD to produce
bronchodilation
• Nasal spray to relieve rhinorhea
• reduces bronchial secretions
• Reduces formation of mucus plug
 Tiotropium
• A long acting antimuscarinic, anticholinergic
agent
• Produces bronchodilation
• Indicated for maintenance in COPD
• Not indicated for acute episodes
 Benztropine
• Centrally acting anticholinergic drug
• More selective for muscarinic receptors in the
brain
• Used to decrease symptoms of parkinson’s
disease – tremors, spasticity, salivation
• In patients who have demonstrated a minimal
response to levodopa
 Oxybutynin
• Increases bladder capacity
• Decreases voiding frequency by an
antispasmodic effect on smooth muscle
• Urinary incontinence