Drugs Affecting the
Autonomic Nervous System
Doncy Eapen, PHD, APRN, FNP-BC
Seema Aggarwal, PHD, APRN, AGNP-C
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Agenda
Review of autonomic nervous system (ANS)
Adrenergic agonists
Adrenergic antagonists
Alpha blockers
Beta blockers
Nonspecific blockers
Cholinergics
Anticholinergics
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Nervous System
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ANS- NEUROTRANSMITTERS
ACETYLCHOLINE NOREPINEPHRINE
Cholinergic- fibers that Adrenergic- fibers that
release acetylcholine release norepinephrine
Receptors- Nicotinic & Receptors- Alpha &
Muscarinic Receptors Beta Receptors
Alpha Receptors- Alpha
1, 2 & 3
Beta Receptors- Beta
1& 2
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Autonomic Nervous System
Parsympathetic Sympathetic
Cholinergic Adrenergic
Constricted pupils Dry mouth
Increased saliva Dilated pupils
Bronchoconstriction Increased contractility
Increased gastrointestinal Increased heart rate
mucus Bronchodilation
Bladder fundus Bladder fundus
contraction relaxation, sphincter
contraction
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ACh causes
increased
“SLUDGE-M”:
Salivation
Lacrimation
Urination
Diarrhea
GI motility
Emesis
(possibly)
Miosis
OR
“DUMBELS”
Diarrhea
Urination
Miosis
Bronchorrhea
Emesis
Lacrimation
Saliva/
sweating
Anti-Cholinergic Effects Cholinergic Effects
“Think about what happens when you are
running from a bear chasing you”
Terminology Review
2 Types of Drug Actions at the
Receptor
Agonist
-mimetic
Antagonist
-lytic
Inhibitor
Blocker
Autonomic Nervous System Terms
Parasympathetic
Cholinergic [acetylcholine]
Muscarinic
Sympathetic
Adrenergic [adrenalin]
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Classification of ANS Drugs
Adrenergic drugs
Sympathomimetic, Adrenergic agonists
alpha (-1 or -2) adrenergic, beta (-1 or -2)
adrenergic
Adrenergic-blocking drugs
Sympatholytic, Alpha-antagonist, Alpha-
adrenergic antagonist, Anti-adrenergic
alpha (-1 or -2) blockers, beta (-1 or -2) blockers
Cholinergic drugs
Parasympathomimetic, Muscarinic agonist,
Cholinomimetic
Cholinergic-blocking drugs
Parasympatholytic, anticholinergic, or
antimuscarinic, Cholinergic antagonist
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ADRENERGIC DRUGS
Adrenergic Agonists (“-ine”)
AKA: Sympathomimetics, etc
MOA: Act on adrenergic receptors
Exert their pharmacologic effects by activating, either directly or indirectly,
alpha adrenergic, beta adrenergic, or dopaminergic receptors. Indirect-
acting compounds are usually slower in onset of action and have a longer
duration of action.
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Adrenergic Receptor Stimulation
Alpha1 receptors: vasoconstriction,
mydriasis, GI/ bladder sphincter contraction
Alpha2 receptors: vasodilation (lower BP)
Beta1 receptors: cardiac stimulation
(increase heart rate, contractility)
Beta2 receptors: bronchodilation,
vasodilation, GI relaxation, uterine relaxation,
glycogenolysis (hyperglycemia)
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Uses of Adrenergic Drugs
Eye: Mydriasis (dilate eyes for eye
exam)
Resp: Cause bronchodilation and
manage anaphylactic shock
CV: Improve myocardial contractility,
increase in heart rate and blood
pressure
GI/GU: Decrease peristalsis
Endocrine: Increases blood sugar
Prolong local anesthetics
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General ADRs of Adrenergic Drugs**
Fear
Restlessness
Headache
Tremor
Palpitations
Pallor
Serious ADRs
Stroke
V-Fib
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Phenylephrine (Neo-synephrine)
Receptor: Selective Alpha-1 Agonist
Action: Vasopressor
Uses: Treat congestion, hypotension,
uveitis
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Alpha2 Agonists: Clonidine (Catapres)
MOA: Causes vasodilation by stimulating inhibitory alpha-adrenergic receptors in
the brain (centrally)
Uses
Lowers blood pressure (2nd or 3rd line) and heart rate
Used for treatment of withdrawal symptoms (ETOH, nicotine, heroin)
Used for attention deficit hyperactivity disorder
Adverse drug reactions (ADRs)
Sedation, dry mouth, and postural hypotension occur but these usually decrease
after several weeks of therapy. Sodium and water retention may occur.
Bradycardia, Skin rashes, constipation, urinary retention, impotence, and
nightmares may occur .
Abrupt discontinuation of clonidine can result in Rebound
Hypertension as soon as 8 and as late as 36 hours after the last dose.
Gradually taper over 4 days.
Rational drug selection: Caution in elderly because they are at risk for orthostatic
hypotension and fluid retention. Cat C Pregnancy
Monitoring: Dose may need adjustment in renal pts
Education: Teach the pt to not stop the drug suddenly.
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Alpha2 Agonists: Methyldopa (Aldomet)
MOA: Causes vasodilation by stimulating inhibitory alpha-
adrenergic receptors in the brain (centrally)
Uses: Lowers blood pressure
Adverse drug reactions (ADRs)
Sedation, hepatotoxicity (elevations of transaminase
enzymes; fever, malaise & jaundice may occur),
development of a positive Coomb's test (in 10-20% of
patients taking 1 g daily for > 6 mo; hemolytic anemia
does not occur), flu-like symptoms. Retention of sodium
and weight gain may occur during treatment.
Abrupt discontinuation can result in
rebound hypertension as soon as 8 and as late as
36 hours after the last dose. Gradually taper over 4 days.
Rational drug selection: Cat B Pregnancy, Pts with renal
impairment need adjustment of dosing frequency.
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Dobutamine (Dobutrex)
Receptor: Beta-1 agonist
Use: Cardiac Decompensation
ADR: Increases heart rate and blood
pressure; angina
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Beta2 Agonists: Albuterol
Relatively selective Beta-2 agonist
Use: Bronchodilation
ADRs: CNS stimulation, palpitation (1-10%), tremors (1-
20 %), shakiness (1-20%), hyperactivity (1-20%),
headache (2-27%), and nausea & vomiting (2-15%).
May cause irritable behavior in infants
Clinical use in adults and children as young as 4 y/o
Rational drug selection: Caution: Patients at risk include
diabetics, hyperthyroidism, subjects with seizures
disorders, and the elderly. Excessive use may cause death,
cause unknown but probably cardiac arrest. Oral use may
delay preterm labor.
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Epinephrine (Adrenalin)
Receptors: Alpha 1 & 2; Beta 1 & 2
Uses
Prolong local anesthetics
Treat allergic reactions
CPR
Status Asthmaticus
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Norepinephrine (Levarterenol)
Receptors: Alpha 1; Less Beta 1
Uses: Treat hypotension
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Dopamine (Intropin)
Receptors: Dopamine; Beta-1; Alpha 1
(dose dependent)
Causes: Renal Vasodilation; Stimulates
heart
Use: Shock syndrome
ADR: Palpitations, hypotension
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Pseudoephedrine & Amphetamine
Pseudoephedrine (Sudafed)
Receptors: Alpha & Beta-2
Uses: Decongestant
Amphetamine/ Methylphenidate (Ritalin)
Receptors: Direct and Indirect Adrenergic
Uses: ADHD; Narcolepsy
ADR: Nervousness, Insomnia, arrhythmias,
tachycardia, headache
Warnings: HBP; CAD; Glaucoma; Hyperthyroidism;
BPH, DM
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ADRENERGIC
BLOCKING
DRUGS
Adrenergic Antagonists
“Blockers”
Alpha blockers
Action: block alpha receptors leading to vasodilation
Used to treat HTN, benign prostatic hyperplasia (BPH), Raynaud’s
disease, and migraine headaches
Nonselective (Phentolamine (Regitine))
Selective Alpha-1- see next slide
Beta blockers
Action: antagonize or block the effects of catecholamines (epi, NE, dopa);
decreases heart rate and reduces vascular smooth
muscle tone/ resistance
Drugs can be “selective” to beta1 receptors or “nonselective” to beta1 and
beta2 receptors
Mainly used for HTN and post myocardial infarction (MI)
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Alpha-1 Blockers (“-zosin”)
Prazosin (Minipress), Doxazosin (Cardura), Terazosin (Hytrin):
Used for HTN
Tamsulosin (Flomax): Used for BPH
Selective Alpha-1 Antagonist/ Blocker
ADRs: Fluid retention, Orthostatic HTN (plus dry mouth,
constipation, urinary retention, etc)
Warning: 1st dose effect
excess postural hypotension that can occur within 30-
90 min of the first few doses
The patient will adjust to the medication with
successive doses
To avoid: Take at bedtime; start at 1mg and titrate up
every 2 weeks
Rational Drug Selection: Doxazosin less likely to cause
1st dose effect
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Beta Blockers (-”olol”)
Propranolol (non-selective) vs. atenolol (selective)
Uses: Angina, HTN, Heart failure, Arrhythmias, Migraine prophylaxis, Thyrotoxicosis
ADRs:
All: Dizziness, lethargy/ fatigue, nightmares, mental status changes in elderly, impotence
Beta-1 blockade: bradycardia, reduced cardiac output, precipitation of heart failure, AV heart
block and rebound cardiac excitation (however they are 1 st line drugs in certain types of heart
failure, given in left ventricular dysfunction).
Beta-2 blockade: bronchoconstriction and hypoglycemia (from inhibition of glycogenolysis)
Warning: DO NOT STOP ABRUPTLY (life threatening especially in pts with angina and CAD)
Acute discontinuation of beta blockers can result in excess sympathetic activity seen in 24-48
hours, due to an increase in beta receptors (up-regulation) during blockade. Myocardial ischemia
or cardiac arrhythmias may occur. Can be minimized by withdrawing these drugs gradually
(decrease dose by a half every 4 days- can take 1 to 2 weeks).
Contraindicated: (Esp. non-selective) Asthma or any bronchospastic condition, Caution in diabetics-
masks hypoglycemic symptoms EXCEPT diaphoresis), Avoid in pregnant & nursing women
Interactions: OTC Cold remedies (pseudoephedrine, ephedrine, phenyephrine)- can have unopposed
alpha-adrenergic stimulation (excessive HTN & tachycardia); Clonidine (fatalities)
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Combined Alpha &Beta Adrenergic Antagonists
Carvedilol & Labetalol
MOA- Combined selective alpha 1 adrenergic and beta blockade decrease BP, decrease
peripheral resistance, decreases myocardial oxygen demand and lower cardiac work load
Uses : Carvedilol & Labetalol- Hypertension
Carvedilol also for CHF
ADR- Similar to beta blockers , but fewer cardiac and CNS related reactions
- Orthostatic hypotension is higher than beta blockers and is related to alpha
adrenergic blockade
- Bronchospasm, may mask symptoms of hypoglycemia
Monitoring – LFT , RFT
Warning- Do not stop abruptly , may precipitate ventricular arrythmias. Taper the
dose one-half every 4 days over a period of 1 to 2weeks
- Caution in older adults due to the risk of orthostatic hypotension.
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CHOLINERGIC
DRUGS
Cholinergic Agonists
AKA: parasympathomimetics, muscarinic agonists
Direct-acting cholinergic drugs
Prototype: bethanechol (Urecholine)
Prototype: pilocarpine (Pilocar)
Indirect-acting cholinergic drugs
Cholinesterase inhibitors
Peripheral-Acting: Prototype: neostigmine bromide
(Prostigmin)
Central-Acting: Donepezil (Aricept)
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Main Uses of Cholinergic Drugs
Eyes: Decrease intraocular pressure in glaucoma, miosis
Resp: Stimulates secretions in the tracheobronchial tree,
produces bronchoconstriction
Cardiovascular: Decrease in heart rate and force of contractility is
due to cholinergic innervation of the SA and AV nodes and atrial
muscle.
GI: Increased tone and amplitude of contraction, peristaltic
activity, and secretory action.
Urinary tract: Increase in ureteral peristalsis and contraction of
the detrusor muscle.
Neuromuscular: Treat Myasthenia gravis, Reverse neuromuscular
block
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General ADRs of Cholinergic Drugs
GI discomfort
nausea, vomiting, diarrhea, belching, salivation, and
intestinal cramps
Bradycardia
Bronchoconstriction
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Direct-acting cholinergic drugs: Bethanechol (Urecholine)
MOA
Increases tone of detrusor muscle and causes bladder
contractions
Increases tone of the lower esophageal sphincter
Clinical Indications
Urinary retention (Post-op & post-partum)
ADRs
Initially: Abdominal discomfort/ epigastric pain, salivation,
flushed skin, sweating, nausea, vomiting, miosis, and urinary
urgency are common.
Toxic reactions: include intense cramping, diarrhea,
bradycardia, and bronchoconstriction.
Contraindications: COPD, asthma, hyperthyroidism, peptic
ulcer
Education: To avoid nausea & vomiting, take 1 hour before or
2 hours after meals.
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Direct-acting cholinergic drugs: Pilocarpine (Pilopine)
Used primarily as an ophthalmic solution in the
treatment of open-angle glaucoma where, by
contracting the ciliary muscle, outflow of aqueous
humor is improved and intraocular pressure
reduced within minutes.
Used also to treat of xerostomia and Sjogren ’s
syndrome because it increases salivation.
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Indirect-acting cholinergic drugs:(Acetyl)cholinesterase inhibitors
Prototype: neostigmine bromide (Prostigmin); Also use pyridostigmine
(Regonol)
MOA: These drugs produce reversible inhibition of AChE (which destroys
Ach) by formation of a carbamyl-ester complex which dissociates slowly,
hence provides longer action of Ach. They act preferentially at the
neuromuscular junction (NMJ) and restore skeletal muscle strength by
increasing the availability of acetylcholine.
Use: Myasthenia gravis and Nondepol Neuromuscular Blockade Reversal
ADRs: nausea, diarrhea, and excessive salivation. Caution in patients
with asthma. If muscarinic effects of such therapy are prominent, they
can be controlled by the administration of atropine.
Note that there is a short amount of time between the occurrence of
ADRs and Toxicity- emergency treatment needed if you see fasciculations
of voluntary muscles.
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Indirect-acting cholinergic drugs:Central (acetyl)cholinesterase
inhibitor
Donepezil (Aricept)
MOA: inhibits AChE; thus causing an increase in Ach
Use: treatment of mild to moderate Alzheimer's disease. Among
those who benefit, improvements are seen in quality of life and
cognitive functions (eg, memory, thought, reasoning). There is no
evidence the drug leads to substantial functional improvement
or prevents progression of Alzheimer’s.
ADRs: Most ADRs are related to increased cholinergic
(muscarinic) effects including GI effects such as nausea and
diarrhea, increases gastric acid secretion (monitor for occult
bleeding), syncope, bradycardia (thus should be taken at
bedtime)
Has advantages over other drugs such as Tacrine- (once-a day
dosing), lower side effect profile, and does not require LFTs for
hepatoxicity.
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CHOLINERGIC
BLOCKING
DRUGS
(ANTICHOLINERGICS)
Anticholinergic Drugs
AKA: cholinergic blockers, muscarinic antagonists
MOA: Block Ach at muscarinic receptors
Prototype: atropine
Uses
Eyes: Mydriasis
CV: Block vagal impulses to heart; Reverse sinus bradycardia (increase
heart rate)
Resp: Bronchodilation, Suppress respiratory secretions pre-op
GI: Decreased secretions and tone
GU: Bladder spasms
CNS
Treat tremors/rigidity of Parkinsonism
Treat EPS from psychotropic medications
Sedation
Motion Sickness
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General ADRs of Anticholinergics
Photophobia
Increased Intraocular Pressure
Dry Mouth
Constipation
Urinary retention
Drowsiness
Central Anticholinergic Syndrome/ Anticholinergic toxicity
(antidote is physostigmine salicylate- increases Ach)
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Atropine and Scopolamine
Atropine or scopolamine is administered prior to induction of anesthesia
to protect heart from vagal reflexes and prevent excessive
salivary & respiratory secretions. Patients with glaucoma
require special consideration.
Sedation: Scopolamine is 100 times more sedative than atropine in
depressing the ascending reticuloarousal system (ARAS). Scopolamine can
also cause amnesia. Occasionally scopolamine may cause restlessness or
somnolence, particularly in the elderly. (Glycopyrrolate [Robinul], a
quaternary amine, is devoid of sedative effect)
Atropine is used to reverse severe sinus bradycardia in
adults and neonates, especially when due to parasympathetic influence
(e.g., digoxin, beta blockers).
Biliary & Ureteral Smooth Muscle Spasm: Atropine
decreases the tone of the smooth muscle of the biliary tract & ureter and
produce relaxation.
Motion Sickness Prevention: Protection is greatest if the
scopolamine is applied as a patch [Transderm-Scop] behind the ear
at least four hours before the noxious stimulus.
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Ipratropium (Atrovent)
Bronchoconstriction: Anticholinergic drugs can
relax bronchial smooth muscles by blocking the constrictor
effects of the vagus nerve. The anticholinergic drugs are
more effective bronchodilators when administered by
aerosol inhalation (e.g., ipratropium [Atrovent], a
quaternary ammonium compound).
In spite of their bronchodilatory effect, systemic
anticholinergics should be used cautiously in asthmatic
patients because of drying of secretions and increased risk
of mucus plugs
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Oxybutynin and Tolterodine
Oxybutynin (Ditropan XL) is the prototype
of overactive bladder drugs. Oxybutynin is both an
antimuscarinic and an antispasmodic. It easily crosses
the blood-brain barrier, thus has a higher rate of CNS
adverse effects. inform the patient that adverse
effects include xerostomia (70%) constipation, urinary
retention, and blurred vision. Alcohol may enhance
the drowsiness
Tolterodine (Detrol) is another commonly
advertised drug for overactive bladder.
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Benzotropine and Diphenhydramine
Parkinson’s Disease & extrapyramidal symptoms of
antipsychotics. Parkinsonian tremor and rigidity seem to
result from a relative excess of cholinergic activity in the
basal ganglia system. The tremor of Parkinson’s disease is
reduced by centrally acting antimuscarinic drugs (e.g.,
benztropine [Cogentin]; trihexyphenidyl
[Artane]).
Diphenhydramine [Benadryl] is often
recommended to alleviate extrapyramidal symptoms (EPS)
associated with conventional antipsychotic agents.
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Somatic Nervous
System
Somatic NS Drugs
Nondepolarizing Agents
Tubocurarine is the prototype drug but is no longer available in
the US
Actions of these agents can be reversed by
acetylcholine ()whose concentration is increased by use
of cholinesterase inhibitors
Depolarizing Agents
Succinylcholine [Anectine] (two acetylcholine molecules
attached) is the only agent. Its action cannot be reversed by
drugs that increase ACh concentrations. It has a very
brief duration of action (< 8 min) and is metabolized by
pseudocholinesterase (but not by acetylcholinesterase).
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