Drugs acting on the ANS

introduction

Clinical pharmacist :
Dr. Fatima Bani Salama
Learning objectives.
➢ Introduction to the autonomic nervous system.

➢ Adrenergic drugs.

➢ Adrenergic antagonist drugs.

➢ Cholinergic drugs.

➢ Cholinergic antagonist drugs.

Overview of Nervous System
 Autonomic Nervous System (ANS)

➢ Functions:

✓ regulate blood pressure, heart rate, respiration,

body temperature, water balance, urinary
excretion, and digestive functions, among other
things.

✓ This system exerts minute-to-minute control of

body responses, which is balanced by the two
divisions of the ANS.
Divisions:

The ANS is divided into

two branches:
✓sympathetic nervous system

✓parasympathetic nervous system.

====== Most organs in the body are

innervated by both division.
 Neurotransmitters in ANS
Sympathetic nervous Parasympathetic
system nervous system

Epi NE Ach

NT === communications between nerve cells

Neurotransmitters in ANS
Receptors in ANS
Synthesis and storage of Ach
Synthesis and storage of NE
 Drugs acting on the sympathetic
nervous system
• Adrenergic drugs:
– Adrenergics.
– Adrenergic agonists.
– Sympathomimitic drugs.

• Adrenergic-blocking drugs:
– Adrenergic antagonists.
– Sympatholytic drugs.
 Drugs acting on the parasympatheic
nervous system
• Cholinergic drugs:
– Cholinergic agonists.
– Parasympathomimetics.
– Cholinergics.

• Cholinergic-blocking drugs:
– Cholinergic antagonists.
– Parasympatholytics.
Adrenergic
Drugs
➢ Adrenergic compounds have a wide variety of therapeutic
uses depending on their site of action and their effect on
different types of adrenergic receptors.

➢ adrenergic agonists = sympathomimetics chemically

classified as catecholamines.
 Overview

• Mimic the effects of SNS neurotransmitters

(catecholamines)
– Norepinephrine (NE)
– Epinephrine (EPI)
– Dopamine
➢ Adrenergic receptors: Many physiologic responses are
produced when they are stimulated or blocked. divided
into:
✓ alpha-adrenergic receptors
✓ beta-adrenergic receptors
✓ Dopaminergic Receptors
❑alpha1-adrengic receptors located on postsynaptic
effector cells

❑alpha2-adrenergic receptors are located on the

presynaptic nerve terminals.

❖The predominant alpha-adrenergic agonist response is

vasoconstriction
central nervous system stimulation.
• Stimulation of alpha1-adrenergic receptors on
smooth muscles results in

– Vasoconstriction of blood vessels

– Relaxation of GI smooth muscles (decreased
motility)
– Constriction of bladder sphincter
– Contraction of uterus
– Male ejaculation
– Contraction of pupillary muscles of the eye
(dilated pupils)
• alpha2-adrenergic receptors
not of great significance either physiologically
or pharmacologically.
➢ beta-adrenergic receptors are all located on postsynaptic
effector cells.

❑ beta1-adrenergic receptors are primarily located in the heart .

(cardiac stimulation.)

❑ beta2-adrenergic receptors are located in the smooth muscle

fibers of the bronchioles, arterioles, and visceral organs.
(in bronchial, gastrointestinal (GI), and uterine smooth muscle
relaxation; glycogenolysis)
• beta1-adrenergic receptors (cardiac stimulation )
– Increased force of contraction (positive inotropic effect)
– Increased heart rate (positive chronotropic effect)
– Increased conduction through AV node (positive dromotropic
effect)

• beta2-adrenergic receptors
– Bronchodilation (relaxation of the bronchi)
– Uterine relaxation
– Glycogenolysis in the liver
– Increased renin secretion in the kidneys
- Relaxation of GI smooth muscles (decreased motility)
Beta-Adrenergic Receptors
➢Dopaminergic Receptors
• Stimulated by dopamine
• Causes dilation of the following blood
vessels, resulting in increased blood flow
– Renal
– Coronary
– Cerebral
Responses to Stimulation
Mechanism by which stimulation of a nerve
fiber results in a physiologic response:
 Catecholamines
➢ Endogenous substances:
✓ Epinephrine.
✓ Nprepinephrine.
✓ Dopamine.
(also available in synthetic drug form)

➢ Exogenous substances:
✓ Dobutamine.
✓ Phenylephrine.
1- direct acting sympathomimetics.

Epinephrine
 2- indirect acting sympathomimetics.

Amphetamine
when given, causes the release of the catecholamine from storage sites (vesicles)
in the nerve endings; it then binds to the receptors and causes a physiologic
response.
3- mixed acting sympathomimetics

Ephedrine
➢There are also noncatecholamine
adrenergic drugs
➢Alpha-Beta agonists:
Affect both alpha and beta receptors.
✓Epinephrine and Norepinephrine.
✓Dopamine and Dobutamine.
✓Ephedrine.
➢Alpha-agonists:
✓Clonidine (Catapres).
✓Midodrine (ProAmatine).
✓Phenylephrine.
➢Beta-Agonists:
✓Albuterol (Proventil).
✓Metaproterenol (Alupent).
✓Salmeterol (Serevent).
✓Terbutaline (Brethaire)
Indications

❑Respiratory indications
❑Indications for topical nasal decongestants
❑Ophthalmic indications
❑Cardiovascular indications
The beta2 agonists cause bronchodilation

asthma and bronchitis.

e.g. (salbutamol, formetrol, salmeterol
and terbutaline).
Respiratory indications
1- as bronchodilators
 Indications (cont’d)
• Treatment of nasal congestion
– Alpha1-adrenergic receptors (constriction of dilated
arterioles and reduction in nasal blood flow, which thus decreases
congestion)

– Examples: epinephrine, ephedrine,

naphazoline, oxymetazoline, phenylephrine,
and tetrahydrozoline
Nasal congestion
Nursing Implications
• Overuse of topical nasal decongestants may
cause rebound nasal congestion or
ulcerations
 Ophthalmic indications
• Reduction of intraocular pressure and
dilation of pupils.(alpha-or-beta2-adrenergic
receptors)

• Temporary relief of conjunctival congestion

(alpha-adrenergic receptors causing arteriolar
vasoconstriction)
 CVS indications
• Support the cardiovascular system during
cardiac failure or shock.

• Common vasoactive adrenergic drugs include

dobutamine, dopamine, ephedrine,
epinephrine, fenoldopam, midodrine,
norepinephrine, and phenylephrine.
 Epinephrine/ adrenaline

What are
the
indications
of this drug?
➢ endogenous vasoactive catecholamine.

➢ administered in emergency situations

➢ primary vasoactive drugs used in many advanced cardiac life

support protocols.
➢ dose related:

✓ At low dosages it stimulates mostly beta1-adrenergic receptors,

increasing the force of contraction and heart rate. It is used to
treat acute asthma and shock at these dosages.

✓ At high dosages, it stimulates mostly alpha-adrenrgic receptors,

causing vasoconstriction, which elevates the blood pressure.
Dopamine/ Dobutamine

WHAT IS THE
DIFFERENCE?????
• Contraindications: The only contraindications
to the use of adrenergic drugs are known drug
allergy and severe hypertension
• Adverse effects:
➢ Alpha-Adrenergic Adverse Effects
✓ CNS: Headache, restlessness, excitement, insomnia, euphoria
✓ Cardiovascular: Palpitations (dysrhythmias), tachycardia,
vasoconstriction, hypertension
✓ Other: Loss of appetite, dry mouth, nausea, vomiting, taste changes
(rare)

➢ Beta-Adrenergic Adverse Effects

✓ CNS: Mild tremors, headache, nervousness, dizziness
✓ Cardiovascular: Increased heart rate, palpitations (dysrhythmias),
fluctuations in BP
✓ Other: Sweating, nausea, vomiting, muscle cramps
Nursing Implications (cont’d)
• With chronic lung disease
we will discuss in details later……………
Nursing Implications (cont’d)

• Administering two adrenergic drugs

together may precipitate severe
cardiovascular effects such as tachycardia
or hypertension
Nursing Implications (cont’d)

• Monitor for therapeutic effects

(cardiovascular uses)
– Decreased edema
– Increased urinary output
– Return to normal vital signs
– Improved skin color and temperature
THE END
Adrenergic
-Blocking
Drugs
 Adrenergic Blockers
• Also known as:
– Adrenergic antagonists
– Sympatholytics
– Alpha-blockers, beta-blockers, or alpha-beta
blockers
 Adrenergic Blockers (cont’d)
• Classified by the type of adrenergic
receptor they block

β blockers α blockers

β1 β2 α1 α2
• Nonselective alpha blockers:
• Phentolamine.

• Alpha-1 blockers:
• Alfuzosin (Xatral).
• Doxazosin (Cardura).
• Tamsulosin (Omnic).
• phenoxybenzamine
• Beta blockers:
• nonselective:
• Carteolol (Carteol E/D).
• Propranolol (Inderal).
• Timolol.

• Cardioselective beta-1 blockers:

• Atenolol (Tenormin).
• Betaxolol (Kerlone).
• Bisoprolol (Concore).
• Metoprolol (Betaloc Zok).

• Nonselective adrenergic blockers:

• Carvedilol.
• Labetalol
➢Adrenergic blockade at these receptors leads
to effects such as:

✓ vasodilatation
✓ reduced blood pressure
✓miosis (papillary constriction)
✓ reduced smooth muscle tone in organs like
the bladder and prostate.
 Alpha-Blockers
Mechanism of action and drug effects
 Alpha-blocker Drugs

• Doxazosin.
• Prazosin.
• Terazosin .
• Tamsulosin.
• Alfuzosin.
 Indications:

• Treat HTN (arterial and venous dilation).

• BPH (decrease resistance to urinary outflow).

• Tamsulosin and alfuzosin are used exclusively for

treating BPH
• terazosin and doxazosin can be used for both
hypertension and BPH.
 Beta Receptors
• Beta1 receptors
– Located primarily on the heart
– Beta-blockers selective for these receptors
are called cardioselective beta-blockers

• Beta2 receptors
– Located primarily on smooth muscle of bronchioles
and blood vessels
➢ Other beta-blockers block both beta1- and beta2-
adrenergic receptors (nonselective beta-blockers).

➢ Two beta-blockers, carvedilol, and labetalol, also have

an alpha receptor-blocking activity, especially at higher
dosages
 Indications

• Angina
• Cardioprotective
• Dysrhythmias
• Migraine headache
• Antihypertensive
• Heart failure
• Glaucoma (topical use)
Nonselective beta-blockers XXXXXXXXXX
 Adrenergic-Blocking Drugs:
Nursing Implications
• Assess for allergies and history of COPD,
hypotension, cardiac dysrhythmias,
bradycardia, heart failure, or other
cardiovascular problems
– Any preexisting condition that might be
exacerbated by the use of these drugs might
be a contraindication to their use
 Adrenergic-Blocking Drugs:
Nursing Implications (cont’d)

• Remember that alpha-blockers may precipitate

hypotension

• Remember that some beta-blockers may

precipitate bradycardia, hypotension,
heart block, heart failure, and
bronchoconstriction
 Adrenergic-Blocking Drugs:
Nursing Implications (cont’d)
• Encourage patients to take medications
as prescribed

• Instruct patients that these medications should

never be stopped abruptly
 Adrenergic-Blocking Drugs:
Nursing Implications (cont’d)
• Teach patients to change positions slowly to prevent
or minimize postural hypotension

• Instruct patients to avoid caffeine (excessive

irritability)

• Instruct patients to avoid alcohol ingestion and

hazardous activities until blood levels become stable
 Adrenergic-Blocking Drugs:
Nursing Implications (cont’d)

• Monitor for adverse effects

• Monitor for therapeutic effects
– Decreased chest pain in patients with angina
– Return to normal BP and HR
– Other specific effects, depending on the use
Cholinergic
Drugs
 Mechanism of Action

• Direct-acting cholinergic agonists

• Indirect-acting cholinergic agonists
 Indirect-Acting
(Cholinesterase Inhibitors)
• Reversible
– Bind minutes to hours
• Irreversible
– Bind permanently.
 Drug Effects
• At recommended doses, cholinergics
primarily affect muscarinic receptors
• At high doses, cholinergics stimulate
nicotinic receptors
 Indications
direct-acting drugs
It lacks therapeutic
importance

Because rapid Multiplicity of

inactivation be actions
AchE
Direct-acting drug—bethanechol
Direct-acting drug—bethanechol
Succinylcholine.
 Succinylcholine
• Work as Ach but is more resistant to AchE
enzyme.
• Also classified as neuromascular blocking
agents
• Some books classified as cholinergic blocking
agents
• Used in general anesthesia.
 Indications
indicrect-acting

- REVERSIBLE.
- IRREVERSIBLE
Reversible
 Indications (cont’d)
• Indirect-acting drugs
– Used for diagnosis and treatment of
myasthenia gravis
 Indications (cont’d)
• Indirect-acting anticholinesterase drugs
– Used for treatment of Alzheimer’s disease
• donepezil
• Tacrine
• galantamine (Razadyne)
• rivastigmine (Exelon)
 Adverse Effects
• Adverse effects are a result of overstimulation
of the PSNS
 Interactions
• Anticholinergics, antihistamines,
sympathomimetics
– Antagonize cholinergic drugs, resulting in
decreased responses
• Other cholinergic drugs
– Additive effects
Irreversible
Nursing Implications (cont’d)

• Medications should be taken as ordered

and not abruptly stopped
• Doses should be spread evenly apart
to optimize the effects of the medication
• Overdosing can cause life-threatening
problems.
Nursing Implications (cont’d)
• When cholinergic drugs are prescribed for
Alzheimer’s disease, be honest with
caregivers and patients that the drugs are
for management of symptoms (not a cure)
• Therapeutic effects of anti-Alzheimer’s
drugs may not occur for up to 6 weeks
Nursing Implications (cont’d)

• Atropine is the antidote for cholinergics,

and it should be available in the patient’s
room for immediate use if needed
The end
 Cholinergic-
Blocking Drugs
 Definition
• Also known as anticholinergics
 Mechanism of Action
• Competitive antagonists
 Chemical Class
Natural Synthetic/Semisynthetic
atropine benztropine clidinium
belladonna dicyclomine glycopyrrolate
hyoscyamine homatropine ipratropium
scopolamine isopropamide methscopolamine
oxybutynin propantheline
tolterodine trihexyphenidyl
Many Others
Drug effects
 Indications:
• CVS
• As antidote
• Respiratory.
• In CNS
• Gastrointestinal
• Genitourinary
• Used preoperative
 Indications: CNS
• Decreased muscle rigidity and muscle tremors
– Parkinson’s disease
– Drug-induced extrapyramidal reactions
 Indications: Cardiovascular
• Affect the heart’s conduction system
– Low doses: slow the heart rate
– High doses: increased HR
 Indications: Cardiovascular (cont’d)

• Atropine
• As antidote.
• In ophthalmic uses
 Hyoscyamine

Used to treat GI spasmodic

Decrease secretions
Clidinium
Oxybutynin.
Tolterodine.
Adverse effects
 Nursing Implications (cont’d)
• Medications should be taken exactly as
prescribed to have the maximum therapeutic
effect
• Overdosing can cause life-threatening
problems
• Blurred vision may cause problems with
driving or operating machinery
 Nursing Implications (cont’d)
• Dry mouth may occur; can be handled by
chewing gum, frequent mouth care, and hard
candy
• Check with physician before taking any other
medication, including over-the-counter
medications
• Antidote for atropine overdose is
physostigmine
 Nursing Implications (cont’d)
• Anticholinergics taken by the elderly patient
may lead to higher risk for heatstroke
because of the effects on heat-regulating
mechanisms
• Teach patients to limit physical exertion and
avoid high temperatures and strenuous
exercise
• Emphasize the importance of adequate fluid
and salt intake
 Nursing Implications (cont’d)
• Patients should report the following
symptoms to their physician: urinary hesitancy
and/or retention, constipation, palpitations,
tremors, confusion, sedation or amnesia,
excessive dry mouth (especially if they have
chronic lung infections or disease), or fever
 Nursing Implications (cont’d)
• Monitor for therapeutic effects
– For patients with Parkinson’s disease:
fewer tremors and decreased salivation
and drooling
– For patients with urologic problems: improved
urinary patterns, less hypermotility, increased
time between voiding
• Monitor for adverse effects