FOR NURSING STUDENTS

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Outline
 Introduction
 Cholinergic agonists
 Cholinergic antagonists
 Adrenergic agonists
 Adrenergic antagonist

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 Introduction to nervous system

The neuron (nerve cell) is the basic functional

unit in this system.
Neurons also transmit information from the
brain to the entire body.
The primary parts of this system are the brain
and the spinal cord, called the central nervous
system.
The peripheral nervous system is composed of
nerves that branch out from the spinal cord.
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 Peripheral nervous system divided in to;
◙ the somatic nervous system and the autonomic nervous
system.
 The autonomic nervous system controls the automatic
(involuntary) functions of the body,
 e.g., breathing, digestion, heartbeat, etc.
 The somatic nervous system controls the voluntary
actions of the body,
 e.g., skeletal muscle movements.
 The ANS is further divided into two major portions:
Sympathetic nervous system
Parasympathetic nervous system

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ANS have two neurons from CNS to the effector tissue.
They are called presynaptic and postsynaptic.

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Sympathetic and parasympathetic systems
have opposing actions in some situations ;
 e.g. control of heart rate), but not in others (e.g. salivary
glands).
Sympathetic activity increases in stress ('fight
or flight)
PNS activity predominates ‘rest & digest’.
Both systems exert a continuous physiological
control of specific organs under normal
conditions
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Neurotransmitters in autonomic nervous system

 Acetylcholine and Norepinephrine (noradrenaline)

are the major autonomic neurotransmitters.
 Acetylcholine binds to cholinergic receptors.
◙ Cholinergic receptors are classified into muscarinic and
nicotinic cholinergic receptors.
 The action of ACh is quickly terminated through
hydrolysis by the enzyme acetylcholinesterase.
 Norepinephrine binds to adrenergic receptors.
◙ These receptors are subdivided into alpha and beta
adrenoreceptor types on the basis of both agonist and
antagonist selectivity.
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The binding of norepinephrine to alpha
receptors in the smooth muscle of blood vessels
causes the muscle to constrict.
The binding of norepinephrine to beta
receptors in the smooth muscle of a different
blood vessel produces opposite effects.
The binding of norepinephrine to beta
receptors in cardiac muscle results in a faster
and stronger heartbeat.
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 Cholinergic agonists

Cholinergic agonists can be divided into

directly and indirectly acting drugs.
Direct-acting (agonist)
o Bind to cholinergic receptors, causing
stimulation
Indirect-acting
o Inhibit the enzyme “cholinesterase” and
prolong the effect of endogenous acetylcholine

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 Directly acting cholinergic agonists

These agents may be broadly classified into

two groups:
◙ choline esters
 include Ach and synthetic esters of choline, such as
carbachol and bethanechol, and
◙ naturally occurring alkaloids,
 such as nicotine and pilocarpine

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Pilocarpine
muscarinic agonist and used for the treatment
of glaucoma.
constricts the ciliary muscle in the eye,
 which promotes the outflow of intraocular fluid.

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Bethanecol
Has mainly muscarinic actions
Relaxes sphincters in bladder and GI tract,
allowing them to empty
◙ Helpful for postsurgical atony of the bladder and
GI tract
Dose:10-40 mg oral, 2.5-5.0 mg SC

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Carbachol
Agonist of both muscarinic and nicotinic
receptors
It is useful only as an eye drop to treatment of
glaucoma as second line drug next to
pilocarpine.

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Adverse effects of cholinergic agonists
 bronchoconstriction,
 bradycardia,
 increased gastric acid secretion,
 sweating,
 difficulty in visual accommodation,
 increased salivation.

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 Indirectly acting cholinergic agonists

They inhibit the acetylcholine esterase enzyme

(AchE)
 thus, these drugs do not mimic but increase both the level
and duration of the neurotransmitter.

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According to the mode of action, AChE
inhibitors can be divided into two groups:
◙ irreversible and reversible.
Reversible inhibitors
a. Edrophonium
It is used for diagnosis of Myasthenia gravis
Since it has a very short duration of action not for
the treatment of myasthenia gravis

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b.Neostigmine:
Used for the treatment of:
Myasthenia gravis treatment (nicotinic action).
Paralytic ileus (like bethanechol which is direct drug)
Urinary retention
Competitive (non-depolarizing) neuromuscular blockers
intoxication

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c. Physostigmine
used for the treatment of
 Glaucoma and
 Atropine toxicity.

d. Donepezil, Rivastigmine, and Galantamine:

used in treatment of Dementia of Alzheimer’s
disease

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Irreversible inhibitors
 The result is a long-lasting increase in ACh at
all sites where it is released
 Many of these drugs are extremely toxic and
were developed by the military as nerve
agents.
 Parathion and Malathion, are used as
insecticides.

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Adverse effects: (same for both direct and
indirect cholinomimetics)
Mnemonics helpful to remember the muscarinic
(mostly parasympathetic) peripheral effects of
cholinesterase inhibitors are DUMBBELLS:
Diarrhea (Diaphoresis), Urination, Miosis,
Bronchospasm (secretion) Bradycardia, excite
skeletal muscle and CNS (Emesis), Lacrimation,
Lethargy, and Salivate
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Contraindications:
Same for both direct and indirect
cholinomimetics.
o Bronchial asthma
o Peptic ulcer
o Angina pectoris
o urine incontinence
o Intestinal obstruction

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 Cholinergic antagonists

Cholinergic antagonist is a general term for

agents that bind to cholinoceptors (muscarinic
or nicotinic) and prevent the effects of
acetylcholine (ACh) and other cholinergic
agonists.
Nicotinic receptor blockers are ganglionic
blocking drugs or neuromuscular blockers
(skeletal muscle relaxants) depending on the
location of the nicotinic type acetylcholine
receptors.
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 Anti muscarinic agents
Drugs include:
◙ Atropine, Scopolamine (Hyoscine), Ipratropium bromide,
Benztropine, Trihexyphenidyl
 Therapeutic uses
o Parkinson’s disease:
 Benztropine, Biperiden, Procyclidine & Trihexyphenidyl used as
adjunctive therapy
o Motion sickness:
 Scopolamine (oral or transdermal prophylactically 4 hrs. before
journey)
o As Anti-secretory and Preanesthetic medication:
 Atropine used for this purpose
o Urinary incontinence:
 Tolterodine is M3 selective drugs used to relieve urinary frequency,
and urgency and Enuresis in children
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o Asthma:
 Ipratropium bromide is used as inhalational drug.
o COPD patients
o Tiotropium bromide a long acting anti-muscarinic drug and can
be given once daily.
o Bradycardia and partial heart block:
 Atropine is useful
o To reverse the toxicity of organophosphate
(irreversible cholinesterase inhibitors) poisoning:
 IV atropine sulfate every 5-15 min until signs of toxicity
reversed.
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Adverse effects
o Dry mouth, mydriasis, blurred vision
tachycardia, dry eyes, hot & flushed skin, body
temperature increases, constipation,
hallucinations, agitation, delirium which may
progress to depression, collapse of circulatory
and respiratory system, coma and death.
 Simply the adverse effects of muscarinic blocker are anti-
DUMBBELLS.

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 Anti-nicotinic drugs

Two types: ganglion blockers and neuromuscular

blockers
Ganglionic blockers
Ganglionic blockers act on the nicotinic
receptors of both parasympathetic and
sympathetic autonomic ganglia.
 Thus, these drugs block the entire output of the autonomic
nervous system at the nicotinic receptor.
Since responses observed are complex and
unpredictable they are rarely used 31
therapeutically.
Neuromuscular blockers
These drugs block cholinergic transmission
between motor nerve endings and the nicotinic
receptors on the neuromuscular end plate of
skeletal muscle.
act either as antagonists (non- depolarizing
type) or, as agonists (depolarizing type)
receptors on the end plate of the Nm junction.

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i. Non-depolarizing (competitive) blockers
 E.g. tubocurarine, cisatracurium, pancuronium, rocuronium,
and vecuronium
o Used during surgery to relax muscles combined
with anesthetics
 Increase safety of anaesthetics by reducing the dose of
anesthetics required

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ii. Depolarizing blockers
o depolarize the plasma membrane of the muscle
fiber, similar to the action of ACh.
o more resistant to degradation by
acetylcholinesterase and can persistently depolarize
the muscle.
E.g. Succinylcholine
Is useful when rapid endotracheal intubation is
required during the induction of anesthesia
Adverse effects:
 Hyperthermia, apnea and hyperkalemia.

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 Adrenergic agonists

Drugs that stimulate the sympathetic nervous

system.
 norepinephrine (NE) and epinephrine (EPI)

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Effects of adrenoceptor activation

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The sympathomimetic classified by mode of
action into three groups
1.Direct acting
 e.g., norepinephrine and epinephrine

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2.Indirect acting
Increase the availability of norepinephrine or
epinephrine to stimulate adrenergic receptors by
 Causing displacement of stored catecholamines
from adrenergic nerve endings
 e.g., Amphetamine and tyramine)
 Inhibition of reuptake of already released
catecholamines from the synapse
 e.g., Cocaine and tricyclic antidepressants
 Blocking the metabolizing enzymes:
 Monoamine oxidase (MAO) is inhibited by pargyline
 catechol-o-methyltransferase (COMT) is inhibited by
entacapone
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3.Mixed acting sympathomimetics
Drugs that indirectly release norepinephrine
and also directly activate adrenoreceptors.
 e.g., ephedrine, dopamine

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Epinephrine (adrenaline)
Epinephrine interacts with both α and β
receptors.
At low doses, β effects (vasodilation) on the
vascular system predominate,
◙ whereas at high doses, α effect (vasoconstriction) is
the strongest.

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Therapeutic uses of epinephrine
Bronchospasm.
Anaphylactic shock.
Cardiac arrest:
Anesthetics:
 Local anesthetic solutions may contain low concentrations
Epinephrine greatly increases the duration of local
anesthesia by producing vasoconstriction at the site of
injection.

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Epinephrine Side Effects
Nervousness, tremor, insomnia Paradoxical
bronchospasm, Angina, arrhythmias,
Hypertension, Tachycardia Nausea/Vomiting
and Hyperglycemia

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Dopamine
Indications
o Treatment of severe congestive failure
o Treatment of cardiogenic and septic shock.

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Selective alpha 1 agonists
◙ E.g. Phenylephrine
 causes marked arterial vasoconstriction during intravenous
infusion.
 is used as a nasal decongestant and as a mydriasis in
various nasal and ophthalmic formulations.

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Alpha 2 selective agonists:
◙ methyldopa and clonidine
Methyldopa
o it is the preferred agent during pregnancy)
o Causes activation of central alpha2 receptors
 Inhibits SNS activity and leads to a fall in Blood pressure
◙ Adverse effects:
 sedation, dry mouth, bradycardia, hepatotoxicity,
hemolytic anemia

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Beta 1-selective agonists
◙ E.g. Dobutamine
 used for treatment of heart failure, shock and
atrioventricular heart block
Adverse Effects of Beta1 Activation:
◙ tachycardia , dysrhythmias and Angina Pectoris.

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Beta 2 selective agonists
 Used for treatment of asthma
Classified into two based on the duration of
action
i. Short acting:
◙ Albuterol and terbutaline.
ii. Long acting:
◙ Salmeterol and formoterol.
 are the agents of choice for treating nocturnal asthma in
symptomatic patients taking other asthma medications.
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Adverse Effects
Tremor is common adverse effect
 Can be minimized by starting oral therapy with a low
dose of drug and progressively increasing the dose as
tolerance to the tremor develops.
Feelings of restlessness, apprehension, and
anxiety
Tachycardia is a common adverse effect with
systemic administration
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 Adrenergic antagonist

These drugs act by either reversibly or

irreversibly attaching to the adrenoceptors,
 thus preventing activation by endogenous catecholamines

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Non-Selective α-Adrenergic Receptor
Antagonists:
Therapeutic Uses:
Treatment of pheochromocytoma
 Treat patients in preparation for surgery
 Erectile dysfunction
Toxicity and adverse effects
Postural hypotension accompanied by reflex
tachycardia, reversible inhibition of ejaculation
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𝜶 1-Adrenergic Receptor Selective Antagonists
o Inhibits vasoconstriction induced by endogenous
catecholamines;
◙ vasodilation may occur in both arteriolar resistance vessels
and veins,
 Resulting in a fall in blood pressure due to decreased peripheral
resistance.
 Therapeutic use:
o Treatment of hypertension
 prazosin, terazosin, doxazosin)
o Congestive heart failure
o Benign prostatic hyperplasia
 especially Tamsulosine)
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Adverse effects
o Most common side effect is
 postural hypotension and
 syncope when administered for the first time.
o Other side effects: - headache, drowsiness, dry
mouth, blurred vision, stress incontinence

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Beta-adrenergic blocking agents
Two types
o Non-selective beta blockers:
 Propranolol, timolol, nadolol, pindolol
o Cardioselective (Beta1) blockers:
 atenolol, esmolol, metoprolol

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Therapeutic use:
 Angina and Certain tachyarrhythmia
 Myocardial infarction
 Heart failure
Hypertension
 Glaucoma (topical use):
◙ reduce production of aqueous humor
 Eg. timolol

 Hyperthyroidism, migraine headache, anxiety:

 propranolol
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Adverse effects
o Bronchoconstriction:
 non-selective beta blockers like propranolol
o Bradycardia
o Hypoglycemia
Contraindication
o Asthma is an absolute contraindication
o Insulin-dependent diabetes
 Masking of hypoglycemia
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Table: Summary of drugs acting on ANS

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THANK YOU

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