Autonomic nervous system lecture 3

ParasympathlyticParasympathlytic
(Cholinergic antagonists)(Cholinergic antagonists)
(Anticholinergic )(Anticholinergic )
(Cholinergic Blockers)(Cholinergic Blockers)
‫المل ح‬ ‫فاضل‬ ‫محمد‬ ‫ثامر‬ ‫حسان‬
Group – B-

 Agents with high binding affinity for muscarinicAgents with high binding affinity for muscarinic
receptors butreceptors but no intrinsic activityno intrinsic activity. Pharmacologic. Pharmacologic
effects opposite of the muscarinic agonists.effects opposite of the muscarinic agonists.
 Competitive (reversible) antagonists of AChCompetitive (reversible) antagonists of ACh
 Antagonistic responses include:Antagonistic responses include:
decreased contractiondecreased contraction of GI and urinary tract smooth muscles,of GI and urinary tract smooth muscles,
dilation of pupils,dilation of pupils,
reduced gastric secretion,reduced gastric secretion,
decreased saliva secretion.decreased saliva secretion.
A- antimuscarinic agentsA- antimuscarinic agents
(Muscarinic Antagonists(Muscarinic Antagonists):):

A- antimuscarinic agentsA- antimuscarinic agents
(Muscarinic Antagonists):(Muscarinic Antagonists):
1-Atropine (belladonna alkaloid)1-Atropine (belladonna alkaloid)
 (Competitive inhibitors) .(Competitive inhibitors) .
-bind to muscarinic receptors and prevent Ach-bind to muscarinic receptors and prevent Ach
binding.binding.
 reversible blockade of ACh at muscarinic receptors
by competitive binding
-reversal effect of atropine by increasing ACh or
agonist ----> decreased blockade
..

Muscarinic receptor blockade doesMuscarinic receptor blockade does
not interfere with transmission atnot interfere with transmission at
autonomicautonomic ganglionic sites, theganglionic sites, the
adrenal medulla, or skeletal muscleadrenal medulla, or skeletal muscle
fibers.fibers. Sympathetic adrenergicSympathetic adrenergic
functions are not affectedfunctions are not affected..

MUSCARINIC RECEPTOR BLOCKADEMUSCARINIC RECEPTOR BLOCKADE
ALLOWSALLOWS SYMPATHETICSYMPATHETIC DOMINANCEDOMINANCE
IN DUAL INNERVATED ORGANSIN DUAL INNERVATED ORGANS
X

Atropine actionsAtropine actions
 Eye:Eye:
*mydriasis*mydriasis
*unresponsiveness to light*unresponsiveness to light
*cycloplegia*cycloplegia
*increase IOP*increase IOP

 GIT:GIT:
reduce activity of GIT.reduce activity of GIT.
 Urinary system:Urinary system:
reduce hyper motility.reduce hyper motility.
 Cardiovascular system:Cardiovascular system:
at low dose bradycardiaat low dose bradycardia
at high dose tachycardiaat high dose tachycardia
 Secretions:Secretions:
reduce secretionsreduce secretions

Therapeutic uses ofTherapeutic uses of
atropineatropine
1-Ophthalmic:1-Ophthalmic: Ophthalmologic examinations..
mydriatic & cycloplegic effects.mydriatic & cycloplegic effects.
2-antispasmotic agent2-antispasmotic agent : relax GIT & bladder: relax GIT & bladder
((Treatment of smooth muscle spasms).

3-antidot for cholinergic agonists:3-antidot for cholinergic agonists:
Rx of over dose of organophosphateRx of over dose of organophosphate
4-antisecretory agent:4-antisecretory agent:
reduce secretions of respiratory tract andreduce secretions of respiratory tract and
salivary gland .salivary gland .
((Reduction of nasal and upper respiratory
tract secretions in cold and flu)secretions in cold and flu)

Pharmacokinetics ofPharmacokinetics of
atropineatropine
 Absorbed & metabolized by liver.Absorbed & metabolized by liver.
 Eliminated by urine.Eliminated by urine.
 Half life/4hr.Half life/4hr.
 Parenteral preparationsParenteral preparations
(derivatives) are more potent than the(derivatives) are more potent than the
parent compounds.parent compounds.

Adverse effects ofAdverse effects of
atropineatropine
 Dryness of mouthDryness of mouth
 Blurred visionBlurred vision
 Increase in IOPIncrease in IOP
 Attack of glaucomaAttack of glaucoma
 TachycardiaTachycardia
 ConstipationConstipation
 CNS effectsCNS effects
 Collapse of circulatory & respiratory systemsCollapse of circulatory & respiratory systems
 Urine retentionUrine retention

Treatment of atropineTreatment of atropine
poisoningpoisoning
 VentilationVentilation
 Cold spongyCold spongy
 DiazepamDiazepam
 physostigminphysostigmin

Antimuscarinic agentsAntimuscarinic agents
2-scopolamine:2-scopolamine:
 greater actions on CNSgreater actions on CNS (than atropine)(than atropine)
Low doses of scopolamine produce CNS effects
that are not seen with equivalent doses of
atropine.
 (longer duration of action than atropine)(longer duration of action than atropine)
**actions & uses:actions & uses:
prophylaxis of motion sickness drugmotion sickness drug

Antimuscarinic agentsAntimuscarinic agents
3-ipratropium3-ipratropium
useful in Rx of asthma & chronic obstructiveuseful in Rx of asthma & chronic obstructive
pulmonary diseasepulmonary disease
 Administration:
by inhalation as aerosol (to provide maximal
concentration at the site of action)

Synthetic amtimuscarinicSynthetic amtimuscarinic
agentagent
1- Probanthine1- Probanthine
2- Methanthelin bromide2- Methanthelin bromide
 uses : treatment of peptic ulceruses : treatment of peptic ulcer
C/IC/I
GlaucomaGlaucoma
Stomach obstructionStomach obstruction
Old patientOld patient
Cardiac disturbanceCardiac disturbance

B- anti nicotinic agentB- anti nicotinic agent
 Nicotinic Antagonists:Nicotinic Antagonists: Agents that bind toAgents that bind to
cholinergic nicotinic receptors but do not havecholinergic nicotinic receptors but do not have
efficacy.(Competitive antagonists).efficacy.(Competitive antagonists).
Antinicotinic include :
1- Ganglion blockers
2- Neuromuscular blockers
1-ganglionic blockers1-ganglionic blockers
1-Hexamthonim1-Hexamthonim
2-Pentamethanium2-Pentamethanium
3-Trimethaphan.3-Trimethaphan.

Pharmacological effects ofPharmacological effects of
ganglionic blockersganglionic blockers::
 EyeEye: mydriasis , paralysis of accommodation: mydriasis , paralysis of accommodation
 Respiratory tractRespiratory tract: reduce secretions: reduce secretions
 Salivary glands:Salivary glands: xerstomiaxerstomia
 GIT:GIT: reduce secretions & motilityreduce secretions & motility
 Cardiovascular:Cardiovascular: decrease blood pressuredecrease blood pressure
 Urinary tractUrinary tract : urinary retention: urinary retention
 Sweat glandsSweat glands: decrease sweating: decrease sweating
 CNS:CNS: no direct effectsno direct effects

UsesUses
 Operation of neurosurgeryOperation of neurosurgery
 Hypertension with phochromocytomaHypertension with phochromocytoma

22--Neuromuscular blockingNeuromuscular blocking
drugsdrugs
which block Ach at N-M-J(neuromuscular
junction), classified as:
A- Non-Depolarizing Agent:-
Tubocurarine
Gallamine
Pancuronium
B- Depolarizing Agent:-
Suxamethonium
Decamethonium
succinylcholine

Neuromuscular blockers:
 Neuromuscular blockers: Drugs used duringNeuromuscular blockers: Drugs used during
surgical procedures and in intensive caresurgical procedures and in intensive care
units tounits to cause paralysis.cause paralysis.
 Since skeletal muscleSince skeletal muscle contraction is elicitedcontraction is elicited
by nicotinic (NM) cholinergic mechanisms.by nicotinic (NM) cholinergic mechanisms.
 NeuromuscularNeuromuscular blockersblockers interfere withinterfere with
transmission at the neuromusculartransmission at the neuromuscular endend
plate and lack CNS activity.plate and lack CNS activity.

Action Potential
Ca
2+
Motor neuron
Na+
ACH
ACH
ACH
ACH
ACH
ACH
ACH
ACH
ACH
α
α
β
α
α
β
α
αβ
ACH
ACH
ACH
ACH
Na+
Skeletal
Muscle
ACHEsterase
Neuromuscular Blockers

A-non depolarizing:A-non depolarizing:
First drug is curarine(d- tubocurarine)First drug is curarine(d- tubocurarine)(Plant alkaloid).(Plant alkaloid).
 They act asThey act as competitive antagonistscompetitive antagonists at theat the
ACh receptors of the endplate(ACh receptors of the endplate(act by blocking
nAChR).
 Blockade by these agents (such asBlockade by these agents (such as
tubocurarine and pancuronium) can betubocurarine and pancuronium) can be
reversed byreversed by increasing the amount of ACh inincreasing the amount of ACh in
the synaptic cleft,the synaptic cleft, for example, by thefor example, by the
administration of a cholinesterase inhibitor.administration of a cholinesterase inhibitor.

TubocurarineTubocurarine
 Causes muscle paralysis .Causes muscle paralysis .
 Rapid onset of action.Rapid onset of action.
 Therapeutic Use:Therapeutic Use:
 As a muscle relaxant in various surgicalAs a muscle relaxant in various surgical
procedures.procedures.

Mechanism of actionMechanism of action
::
combine with nicotinic receptors & preventcombine with nicotinic receptors & prevent
the binding of Ach(competitive blockers)the binding of Ach(competitive blockers)
..

ActionsActions
 Paralysis of :muscle of face & eye,Paralysis of :muscle of face & eye,
fingers, limbs , neck, trunk &fingers, limbs , neck, trunk &
diaphragm muscles.diaphragm muscles.

Theraputic usesTheraputic uses
 With anesthesia to relax skeletalWith anesthesia to relax skeletal
musclesmuscles
 In tetanusIn tetanus
 Fractures.Fractures.
 Side effectSide effect
1-hypotention .1-hypotention .
2- bronchospasm2- bronchospasm

Drugs interactionsDrugs interactions
1- cholinestrase inhibitors1- cholinestrase inhibitors
e.g neostigmine, physostigmine &e.g neostigmine, physostigmine &
edrophonium.edrophonium. (produce antagonist effect)(produce antagonist effect)
2-halogenated hydrocarbon anesthetics2-halogenated hydrocarbon anesthetics
e.g halothanee.g halothane (increased muscle relaxant )(increased muscle relaxant )
3-aminoglycoside antibiotics3-aminoglycoside antibiotics
e.g gentamicine.g gentamicin (increased muscle relaxant )(increased muscle relaxant )

 Botulinum Toxin (Botox):Botulinum Toxin (Botox):
 ToxinToxin produced by the bacteriumproduced by the bacterium ClostridiumClostridium
Botulinum.Botulinum.
 purified & highly diluted for therapeutic usepurified & highly diluted for therapeutic use
 Prevents Acetylcholine release from thePrevents Acetylcholine release from the
nerve terminal.nerve terminal.
 ProducesProduces flaccid paralysisflaccid paralysis of skeletal muscleof skeletal muscle
, Inhibition lasts from several weeks to 3 to 4, Inhibition lasts from several weeks to 3 to 4
months.months.
 Immuno resistance may develop withImmuno resistance may develop with
continued use.continued use.

Botulinum toxin
• The acetylcholine
vesicle release
process is
blocked by
botulinum toxin

Therapeutic use botulinum toxin
• Dermatological / Cosmetic Uses:Dermatological / Cosmetic Uses:
• Local facial injections of botulinum toxin are widely used
for the short-term treatment (1–3 months per treatment) of
wrinkles associated with aging around the eyes; neck and
mouth to control muscle spasms and to facilitate muscle
relaxation .
• Local injection of botulinum toxin has also become a useful
treatment for generalized spastic disorders (eg, cerebral
palsy).
• Most studies have used type A botulinum toxin, but type B
is also available.
• Prevent excessive sweating (palm).

Autonomic nervous system lecture 3

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Autonomic nervous system lecture 3