Parasympathlytic


(Cholinergic antagonists)
(Anticholinergic )
(Cholinergic Blockers)

 A- antimuscarinic agents

(Muscarinic Antagonists):

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

(Muscarinic Antagonists):


1-Atropine (belladonna alkaloid)

" (Competitive inhibitors) .
-bind to muscarinic receptors and prevent Ach binding.
" reversible blockade of ACh at muscarinic receptors by
competitive binding

-reversal effect of atropine by increasing ACh or
agonist ----> decreased blockade
-atropine is central & peripheral muscarinic blocker.
Muscarinic receptor blockade does not interfere with
transmission at autonomic ganglionic sites, the adrenal
medulla, or skeletal muscle fibers. Sympathetic
adrenergic functions are not affected.

X X
MUSCARINIC RECEPTOR BLOCKADE ALLOWS
SYMPATHETIC DOMINANCE IN DUAL
INNERVATED ORGANS

X
Atropine actions
" Eye:
*mydriasis
*unresponsiveness to light
*cycloplegia
*increase IOP
" GIT:
reduce activity of GIT.
" Urinary system:
reduce hyper motility.
" Cardiovascular system:
at low dose bradycardia
at high dose tachycardia
" Secretions:
reduce secretions
 Therapeutic uses of atropine

1-Ophthalmic: Ophthalmologic examinations.

mydriatic & cycloplegic effects.
2-antispasmotic agent : relax GIT & bladder
(Treatment of smooth muscle spasms).
3-antidot for cholinergic agonists:
Rx of over dose of organophosphate
4-antisecretory agent:
reduce secretions of respiratory tract and
salivary gland .
(Reduction of nasal and upper respiratory
tract secretions in cold and flu)
Pharmacokinetics of atropine
" Absorbed & metabolized by liver.
" Eliminated by urine.
" Half life/4hr.
" Parenteral preparations (derivatives)
are more potent than the parent
compounds.
 Adverse effects of atropine

" Dryness of mouth

" Blurred vision
" Increase in IOP
" Attack of glaucoma
" Tachycardia
" Constipation
" CNS effects
" Collapse of circulatory & respiratory systems
" Urine retention
Treatment of atropine poisoning
" Ventilation
" Cold spongy
" Diazepam
" physostigmin
 Antimuscarinic agents

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

3-ipratropium
useful in Rx of asthma & chronic obstructive
pulmonary disease
" Administration:
by inhalation as aerosol (to provide maximal
concentration at the site of action)
 Synthetic amtimuscarinic agent

1- Probanthine
2- Methanthelin bromide
"uses : treatment of peptic ulcer
"C/I
"Glaucoma
"Stomach obstruction
"Old patient
"Cardiac disturbance
B- anti nicotinic agent
" Nicotinic Antagonists: Agents that bind to
cholinergic nicotinic receptors but do not have
efficacy.(Competitive antagonists).
Antinicotinic include :
1- Ganglion blockers
2- Neuromuscular blockers
1-ganglionic blockers
1-Hexamthonim
2-Pentamethanium
3-Trimethaphan.
 Pharmacological effects of ganglionic
blockers:

" Eye: mydriasis , paralysis of accommodation

" Respiratory tract: reduce secretions
" Salivary glands: xerstomia
" GIT: reduce secretions & motility
" Cardiovascular: decrease blood pressure
" Urinary tract : urinary retention
" Sweat glands: decrease sweating
" CNS: no direct effects
Uses
" Operation of neurosurgery
" Hypertension with phochromocytoma
 2- Neuromuscular blocking drugs
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 during
surgical procedures and in intensive care
units to cause paralysis.
" Since skeletal muscle contraction is elicited
by nicotinic (NM) cholinergic mechanisms.
" Neuromuscular blockers interfere with
transmission at the neuromuscular end
plate and lack CNS activity.
 Neuromuscular Blockers
Na+
Na +

Ca

α
2+

β
Ac ACH
tio

α
nP
ote
nti
a l

ACH ACH
ACH ACH
ACH ACH

α
ACH

β
ACH ACH
Motor neuron

α
ACH
ACH
ACH α
βα ACHEsterase

Skeletal
Muscle
 A-non depolarizing:
First drug is curarine(d- tubocurarine)(Plant alkaloid).
" They act as competitive antagonists at the
ACh receptors of the endplate(act by blocking
nAChR).
" Blockade by these agents (such as
tubocurarine and pancuronium) can be
reversed by increasing the amount of ACh in
the synaptic cleft, for example, by the
administration of a cholinesterase inhibitor.
Tubocurarine
" Causes muscle paralysis .
" Rapid onset of action.
" Therapeutic Use:
" As a muscle relaxant in various surgical
procedures.
 Mechanism of action

1- at low dose :
combine with nicotinic receptors & prevent
the binding of Ach(competitive blockers)
2-at high dose:
block the ion channels of the end plate.
Actions
" Paralysis of :muscle of face & eye,
fingers, limbs , neck, trunk &
diaphragm muscles.
Theraputic uses


" With anesthesia to relax skeletal

muscles
" In tetanus
" Fractures.

"Side effect
1-hypotention .
2- bronchospasm
 Drugs interactions

1- cholinestrase inhibitors
e.g neostigmine, physostigmine &
edrophonium. (produce antagonist effect)
2-halogenated hydrocarbon anesthetics
e.g halothane (increased muscle relaxant )
3-aminoglycoside antibiotics
e.g gentamicin (increased muscle relaxant )
" Botulinum Toxin (Botox):
" Toxin produced by the bacterium Clostridium
Botulinum.
" purified & highly diluted for therapeutic use
" Prevents Acetylcholine release from the
nerve terminal.
" Produces flaccid paralysis of skeletal muscle
, Inhibition lasts from several weeks to 3 to 4
months.
" Immuno resistance may develop with
continued use.
 Botulinum toxin

• The acetylcholine
vesicle release
process is
blocked by
botulinum toxin
 Therapeutic use botulinum toxin
• 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).