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1. SUBMITTED TO:
SUBMITTED BY:
PARASYMPATHOMIMETICS
AND
PARASYMPATHOLYTICS
CMS:

2. PARASYMPATHOMIMETIC
A parasympathomimetic drug, sometimes called a cholinomimetic drug, is a substance
that stimulates the parasympathetic nervous system. These chemicals are also called
cholinergic drugs because acetylcholine is the neurotransmitter used by the PSNS.
CLASSIFICATION OF PARASYMPATHOMIMETICS
DIRECT ACTING
CHOLINE ESTERS:
Acetylcholine
Carbachol
Methacholine
Bethanechol
CHOLINOMIMETIC
AGONISTS:
MAINLY MUSCARINIC AGONISTS:
1.Natural Alkaloids:
Muscarine
Pilocarpine
Arecholine
2.Synthetic Alkaloid:
Oxotramorine
SELECTIVEM3 AGONIST:
Cevimeline
MAINLY NICOTINIC AGONISTS
1.1.Natural Alkaloids:
Nicotine
Lobeline
1.2.Synthetic Alkaloids:
Dimethylphenylpiperazinium
(DMPP)
Varenicline
1.3.Tertiary alkaloids
Pilocarpine
Nicotine
Lobeline
1.4.Quaternary amines
Muscarine
INDIRECTLY ACTING
REVERSIBLE
ANTICHOLINESTERASES:
CARBAMATES:
1.Tertiary amines [cancross
blood brain barrier]
Physostigmine
2.Quaternary Ammonium
compounds[cannot cross blood
brain barrier]
Neostigmine
Pyridostigmine
Distigmine
Ambenonium
Demecarium
ALCOHOLS:
Edrophonium
MISCELLANEOUS:
Tacrine
Donepezil
Galantamine
Rivastigmine
IRREVERSIBLE
ANTICHOLINESTERASES:
(OrganophosphorusCompounds)
1.Therapeutically useful:
Ecothiophate
2.War Gases:
Sarin
Tuban,
Soman
3.Insecticides:-
Parathion
Malathion
DiisopropylFlurophosphate(DFP)
TetramethylPyrophosphate
(TMPP)
Octamethyl
Pyrophosphotetraamide (OMPA)

3. PHARMACOKINETICS
 Acetylcholine & other Choline esters have a permanently charged
quaternary ammonium group in their structure.
 All are hydrolysedinthe GIT
 Choline esters are poorly absorbed and poorly distributed into CNS
 Methacholine is resistantto hydrolysis by cholinesterase
 Carbamic acid esters carbacholand bethanechol- mostresistant-longer
duration of action
 The tertiary natural cholinomimetic alkaloids (pilocarpine, nicotine,
lobeline) are well absorbed.
 Muscarine, quaternary amine is toxic when ingested presentin certain
mushrooms.
 Excretion mainly by the kidneys
MECHANISM OF ACTION
 G –protein linked (Muscarinic)
 Ion channel (Nicotinic)
DIRECT ACTING (AGONISTS): Bind to cholinergic receptor causing stimulation.
INDIRECTACTING: Inhibitthe enzyme“cholinesterase”
Result: More Ach is available at the receptors.
 REVERSIBLE:
Bind to cholinesterasefor a period of minute to hours.
 IRREVERSIBLE:
Bind to cholinesteraseand forma permanent covalent bond.
The body mustmake new cholinesterases.

4. BINDING OF DRUG WITH RECEPTOR
(ALPHA-1 ADRENDERGIC, MUSCARINIC- CHOLINERGIC)
PHOSPHATIDYL INOSITOL 4-5 BIPHOSPHATE
ACTIVATION OF PHOSPHOLIPASE-C
DIACYL GLYCEROL INOSITOL 1.4.5 TRIPHOSPHATE
(CONFINEDTO MEMBRANE) (DIFFUSES INTO CYTOSOL)
ACTIVATION OF PROTEIN KINASE C RELEASE OF Ca++ FROM
INTERCELLULAR
SOURCES
ENTRY OF Ca++ THROUGH THE CA++
CHANNEL FORMATION OF Ca++ CALMODULIN
COMPLEX
ALTERATION IN THE ACTIVITY OF Ca++
DEPENDENT ENZYMES
EFFECT

5. PHARMACOLOGICAL ACTIONS (organ system
effects)

6. CLINICAL INDICATIONS
GASTROINTESTINAL ANDGENITOURINARY:
Bethanechol (Urecholine)
 GI smooth muscle stimulant
 postoperativeabdominal distention
 paralytic ileus
 esophageal reflux; promotes increased esophagealmotility
(other drugs aremore effective, e.g. dopamine antagonist
(metoclopramide) or serotonin agonists (cisapride)
 Urinary bladder stimulant
 post-operative; post-partumurinary retention
Alternative to Pilocarpine to treat diminished salivation secondary e.g. to
radiation
Carbachol not used due to more prominentnicotinic receptor activation
Methacholine
 used for diagnostic purposes.
 testing for bronchial hyperreactivity and asthma

7. OPTHALAMIC USES:
o Acetylcholine and Carbachol may be used for intraocular useas a
miotic in surgery
o Carbachol may be used also in treatment of glaucoma.
o Pilocarpine is used in management of glaucoma and has become the
standard initial drug for treating the open-angle form.
o Sequential adminstration of atropine (mydriatic) and pilocarpine
(miotic) is used to break iris-lens adhesions.
ADVERSE EFFECTS
(Overstimulation of Muscarinic and Nicotinic Receptors)
 Miosis
 Salivation
 Sweating
 Bronchial constriction
 Vomiting and diarrhea
 Myasthenia gravis
 Neuromuscular blockade(nicotinic effect)
 CNS effects: high doses

8. PARASYMPATHOLYTICS
A parasympatholytic agentis a substanceor activity that reduces the activity of
the parasympathetic nervous system.
OR
Drugs which bind with the cholinergic receptors and block the action of the Ach or
Ach like drugs.
CLASSIFICATION
 Muscarinic antagonists (Parasympatholytics)
(Atropine, hyoscine, homatropine)
 Ganglionblocking drugs
(Hexamethonium, gallamine)
 Neuromuscular blocking drugs
(Calcium antagonists, hemicholinium, magnesium
ions)
PHARMACOKINETICS
 Absorption: –The natural alkaloids and mosttertiary antimuscarinic drugs
are well absorbed fromthe gut and conjunctivalmembranes – some even
over the skin (scopolamine) – Penetrates cornea freely – Quaternary ones –
only upto 30%
 Distribution: –Atropineand the other tertiary agents are widely distributed
in the body – Scopolamineis rapidly and fully distributed into the central
nervous systemwhereit has greater effects than most other antimuscarinic
drugs – Quaternary derivatives arepoorly taken up by the brain
 Metabolism: –Atropine is metabolized in liver by conjugation and 60%
excretes unchanged in urine – Effects disappear quickly within 2 Hrs except
eye

9. MECHANISM OF ACTION
 Act by occupying receptor sites at parasympathetic nerveendings, thereby
leaving fewer receptor sites free to respond to acetylcholine
 Distribution of receptors is broad so effects of anticholinergics will be
diffuse.
 Atropine causes reversible(surmountable) blockadeof cholinomimetic
actions at muscarinic receptors – blockade by a small doseof atropine can
be overcome by a larger concentration of acetylcholine or equivalent
muscarinic agonist
 Atropine is highly selective for muscarinic receptors, does not distinguish
between the M1, M2, and M3
 Some quaternary amine antimuscarinic agents havesignificant ganglion-
blocking actions.
PHARMACOLOGICAL ACTIONS
ATROPINE:
Central Nervous System:
 OverallCNS stimulant
 Atropine has only peripheral effects and minimal minimal stimulant effect
on CNS
 low entry.
 Scopolamine has more marked central effects
 Amnesia and drowsiness
 Atropine stimulates many medullary centres
 Vagal, respiratory and vasomotor
 Depresses vestibular excitation
 Antimotion sickness property
 Block basalganglia cholinergic over activity
 Blocks tremor, rigidity
CVS:
 Moderate and high doses: TACHYCARDIA
 Blockade of M2 receptor on SA node(vagal tone decreases HR)

10.  Higher the vagal tone
 More Bradycardia - in young adults
 AVN – Atropine produces PS blockade
 Higher AV conduction rate (reduced PR interval in ECG)
 IM/SCinjection initially
 Transient BRADYCARDIA
 May be due to inhibition of prejunctionalpostsynaptic M1 autoreceptor
inhibition (not due to stimulation of vagal centre)
 Evidenced by Pirenzepine injection does not cross BBB
BP:
 Parasympathetic impulses are not involved in maintenance of vascular tone
 Little increase due to tachycardia and VMC
 But, histamine release cause direct vasodilatation
 However, No marked effect on BP
Eye:
 Mydriasis
 Topical atropine and other tertiary antimuscarinic drug - results in
unopposed sympathetic dilator activity and mydriasis
 Cycloplegia: desirable in Ophthalmology
 Photophobia and blurring of near vision
 IOP rises: hazardousin narrow angleglaucoma
 Dry Eye: Not desirable
 Atropine on Smooth Muscle
 GIT:
 Relaxation – mediated by M3 blockade
 Contraction of Stomach and Intestinereduced – constipation
 But, less peristalsis suppression –ENS (with other neurotransmitters
involved)
 More effective to exogenous Ach administration

11. Respiratory:
 Bronchodilatation (COPD)
 Also antagonizes Histamine, PG, leukotrienes etc. mediated vagal
overactivity
Urinary:
 Relaxation of ureter and bladder
 BHP
 Sometimes usefulin neurogenic bladder/enuresis
 Atropine on Glands
 Decreases salivary, sweat, tracheobronchialtreeand lacrimal secretions
 dryness of mouth, dry skin and conjunctiva and difficulty in swallowing
 Decreases acid pepsin and mucus secretion and overallvolume (pH changes
little)
 H2 blockers are more effective
 No effect on intestinal and pancreatic secretion
 No effect on bile production
Temperature:
 Increases –decreasesweating + stimulation of temperature regulating
centre in hypothalamus
 Local anaesthetic action: on cornea
CLINICAL INDICATIONS
 Uses include GI, GU, ophthalmic and respiratory disorders, bradycardia and
in Parkinsons disease.
 Used preoperatively
Use In GI Disorders:
 Helpful in treating irritable colon or colitis
 Useful in gastritis, pylorospasmand ulcerativecolitis as they slow motility

12. Use in GU disorders:
 Antispasmotic effects seen in overactivebladder and in urinary
incontinence
Ophthalmological Use:
 Mydriatic and cycloplegia for examinations and surgery
Respiratory Uses:
 In bronchospasmwhether related to asthma or COPD
 Atroventvery useful for its bronchodilating effects
Cardiological Uses:
 Atropine is used to increase heart rate in symptomatic bradycardias and
higher blocks.
Parkinsons Disease:
 Useful in those with minimal side effects
 Those who cannot take Levodopa
 Helpful in decreasing salivation, spasticity and tremors
Preoperative Uses:
 Help prevent vagal stimulation and potential bradycardia
 Reduce respiratory secretions as well
ADVERSE EFFECTS
• Dry skin, dry mucous membranes, dry mouth
• Mydriasis, blurred vision
• Urinary retention
• Risk of acute urinary retention greatest in 1st30 days of therapy [4]
• Constipation
• Abdominal pain
• Tachycardia

13. • Dizziness
• Drowsiness
• Nausea
• Confusion, delirium
• Hyperthermia
• Thirst
• Chronic use may increaserisk of dementia [1]
• Use of anticholinergics by cognitively normal elderly is associated with
increased brain atrophy & dysfunction & clinical decline
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