4.cholinergic and anticholinergics

Drugs Acting On Drugs Acting On Autonomic Nervous Autonomic Nervous System (ANS)System (ANS)

Neurotransmitters Neurotransmitters Sympathetic: noradrenaline

(norepinephrine) Parasympathetic : acetylcholine

Cholinergic receptorsCholinergic receptors

Muscarinic: M1 – M5

Activated by muscarine Nicotinic: NM, NN

Activated by nicotine

Actions of AchActions of Ach

Acetylcholine – major neurotransmitter of PNS

Actions of Ach

Characteristics

M1 (neuronal)

M2

(cardiac)M3 (glandular)

Location & Function

• Ganglia – impulse transmission

• SA node -Decreased rate of impulse generation • AV node –decreased conduction velocity • Atrium, ventricle-decreased contractility

• Exocrine glands-secretion

• Visceral smooth Muscle – contraction

Actions of Ach

Characteristics

M1 (neuronal)

M2

(cardiac)M3 (glandular)

Location & Function

• Ganglia – impulse transmission

• SA node -Decreased rate of impulse generation • AV node –decreased conduction velocity • Atrium, ventricle-decreased contractility

• Exocrine glands-secretion

• Visceral smooth Muscle – contraction

Actions of Ach

Characteristics

M1 (neuronal)

M2

(cardiac)M3 (glandular)

Location & Function

• Ganglia – impulse transmission

• SA node -Decreased rate of impulse generation • AV node –decreased conduction velocity • Atrium, ventricle-decreased contractility

• Exocrine glands-secretion

• Visceral smooth Muscle – contraction

Actions of Ach

Characteristics

M1 (neuronal)

M2

(cardiac)M3 (glandular)

Location & Function

• Ganglia – impulse transmission

• SA node -Decreased rate of impulse generation • AV node –decreased conduction velocity • Atrium, ventricle-decreased contractility

• Exocrine glands (salivary, sweat) -secretion

• Visceral smooth Muscle (bronchus, bladder, GIT) – contraction

Actions of Ach

Characteristics NM

(muscle type)NN

(neuronal type)

Location & Function

Skeletal neuromuscular junction (NMJ) – contraction

• Autonomic ganglia– impulse transmission

Actions of ACh on eye

Muscarinic:Eye: -Circular muscle of iris (M3)- contraction-

miosis-Ciliary muscle (M3) – contraction- eye’s

focus is accomodated for near vision – spasm of accomodation

-Better drainage of aqueous humor – reduced intraocular pressure

-Lacrimal glands (M3) - lacrimation

Acetylcholine Acetylcholine No therapeutic use because i) Ultra short action: rapidly

hydrolyzed by cholinesterasesii)Widespread and nonselective

activity: act on all receptors

Drugs which mimic the actions of Ach are called as cholinergic drugs or parasympathomimetic drugs or cholinomimetic or cholinergic agonists

Classification

1. Directly actingMethacholine, bethanechol,

pilocarpine Act on muscarinic receptors

2. Indirectly acting (Anticholinesterases)

A. Reversible : Physostigmine, neostigmine, pyridostigmine, edrophoniumB. Irreversible: Organophosphates: Parathion, Malathion

Mechanism of action of Anticholinesterases

Inhibit acetylcholinesterase (AChE) enzyme

Ach ----------- Choline + acetate AChE

Accumulation of Ach Action

Neostigmine

____

Therapeutic uses

Ophthalmic use : i) Glaucoma ii)To counteract the effects of mydriatics iii) To break adhesions between the iris

and lens or iris and corneaMyasthenia gravis : neostigmineBelladona (Atropine) poisoning : Physostigmine – specific antidote

Irreversible AChE inhibitorsIrreversible AChE inhibitors

Mainly used as insecticides and pesticides

Adverse effects of Adverse effects of anticholinesterases anticholinesterases Diarrhea, urination,

bronchoconstriction, lacrimation, salivation, sweating, bradycardia, fasciculation of skeletal muscle

Organophosphorus poisoning: treated with an anticholinergic, atropine

Anticholinergic Anticholinergic DrugsDrugs

ClassificationNatural alkaloids : Atropine* (prototype), Scopolamine

(Hyoscine)Semisynthetic derivatives :Homatropine*, ipratropium bromide,

tiotropium bromideSynthetic compounds :i) Mydriatics – Cyclopentolate*, tropicamideii)Antiparkinsonian – Benzhexol, Biperiden,

Benztropine

iii) Antisecretory- antispasmodics –Dicyclomine PirenzepineGlycopyrrolate

Semisynthetic and synthetic anticholinergics - Atropine substitutes

Pharmacological actions of Pharmacological actions of atropineatropine

CNS :

High doses – restlessness, delirium, disorientation

CVS :Tachycardia

Eye :mydriasis : “Passive mydriasis”Photophobia, abolition of light reflex“Paralysis of accomodation or

cycloplegia”Rise in IOPDecrease in lacrimation – dry eyes

Respiratory system :Bronchodilatation Decreased secretions GIT :Reduce gastric acid secretionReduced tone and motility of gut,

constriction of sphincters – constipation

Genitourinary tract :Relaxation of ureter and urinary bladder –

urinary retentionGlands :Decreases sweat, salivary,

tracheobronchial and lacrimal secretionBody temperature :Rise in body temperature“Atropine fever”

Uses of atropine Uses of atropine Preanaesthetic medication: to

decrease secretionOraganophosphorous poisoning

Therapeutic uses Therapeutic uses Motion sickness : Scopolamine Parkinson’s disease :benzhexol,

benztropine etc.Bronchial asthma : ipratropium and

tiotropium bromidePreanaesthetic medication :

glycopyrrolate , As mydriatic during fundoscopy and

testing of refractive error – Tropicamide, cyclopentolate

Side effects of atropine :Dry mouthBlurred vision and photophobiaUrinary retentionConstipationDry, hot skinPrecipitation of glaucomaDecreased sweating