Acetylcholine (ACh) is a major neurohumoral transmitter at autonomic, somatic as well as central sites.

Acetylcholine is synthesized locally in the cholinergic nerve endings by the following pathway-

cholinorceptors

muscarinic

nicotinic

M2

M1
LOCATION AND FUNCTION NATURE TRANSDUCE R MECHANISM
Autonomic ganglia, gastric glands, CNS

M2
SA node, AV node, atrium, ventricle, cholinergic nerve endings, visceral smooth muscle, CNS

M3
Visceral smooth muscle, iris, ciliary muscle, exocrine glands, vascular endothelium

G-protein coupled

G-protein coupled

G-protein coupled

IP 3/ DAG increased cytosolic calcium PLA 2 increasedPG synthesis

Potassium channel opening, decreased cAMP by inhibiting adenylyl cyclase

IP 3/ DAG increased cytosolic calcium PLA 2 increasedPG synthesis

LOCATION AND FUNCTION NATURE

Neuromuscular junction Intrinsic ion channel

Autonomic ganglia, adrenal medulla, CNS Intrinsic ion channel

TRANSDUCER MECHANISM

Opening of sodium and potassium channels

Opening of sodium, potassium and calcium channels

Also called cholinomimetic or parasympathetic drugs These are drugs which produce actions similar to that of ACh, either by directly interacting with cholinergic receptors (cholinergic agonists) or by increasing availability of ACh at these sites Choline (anticholinesterases).
Cholinergic agonists esters alkaloids

Cholinergic drugs Anticholineesterases

Reversible

irreversible

Actions can be divided as 1. Muscarinic actions: Heart Blood vessels Smooth muscles Glands Eye 2. Nicotinic actions Autonomic ganglia Skeletal muscles 3. CNS

Choline esters

Alkaloids

acetylcholine

Muscarine

Methacholine

Pilocarpine

Carbachol

Arecoline

Bethanechol

EXAMPLE: BETHANECHOL (Dose: 10--4 0 mg oral, 2.5-5 mg s.c.; UROTONIN 25 mg tab.) PILOCARPINE (PILOCARPINE HCL OPHTHALMIC SOLUTION USP by bausch and lomb, PILOCAR 1%, 2%, 4% eye drops, ACARPINE 0.9% eyedrops, PILODROPS 2 % eyedrops.)

Anticholinesterases (anti-ChEs) are agents which inhibit ChE, protect ACh from hydrolysis-produce cholinergic effects in vivo and potentiate Ach both in vivo and in vitro. Some anti ChEs have additional direct action on cholinergic receptors
Anticholinesterase s

Reversible

Irreversible

Carbamates

Acridine

Organophosphate s

Carbamates

Schematic representation of reaction of acetylcholine (A-D), or carbamate anticholinesterase (E, F). organophosphate anticholinesterase {G) with cholinesterase enzyme; and reactivation of phosphorylated enzyme _oxime

Physostigmine

BI-MILTIC 0.25% eye drops with 2% pilocarpine nitrate.

Neostigmine
Pyridostigmine Adrophonium Tacrine Others

PROSTIGMIN, MYOSTIGMIN, TILSTlGMlN 15 mg tab, 0.5 mg/ m l in 1 ml and 5 ml inj.

DISTINON, MYESTIN 60 mg tab; 1-3 tab TDS.

Anticholinesterases are easily available and extensively used as agricultural and household insecticides; accidental as well as suicidal homicidal poisoning is common. Symptoms: Irritation of eye, lacrimation, salivation, sweating, copious tracheo-bronchial secretions, miosis, blurring of vision, breathlessness, involuntary defecation and urination. Fall in BP, bradycardia or tachycardia, cardiac arrhythmias, vascular collapse. Muscular fasciculations, weakness, respiratory paralysis (central as well as peripheral). Excitement, tremor, ataxia, convulsions, coma and death. Death is generally due to respiratory failure

Treatment : Termination of further exposure to poison Maintain positive pressure airway Supportive measure to control BP Specific antidote: Atropine 2 mg i.v. and cholinesterase reactivators (pralidoxime: (NEOPAM, PAM-A IN by s.g.pharma. 500 mg/20 ml infusion, LYPHE 1 g/vial for inj . By neon laboratories)

1.

2. 3.
4.

5. 6. 7.

As miotic In glaucoma : pilocarpine and physostigmine To reverse the effect of mydriatics after refraction testing. To prevent formation of adhesions between iris and lens or iris and cornea Myasthenia gravis: neostigmine Postoperative paralytic ileus/urinary retention: 0.5-1 mg s.c. neostigmine Postoperative decurarization: Neostigmine 0.5-2.0 mg i.v. Cobra bite Belladona poisoning: Physostigmine 0.5-2 mg i.v. Alzheimers disease

Conventionally, anticholinergic drugs are those which block actions of ACh on autonomic effectors and in the CNS exerted through muscarinic receptors

Anticholinergics

Natural alkaloids (atropine , hyoscine)

Semi synthetic derivatives (homatropine, ipratropium bromide)

Synthetic compounds

Mydriatics (cyclopentolate)

Anti secretory, antispasmodics

Vasicoselective ( oxybutynin)

Quartenery compounds (propantheline)

Tertiary amines (dicyclomine)

Antipakinsonian (biperidin)

CNS: stimulant CVS:tachycardia Eye: increased i.o.t., mydriasis Smooth muscle: relaxation Glands : decreased secretions Body temperature: rises Local anesthetic :on cornea

DRUG ATROPINE

USE Antidote to anticholinesterase poisoning, mydriasis

MARKET FORMULATION ATROPINE SULPHATE: 0.6 mg/ml inj , 1% eye drop/ointment; ATROSULPH 1 % eye drop, 5% eye oint Hyoscine hydrobromide: 0.30.5 mg oral, i.m.; also as transdermal patch. B USCOPAN 1 0 mg tab., 20 mg/ml amp.

HYOSCINE

Motion sickness

HYOSCINE BUTYLBROMIDE

esophageal and gastrointestinal spastic conditions.

ATROPINE METHONITRATE

abdominal colics and hyperacidity.

MYDRlNDON 1 mg (adult), 0.1 mg (child) tab; in SPASMOLYSJN 0.32 mg tab; IPRA VENT 20 )lg and

IPRATROPIUM BOMIDE

COPD

PROPANTHELINE OXYPHENONIUM

peptic ulcer and gastritis. peptic ulcer and gastrointestinal hypermotility

PROBANTHINE 15 mg tab. ANTRENYL 5, 10 mg tab.

CLIDINIUM

gastritis, irritable bowel syndrome, colic peptic ulcer

In SPASRIL, EQUIREX 2.5 mg tab with chlordiazepoxide 5 mg. NORMAXIN 2.5 mg with dicyclomine 10 mg with chlordiazepoxide 5 mg
In STELABID, GASTABID 5 mg tab. with trifluoramine 1 mg. GLYCO-P 0.2 mg/ml amp., 1 mg in 5 ml vial, PYROLATE 0.2 mg/ml, 1 ml, 10 ml amp

ISOPROPAMIDE

Git problems

GLYCOPYRROLATE

Pre anesthetic medication

DICYCLOMINE

Antispasmodic, antiemetic

CYCLOMINOL, 20 mg tab., 10 mg/ml liquid; DICLOMIN 10 mg, 20 mg tabs, CYCLOPAM INJ. 10 mg/ml , 10 ml, 30 ml amp/vial, also 20 mg tab with paracetamol 500 mg; in COLIMEX 20 mg with paracetamol tab, 10 mg/ml drops with dimethicone.
OXYBUTIN CYSTRAN, OXYSPAS 2.5 mg and 5 mg tabs. HOMATROPINE EYE, HOMlDE 1%, 2% eye drops. CYCLOMID EYE 0.5%, 1 %; CYCLOGYL 1 <;, eye drops.

OXYBUTYNIN

detrusor instability, urge incontinence mydriasis

HOMATROPINE

CYCLOPENTOLATE

Mydriasis and cycloplegia

As antisecretory Pre anesthetic medication Peptic ulcer Pulmonary embolism As antispasmodic Bronchial asthma, asthmatic bronchitis,COPD As mydriatic and cycloplegic Diagnostic Therapeutic As cardiac vagolytic Central action Parkinsonism Motion sickness

The actions of cholinergic and anticholinergic drugs are just the opposite of each other. Knowing the aspects of one can help in memorising the affects of the other category. For example: Actions on CVS: ????????? Actions on eyes:???????? Actions on glands: ?????????? Actions on visceral smooth muscles: ???????

PRESENTED BY : HIMANI MITTAL ROLL NO: 15146