INDIRECTLY ACTING

CHOLINERGIC DRUGS
DR PRIYANKA BNYS
DEPT OF PHARMACOLOGY
ANTICHOLINESTERASE
• Drugs which inhibits enzyme cholinesterase
• Inhibit acetyl co-A & butyryl co-A
• They are either esters of carbamates or derivatives of phosphates
MECHANISM OF ACTION
Anticholinerase
Binds with AchEs & inactivate them

Ach is not hydrolysed & gets accumulated

• Ach contains anionic & esteric site
PHARMACOLOGICAL ACTIONS
• Actions similar to cholinergic stimulation, since they accumulate Ach
• Lipid soluble compounds
• Well absorbed & reach CNS
• Both central & peripheral effects
• EX – Physostigmine, Organophosphates
• Quarternary ammonium compounds
• Poorly absorbed in Gut
• Does not cause BBB
• Mostly peripheral effect
• EX – Neostigmine
• Stimulate both sympathetic & parasympathetic ganglia

• CVS – parasympathetic ;
• bradycardia,hypotension,negative ionotropic effects, fall in cardiac output
• High dose – BP increases due to symp. Stimulation
• GIT , Respiratory tract,Eye – similar to choinomimetics
• In higher dose, can cause convulsions followed by coma and
respiratory arrest.
• At NMJ,
• low dose- Increase force of contraction;
• large dose cause persistent depolarization and result in paralysis
 1. PHYSOSTIGMINE :
• Alkaloid obtained from plant Physostigma venenosum
• Lipid soluble, tertiary ammonium compound
• Better penetration into tissues; Crosses BBB
• Available for IV injection, as 0.1 – 1% eye drops, and in combination with pilocarpine
nitrate 2%

USES :
• GLAUCOMA – As eyedrops;
• POISONING - Atropine & Tricyclic antidepressant poisoning; 0.5 mg oral or 0.5 mg IV
 2. NEOSTIGMINE :
• Synthetic quarternary ammonium compound;
• Poorly absorbed from Gut; does not cross BBB
• USES :
• Myasthenia gravis
• Post operative paralytic ileus
• Atony of urinary bladder
• Enhance skeletal muscle strength and force of contraction in Myasthenia
Gravis
• By Anticholinesterase activity; by direct stimulation of nicotinic Nm
receptor; By enhancing release of Ach amount during each potential.
DOSE : 15- 30 mg TDS- QID PROSTIGMIN; MYOSTIGMINE- 15 mg tab 0.5
mg/ml inj
• 3. PYRIDOSTIGMINE –
• Similar to neostigmine; Longer acting ; used in Myasthenia gravis
• DOSE :60-180 mg TDS; Myestin 60 mg tab

• 4. AMBENONIUM – Longer acting congener of Neostigmine

• 5. EDROPHONIUM –
• Quarternary ammonium compound; binds only to anionic site
• Rapid and short acting (10- 20) mins
• USES – Diagnosis of Myasthenia gravis; IV in snakebite; Curate poisoning

• 6. RIVASTIGMINE -
• Longer acting carbamate
• Selectively bindsto Ach in brain
• Lipid soluble- Rapidly absorbed , reaches brain and augments cholinergic transmission in brain
• USES- RXx of Mild to moderate Alzheimer’s disease
• Start with 1.5 mg BD dose & gradually increase at two weeks interval to a maximum of 6 mg BD
• Exelon 1.5,3,4,5 & 6 mg tab
 7. TACRINE :
• Lipophilic acridine, enhances Ach level in brain
• Uses – Alzheimer disease
• Hepatotoxic

8. GALANTAMINE :
• Similar to rivastigmine with good oral bio availability of 90 %
• Dose – 8-6 mg BD in Alzheimer
• GALAMER 4 mg Tab
USES :
1. AS A MIOTIC :
• Physostigmine causes miosis, spasm of accommodation and decrease in IOP
2. MYASTHENIA GRAVIS
• Improve muscle strength & symptomatic improvement
3. POISONING DUE TO ANTI CHOLINERGIC DRUGS :
• Physostigmine – Atropine poisoning
• Poisoning of Other drugs like phenothiazines, tricyclic anti depressants, anti histamines
4. CURARE POISONING
• Neostigmine & Pyridostigmine can be used
• Though edraphonium is fast acting, it is less effective than neostigmine
5. POSTOPERATIVE PARALYTIC ILEUS & URINARY RETENTION
• Neostigmine – 0.5- 1mg subcutaneously
6. COBRA BITE
• Cobra venom – neurotoxin; Cause skeletal muscle paralysis
• IV Edraphonium prevents repiratory paralysis
7. ALZHEIMER DISEASE – Tacrine not preferred,because it will cause hepatotoxicity
 IRREVERSIBLE ANTICHOLINESTERASE
• Organophosphorous compounds – Powerful inhibitors of AchE enzyme ; Binding is stable by covalent bonds
• Binds only to esteric site and it is phosphorylated
• Effects similar to Cholinergic stimulation as Ach accumulates in all tissues
• Except echothiophate all are lipid soluble , absorbed from all routes including intact skin
• USES :
• Glaucoma,- Echothiophate eye drops

ORGANOPHOSPHOROUS POISONING :
• ACUTE TOXICITY – occupational, accidental or suicidal
• Symptoms result from muscarine and nicotinic and central effects
• SYMPTOMS :
• Vomiting, Abd . Cramps, Diarrhoea, Miosis, Sweating, increased salivary,tracheobronchial and gastric secretions
& bronchospasm, hypotension, muscular twitchings, weakness, convulsions, coma
• Death due to respiratory paralysis

TREATMENT :
• Remove clothes, wash with soap; Orally means, gastric lavage must be given
• Adapt prone position to avoid aspiration of secretions; Maintain BP & patent airway
• IV Atropine 2 mg every 10 mins till pupil dilates;Upto 50- 100 mg;
• Continuous monitoring, because of reappearance of symptoms due to delayed absorption
• Cholinesterase reactivators –Pralidoxime,obidoxime,diacetylmonoxime
CHRONIC ORGANOPHOSPHOROUS TOXICITY :
• OP Compounds – Produce neurotoxicity(poly neuropathy0 several days after exposure
• Symptoms – weakness, fatigue, ataxia sensory disturbance, muscle twitching, flaccid paralysis,