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Table of Contents

Cholinergic Drugs

Content

ANS

• Cholinergic drugs

• Pharmacology of acetylcholine

• Organophosphorous poisoning and its treatment

Intended Learning Outcomes

At the end of this lecture, student will be able to

• List the cholinergic drugs

• Explain the pharmacology of acetylcholine

• Describe pharmacokinetic of Ach

• Explain organophosphorus poisoning

• Describe treatment of poisoning

Cholinergic Drugs (Parasympathomimetics)

• + effector cells innervated by cholinergic nerves

• Ester of choline

– Acetylcholine, methacholine, carbachol, bethanechol

• Cholinomimetic alkaloids

– Pilocarpine, muscarine, arecholine

• Choline esterase inhibitors (Anticholine esterase)

– Physostigmine, neostigmine, organophosphorus compounds

Pharmacological Actions of Acetylcholine

CVS

• Heart

– + vagus nerve

– Depress SA Node: negative chronotropic

– Decrease FOC: negative Inotropic

– May cause AV block

– Increase CV

• Blood vessels

– Dilate skin, mucous membrane blood vessels

– M3 – R: release NO

– Dilates coronary arteries

– Doubtful effect: cerebral, pulmonary vessels

– IV: transient flushing, sense of warmth in skin, throbbing headache

– Decrease PR – BP Falls

Smooth muscle

• GIT: increase tone and peristalsis

• Gall bladder: Contraction

• Bladder: Detrusor muscle contraction, trigonal sphincter relaxation

• Bronchial smooth muscle: constriction, bronchospasm

• Ureter: usually contraction

• Uterus: inconsistent response

Secretions

• Increase gastric, intestinal, pancreatic, bronchial, salivary, lacrimal, nasopharyngeal

• Increase bronchial secretion: accompanied by bronchospasm

• May result in cough and dyspnea

• Salivary: profuse and watery

• Sweat glands: increase sweating

Eye

• Instillation – no effect

• Intracarotid injection: miosis

• Contraction of circular muscle fibers

• Decrease IOP

• Increase the drainage of ocular fluid through canal of Schlemm

• Contraction of ciliary muscle

• Relaxation of suspensory ligaments

• Lens bulge into the anterior chamber

• Increase thickness, decrease focal length

• Vision fixed for short-distance

• Spasm of accommodation

Autonomic ganglia

• Ach+ ganglia

• Post ganglionic site: Increase NA/ Ach

• NA: BP- Peripheral vasoconstriction

• Large dose: Adrenal medulla +

• Sustained increase in BP

Myoneural Junction

• Contraction of skeletal muscle

• High conc: paralysis by persistent depolarisation

Miscellaneous

• Essential for normal behaviour and cognition

• Does not cross BBB

Uses

• Extreme transient action

• Not used in clinical practice

• Substitutes : Effective orally

• More selective in actions

Cholinergic Drugs

Cholinomimetic alkaloids

• Pilocarpine (P. microphyllus, P. jaborandi)

• Muscarine (Amanita muscaria)

• Arecholine (Areca catechu)

• Cevimeline

– M3 agonist

– Incerase salivary and lacrimal secretion

– Used in dry mouth

Choline esterase inhibitors (Anticholine esterases)

• Inhibits true and peudo choline esterase

• Prevent inactivation of Ach

Reversible choline esterase inhibitors

• Natural: Physostigmine

• Synthetic: Neostigmine, pyridostigmine, ambenonium, demecaium, edrophonium, tacrine, rivastigmine

Irreversible choline esterase inhibitors

• OPC

• Useful: Di isopropyl fluorophosphate, metrifonate, echothiophate

• Insecticides: Fenthion, malathion, sumithion, monocrotophos, octamethyl pyrophosphotetramide

Uses of reversible Anti ChE

• Glaucoma

• For decurarisation, Curare poisoning

• MG

• GIT: Post-operative paralytic ileus

• Urinary retention (Rare)

• AD

• Snake venom poisoning

Irreversible Anti ChE

• Absorbed by all the routes

• Cross BBB

• Glaucoma: echothiophate

• Worm infestation: dichlorvos, dichlorofos (Not used)

• Toxicological importance

OPC Poisoning

Muscarinic effects

• Eyes: Miosis, spasm of accommodation, headache, conjunctival hyperemia

• inhalation: bronchospasm, cough, increased secretions, tightness in the chest

• Ingestion: anorexia, nausea, vomiting, abdominal cramps, tenesmus, and diarrhea

• Severe bronchospasm, pulm. edema – fatal

Nicotinic effects

• Fasciculations, twitching, generalized weakness, depolarisation type paralysis

Central effects

• Giddiness, anxiety, confusion, ataxia, hypotension, respiratory depression, convulsion, coma

• Death – due to respiratory paralysis

Neurotoxic effects

• Demyelination of nerve tracts in CNS & PNS

• Permanent functional derrangements

• Not related to ChE inhibition

• Weakness, fatiguability, twitching, loss of tendon reflexes

Treatment of acute OPC Poisoning

• Remove soiled clothes

• Wash soiled skin/ eyes

• Nurse in prone position

• Clear mouth, throat

• Insert airway/ intubate

• Gastric lavage

• Atropine in sufficient qty.

• ChE activator: Pralidoxime (1-2 g)

• Supportive measures: Oxygen, shock treatment

• Convulsion: Diazepam

• Vigilance for delayed toxicity

• Note: Mouth-to-mouth respiration to be avoided

FAQ

Are Cholinergic Drugs addictive?

Cholinergic Drugs, when used as prescribed by a healthcare professional, are generally not considered addictive. However, like many medications, dependence can develop if they are misused or abused. It’s crucial to follow the recommended dosage and consult with a healthcare provider to minimize the risk of addiction.

Can these medications improve cognitive function in healthy individuals?

While Cholinergic Drugs are primarily prescribed for treating neurological disorders, some individuals may use them off-label in an attempt to enhance cognitive function. The evidence supporting cognitive enhancement in healthy individuals is limited, and the use of these medications for this purpose should be approached with caution. Always consult with a healthcare professional before considering such use.

What are the long-term effects of Cholinergic Drug use?

The long-term effects of Cholinergic Drug use can vary depending on the specific medication and individual factors. In some cases, prolonged use may lead to tolerance or diminishing therapeutic effects. Long-term use should be monitored by a healthcare provider to assess both the benefits and potential risks associated with continued medication.

How quickly do Cholinergic Drugs take effect?

The onset of action for Cholinergic Drugs varies among different medications. Some may act relatively quickly, while others may require more time to exert their effects. It is essential to follow the prescribed dosage and be patient with the treatment process. If there are concerns about the medication’s efficacy, consult with a healthcare professional.

Are there natural alternatives to Cholinergic Drugs for cognitive enhancement?

Yes, several natural alternatives are believed to support cognitive function. These include a healthy diet rich in antioxidants, regular exercise, and sufficient sleep. Additionally, certain supplements like omega-3 fatty acids and vitamins may contribute to cognitive well-being. However, always consult with a healthcare provider before incorporating any supplements into your routine.

Can Cholinergic Drugs be used to treat Alzheimer’s disease?

Cholinergic Drugs, such as acetylcholinesterase inhibitors, are commonly prescribed to manage symptoms of Alzheimer’s disease. These medications aim to enhance acetylcholine levels in the brain, which can temporarily improve cognitive function in individuals with Alzheimer’s. However, they do not cure the disease, and their effects may vary from person to person.