Cholinergics and Anticholinergics Flashcards
What aids in the release and Acetycholine?
ChAT- choline acetyltranferase
VAMP- vescicle- associated membrane proteins
SNAP- synaptasome-associated proteins
AchE- Acetylcholinesterase
Cholinergic agents
AKA cholinergic agonists, parasympathomimetics, cholinomimetics
Mimics Acetylecholine (ACh)
Cholinoceptors
Mediates the parasympathetic activity
Muscarinic and nicotonic receptors
M1 receptor
Nerves, CNS, ENS
Pirenzepine and telezepine
Pirenzepine
Inhibits gastric acid secretion and reduces muscle spasm
Treatment of peptic ulcers
Chronic obstructive pulmonary disease
Telezepine
More potent inhibitor of gastric acid than pirenzepine
Treating peptic ulcers in humans
M2 receptor
Heart, nerves, smooth muscle (cardiac M2)
Tripitramine and methoctramine
Tripitramine
Selective antagonist for M2 receptors
Blocks cholinergic bradycardia
Methoctramine
Cardiac M2 muscarinic receptor antagonist
M3 receptor
Other visceral organs: bladder constriction, bronchoconstriction, increases exocrine gland secretion, increases gut motility, miosis via pupillary sphincter
Darifenacin and solifenacin
Darifenacin
Selective antagonist of M3 receptor
Treatment of overactive bladder
Solifenacin
Selective M3 receptor antagonist
Urinary antispasmodic, treatment of overactive bladder
Direct acting cholingeric stimulants
Acts directly on cholinergic receptors
Cholingeric (muscaneric) agonists
Includes cholinesters (acetylcholine, methacholine, bethanechol, carbachol) and alkaloids (muscarine and pilocarpine)
Indirect acting cholinergic stimulants
Inhibits the breakdown of AcH by inhibiting cholinesterase
Includes carbamates (reversible) and phosphates (irreversible)
Why is ACh administration difficult in clinics?
Non selective (acts everywhere)
Rapidly deactivated (AChE and short half-life)
Cholinesters and natural alkaloids
Absorption: polarity dependent, IV IM and SQ for local effects
Metabolism: AChE dependent
Therapeutic uses for muscarinic agonists
Treatment of urinary bladder disorders, xerostomia (dry mouth), diagnosis of bronchial hyperreactivity, opthalmology , glaucoma treatment
Pharmacological effects that AcH has on the cardiovascular system
Inhibitory effects:
Vasodilation
Decrease in HR, conduction velocity in AV node and force of cardiac contraction
Pharmacological effects that AcH/ cholinergic drugs has on the GI tract
Excite the smooth muscles of the GI tract
Increased activity, motility, secretion and urinary frequency
Pharmacological effects that AcH/ cholinergic drugs has on the eye
Miosis (constriction) and decreased intraocular pressure
What overall effects does does AcH/ cholinergic drugs have on the body
Increased secretion from every body system
Increased salivation and sweating
Pharmacological effects that AcH/ cholinergic drugs has on the respiratory tract
Increases parasympathetic activity (bronchocontriction)
Increased tracheobronchial secretion and stimulation of the chemoreceptors of the carotid and aortic bodies
Effects of recommended doses of cholinergic drugs
Affects muscarinic receptors
Desired effects are primarily due to muscarinic receptor stimulation
Effects of high doses of cholinergic drugs
Stimulates the nicotonic receptors
Undesirable effects due to stimulation of nicotinic receptors (toxic)
Adverse reactions of cholinergic drugs
Overstimulated effects of cholinergic system
Salivation, lacrimation, urination, defecation, gastrointestinal cramps and emesis (SLUDGE)
Contraindications of cholinergic drugs
Bronchial asthma
Hyperthyroidism
GI or urinary tract obstruction
Myastenia gravis treated with neostigmine
Peptic ulcer disease
Severe cardiac disease
Acetylcholine uses
Rarely given systemically
Topical 1% solution for the induction of miosis during ophthalmologic surgery
Methacholine uses
Diagnosis of bronchial airway hyperactivity (long acting, so not clinically used as much)
Carbacol (carbamylcholine) uses
To produce miosis in ophthalmology (after cataract surgery)
Treatment of colic and impaction of the intestinal tract
Rumen atony and impaction
Bethanechol (carbamylmethylcholine chloride; urecholine) uses
Increases tone and motility fo dilated bladder and Gi tract
Treat urinary bladder atony in cats with urolithiasis
Xerostomia
Sjogren syndrome
Pilocarpine uses
Treating glaucoma
Neurogenic keratoconjunctivitis sicca in dogs (lowering intraocular pressure)
How does pilocarpine affect the body?
Increases secretion of digestive system, peristaltic motility of GI tract, and constriction of pupil
Naturally occurring cholinomimetic alkaloids
Pilocaprine, muscarine and arecoline
Plant alkaloids that exert cholinomimetic activities with minimal activity at nicotinic sites
DON’T INHIBIT CHOLINESTERASE ENZYME
Where are the natural cholinomimetic alkaloids found?
Pilocarpine (leaves)
Arecoline (seed)
Muscarine (mushroom)
Effects of indirect acting cholinomimetics
Inactivate or inhibit the AChE
Prolonging lifetime of ACh
Anticholinesterase agents or cholinesterase enzyme inhibitors
What causes mycetism or cholinergic toxicity
Higher consumption of wild mushrooms (culinary)
Overdose of cholinergic drugs
Ex: A. muscaria and A. phalloid
Symptoms of cholinergic toxicity
Excessive sludge- excessive sweating, bronchospasm, headache, visual disturbances, abdominal colic, hypotension, shock and bradycardia
Treatment of cholinergic toxicity
Atropine: 1-2 mg IM injection to reverse symptoms
Effects of anticholingeric drugs
Bladder relaxation
Bronchodilation
Decrease exocrine gland secretion
Decrease gut motility
Mydriasis
Anticholinergics/ Muscarinic antagonists
Atropine (main) and Scopolamine- competitive inhibitors (belladona alkaloids)
Benztropine (anti)
CNS
Treats parkinsons
Ipratopium (anti)
Bronchi (bronchial smooth muscles)
Bronchodialte in asthma and COPD
Oxybutinin (anti)
GI
Treats transient cystitis and postoperative bladder
Scopolamine (anti)
CNS
Prevents motion sickness
Small animals: antispasmodic and antisecretory (diarrhea)
Horse: relax the rectum for rectal exam
Clinical uses of atropine
Pre-aesthetic to prevent/ reduce secretions
Antispasmodic of intestinal, urinary or biliary duct
Bronchodilator
Cardiac stimulant
Antidote to anticholinesterase agents
Mydriatic
Control of pain
Relief of heaves in horses
Propantheline:
Anti-secretory and antispasmodic effects treating diarrhea
Reduce colonic peristalsis in horses
Isopropamide
Provides long duration, treatment of peptic ulcers and other GI disorders involving hyperacidity
Used for antiemetic, antidiarrheal, anticholinergic and antiarrhythmic effects
Used with prochlorperazine
Glycopyrronium
Adjunct to general anesthesia
Decreases acid secretion in stomach
How do anticholineric drugs affect the CNS
Depending on the dose, drugs can cause stimulation or depression
How do anticholineric drugs affect exocrine glands
Reduce the flow of volume of secretion in the respiratory, GI and genitourinary tracts
How do anticholineric drugs affect smooth muscles
Relax smooth muscles in respiratory and GI tracts
Delay gastric emptying and decrease sophageal gastric emptying
Causes bronchial dialtion
How do anticholineric drugs affect the eye
Cause mydriasis and cycloplegia
Reversible ndirect acting cholinergic uses
Physostigme- atropine overdose
Neostigme/ pyridostogme- MG
Edrophonium- diagnose MG
Ecothiophate- glaucoma
Irreversible indirect cholinergic uses
DFP- district pupil in glaucoma
Soman, Tabun, Sarin- nerve gases
Dichlorvos- oral anthelmintic and pesticides
