Cholinergic Flashcards
Physostigmine
Carbamate (reversible competitive inhibitor of AChE)- used to treat wide angle glaucoma, can facilitate development of cataracts, enter CNS and reverse the effects of atropine and other antimuscarinics
Edrophonium
Simple competitive reversible inhibitor of AChE- used to test of myasthenia gravis
Neostigmine
Carbamate- treatment for myasthenia gravis and loss of tone in GI tract and bladder
Pyridostigmine
Carbamate- used in myasthenia gravis and prophylactic to nerve gas exposure
Organophosphates (‘irreversible’ inhibitors of AChE)
Ecothiophate- only clinically useful one, used to treat glaucoma
Malathion/parathion- farm insectacides
Sarin/soman- nerve gas
Donepezil/rivastigmine
Galamantine
Orally active cholinesterase inhibitors used in the treatment of Alzheimer’s
Atropine
Muscarinic antagonist. Long-lasting mydriasis which is used for opthalmoscopic examination (now other agents are preferred). It is also used as a “pharmacological patch” to treat amblyopia.
Cycloplegia – used in children to permit accurate determination of refractive errors.
Sinus bradycardia and atrioventricular block
Reduction of salivary and respiratory secretions, thereby preventing airway obstruction in
patients receiving general anesthesia (now other agents are preferred)
Intestinal spasms and pain. Reduction of gastric acid secretion (now other agents such as proton pump inhibitor and histamine receptors blockers are preferred)
Reversal of muscarinic or acetylcholinesterase inhibitor poisoning.
Prevention of muscarinic side effects in patient receiving cholinesterase inhibitors for Myasthenia gravis.
Prevention of muscarinic side effects in patient receiving neostigmine to reverse
neuromuscular block (glycopyrrolate preferred)
Mixed with diphenoxylate (a mild opioid agonist). This combination known as Lomotil is used as an antidiarrheal.
Scopolamine
Muscarinic antagonist. Motion sickness; the major side effect is drowsiness. Administered as a patch.
Tropicamide, Cyclopentolate, Homatropine
Muscarinic antagonist. Fast but short acting mydriatic agents. (May be used in combination with an alpha adrenergic agonist)
Ipratropium
Muscarinic antagonist. Quaternary amine that administered by inhalation Ipratropium is used as a bronchodilator. Particularly effective for use in chronic obstructive pulmonary disease (COPD). Tiotropium - similar to ipratropium, but longer acting
Tolterodine
Muscarinic antagonist (Bladder). Management of overactive bladder with symptoms of increased urinary frequency, urgency, nocturia, and incontinence.
Thought to have fewer adverse effects such dry mouth and blurred vision.
Contraindicated for individuals with narrow-angle glaucoma
Dicyclomine
Muscarinic antagonist (GI). Relaxes intestinal smooth muscle. Used to for irritable bowl symptoms.
Benztropine
Used to relieve extrapyramidal symptoms in Parkinson’s patients or in patients taking
antipsychotics
Glycopyrrolate
Muscarinic antagonist. Low doses preferentially inhibit secretion, so the drug is used preoperatively to inhibit secretions.
Prevention of excessive generalized sweating
Prevention of muscarinic side effects in patient receiving neostigmine to reverse
neuromuscular block.
ADVERSE ACTIONS OF ANTI-MUSCARINICS
Dry mouth (xerostomia)
Blurred vision (mydriasis and cycloplegia)
Hot, flushed skin (anhidrosis and cutaneous vasodilitation)
Constipation
Difficulty in urinating
Tachycardia
CNS effects: confusion, sedation, delirium
(“Dry as a bone; red as a beet; hot as a hare; blind as a bat; mad as a hatter”)
CLASSES OF OTHER DRUGS IN WHICH SOME MEMBERS HAVE ANTI-MUSCARINIC ACTIVITY (THIS IS IMPORTANT)
Antihistamines (eg. diphenhydramine) Antidepressants - tricyclics (eg. amitriptyline) [unfortunately, attempted overdoses with tricyclic antidepressants are still very common] Phenothiazine antipsychotics (eg. chlorpromazine)
Hexamethonium
nACHR antagonist (ganglionic) first effective anti-hypertensive (not used anymore). Problems of poor absorption and autonomic side effects led to discontinuation of its use.
Bethanechol
Muscarinic agonist (GI). Postop/ Postpartum for bladder Promote salivation
Acetylcholine
It has limited clinical use but can be used intraocularly to produce miosis after the extraction of the lens. Also, it may be used during diagnostic coronary angiography where intracoronary injection causes vasodilation. Can be used to diagnose vasospastic angina where intracoronary injection of the acetylcholine has a direct on smooth muscle causing contraction.
Methacholine
may be used for diagnosis of bronchial hyperreactivity and asthmatic conditions, very carefully.
Carbachol
used for wide-angle glaucoma, only when other cholinomimetics are no longer effective.
Bethanechol
used postoperatively after abdominal surgery and postpartum to reduce bladder distention; alternative to pilocarpine for promotion of salivation under conditions of xerostomia
SIDE EFFECT OF CHOLINE ESTERS
sweating, cramps and diarrhea, excess salivation, decreased
pulse, etc. (DUMBELS)
CONTRAINDICATIONS FOR USE OF CHOLINE ESTERS
Asthma; may precipitate an asthmatic attack due to muscarinic-mediated bronchial contraction
Urinary obstruction
Acid-peptic disease; may induce gastric acid secretion
Pilocarpine
activates primarily muscarinic receptors. It may be used as miotic agent (eye drops; last about 1 day), particularly for wide-angle glaucoma. Narrow-angle glaucoma is a medical emergency, usually requiring surgery. Pilocarpine plus physostigmine (anti-cholinesterase) are often used initially, for immediate control of intraocular pressure, before surgery.
ATROPINE
1) Ocular effects of atropine –
A. Mydriasis - Relaxes the iris sphincter, which allows sympathetic tone to predominate on the radial muscle.
B. Blocks accommodation – Relaxes/paralyzes the ciliary muscle, which increases tension on the ligaments, thereby flattening the lens.
C. Inhibits lacrimation
2) Cardiac effects of atropine –
A. Standard doses may increase heart rate and atrioventricular conduction by blocking vagal input.
B. Very low doses may initial decrease heart rate by first blocking presynaptic receptors.
3) Respiratory effects of atropine –
A. Bronchial smooth muscle relaxation and dilation
B. Inhibit secretions
4) Gastrointestinal and urinary tract effects –
A. Reduces lower esophageal muscle tone
B. Relaxes gastrointestinal tone, (not the sphincters) prolonging intestinal transit time
C. Inhibits gastric acid secretion
D. Relaxes detrusor muscle of the bladder causing urinary retention
5) Central nervous system effects of atropine
A. Atropine and scopolamine are tertiary amines, therefore, they can be distributed to the CNS.
B. Scopolamine is generally more sedating than atropine
C. Atropine first causes stimulation, followed by a sedating effect.
D. High doses can cause confusion and/or hallucinations.
6) Other effects of atropine –
A. Inhibits sweating, possibly leading to hyperthermia which then causes cutaneous vasodilation.
Atropine uses
Long-lasting mydriasis which is used for opthalmoscopic examination (now other agents are
preferred). It is also used as a “pharmacological patch” to treat amblyopia.
Cycloplegia – used in children to permit accurate determination of refractive errors.
Sinus bradycardia and atrioventricular block
Reduction of salivary and respiratory secretions, thereby preventing airway obstruction in patients receiving general anesthesia (now other agents are preferred)
Intestinal spasms and pain.
Reduction of gastric acid secretion (now other agents such as proton pump inhibitor and histamine receptors blockers are preferred)
Reversal of muscarinic or acetylcholinesterase inhibitor poisoning.
Prevention of muscarinic side effects in patient receiving cholinesterase inhibitors for Myasthenia gravis.
Prevention of muscarinic side effects in patient receiving neostigmine to reverse neuromuscular block (glycopyrrolate preferred)
Mixed with diphenoxylate (a mild opioid agonist). This combination known as Lomotil is used as an antidiarrheal.
Scopolamine
Motion sickness; the major side effect is drowsiness. Administered as a patch.
Tropicamide, Cyclopentolate, Homatropine
Fast but short acting mydriatic agents. (May be used in combination with an alpha adrenergic agonist)
Ipratropium
Quaternary amine that administered by inhalation
Ipratropium is used as a bronchodilator. Particularly effective for use in chronic obstructive pulmonary disease (COPD).
Tiotropium - similar to ipratropium, but longer acting.
Tolterodine
Management of overactive bladder with symptoms of increased urinary frequency, urgency, nocturia, and incontinence. Thought to have fewer adverse effects such dry mouth and blurred vision.
Contraindicated for individuals with narrow-angle glaucoma
DICYCLOMINE
Relaxes intestinal smooth muscle. Used to for irritable bowl symptoms.
Glycopyrrolate
Low doses preferentially inhibit secretion, so the drug is used preoperatively to inhibit secretions.
Prevention of excessive generalized sweating
Prevention of muscarinic side effects in patient receiving neostigmine to reverse neuromuscular block
Benztropine
Used to relieve extrapyramidal symptoms in Parkinson’s patients or in patients taking antipsychotics
ADVERSE ACTIONS OF ANTI-MUSCARINICS
Dry mouth (xerostomia)
Blurred vision (mydriasis and cycloplegia)
Hot, flushed skin (anhidrosis and cutaneous vasodilitation)
Constipation
Difficulty in urinating
Tachycardia
CNS effects: confusion, sedation, delirium
(“Dry as a bone; red as a beet; hot as a hare; blind as a bat; mad as a hatter”)
CLASSES OF OTHER DRUGS IN WHICH SOME MEMBERS HAVE ANTI-MUSCARINIC ACTIVITY
Antihistamines (eg. diphenhydramine)
Antidepressants - tricyclics (eg. amitriptyline) [unfortunately, attempted overdoses with
tricyclic antidepressants are still very common]
Phenothiazine antipsychotics (eg. chlorpromazine)
Action of Nicotine
Stimulation of autonomic ganglia followed by ganglionic blockade (dose-dependent)
Stimulation of adrenal medulla (possible significant secretion of epinephrine)
Stimulation of CNS: alerting response; change in respiration
nicotine toxicity
Gastrointestinal – nausea, vomiting, salivation, diarrhea
Cardiovascular – tachycardia/bradycardia, hypertension/hypotension, arrhythmia
CNS – lethargy, confusion, seizures, coma
Peripheral nervous system – diaphoresis,
Muscles - tremors, fasiculations, weakness, paralysis
Endocrine – increased epinephrine release
MECAMYLAMINE
Antagonist at nAChR at ganglion. Improve GI absorption,
Tourette’s syndrome
HEXAMETHONIUM
Antagonist at nAChR at ganglion. Prevents baroreceptor reflex
Mecamylamine
nAchR antagonist (ganglionic)l. Can be used to improve gastrointestinal absorption. Recent interest in its use for Tourette Syndrome.
Methacholine
Muscarinic agonist. Test for bronchial hyperreactivity (carefully; dangerous drug)
Carbachol
AchR agonist. Wide angle glaucoma (second-or third-line)
Pilocarpine
Partial muscarinic agonist. Miotic agent for wide-
angle glaucoma; also used with acetylcholinesterase inhibitor for emergency treatment of narrow-angle glaucoma; Promote salivation
