Cholinergic Agonists & Antagonists Flashcards
Muscarinic Agonist Prototype
Acetylcholine
Acetylcholine - Pharmacokinetics
(+) charge, does not cross BBB
short duration of action
non-selective
Acetylcholine effects on vascular system
vasodilation - stimulate M3 receptors on vascular endothelium, releases NO, diffuses into vascular smooth muscle cells, causing relaxation
Acetylcholine effects on cardiac system
(-) chronotropic effect (m2 mediated)
(-) inotropic effect (calcium mediated)
(-) conduction velocity
In the presence of atropine, ACh-induced stimulation of sympathetic ganglia can be observed as…
atropine selectively inhibits muscarinic receptors, so we see vasoconstriction and increased HR
Effect of ACh for ophthalmic use
produces rapid and complete miosis
ciliary muscle contraction –> open trabecular meshwork –> increase aqueous humor to reduce IOP
Acetylcholine (drug) adverse effects
bradycardia, hypotension
General properties of all synthetic choline esters/cholinomimetic alkaloids
more selective and prolonged action than ACh
esters do NOT cross BBB, alkaloids do
used for bladder disorders, xerostomia, and diagnosis of bronchial hyperreactivity, and ophthalmic indications
What is the prototype ester?
bethanechol
How is the action of bethanechol prolonged (compared to ACh)?
resistant to hydrolysis by cholinersterases
Bethanechol effect on smooth muscle
increases contraction of bladder and GI tract
Bethanechol - Therapeutic Uses
postop and postpartum urinary retention
GERD and gastric atony
The two types of esters
Bethanechol - prototype
methacholine - other
Prototype Alkaloid
Pilocarpine
Action of Pilocarpine
partial agonist of all muscarinic receptors
Pilocarpine - Admin/Use
topical admin - miosis and blurred vision of distant objects, and fall in IOP
Pilocarpine - therapeutic uses
xerostomia
wide-angle glaucoma
Alkaloid, selective M3 agonist
Cevimeline
Cevimeline affinity for cardiac M2 receptors
low
Cevimeline is usually prescribed for…
Sjogren’s Syndrome
Longer duration and fewer side-effects, pilocarpine or cevimeline?
Cevimeline
Toxicity indications for muscarinic agonists
sweating
hypotension
GI effects
Contraindications for muscarinic agonists
hyperthyroidism
asthma
peptic ulcer
Muscarinic agonist antidotes
atropine
epinephrine
Muscarinic Antagonist Prototype
atropine
Chemical classification of atropine
belladonna alkaloid
Atropine - MOA
competitive blockade of muscarinic receptors
- produces opposing effect of muscarinic receptor
- super high doses –> nicotinic blockade too
- no muscarinic selectivity
Atropine - Pharmacokinetics
cross BBB
blocks receptors in blood vessels, sweat glands, and CNS
Tissue Response is oral dose-dependent
Very low dose - salivary & bronchial secretions suppressed
low dose - mydriasis, cycloplegia, tachycardia
medium - tone/motility of GI tract and bladder reduced
high - gastric acid secretions partially reduced
Atropine - CNS effects
low dose - mild excitation
toxic dose - hallucinations, delirium resembling psychosis
Atropine - Ocular effects
mydriasis - photophobia
cycloplegia - blurred near vision
Atropine - CV effects
heart - tachy, result of blocking vagal impulses
circulation - no effect @ normal dose, flushing reaction
Atropine - respiratory effects
decreased bronchial secretions
relaxed bronchial smooth muscle
Atropine - GI effects
inhibit salivation
reduced tone/motility
partial reduction in gastric acid secretion
Atropine - therapeutic use
pre-op: reduce secretions
brady/AV block: cardiac resuscitation
mydriasis/cycloplegia (but, long duration of action)
AChE inhibitor poisoning: muscarinic effects
Atropine - Adverse effects
dry mouth, blurred vision, photophobia, tachy, GI distress, hot/dry skin, urinary retention, confusion
Atropine - Contraindication
prostatic hypertrophy and narrow-angle glaucoma
Atropine - antidote
physostigmine: elevates synaptic concentration of agonist ACh
Scopolamine
muscarinic antagonist
Scopolamine - CNS penetrance
scopolamine better at CNS penetration than atropine
Scopolamine - uses
sedative with euphoric effects
suppress emesis/motion sickness, blocks M receptors in vestibular apparatus
Scopolamine - admin route
transdermal
Ipratropium bromide drug classification
muscarinic antagonist
Ipratropium bromide - characteristics
quaternary amine
dose NOT cross BBB
Ipratropium bromide - therapeutic use
bronchodilator for COPD/asthma
ipratropium bromide - admin route
inhalation, therefore minimal systemic effects
Tropicamide - drug classification
muscarinic antagonist
tropicamide - action
used for eye surgeries and causes mydriasis and cycloplegia (SHORT DURATION OF ACTION)
Tolterodine - drug classification
muscarinic antagonist
Tolterodine - receptor target & use
non-selective muscarinic antagonist
treats OAB
Tolterodine - MOA
unclear…
believed to inhibit detrusor muscle contraction during filling
increase bladder capacity and decrease sensation of urgency (blocks basal release of ACh during bladder filling)
Tolterodine - Efficacy
modest, takes up to 4 weeks to reach full efficacy
effective in ~30% of patients & anti-ACh side effects limit dose escalation
What is a major concern associated with Tolterodine?
CNS-related anticholinergic effects, esp. problematic in cognitively-impaired geriatric patients
