Muscarinic Agonist Flashcards
Diabetic autonomic neuropathy
- metabolic insult to nerve fibers
- neurovascular insufficiency
- autoimmune damage
- neurohormonal growth factor deficiency
Cardiovascular autonomic neuropathy
- clinically most important form
- increased risk of silent myocardial ischemia/mortality
Autonomic dysfunction with alcoholism + chronic liver disease
- autonomic, mainly vagal, nerve dysfunction is common with these two conditions
- advanced chronic liver disease characterized by peripheral arterial vasodilation + increased plasma [catecholamine].
Organism responsible for botulism poisoning
Clostridium botulinum, present in soil and water
Source of botulism poisoning
foodborne, wound borne
Action of botulism
- inhibits the release of acetylcholine
- cleaves SNARE proteins including synaptobrevin
Symptoms of botulism
weakness, trouble seeing, fatigue, trouble speaking
Graves disease description
- autoimmune disease
- thyroid stimulating Ig
- stimulate secretion of Thyroxine(T4) and Triiodothyronine(T3)
Symptoms of Grave’s disease
- mimic hyperadrenergic state
- feeling hot
- excessive sweating
- irregular heartbeat/tachycardia
- diarrhea/hyperdefecation
- dry eyes
- weight loss
- hypertension
Treatment of Grave’s disease
- treatment with Beta-blocker
- contraindication for use of muscarinic agonists
Relationship between thyroid and adrenal
- adrenal gland activation(stress) => glucocorticoids inhibit enzyme that converts T4 to T3.
- interaction between PANS, SANS, and Thyroid function
Reduced body weight and its action on thyroid and adrenal
- T3 decrease
- SANS decrease
- PANS increase
Elevated body weight and its action on thyroid and adrenal
- T3 increase
- SANS increase
Hypothyroidism
- desensitization of adrenergic receptors
Hyperthyroidism
- sensitization of adrenergic receptors
Undiagnosed hypothyroidism
- iodine deficiency
Hashimoto’s disease
- autoimmune disease
- Abs attacks thyroid
Symptoms of hypothyroidism
- cold
- dry skin
- constipation
- slowed heart rate
- weight increase
- hair loss
Cholinergic stimulation on Urinary tract
- increase ureteral peristalsis
- decrease bladder capacity
- increase voiding pressure
Cholinergic stimulation on Blood pressure
- increase blood pressure
Cholinergic stimulation on GI
- increase GI tone
- contractility
- increased secretory activity
Cholinergic stimulation on Respiratory
- bronchoconstriction
- mucus secretion
- increase secretion from all glands including salivation, sweat, lacrimal, digestive, tracheobronchial
Cholinergic stimulation on Eye
- miosis
- drainage of anterior chamber
Cholinergic stimulation basic two drugs
- acetylcholinesterase inhibitors
- muscarinic agonists
Muscarine and muscarinic receptors
- aminita muscaria : kills flies
- contains alkaloid muscarine
- first parasympathomimetic
- can cross BBB and cause convulsions
Direct acting cholinergic receptor agonists are?
Esters
Molecular description of cholinergic receptor agonist
- polarity(quartanary ammonium)
- limited CNS distribution, and GI absorption
4 drugs of the direct acting cholinergic receptor agonist
acetylcholine carbachol methacoline(provocholine) bethanechol(urecholine) muscarine pilocarpine
Cholinergic agonist OD risk by acting on nicotinic receptors
acetylcholine
carbachol
methacholine
Short acting cholinergic agonist
acetylcholine
methacholine
Methacholine and Asthma/COPD diagnosis
- use to diagnose bronchial hyperreactivity
- bronchial challenge test
- respond to lower drug dose
Open/narrow angle glaucoma
- clogged trabecular meshwork
- slow progression
Closed-angle glaucoma
- iris and ciliary body block the canal of schemm and trabecular network
- fast progression
Treatment for open/narrow angle glaucoma
Tinolol (Beta-blocker)
-stretch open meshwork
Action on closed angle glaucoma
M3 contraction to pull ciliary body away
Muscarinic agonists for treatment of glaucoma
Carbachol
Pilocarpine
Carbachol description
- primarily used for glaucoma
- 2 to 5min onset, 4-8hr duration
- longer acting than pilocarpine
Pilocarpine description
- relieves block of canal of schlemm
- partial agonist (less headache)
Adverse effects of pilocarpine
- sweating, salivation, diarrhea, bronchial mucus secretion
- bronchospasm, bradycardia, vasodilation
- miosis; blurred vision, impaired night vision
- reduced BBB function; epilepsy
Bethanechol description
- muscarinic selective
- orally or subQ
Contraindications of Bethanechol
- urinary retention; avoid use in bladder outlet obstruction(bladder stone, prostate hyper. tumor)
- post operative ileus(GI atony)
Cevimeline and pilocarpine description
- xerostomia(dryness of mouth)
- following head/neck irradiation
- sjogren’s disease/syndrome
Nicotine description
- full agonist
- protonated at acidic pH
- absorbed in mouth and lung
Side effects of nicotine
- irritation at site
- fast/irregular heart beat
- difficulty breathing
Contraindication of nicotine
cardiovascular disease
Varenicline(chantix) description
- alpha4beta2 nicotinic receptor partial agonist
- activates nicotine receptor much less than nicotine
- blocks nicotine from binding
- well tolerated
Side effects of varenicline
- GI related
- nausea, constipation, gas, vomiting
- altered dreams
