Lecture 12: Cholinergic Agonists Flashcards
Describe cholinergic transmission
- ACh synthesized from choline and acetyl CoA
- Stored in vesicles
- Depolarization and influx Ca2+ causes vesicular fusion and release
- Stimulates cholinergic or muscarinic receptors
- Alters target cell function
- Hydrolyzed by AChE and endocytosed
What receptor does Bethanecol target
M receptor agonist
T or F: all uses for Bethanecol are extra label
True
What are the indications for use for Bethanecol
- GI and bladder atony in cats, dogs and maybe horses
- Cecal displacement in cows
- Equine gastric ulcer syndrome
Why might you not want to use bethanecol to treat cecal displacement in cows
Requires compounding
What are the pharmacodynamics of bethanecol
Affect GI and urinary systems most strongly
M receptor agonist- direct cholinergic agonist
How is Bethanecol administered in dogs and large animals
Dogs- PO
Large animals- SQ
What are the adverse effects of bethanecol
Overextension of the therapeutic effect—-> too much GI and bladder motility
What can bethanecol cause in horses
Colic
What are some contraindications for bethanecol
- GI obstruction
- Blocked urethra
- Gastric ulcers in small mammals
- Hyperthyroidism
- Bradycardia, hypotension, vagal nerve dysfunction
- Asthma
7.epilepsy - Recent GI surgery
Why is bethanecol only contraindicated in small animals with GI ulcers but is used as a treatment for large animals
Large animals gastric pH is much higher and the purpose of increased GI motility is to remove the gastric acid. In small mammals it would just make it worse
Why is bethanecol contraindicated in hyperthyroid patients
HR for hyperthyroid patients is so high that an abrupt change can induce atrial fibrillation
what do M receptor agonists do to the respiratory system
Stimulate PNS system so bronchoconstriction
Why do you not want to use bethanecol after a recent GI surgery
Rip sutures
How do indirect cholingeric agonists like neostigmine and pyridostigmine work
Competitive antagonism with acetylcholine for acetylcholinesterase, so they tie up AChE so it will leave ACh alone and can increase its time in cleft
What are some etiologies for myasthenia gravis
- Autoimmune attack of NM receptors
- Paraneoplastic- thymoma
- Treatment with methinazole in cats with hyperthyroidism
- Congenital
What are the labeled indications for neostigmine
GI or bladder atony especially following surgery
Labeled for use in sheep, swine, cattle and horses
What is the extra label use of neostigmine
Diagnosis and treatment of myasthenia and reversal fo NMJ blockade (atracurium)
What is the absorption of neostigmine
Administered IV so 100%
What is the distribution of neostigmine
0.13l/kg in labs
What is the metabolism for neostigmine
Plasma cholinesterases and liver
What is the elimination for neostigmine and t1/2
Urinary, t 1/2- 40 seconds
What is an adverse effect of neostigmine
Cholinergic crisis
What happens during a cholingeric crisis
Decrease BP, decrease HR, bronchoconstriction
What is the labeled used for pyridostigmine bromide
Treatment of myasthenia gravis in dog
Why is pyridostigmine bromide extra label use in cats
Because myasthenia like symptoms are usually a result of treatment with methinazole for hyperthyroidism so take patient off drug and symptoms resolve
What is the absorption of pyridostigmine bromide
Not well characterized
What is the distribution of pyridostigmine bromide
1L/kg in labs
What is the metabolism of pyridostigmine bromide
Plasma cholinesterases and liver
What is the elimination and t1/2 for pyridostigmine bromide
Urinary, t1/2-2 minutes
What are the adverse effects of pyridostigmine bromide
- Tolerance due to downregulation of Nm receptors so must increase dose
- Intussusception- usually a result of high doses
What do cholinergic agonists do to heart, lungs, GI, eyes, GU and vasculature
Heart: decrease HR
Lungs: bronchoconstriction
GI: increase motility
Eyes: miosis, tear formation, decrease IOP
GU: relax sphincter and contract fundus to promote urination
Vasculature: direct acting agonist act on M receptors in vasculature and decrease BP via vasodilation
