Cholinergic Agonist Flashcards
What are the subtypes and characteristics of cholinoceptors?
Muscarinic: M1-M5
Nicotinic: Nn, Nm
Differentiate the actions of direct and indirect cholinergic agonist:
Differentiate between the two types of direct-acting cholinergic receptor agonist, alkaloid and choline esters:
Choline esters: very hydrophillic = doesn’t cross the BBB, and thus exhibits low levels of cytotoxicity. However, an excessive amount of acetylcholine must be given by IV to comepensate for the decreased distribution.
Alkaloid:
List four major direct-acting cholinergic agonists (choline esters): Acetylcholine chloride, methacholine chloride, carbachol chloride, bethanechol chloride.
Note their susecptibility to cholinesterase, muscarinic action and nicotinic actions.
Acetylcholine chloride is used as an opthalmic solution, and it stimulates the cholinoceptors in the sphincter muscle of the iris, causing the pupil to constrict.
For each non-selective direct-acting muscarinic & nicotinic receptor agonnist below, list the MOA, uses and adverse reactions:
- Acetylcholine
- Carbachol
Acetylcholine: can inhibit its own release from presynaptic nerves. systemic effects: bradycardia, hypotension, flushing, breathing difficulties, and sweating.
Carbachol: causes miosis, and a reduction of elevated IOP in patients with open-aangle glaucoma. Adverse effects inclue ocular irritation, lacrimation, blurred vision, miosis, and headaches.
For each muscarinic-selective direct-acting receptor agonnist below, list the MOA, uses and adverse reactions:
- Bethanochol
- Cevimeline (Evoxac)
- Pilocarpine
Bethanochol: directly acts on M1, M2, and M3 receptors causing increased secretion, smooth muscle contraction/relaxation of vascular smooth muscle, and changes in heart rate. It is used to treat urinary retention. Adverse reactions include muscarinic effects and bromchospasm in asthmatics.
Civemeline (Evoxac): selectively binds M3 receptors. Treatment: Xerostomia (dry eyes and mouth) in Sjogren’s syndrome. Given orally.
Pilocarpine: used in the treatment of glaucoma (both open-angle and acute angle-closure). a direct acting muscarininc (M1, M2, M3) receptor partial agonist. Used in the treatment of Sjogren’s syndrome.
What is Sjogren’s syndrme and how does it cause Xerostomia (dry mouth)? What is the drug of choice for this condition?
Sjogren’s syndrome is an autoimmune disease wherein the immune cells attack and destroy the exocrine glands that produce tears and saliva. The drug of choice for this condition is Cevimeline, which is given orally.
Note the cholinomimetic alkaloids:
- muscarine
- pilocarpine
- nicotine
- lobeline
An adverse side effect for the use of nicotine is an increased blood pressure, racing heartbeat, headache, and other sympathetic symptoms along with parasympathetic symptoms. Why are both of these symptoms expressed?
Nicotinic receptors are located at nerve ganglion and NMJ. Due to their location on nerve ganglion, both the SNS and the PNS can be affected.
What is the drug varenicline used for?
Smoking cessation. Varenicline is a partial agonist at the nicotinic receptor.
List the two direct acting cholinergic receptor agonists:
- nicotine
- Varenicline
Indirect-acting cholinomimetic agonists are similar to direct-acting cholinomimetic agonists in many area except…
Their effects on arteriolar tone and blood pressure are less pronounced due to the lack of parasympathetic innervation on vascular cells.
T or F: The drug butyrylcholinesterase important in the physiologic termination of synaptic Ach action?
FALSE, little role is played by this indirect-acting cholinomimetic drug.
What are the classes of acetylcholine esterase (AChE) inhibitors?
Acetylcholine esterase (AChE) inhibitors are divided into two main classes: Reversible and Irreversible.
Reversible: divided into two classes based on their chemical structures- Carbamates and Simple alcohols
Irreversible: Organophosphates (all)
T or F: Carbamates are readily absorbable by the body?
FALSE
The quaternary structure of carbamates renders them highly hydrophilic. Thus, large doses are required for oral administration than for parenteral injection.
What is the MOA for neostigmine?
Neostigmine is a, AChE inhibitor that not only binds to AChE, but also activates nAChRs at the NMJ and can reverse the effects of non-depolarizing neuromuscular blockade.
List the common indirectly acting cholinergic agonst. Describe their usage and duration of action:
Recall, unlike most organophosphates, Echothiophate is NOT well absorbed from the skin.
