Cholinomimetic Agents Flashcards
Define cholinomimetic agent
Nonaceytlcholine compounds that mimic actions of acetylcholine.
How do cholinomimetic agents act on the body?
- As stimulants (DIRECT AGONIST): Directly binding to ACh receptors
- As cholinesterase inhibitors (indirect agonist):
Indirect cholinergic action by preventing breakdown of ACh
or-if ACh doesn’t get broken down, stays around longer in synapse and allows it to continue to produce cholinergic actions.
What are the two groups of direct acting cholinomimetics?
- Esters of choline (acetylcholine)
2. Alkaloids (muscarine and nicotine)
T/F Quarternary Ammoniums are Hydrophobic?
F. Quarternary Ammoniums aka choline esters are Hydrophillic and poorly penetrate into CNS
What are Quaternary ammonium hydrolyzed by?
Acetylcholinesterase (AChE). The variance of the rate of hydrolysis effects the half-life of the drug.
What do variations in chemical structure alter in regards to quaternary ammoniums?
Potency, and susceptiblity to hydrolysis by AChE
What are 4 examples of cholinomimetic alkaloids
- Muscarine
- Pilocarpine
- Nicotine
- Lobeline
T/F cholinomimetic alkaloids are poorly absorbed after oral administrations?
F. cholinomimetic alkaloids are well absorbed after oral administration.
T/F cholinomimetic alkaloids have a large volume of distribution?
T. The lipid soluble characteristic of alkaloids allow for a large volume of distribution (typically the structure is tertiary amine-but can be quaternary as well)
T/F cholinomimetic alkaloids are able to cross the blood brain barrier into CNS
T The lipid soluble characteristic of alkaloids allows it to cross the blood-brain barrier into the CNS (including muscarine)
T/F cholinomimetic alkaloids are susceptible to AChE
F cholinomimetic alkaloids are not susceptible to AChE-they rely on other mechanisms of metabolism
What is the indirect action of cholinomimetics?
Normally the action of ACh is terminated by AChE. Indirect cholinomimetics inhibit AChE therefore prolonging the presence and actions of ACh at all ACh receptors (M,N,NMJ and brain)
What are the 3 chemical groups of AChE inhibitors? (continuum)
- Simple alcohols-bind weakly and reversibly to AChE (shorter half life <10 minutes)
- Carbamate esters-Bind reversibly but tighter (extends 1/2 life 30 min to 6 hours)
- Organophosphates-Covalent binding is extremely stable (nearly irreversible) creates a very long half-life of hundreds of hours.
What organs do cholinomimetics effect regardless of direct or indirect status?
Eye
Respiratory system
GI tract
GU tract
How do cholinomimetics effect the eye?
- miosis-pupillary constriction
2. accommodation
What role do muscarinic agonists and AChE inhibitors play in intra-ocular pressure?
Muscarinic agonists and AChE inhibitors REDUCE intra-ocular pressure in narrow and wide angle glaucoma by allowing the the outflow of aqueous humor. (drugs: pilocarpine, physostigmine)
What effect do cholinomimetics have on the respiratory system?
Cause contraction of smooth muscle in bronchial tree, and stimulates secretions form tracheobronchieal mucosa (obviously we wouldn’t WANT to do this).
What are the cholinomimetic effects on the GI tract?
Increased secretory and motor activity in the gut (fight or flight).
stims-salivary,gastric glands, pancreas, and small intestine
increases peristalsis
relaxes most GI sphincters
What are cholinomimets used to achieve in GI disorders
Agents can be used to correct depressed smooth muscle activity and increase motility: Post operative ileus, and congenital megacolon. (neostigmine)
What effect do cholinomimetics have on the GU tract?
Trigger voiding of the bladder.
What are the clinical uses for cholinomimetics?
Tx. urinary retention (meds bethenacol, neostigmine)
What organs are effected differently dependent on Direct or indirect action of cholinomimetics?
CV systems Secretory Glands CNS Peripheral NS Neuromuscular Junction
T/F We often use direct cholinomimetics as a heart medication
F. This drug increases and decreases the heart rate by reducing peripheral vascular resistance. When the drop in BP occurs as a result of vasodilation the heart compensates by increasing the HR- Because this med also decreases the heart rate by decreasing the firing at the sinoatrial node the patient will result in bradycardia and reduce cardiac output! it is unpredictable so we don’t use it as a heart medication.
T/F ACh agonist are used in cardiovascular medicine because there aren’t any other drugs that do this well.
False there are drugs that work better and more predictably and are used in CV med instead of ACh agonists.
What is the role of indirect cholinomimetics in the CV system?
Bradychardia and drop in cardiac output. AChE inhibitors allow for the parasympathetic side to overcome what happens on the sympathetic side (there are more ACh receptors on the parasymp side). this results in a modest DROP in BP
What are signs of toxicity in Muscarinic Agonists? What do you tx with?
SLUD-salivation, lacrimation, urination, defecation. TX with atropine, an anticholinergic
What are signs of toxicity of direct nicotinic agonists? What do you tx with?
CNS stim-convulsions, coma, respiratory arrest, skeletal muscle depolarization leading to blockate and resp paralysis, and HTN and cardiac arrhythmias. TX is supportive until drug is metabolized
What are signs of cholinesterase inhibitor toxicity? What is the TX?
Often related to organophosphates-DUMBBELLS- diarrhea, urination, mitosis, bradycardia, bronchoconstriction, emesis, lacrimation, salivation, sweating. TX includes
- monitor VS
- Decontaminate if possible (vomitting)
- Antidote with parenteral atropine or pralidoxime (2-PAM) which reactivated inhibited AChE before the full covalent bond forms through “aging”
