Cholinergic Agonists Flashcards
Direct Acting Cholinergic Agonists MOA
1) muscarinic receptor agonists
- choline esters, pilocarpine
2) nicotinic receptor agonists
- nicotine
Indirect Acting Cholinergic Agonists MOA
1) Inhibitors of cholinesterases
- carbamates, organophosphates
2) Stimulators of ACh release
- Black Widow Spider venum, metoclopramide (GI drug)
Choline Esters
“the ABCs of cholinergics”
=direct acting structural analoges of ACTH
Acetylcholine (Miochol)- miotic eye surgery
Bethanechol (Urecholine)- bladder, paralytic ileum
Carbachol (Miostat)- constant miosis, glaucoma (long acting)
Methacholine (Provocholine)- used to access bronchial hypersensitivity in asthma
Choline Esters MOA
Direct activation of cholinergic receptors.
- muscarinic activity
Choline Esters Effects
DUMBELS
diarrhea, urination, miosis, bradycardia, excitation of SKM, lacrymation, salivation/sweating
Natural Alkaloids
Muscarine and Pilocarpine
Muscarine Intoxication
wild mushrooms!
-accidental intoxication- abdominal cramping, tightness in chest, over secretion
rx for intoxication: pump stomach, atropine (muscarinic antagonist)
Pilocarpine Uses
1) xerostomia
(dry mouth- to induce salivation) and
2) glaucoma
(to induce outflow of aqueous humor, thus, reducing intraocular pressure).
Uses of Muscarinic Agonists
eye surgery glaucoma nonobstructive atony of the bladder paralytic ileus xerostomia diagnosis of bronchial hyper-reactivity
Contraindications of Muscarinic Agonists
peptic ulcers - (stimulate acid secretion)
bronchial asthma- (worsens constriction)
hyperthyroidism- (can cause arrhythmia)
Cholinesterase Inhibitors MOA
Inhibit AChE and pChE -> prevents the destruction of ACh
Carbamate esters
Bind to active site of AChE enzyme -> preventing binding of ACh
Edrophonium
Binds reversibly to AChE -> preventing access by ACh
Organophosphates
“IRREVERSIBLE”
= phosphorylate AChE => extremely stable and hydrolyzed at very slow rate.
Undergoes AGING- (breaking of one of the oxygen-phosphorus bonds of the inhibitor) further strengthening the phosphorylated enzyme.
Name Four Reversible ChE-Inhibitors
Physostigmine- Crossed BBB
Edrophonium- short acting
Pyridostigmine- long acting
Neostigmine
Uses for Reversible ChE-Inhibitors
Paralytic ileum/neurogenic bladder
Glaucoma
Myasthenia Gravis
Reversal of N-M blockade (used by anesthesiologists)
Anti-muscarinic Drug Intoxication Rx
Alzheimer’s Disease- Donepezil (Aricept), Rivastigmine
Name Three Organophosphates
Echothiophate- eye drops
Malathion/Parathion- agricultural pesticides
Soman/Sarin- warfare
Toxicities of ChE Inhibitors
DUMB BELS bronchoconstriction miosis excessive secretions diarrhea urinary incontinence, alterations in heart rate and blood pressure tremors, convulsions
Antidotes to organophosphates
1) Atropine- blocks muscarinic effects
2) Pralidoxime- cholinesterase reactivator. Must be used before aging takes place!
3) Benzodiazepines (lorazepam)- reduce or prevent seizure activity
Nicotine MOA
Binds to α - subunits of nicotinic receptors -> increase in Na+ influx.
Nicotine Effects
CNS- increased focus, tremors, seizures
CVS- sympathomimetic effects
GI- increased acid secretion and motility
Nicotine Pharmacokinetics
HIGHLY LIPID Soluble
Well absorbed from all routes of administration
Nicotine: Acute intoxication
ie. sprayed pesticide or too many nicotine patches.
- Respiratory failure, cardiovascular collapse, nausea, vomiting, headache, dizziness, palpitations, and convulsions
Nicotine: Chronic intoxication
- Tolerance and physical dependence.
- Respiratory disease, cardiovascular disease and cancer
Nicotine Uses
Smoking cessation
Nicotine gum, inhaler, nasal spray, transdermal patch
Drugs used for smoking cessation
- Nicotine replacement (patches, gum, etc)
- Bupropion (Zyban)= antidepressant
- Varenicline (Chantix)= direct acting nicotinic partial agonist
