Pharmacology

Muscarinic Cholinergic Agonists

Drug | Indication | General Info |

Acetylcholine | None | Nonselective actions on cholinergic receptors↓HR, ↓SV, ↓BP (when administered by injection; by acting on M3 receptors), ↑intestinal and bronchiolar secretionsDisadvantages: rapidly hydrolyzed and nonselective → many side effects |

Methacholine | Diagnostic: assess bronchiolar reactivity | Relatively selective for M receptorsCV effects if given IVBronchoconstrictor action |

Bethanechol | Atony of G-I-U smooth muscle (esp. postoperatively) | Selective for M receptorsNot hydrolyzed by aceylcholinesterase |

Carbachol | Rarely used – can be used for glaucoma (Lippincott’s) | Nonselective actions on both N and M receptorsLong-acting |

Muscarine | Not used as a drug | Naturally occurring in poisonous mushrooms |

Pilocarpine | Glaucoma (↓IOP)Xerostomia 2⁰ to Sjogren’s syndrome | Selective for M receptorsMiotic (constriction of the pupil): ↓IOP by acting on the circular muscleHas CV effectsNaturally occurring |

Cevimeline | Xerostomia | SyntheticSelective for M receptorsFewer CV effects than Pilocarpine |

* M-agonists increase: bronchospasm, GI cramps/diarrhea, miosis, sweating, urination, lacrimation, salivation, bradycardia (use caution in patients with asthma, ulcers or hypertension)

* M-agonists, when injected can cause vasodilation. Binding to endothelial cell M3 receptors can activate NO synthase which produces NO causing vasodilation.

* M1 receptors:

* Location: CNS neurons, ganglion cells near parietal cells of stomach

* Signalling: involves phospholipase C →IP3→Ca2+

* Application: Alzheimer’s Disease, ulcers (M1 antagonists used)

* M2 receptors:

* Location: heart, postganglionic nerve ending (i.e.- located on the presynaptic side), some smooth muscle

* Signalling: involves inhibition of adenylate cyclase and activation of K+ channels which allow K+ to enter and hyperpolarize the cell

* Application:...