cholinergicsVT.doc - I Cholinergic Agonists a Including both direct acting agonists and indirect acting drugs that inhibit ACHE b Learning Objectives

cholinergicsVT.doc - I Cholinergic Agonists a Including...

This preview shows page 1 - 3 out of 9 pages.

I. Cholinergic Agonists a. Including both direct acting agonists and indirect acting drugs that inhibit ACHE b. Learning Objectives for Cholinergic Agonists i. Describe/explain the processes of ACH synthesis, release and inactivation ii. Identify sites and effects of muscarinic and nicotinic receptor activation including receptor subtype locations and effects when activated iii. Identify intracellular signaling pathways for M1, M2, M3, Nn and Nm receptors iv. Compare/contrast direct and indirect cholinergic agonists v. Describe the therapeutic uses, mechanisms of action, and adverse effects of cholinergic agonists c. Autonomic Nervous System Dominance i. Sympathetic: Arterioles (adrenergic), veins (adrenergic) and sweat glands (cholinergic) ii. Parasympathetic: Everything else!!! iii. Why is autonomic dominance therapeutically important? Hint: think about what would happen when you give a drug that blocks either sympathetic or parasympathetic transmission. d. Therapeutic Uses of Drugs Affecting Cholinergic Transmission (as a review exercise, list one drug for each use below) i. Modulation of GI tone ii. Xerostomia (dry mouth) iii. Glaucoma iv. Motion sickness and antiemesis v. Neuromuscular disease (e.g., myasthenia) vi. Neuromuscular block during surgery vii. Ganglionic block during aortic dissection viii. Dystonia (abnormal muscle tone, movement) ix. Vagally-mediated bradycardia x. Mydriasis xi. Bronchodilation in COPD/asthma xii. Bladder spasm/urinary incontinence xiii. Cosmetic (decrease skin lines and wrinkles) xiv. Alzheimer’s Disease, dementia e. Muscarinic Receptor Subtypes i. M1 1. “neural”, located in cortex, hippocampus, and striatum 2. Involved with learning and memory, implicated in Alzheimer's ii. M2 1. Heart, negative inotropic (slight) and chronotropic 2. Decreased SA node firing rate, decreased AV node conduction velocity iii. M3 1. Smooth muscle (contraction) and glands (secretion) 2. Selective M3 antagonists developed for overactive bladder 3. Synthesis of nitric oxide (NO), EDRF; important for vascular relaxation iv. Ignore M4 and M5 f. Some terms to review i. Cholinomimetic – a drug that results in the stimulation of ACH receptors, can be either direct or indirect ii. Cholinergic – involving the synthesis, release or action of ACH iii. Anticholinesterase – inhibits ACHE, an acetylcholinesterase inhibitor or ACHEI iv. Anticholinergic – a drug that blocks ACH receptors, either N or M 1
Image of page 1
v. Antimuscarinic – a drug that blocks M receptors vi. Antinicotinic – a drug that blocks N receptors vii. Miosis – small pupil (constriction of iris sphincter muscle) viii. Mydriasis – large pupil (relaxation of iris sphincter muscle) ix. Bradycardia – slow heart rate, decreased SA node firing rate x. Tachycardia – rapid heart rate, increased SA node firing rate g. Binding of ACH to M2 receptor Binds to subunits 3 and 5 (ionic bonding to 3 and hydrogen bonding of carbonyl and ester O to subunit 5) h. Classic SAR for Muscarinic Cholinergic Agonists i. Nitrogen atom capable of bearing a positive charge, preferably a quaternary ammonium salt ii.
Image of page 2
Image of page 3

You've reached the end of your free preview.

Want to read all 9 pages?

  • Spring '14
  • VanTyle,WKent

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture