Cholinoceptor Blocking Agents Pawitra Pulbutr M.Sc. In Pharm (Pharmacology)

Objectives นิสิตมีความรู้ความเข้าใจถึงเภสัช วิทยา กลไกการออกฤทธิ์ เภสัช จลนศาสตร์ การใช้ประโยชน์ทาง คลินิก อาการไม่พึงประสงค์ ข้อควร ระวังการใช้ยาของที่ออกฤทธิ์ต้านโค ลิโนเซปเตอร์

Cholinoceptor Blocking Agents oInhibit binding of ACh or cholinoceptor agonist to cholinoceptor oCholinoceptor antagonist/ blocker oParasympatholytic … Not appropriate oAntimuscarinic receptor oAntinicotinic receptor oGanglionic blocker oNeuromuscular blocker

Basic Pharmacology of Muscarinic blocker Prototype = “ Atropine ” Tertiary amine derivative Quaternary amine derivative … increase peripheral effect Atropine (Hyoscyamine) Atropa belladonna (deadly nightshade) Datura stramonium (jimsonweed or thorn apple) L (-) hyoscyamine = natural occur d,l- hyoscyamine = commercial available Scopolamine (Hyoscine) Hyoscyamus niger L (-) hyoscine = natural occur L-isomer is more active than d-isomer

Organ System Effects oCNS oAtropine oCNS stimulation … also sedative effect oScopolamine … More CNS effect oDrowsiness, amnesia oToxic dose … excitement, agitation, hallucination, coma oUse oTremor in Parkinson ’ s disease oOvercholinergic activity … Too much ACh oLack of dopaminergic activity in brain oAntimuscarinic agent + Dopamine precursor oMotion sickness … Vestibular disturbance o Scopolamine

Eyes oCholinoceptor … Control pupillary contractor muscle & ciliary muscle oAnticholinoceptor oMydriasis oInhibit ciliary muscle contraction oCycloplegia oFocus defect oUse in ophthalmology oCaution in glaucoma … increase intraocular pressure oDecrease lacrimal secretion, sandy eyes

CVS Atropine at heartAtropine at heart Low dose … Inhibit presynaptic cholinoceptor first … increase ACh release … bradycardia Moderate to high dose … Relative tachycardia AV node (+) dromotropic … Shorten PR interval Less effect on ventricle Total effect of Atropine >>> Modest effect in normal hemodynamic Tachycardia Less effect on BP

Respiratory system oVagal innervation … Smooth muscle & secretory gland oAtropine oBronchodilation oDecrease secretion oUse oAsthma … less effective than  2-agonist oChronic Obstruction Pulmonary Disease (COPD) oPremedication of inhalant anesthetic agent … decrease secretion & laryngospasm

GI tract Decrease GI motility & secretion Prolong gastric emptying time & intestinal transit time Partially effect … ENS controlled by local hormone & other noncholinergic neuron Decrease saliva … dry mouth Less effect on gastric secretion Mostly on basal secretion Pirenzepine, Telezepine … decrease gastric acid secretion No effect on pancreatic & intestinal secretion … under hormonal control Use Peptic ulcer … Not use recently Control diarrhea from parasympathetic system overactive Spasmolytic action

Genitourinary tract oRelaxation of ureter & bladder oDecrease voiding oUse … urinary tract spasm … inflammation oCaution in elderly male … BPH>>> urinary retention oNo effect on uterus

Sweat gland Inhibit thermoregulatory sweating Inhibit eccrine gland secretion Controlled by cholinergic sympathetic nerve May cause … Atropine fever

Clinical Pharmacology Parkinson ’ s disease Motion sickness Mydriasis Adjunct to general anesthesia Asthma/ COPD Hyperactive carotid sinus reflex … fainting Antispasmodic, traveller diarrhea, peptic ulcer Urinary urgency Urolithiasis Cholinergic poisoning

ADRs of anticholinoceptor Depends on desired effect Cholinoceptor blocking effect Dry mouth, mydriasis, tachycardia, hot flush, agitation, delirium, increase body temperature (esp infant) Reversal of atropine overdosage Symptomatic ACh E inhibitor … physostigmine … ADRs

Contraindication of Atropine oGlaucoma oAngle closure glaucoma oElderly male oBPH oPeptic ulcer oDecrease gastric emptying