Pharmacology Lectures - FL24New-212-222 PDF

3. Parasympatholytics 212  Cholinergic Antagonists Drugs that: bind/inactivate cholinergic receptors (hence called cholinergic antagonists) antagonize the action of cholinergic agonists (hence called cholinolytics) antagonize parasympathetic effect...

3. Parasympatholytics 212  Cholinergic Antagonists Drugs that: bind/inactivate cholinergic receptors (hence called cholinergic antagonists) antagonize the action of cholinergic agonists (hence called cholinolytics) antagonize parasympathetic effect (hence called parasympatholytics) Cholinergic antagonist = Cholinolytics = Parasympatholytics Two main classes: Muscarinic Antagonists (antimuscarinics): Competitive antagonists Wide clinical applications Nicotinic Antagonists : Ganglion-specific blockers: no clinical application Neuromuscular junction blockers: muscle relaxants 213 Cholinergic Antagonists 214  Muscarinic Antagonists: atropine an alkaloid of Atropa belladonna (deadly nightshade) has high affinity for muscarinic receptors Effects: Eye mydriasis (unresponsive to light & inability to focus) increase intra-ocular pressure --- exacerbate glaucoma GIT reduce GIT motility antispasmodic Urinary decrease hypermotility states of bladder CVS low dose: decrease heart rate high dose: increase heart rate toxic dose: cutaneous vasodilatation (no effect on BP) Secretions The most sensitive to atropine are: salivary, bronchial and sweat glands. It blocks salivation, sweating and tears (may cause increase in body temperature). 215  Muscarinic Antagonists: atropine Therapeutic uses dilation of the eye for retinal examination antispasmodic agent antidote for cholinergic agonist --- cross BBB --- useful in organophosphate poisoning & mushroom poisoning anti–secretary agent prior to surgery Pharmacokinetics well absorbed metabolized in the liver and eliminated in the urine half-life is 4 hours Adverse effects anticholinergic effects CNS: confusion, hallucinations and delirium In toxic doses may cause collapse of circulatory and respiratory system 216  Short Acting Muscarinic Antagonists (SAMA): ipratropium, hyoscine Ipratropium Blocks M1 and M3 (M2 is presynaptic) Dilates bronchial smooth muscles --- useful in treatment of asthma and bronchitis, COPD Chronic Obstructive Pulmonary Disease Hyoscine (scopolamine) Crosses CNS with greater action than atropine and longer duration --- useful in motion sickness 217 Long Acting Muscarinic Antagonists (LAMA) Aclidinium M3 antagonist, used as bronchodilator alone or with a long-acting beta2 agonist (LABA) or with a LABA plus inhaled corticosteroid in treating COPD patients (an option for people who find it difficult to use other LAMAs) 218  Neuromuscular Blockers Non-depolarizing (competitive) Agents e.g. tubocurarine (derived from plant, arrow poison in S-America) Mechanism of action acts by competing with ACh for binding to the Nm receptors prevents depolarization of the endplate action can be reversed by increasing ACh concentrations (e.g. AChase inhibitors) Effects & Uses paralysis of face and eyes muscles then fingers and trunk muscles and lastly diaphragm muscles tubocurarine is not absorbed orally => no risk eating the prey used as adjuvant in anesthesia similar to tubocurarine Adverse effects interacts with several drugs death occurs through respiratory paralysis tubocurarine triggers histamine release => blood pressure drops 219 Neuromuscular Blockers Depolarizing Agents e.g. succinylcholine Mechanism of action acts like ACh – stimulates the Nm receptors ‫تشنج‬ initial depolarization causes fasciculation (Phase I) and persistent depolarization causes flaccid paralysis (Phase II ~ 10 mins) tone ‫العضالت تصبح رخوة لغياب‬ hydrolyzed by plasma (Pseudo-)Cholinesterase and not by end plate AChase Effects & uses endotracheal intubation (induction of anesthesia) during electro-shock therapy (ECT; ElectroConvulsive Therapy)) Adverse effects condition characterized by rapid muscle contractions, a dangerously high fever, and metabolic disturbances may cause malignant hyperthermia when used with halothane inhaled anesthetics apnea (cessation of breathing) in genetically deficient plasma ACholinesterase 220  Clinical Uses of Cholinergic Antagonists & Neuromuscular Blocking Agents Antagonists: Eye pupil dilation for examination: atropine blocks muscarinic receptors causes dilation of iris sphincter muscles. It also relaxes ciliary muscle thus loss of focus of accommodation CVS atropine to increase heart rate in shock GIT antispasmodic agent: hyoscine to relive abdominal cramps peptic ulcer: pirenzepine blocks M1 gastric parietal cells which reduce release of HCl Respiratory asthma: ipratorpium (given by nebulizer) M3 antagonist) COPD: aclidinium with LABA or LABA and corticosteroids (M3 antagonist) Others atropine acts as antidote for cholinergic agonist --- cross BBB --- useful in organophosphate poisoning & mushroom poisoning motion sickness: hyoscine as transdermal patches relief nausea and vomiting associated with travel Neuromuscular blocking agents: anesthesia; surgery 221 Some Cholinerigc Antagonists Uses Eyes dilatation parkinsons disease Peptic ulcer Motion sickness Asthma GIT 222