Antimuscarinic Agents


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Antimuscarinic Agents

  1. 1. Antimuscarinic agents <ul><li>These are the drugs which blocks the actions of Ach especially mediated through muscarinic receptor. </li></ul><ul><li>Classification </li></ul><ul><li>Natural alkaloids </li></ul><ul><li>Atropine </li></ul><ul><li>Hyoscine (Scopolamine) </li></ul><ul><li>Semi synthetic derivatives </li></ul><ul><li>Homatropine </li></ul><ul><li>Homatropine methyl bromide </li></ul><ul><li>Atropine methonitrate </li></ul><ul><li>Hyoscine methyl bromide </li></ul>
  2. 2. <ul><li>Hyoscine butyl bromide </li></ul><ul><li>Ipratropium bromide </li></ul><ul><li>Tiotropium bromide </li></ul><ul><li>Synthetic compounds </li></ul><ul><li>a) Mydriatics </li></ul><ul><li>Cyclopentolate </li></ul><ul><li>Tropicamide </li></ul><ul><li>b) Antisecretory -antispasmodics </li></ul><ul><li>Θ Quaternary ammonium compounds </li></ul><ul><li> Propantheline </li></ul><ul><li> Oxyphenium </li></ul><ul><li> Clidinium </li></ul><ul><li> Pipenzolate </li></ul><ul><li> Glycopyrrolate </li></ul>
  3. 3. <ul><li>Θ Tertiary amines </li></ul><ul><li> Dicyclomine </li></ul><ul><li> Pirenzepine </li></ul><ul><li> Telenzepine </li></ul><ul><li> Oxybutynin </li></ul><ul><li> Flevoxate </li></ul><ul><li>c) Antiparkinsonian drugs </li></ul><ul><li> Benzhexol </li></ul><ul><li> Procyclidine </li></ul><ul><li> Biperiden </li></ul><ul><li> Benztropine </li></ul><ul><li> Cycrimine </li></ul><ul><li> Ethopropazine </li></ul>
  4. 4. <ul><li>Miscellaneous </li></ul><ul><li>Tricyclic antidepressants </li></ul><ul><li>Phenothiazines </li></ul><ul><li>Antihistaminics </li></ul><ul><li>Disopyramide </li></ul><ul><li>M/A </li></ul><ul><li>Belladonna alkaloids like atropine block the muscarinic effects of Ach. </li></ul><ul><li>This is a competitive inhibition which is reversed by an increase in the concentration of Ach at the muscarinic neuroeffector site. </li></ul><ul><li>They do not interfere with the release of Ach at the cholinergic nerve endings. </li></ul>
  5. 5. <ul><li>Pharmacological actions </li></ul><ul><li>CNS </li></ul><ul><li>At low doses atropine do not cross BBB. </li></ul><ul><li>At higher doses it produce CNS stimulant action. </li></ul><ul><li>` Hyoscine produce CNS depressant effect even at low doses. </li></ul><ul><li>Atropine stimulates many medullary centers – vagal, respiratory, vasomotor. </li></ul><ul><li>It depresses vestibular excitation and has antimotion sickness property. </li></ul><ul><li>It suppresses the tremor and rigidity of parkinsonism by blocking the cholinergic over activity in basal ganglia. </li></ul>
  6. 6. <ul><li>In high doses cause cortical excitation, restlessness, disorientation, hallucinations and delirium followed by respiratory depression and coma. </li></ul><ul><li>CVS </li></ul><ul><li>In heart, M 2 receptor is blocked by atropine in S.A node and A.V node leads to tachycardia. </li></ul><ul><li>It also blocks muscarinic autoreceptors on vagal nerve endings augmenting ach release, this leads to </li></ul><ul><li>Predominant bradycardia and finally tachycardia. </li></ul>
  7. 7. <ul><li>Blood vessels </li></ul><ul><li>Atropine at high doses has direct vasodilatory effect and also enhances the release of histamine. This leads to hypotension. </li></ul><ul><li>Ach vasodilatation </li></ul><ul><li>Eye </li></ul><ul><li>Topical instillation of atropine causes mydriasis, lack of light reflex and cycloplegia lasting 7-10days. </li></ul><ul><li>This results in photophobia and blurring of near vision. </li></ul><ul><li>Intra occular tension tends to rise, specially in narrow angle glaucoma. </li></ul>־ Atropine
  8. 8. <ul><li>Smooth muscle </li></ul><ul><li>All visceral smooth muscles are relaxed by atropine (M 3 blocked). </li></ul><ul><li>The tone & contraction of stomach and intestine are reduced; the passage of chyme is slowed – constipation may occur, spasm may be relieved. </li></ul><ul><li>Atropine causes bronchodilatation and reduces air way resistance, specially in COPD and asthma patients. </li></ul><ul><li>It has a relaxant action on ureter and urinary bladder; </li></ul><ul><li>Urinary retention may occur in older males with BPH. </li></ul><ul><li>relaxation of biliary tract and uterus is minimal. </li></ul>
  9. 9. <ul><li>Glands </li></ul><ul><li>Atropine decreases sweat, salivary, tracheobronchial and lachrymal secretion (M 3 blockade). </li></ul><ul><li>Skin & eye become dry, talking and swallowing may be difficult. </li></ul><ul><li>It also decreases G.I secretions like pepsin, mucous, HCl etc. </li></ul><ul><li>Body temperature </li></ul><ul><li>Rise in body temperature occurs at higher doses. It is due to both inhibition of sweating as well as stimulation of temperature regulating centre in the hypothalamus. </li></ul><ul><li>Local anesthetic effect </li></ul><ul><li>Atropine has a mild anesthetic action on the cornea. </li></ul>
  10. 10. <ul><li>Pharmacokinetics </li></ul><ul><li>A rapid by G.I.T and cornea on topical application. </li></ul><ul><li>D crosses BBB and produces CNS effects </li></ul><ul><li>M in liver (50%) </li></ul><ul><li>E urine, as metabolite or unchanged form </li></ul><ul><li>t ½ 3 – 4hrs. </li></ul><ul><li>Preparations & dose </li></ul><ul><li>Atropine sulfate : 0.6 – 2mg I.M; I.V </li></ul><ul><li> 10 μ g/kg for children </li></ul><ul><li> 1 – 2% topically in eye. </li></ul><ul><li>Hyoscine hydrobromide : 0.3 – 0.5mg oral, I.M, also transdermal patch. </li></ul>
  11. 11. <ul><li>Therapeutic uses </li></ul><ul><li>As antisecretory </li></ul><ul><ul><li>Pre anesthetic medication </li></ul></ul><ul><ul><li>when irritant general anesthetics (ether) are used, prior administration of anticholinergics ( atropine, hyoscine, glycopyrrolate) are imperative to check increased salivary and tracheobronchial secretions. </li></ul></ul><ul><ul><li>Peptic ulcer </li></ul></ul><ul><ul><li>atropine drugs decrease gastric secretion and afford symptomatic relief in peptic ulcer (but it is not using nowadays due to their side effects as well as the entry of H2 – blockers). </li></ul></ul><ul><ul><li>In pulmonary embolism </li></ul></ul><ul><ul><li>To check excessive sweating or salivation . E.g.:- parkinsonism. </li></ul></ul>
  12. 12. <ul><li>As antispasmodic </li></ul><ul><ul><li>Intestinal and renal colic, abdominal cramps. </li></ul></ul><ul><ul><li>Nervous and drug (reserpine, guanethidine) induced diarrhea, functional diarrhea. </li></ul></ul><ul><ul><li>Spastic constipation, irritable colon. </li></ul></ul><ul><ul><li>Pylorospasm, gastric hyper motility, gastritis, nervous dyspepsia. </li></ul></ul><ul><ul><li>To relieve urinary frequency and urgency, enuresis in children </li></ul></ul>
  13. 13. <ul><li>Bronchial asthma, asthmatic bronchitis, COPD </li></ul><ul><li>These drugs are less effective than adrenergic drugs. </li></ul><ul><li>Ipratropium bromide is used in COPD. It has additive bronchodilator action with adrenergic drugs and theophylline. </li></ul><ul><li>As mydriatic & cycloplegic </li></ul><ul><ul><li>Diagnostic :- for testing error of refraction, both mydriasis and cycloplegia are needed. Tropicamide is used widely. </li></ul></ul><ul><ul><li>To facilitate fundoscopy only mydriasis is needed. </li></ul></ul><ul><ul><li>Therapeutic :- atropine is used in the treatment of iritis, iridocyclitis, choroiditis, keratitis and corneal ulcer. </li></ul></ul>
  14. 14. <ul><li>As cardiac vagolytic </li></ul><ul><li>Atropine is useful in counteracting bradycardia and partial heart block in selected patients where increased vagal tone is responsible, e.g.:- in some cases of M.I, digitalis toxicity. </li></ul><ul><li>For central action </li></ul><ul><ul><li>Parkinsonism </li></ul></ul><ul><ul><li>These drugs are used only in mild cases because they are less effective than L-dopa. </li></ul></ul><ul><ul><li>Motion sickness </li></ul></ul><ul><ul><li>Hyoscine is most effective. </li></ul></ul><ul><ul><li>3. Hyoscine has been used to produce sedation and amnesia during labour and to control maniacal states. </li></ul></ul>
  15. 15. <ul><li>To antagonize muscarinic effects of drugs & poisons </li></ul><ul><li>Atropine is an antidote for anti chE and early mushroom poisoning. </li></ul><ul><li>It also block muscarinic actions of neostigmine used for myasthenia gravis, decurarization or cobra envenomation. </li></ul>
  16. 16. <ul><li>Contraindications </li></ul><ul><li>Θ Narrow iridocorneal angle – may precipitate acute congestive glaucoma. </li></ul><ul><li>Θ In patients with BPH – urinary retention may occur. </li></ul>
  17. 17. <ul><li>Interactions </li></ul><ul><li>Absorption of most drugs is slowed. </li></ul><ul><li>L-dopa dose should be increased in presence of these drugs, because the absorption slower and greater peripheral degradation occurs, thereby less of it reaches the brain. </li></ul><ul><li>But in case of tetracycline and digoxin absorption may be increased due to longer transit time in the G.I.T. </li></ul><ul><li>Antacids interfere with absorption of anticholinergics. </li></ul><ul><li>Antihistaminics, tricyclic antidepressants, phenothiazines, pethidine have anticholinergic property – additive side effects with atropinic drugs. </li></ul><ul><li>MAO inhibitors interfere with metabolism of anticholinergic antiparkinsonian drugs - delirium may occur. </li></ul>