1. REVIEW FOR ANS (Part 2) Dr.Soe Aung Myint 17-5-2012 Thursday

2. CA EXAM 21 May, 10:30 to 11:30 AM MCQ For 10 Questions------(20mins) SAQ(3 Qs)+LAQ (1Q)---------(40mins) MCQ -----------------------------10 marks SAQ (3Qs)----------------------- 30 marks LAQ (1Q) ------------------------10marks Total ------------------------------50marks

3. * Which drug is obtained from plant called ephedra vulgaris?......ephedrine Ephedrine cause tachyphylaxis?(indirectly act releasing NA) Uses of adrenaline? (Ana Shock,LA,Haemostatic,Cardiac A,SS) What is used to which NA if given IV infusion?...vitamin C Which drug used in anaphylaxis? Why adrenaline added to LA?..to increase duration of action of LA by causing vasoconstriction Tachyphylaxis is rapid decrease in response to drug after repeated doses over a short period)…

4. * Uses of ephedrine(chronic orthostatic hypotension,asthma,bronchitis) Uses of dopamine(MI,open heart surgery,renal failure,septicaemia,Car Sh) Adv effect of adrenaline? (Nervousness, rest,insomnia, tach,swe,H,N,V) Name of anoretic agent(Amphetamine,ephedrine) nasal decongesant(Phenylephrine,ephedrine,pseu,xylometazoline,oxy…) How does ephedrine cause nasal decongestion? (release of NA) Alpha adrenergic blocker classification and examples,uses and adverse effect Prazosin(first dose should be given at night to prevent syncope)

5. * Step for synthesis of adrenaline Classification of sympathomimetic drugs

6. * Dopamine can be used in cardiogenic shock Atropine can be used as anaesthetic premedication Atropine can cause mydriasis Neostigmine can be used in myasthenia gravis Oxime (pralidoxime) Ach can’t be used therapeutically

7. * Classifications of cholinomimetic drugs with example(ANS Part 1) myasthenia gravis(ANS Part 1) Beta blockers Therapeutic uses MOA Pheochromocytoma Metabolism of adrenaline

8. * Treatment of organophosphate poisoning Muscarinic receptors antagonist

9. Muscarnic receptor antagonist Classification Therapeutic uses Action on the eye

10. Classification***

11. Naturally occurring alkaloids- atropine, hyoscine(scopolamine) Semisynthetic derivatives of theses alkaloids- homatropine.Acting at the muscarinic receptor (antimuscarinic agents)

12. Synthetic congeners Synthetic quaternary compounds: Synthetic tertiary amine compounds:.Acting at the muscarinic receptor (antimuscarinic agents)

13. Synthetic congeners Synthetic quaternary compounds : methantheline, propantheline, oxyphenonium, glycopyrrolate, ipratropium bromide oxyphencyclimine cyclopentolate, tropicamide, dicyclomine flavoxate benztropineSynthetic tertiary amine compounds: oxyphencyclimine, piperidolate, cyclopentolate, tropicamide, dicyclomine hydrochloride, flavoxate hydrochloride, trihexyphenidyl, benztropine

14. Selective M 1 receptor blocker: - pirenzepine.Acting at the muscarinic receptor (antimuscarinic agents)

15. Atropa belladonna and datura stramonium yield the alkaloid atropine Scopolamine (hyoscine) is found in Hyoscyamus niger and Scopolia carniolica Source and members

16. Atropa belladonna

17. Datura stramonium

18. Hyoscyamus niger

19. Scopolia carniolica

20. Therapeutic Uses***

21. CARDIOVASCULAR Treatment of sinus bradycardia following myocardial infarction – Atropine IV

22. OPHTHALMIC*** to dilate the pupil - Atropine & Homatropine Tropicamide eye drops - Tropicamide eye drops (relatively short-acting) & Cyclopentolate eye drops - Cyclopentolate eye drops (long-acting) are newer preparations

23. EYE*** Atropine blocks all cholinergic activity on eye- persistant mydriasis,unresponsiveness to light,cycloplegia(inability to focus for near vision)----7-14 days Tropicamide produce mydriasis for 6hrs Cyclopentolate produce mydriasis for 24hrs

25. Mydriasis

27. NEUROLOGICAL Prevention of Motion sickness – Hyoscine – Hyoscine (orally or transdermally) Parkinsonism especially to counteract movement disorders caused by antipsychotic drugs -Benzhexol, Benztropine

28. RESPIRATORY Bronchial asthma & Chronic Obstructive Pulmonary Disease - Ipratropium or - Tiotropium by inhalation - Tiotropium by inhalation

29. ANAESTHETIC PREMEDICATION to dry secretions Atropine - Atropine - Hyoscine - Hyoscine

30. GASTROINTESTINAL to facilitate endoscopy and gastrointestinal radiology by relaxing gastrointestinal smooth muscle - Hyoscine IV

31. Esophageal varices

32. GASTROINTESTINAL*** as an antispasmodic in irritable bowel syndrome or colonic diverticular disease - Dicyclomine Recommended in initial management of acute biliary colic and cholecystitis

33. Anticholinergic antispasmodic*** Atropine is used as an antispasmodic agent to relax GI tract and gall bladder

35. GASTROINTESTINAL Acute pancreatitis - Atropine decreases pancreatic secretion

36. URINARY to relieve muscle spasm accompanying infection in cystitis Flavoxate and - Flavoxate and - Oxybutynin - Oxybutynin

37. Treatment of cholinergic overactivity and poisoning of mushroom and organophosphorous compounds to block the muscarinic actions - Atropine

38. Atropine Poisoning Treatment activated charcoal  giving activated charcoal to adsorb the drug  Diazepam for excitement Physostigmine  Physostigmine to reverse anticholinergic effects

39. β RECEPTOR BLOCKING AGENTS

40. Beta Blokers*** Classfication Therapeutic uses

41. Classification***

43. Pharmacological Actions Due to blockade of beta-adrenergic receptors 1.lower blood pressure negative inotropic action –   CO,   BP inhibit RAA System  antagonize the release of rennin 2.negative chronotropic action, slow AV conduction leads to bradycardia and heart block. 3.increase airway resistance/ bronchoconstriction due to blockade of  2 receptor 4.eye -   IOP 5.Metabolic and endocrine effect – hypoglycaemia,  HDL/ LDL ratio 6.reduced peripheral blood flow due to reduced cardiac output cause cold extremities

44. Therapeutic Uses***

45. Arrhythmias - beta blockade reduces sympathetic drive to cardiac pacemakers. Those with quinidine-like effect will also reduce excitability. Angina pectoris - β 1 blockade reduces cardiac workload and oxygen consumption. Hypertension - β blockade reduces CO and rate. Also propranolol has central sympathoplegic, and tranquilizing action like reserpine. It does not induce postural hypotension, because it does not inhibit reflexes.

46. Therapeutic Uses Myocardial infarction - cardioprotective effect (reduce acute mortality & prevent recurrence by decreasing cardiac work & reduction in oxygen demand due to slowing & regularization of heart rate.) Phaeochromocytoma - blocks the β agonist effect of catecholamines together with α blockers Hyperthyroidism - Hepatic portal hypertension and oesophageal variceal bleeding - reduction of portal pressure

47. Therapeutic Uses Anxiety - to control somatic symptoms associated with sympathetic over activity such as palpitations and tremor. Migraine - prophylaxis Is recurrent attack of severe and throbbing H/A usually affect one side of head asso with N/V and,Visual dsturb Benign essential tremor - Alcohol and opioid acute withdrawal symptoms

48. Therapeutic Uses Glaucoma - timolol or carteolol eye drops. It acts by decreasing production of aqueous humour by the ciliary body Hypertrophic subaortic stenosis - propranolol is useful, especially for treatment of exertional or other stress induced angina, palpitations, and syncope.

49. Contraindications -impending CHF, -cardiogenic shock, -heart block, -asthma and -hypotension

50. THE ALPHA AND NONSELECTIVE BETA RECEPTOR BLOCKING AGENTS

51. LABETOLOL: * It is used in chronic hypertension; initial dose is 100 mg BD. For emergency control of severe hypertension 50 mg IV may be given over one minute with the patient supine, and repeated at 5 min intervals up to maximum of 200 mg.

52. Skeletal muscle relexant

54. Caused by – local inflammatory causes diseases of Brain and Spinal Cord Upper Motor Neuron Lesions Multiple Sclerosis Cerebral Palsy

55. 1.Drugs that act within CNS Baclofen, Diazepam 2. Drugs that act directly on skeletal muscle*** Dandrolene

56. DIAZEPAM used in spasticity due to spinal cord lesions and cerebral palsy

57. DANTROLENE*** - It is not centrally acting. - It is a direct acting muscle relaxant. - It directly prevents excitation-contraction coupling by decreasing the calcium released from the sarcoplasmic reticulum (not affect the neuromuscular junction or CNS). - It can be used in spasticity of upper motor neurone lesion.

58. DANTROLENE*** - Can also be used in athetoid cerebral palsy, multiple sclerosis, neuroleptic malignant syndrome and malignant hyperthermia syndrome. - It may cause weakness, hepatotoxicity, euphoria, light headedness, dizziness, drowsiness and fatigue as adverse effects.

59. Malignant Hyperthermia*** Inherited condition characterized by rapid extreme and fatal rise in body Temp following the administration of general anaesthesia Result can be destruction of muscle tissue,kidney failure and death…

60. Sympathomimetic Drugs

61. Dopamine* a catecholamine that occurs as the immediate precursor of noradrenaline. It acts both directly on various receptors and indirectly by releasing noradrenaline. dopamine stimulates dopaminergic receptors, β1 receptors and, in high doses, α1 and α2 receptors. Its actions are dose dependent and very complex.

62. Uses: to correct haemodynamic imbalances associated with shock syndrome caused by myocardial infarction, trauma, endotoxin septicaemia, open heart surgery, renal failure and chronic cardiac decompensation (as in congestive heart failure), severe cardiac failure, profound hypotension following removal of phaeochromocytoma.

63. Dosage and Administration The adult dose, administered by IV infusion, is adjusted according to clinical response and ranges from 2.5 mcg/kg/min to a maximum of 60 mcg/kg/min. Dopamine is not marketed for use in children. 200 mg of dopamine in 500 ml of normal saline

64. CARDIOGENIC shock :* Use positive inotropic agents such as dopamine or dobutamine low to moderate doses (  ), they may increase CO & cause relatively little peripheral vasoconstriction. The goal of therapy in shock should be to optimize tissue perfusion, not blood pressure.

65. ANAPHYLAXIS* Anaphylaxis (see under epinephrine) 0.3 – 0.5 mL of 1:1000 epinephrine solution Intramuscular injection may be preferred, since systemic drug absorption from subcutaneous injection is unpredictable in hypotensive patients.

66. SYMPATHOMIMETIC DRUGS

67. Identification of adrenoceptors Alpha & beta receptors were identified by Raymond Ahlquist in 1948. At present, 4 adrenoceptors with subtypes identified are: α 1 – α 1A, α 1B, α 1D α 2 – α 2A, α 2B, α 2D β - β 1, β 2, β 3 D - D 1, D 2, D 3, D 4, D 5

68. Synthesis of Catecholamines Tyrosine   Dopa   Dopamine   Norepinephrine   Epinephrine

69. Classification of sympathomimetic drugs

70. (A) Direct acting Selective α1 agonist - Phenylephrine, Methoxamine, Midodrine α2 agonist - Clonidine, Clenbuterol, Methylnoradrenaline, Apraclonidine, Brimonidine, Guandacine, Guanabenz, Methyldopa, Tizanidine, Dexmedetomidine (centrally acting) β1 agonist - Dobutamine, Xamoterol β2 agonist - Terbutaline, Salbutamol (albuterol), Salmeterol, Formoterol, Ritodrine D1>> D2 agonist - Fenoldopam D2 agonist - Bromocriptine

71. Non selective Non selective α agonist - Oxymetazoline (α1, α2) Non selective β agonist - Isoproterenol (Isoprenaline) (β1 β2) α1 α2 β1 β2- Epinephrine (Adrenaline) α1 α2 β1- Norepinephrine (Noradrenaline) D1=D2 >>β>>α - Dopamine D1, D2, β2 - Dopexamine

72. (B) Indirect acting Releasing agent - Amphetamine, Methamphetamine, Tyramine, Ephedrine Uptake inhibitor - Cocaine, Tricyclic antidepressants MAO/COMT inhibitor - Pargyline, Entacapone

73. (C) Mixed acting Ephedrine - α1 α2 β1 β2 & releasing agents

74. Therapeutic Uses* ADRENALINE (α and β effects) 1.In the emergency treatment of acute anaphylactic shock, it acts as a physiological antagonist. The main effects of anaphylactic reaction are gross swelling of the skin and mucous membrane, which can obstruct breathing, and cardiovascular collapse due to vasodilatation.

75. Therapeutic Uses ADRENALINE (α and β effects) raises the BP (α1), dilates the bronchi (β2) and stimulates the heart (β1) Pulmonary congestion is also alleviated by constriction of mucosal blood vessels. It also has anti-allergic effect. It is given 0.3 to 0.5 ml of 1:1000 solution intramuscularly in anaphylactic shock. For cases like urticaria, and angioneurotic oedema, antihistamines are preferred because of less side effects.

76. Therapeutic Uses ADRENALINE (α and β effects) 2. As an adjunct with local anesthetics. Concurrent administration of adrenaline with local anesthetics reduces circulation to the site, which results in slowing of vascular absorption. This promotes the local effect of the anesthetic and prolongs its duration of action. 3. As a haemostatic agent to control superficial bleeding from arterioles and capillaries in the skin, mucous membranes or other tissues.

77. Therapeutic Uses ADRENALINE (α and β effects) 4. To provide inotropic support in septic shock 5. To treat cardiac arrest in normal heart 6. Bronchial asthma (rarely used now)

79. Beneficial effects of adrenaline in anaphylactic shock: ____a. pharmacological antagonism of chemical mediators ____b. decreasing mucosal edema ____c. decreasing oxygen consumption ____d. increasing the cardiac output ____e. bronchial relaxation N N N Y Y

80. SYMPATHOLYTIC DRUGS

81. 1. THE ALPHA RECEPTOR BLOCKING AGENTS A.  1 Selective Antagonists Prazosin and related drug: Prazosin, terazosin, doxazosin, trimazosin. B.Non Selective  Blockers TOLAZOLINE and PHENTOLAMINE PHENOXYBENZAMINE and DIBENAMINE C.  2 Selective Antagonists YOHIMBINE and IDAZOXAN D.Miscellaneous  Blockers neuroleptic agents (chlorpromazine, haloperidol) and ergot derivative

82. α RECEPTOR BLOCKING AGENTS

83. General Clinical Uses and Side Effects Hypertension non-selective alpha blocking agents(Tola n Pen) are not very useful because of their tendency to produce tachycardia and dysrhythmias and increase GIT activity. Prazosin is used because it does not affect cardiac function. Side effects - postural hypotension, failure of ejaculation and drowsiness (less with prazosin)

84. General Clinical Uses and Side Effects Phaeochromocytoma*** Catecholamine secreting tumor of chromaffin tissue and one of the effects is to cause episodes of severe hypertension. A combination of α and β antagonist is the most effective way of controlling the blood pressure. Labetalol, or a combination of phenoxybenzamine and propranolol are effective for this purpose.

85. Pheochromocytoma*** Diagnosis of pheochromocytoma depend on biochemical evidence of catecholamine production by tumor Plasma free metanephrines,plasma and urinary catecholamines Pentolamine test

86. General Clinical Uses and Side Effects Raynaud’s disease in which bouts of intense sympathetically mediated arterial vasoconstriction occur in the hands and feet, usually in response to cold or vibration, phenoxybenzamine and other α antagonist may be used to reduce the vasoconstriction.

87. β RECEPTOR BLOCKING AGENTS

89. Phentolamine & tolazoline:(sympatholytic,non sel) ----- a. are selective blockers of  1 receptors ----- b. can decrease central sympathetic outflow ----- c. are useful for treatment of essential hypertension ----- d. are indicated for phaeochromocytoma ----- e. can produce adrenaline reversal experimentally N N N Y Y

90. Propranolol:(sympatholytic,beta blocker) ----- a. in high doses stabilizes myocardial cell membrane ----- b. has a wide difference in bioavailability among patients ----- c. is excreted mostly unchanged in the urine ----- d. on sudden withdrawal can produce dangerous effects ----- e. decrease cardiac stimulation during exercise Y Y N Y Y

91. Prazosin: ----- a. blocks  adrenergic receptors non- selectively ----- b. causes dilatation of both arteries and veins ----- c. can decrease central sympathetic outflow ----- d. is useful for treatment of hypertension ----- e. can cause first dose phenomenon N Y N Y Y

92. Non-depolarizing neuromuscular blocking agents are ___ a. Tubocurarine ___ b. Succinylcholine ___ c. Gallamine ___ d. Dexamethonium ___ e. Neostigmine Y N Y N N

93. --- a. produces flaccid paralysis of the skeleton muscle --- b. is more potent than d-tubocurarine --- c. has ganglion blocking action --- d. can increase intraocular pressure --- e. may produce prolonged apnoea in patients with pseudocholinesterase deficiency SUCCINYLCHOLINE Skeletal muscle relaxant Y Y N Y Y

94. Suxamethonium: ----- a. is a reversible neuromuscular blocking agent ----- b. has a short duration of action in normal patients ----- c. can cause release of endogenous histamine ----- d. action can be terminated by physostigmine ----- e. may cause fasciculation and pain as side effects N Y N Y N

95. MOA of Miotic drug on AGC*** Pilocarpine obtained from leaves of pilocarpus microphyllus Prominent muscarinic action Appiled on eye, it causes miosis,ciliary muscle contraction,increase aqueous outflow and fall in intraocular tension Initial therapy in acute ACG

96. *** Myasthenia gravis diagnostic test(ANS Part 1) Beta blockers, therapeutic uses and MOA(Prof Lect)

97. Organization of ANS Concerned with Physiology

98. Thank U for Ur Attention