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O CH 2CH 2CH 2CH 3 CO Amiodarone (173) I CH2CH3 OCH2CH2N CH2CH3 I Amiodarone Hydrochloride: 2-Butyl-3-benzofuranyl)[4-(diethylamino) ethoxy]-3, 5diiodophenyl] methenone (173) is an iodinated benzofuran derivative. Amiodarone suppresses premature ventricular contractions and ventricular tachycardia. Its use is reserved for the treatment of life threatening ventricular arrhythmias refractory to other treatment. Amiodarone is highly lipid-soluble and its half-life is 20-100 days. The precise mechanism of its action is not known. A depressant effect of the drug on inactivated sodium channels has been observed. It is also possible that its antiarrhythmic effects are mediated partly by selectively inhibiting thyroxine action on the heart. Desethylamiodarone is the only metabolite identified. Adverse effects include, pulmonary fibrosis, photosenstivity, corneal microdeposits, thyroid disorders and gray skin discoloration('gray man syndrome'). Iodine can be replaced by bromine and methyl and the benzofuran ring by the benzothiophene ring without loosing activity. Substitution of indolizine for the benzofuran ring in amiiiodarone gave butoprozine with higher antiarrhythmic activity. Class IV Antiarrhythmic Drugs: Calcium-channel Blockers Class IV antiarrhythmic drugs comprise a group of agents which selectively block the slow inward current carried by calcium, i.e., calcium channel blockers. The slow inward current in cardiac cells has been shown to be of importance for the normal action potential in pacemaker cells. It has also been suggested that this inward current is involved in the genesis of certain types of cardiac arrhythmias. Administration of a Class IV drug causes a prolongation of the refractory period in the AV node and the atria, a decrease in atrioventricular conduction, and a decrease in spontaneous diastolic depolarization. These effects block conduction of premature impulses at the AV node and thus are very effective in treating supraventricular arrhythmias. Veraparnil is the prototype drug for this class. Verapamil is considered the drug of choice for supraventricular tachycardia. It is also useful for patients with artrial fibrillation. Not yet approved, but 60-90 mg of diltiazem can be given every 6 hours for prophylactic control against paroxysmal supraventricular tachycardia. Class V Antiarrhythmic Drugs: Anion antagonists Alinidine: 2-N-allyl-N-(2, 6-dichlorophenyl) amino-2imidazolidine (174) is an elective bradycardiac agent. It might restrict anionic membrane currents. Adenosinen (175) does not'fit' into any of the classes of antiarthythmic agents described above. It is used to treat paroxysmal supraventricular tachy-arrhythmias, including those associated with bypass pathways. The adverse effects include headache and hypotension.
Cl Cl CH2CH=CH2 N N N H Alinidine (174) N HOH 2C N OH NH 2 O OH N N Adenosine (175) Official Drugs: Quinidine Sulphate, B.P., I.P. Quinidine sulphate is the dihydrate of (8R,9S)-6'- methoxycinchonan-9-ol sulphate. Quinidine sulphate forms white, needle-like crystals. It is sparingly soluble in water. Quinidine is rapidly absorbed from the gastrointestinal tract, peak plasma concentrations being achieved about 1.5 hours after oral administration of quinidine sulphate. Quinidine and its salts are used to maintain sinus rhythm after cardioversion of atrial fibrillation, and for the prevention and treatment of supraventricular and ventricular arrhythmias. However, other drugs are generally preferred. Quinidine may be used, as an alternative to quinine in the treatment of malaria when quinine is not immediately available. In the prophylaxis of cardiac arrhythmias the oral dose is 0.2 g three or four times daily. In the treatment of atrial fibrillation, 0.2 to 0.4 g dose is given every two to four hours to a total dose of 3 g daily. PreparationI: Quinidine Tablets, (Quinidine Sulphate Tablets, B.P.) Proprietary Name: CIN-QUIN Procainamide Hydrochloride, B.P., I.P. 4- Am i no-N-(2-d iethy lam inoethy I)benzamide hydrochloride. Procainamide may be prepared by interaction between pnitrobenzoyl chloride and NN-diethylethylenediamine, followed by catalytic reduction of the nitro group of the product. Procainamide hydrochloride occurs as a white to yellowish-white crystalline powder. It is hygroscopic. It is very soluble in water. Procainamide hydrochloride is given for the treatment of ventricular arrhythmias particularly those which are resistant to lignocaine and those following myocardial infarction. It is also employed to maintain sinus rhythm after cardio version of atrial fibrillation and has been used for prevention of supraventricular and ventricular arrhythmias. In case oral route is not suitable procainamide hydrochloride may be given intramuscularly. The dose is stated to be 0.5 to 1.5 g. Preparations: p rocainamide Injection, B.P., I.P. Procainamide Tablets, B.P. Proprietary Names: PROCAINAMIDE DURULES; PRONESTYL Disopyramide, B.P. 4-Diisopropylamino-2- phenyl-2-(2-pyridyl)butyramide. It is a white powder, which is slightly soluble in water. CH
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CONTENTS Antianginal Drugs Anticoag
Page 3 and 4:
c) Dihydropyridine derivative: e.g.
Page 5 and 6:
2 (d) 4. H 3C H 3C HO CH-CH 2-O-CH
Page 7 and 8: pentaerythritol, and is supplied di
Page 9 and 10: of' streptokinase, urokinase and ti
Page 11 and 12: Low-molecular-weight Heparins, B.P.
Page 13 and 14: OH COOCH 3 AC 2O Methyl salicylate
Page 15 and 16: Warfarin and other coumarin derivat
Page 17 and 18: Structure-activity Relationship All
Page 19 and 20: Mean Arterial Blood Pressure (MABP)
Page 21 and 22: Table-1 ---------------------------
Page 23 and 24: Ramipril Altace ( Hoechst-Marion) 2
Page 25 and 26: Official drugs: Prazosin Hydrochlor
Page 27 and 28: treatment of hypertension, the dosa
Page 29 and 30: NH ClCH 2CN NCH 2CN Perhydroazocine
Page 31 and 32: B (2). Angiotensin Receptor Antagon
Page 33 and 34: CH3COOC2H5 Diazoxide (90) Cl NH 2 S
Page 35 and 36: Structure-activity Relationships of
Page 37 and 38: N N R Acidic group (102) Acidic gro
Page 39 and 40: Structure-activity Relationships of
Page 41 and 42: HO HO HO HO H 3C CH 3 H Digitoxigen
Page 43 and 44: efractory periods. These are mainly
Page 45 and 46: Structure - Activity Relationship:
Page 47 and 48: Hydralazine is a direct relaxant of
Page 49 and 50: K4[Fe(CN) 6].3H2O + 6HNO3 H2[(NO)Fe
Page 51 and 52: conduction velocity, and decrease s
Page 53 and 54: Synthesis of Moricizine: (153) H N
Page 55 and 56: Tocainide Hydrochloride (±)-2-Amin
Page 57: influx through β-receptor blockade
Page 61 and 62: (iii) Intermediate density lipoprot
Page 63 and 64: Structure-activity Relationship Mev
Page 65 and 66: to the bile acids. Thus due to ente
Page 67 and 68: moderate reduction in cholesterol l
Page 69 and 70: (iii) Other types: (a) Insulin rece
Page 71 and 72: non-crystalline insulin as far as o
Page 73 and 74: for better drug in this series. Sub
Page 75 and 76: Key to general structure X SO 2 NH
Page 77 and 78: Official Drugs: Insulin, B.P. It is
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MEDICINAL CHEMISTRY

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