Cardiovascular Agents

Introduction: Cordiovascular agents represent a group of drugs which have direct action on the heart or other parts of the vascular system so that they modify the total output of the heart or the distribution of blood to certain parts of the circulatory system. They are further classified into the following types : 1. Cardiotonic drugs (Cardiac glycosides). 2. Vasodilators. 3. Antihypertensive (hypotensive) drugs. 4. Antihypercholesterolemic drags. 5. Sclerosing drugs. 6. Antiarrhythmic drugs. Besides these, there are other classes of drugs, which do not necessarily have a direct effect on the cardiovascular system but are of considerable value in the treatment of cardiac disease. These include the diuretics and the anticoagulants. 1. Cardiotonic drugs (cardiac glycosides) These are naturally occurring drugs which are known to occur in certain plants and in toad venom. These have direct action on the heart and are used for the treatment of congestive heart failure and certain cardiac arrhythmic conditions. Ex. Digitozin. a) It is obtained from Digitalis purpurea and Digitalis lanata. It is a glycoside of digitoxigenin. b) Digoxin. It is a Digitalis lanata glycoside of digoxigenin. 2. Vasodilators. These represent a group of drugs which act primarily on the vascular system. Their therapeutic effect is due to their ability to dilate coronary vessels and are therefore used for treating coronary artery diseases and especially in angina pectoris. An ideal coronary vasodilator drug should increase the coronary blood flow without increasing the work of heart out of proportion to the myocardial blood supply and should not divert blood from the coronary circuit by an equal or greater action on other vascular beds. Its effect should be quick in onset and of fairly prolonged duration. It should not produce tolerance. Some of the important vasodilators are amyl nitrate and Glyceryl trinitrate. (a) Amyl nitrite: It is a mixture of isomeric amyl nitrites-but is principally isoamyl nitrite. It may be prepared by the action of nitrous acid on amyl alcohol.

C5H11OH + NaNO 3 + H2SO4 NaHSO4 + H2O + C 5H 11O-N=O Applications: It cannot be administered orally as it is destroyed in stomach. Therefore, it has to be taken by inhalation. Its vasodilator effect is immediate because it is easily absorbed by lung capillaries but duration is very short. It is, therefore, the drug of the choice in angina pectoris. Currently it is recommended in treating cyanide poisoning. Occasionally it is used in whooping cough, sea sickness and asthma. (b) Glyceryl trinitrate (Nitroglycerine or Glonoin): It is the trinitrate ester ofglycerol. It is prepared by adding-glycerol carefully to a mixture of nitric acid and fuming sulphuric acids.
+ 3HNO3





Glyceryl trinitrate


Pentaerythritol tetranitrate (Peritrate. It is an oral vasodilator that reduces peripheral resistance by a direct relaxation of arterial smooth muscle. An ideal antihypertensive drug should produce a reduction in the blood pressure through generalized vasodilatation with fewer side effects Among synthetic antihypertensive agents some important ones are as follows : (a) Hydralazine: It is syntbesised from phthalaldehydic acid (I) by reaction with hydrazine to give 1-(2H)-phthalazinone (II) which is chlorinated to give 1-chlorophthalazine (III). This may result arteriole contraction and increased peripheral resistance to the flow of blood.6-diamino pyrimidin-4-ol O 6-chloro 2. the small arterioles used for transferring blood from the arteries to the tissue capillaries and venus circulation get under excessive stimulation of sympathetic nervous system. Antihypertensive agents (Hypotensive drugs): In resent times. This is harmful in the long run and may lead to death. direct-acting vasodilator that is useful in the treatment of severe 2 . On prolonged treatment a reversible lupus erythematosus like syndrone requires discontinuance of the drug. Its side effects are occasional throbbing headaches and dizziness. As a result.2-dihydro phthalazine 1-hydrazinylphthalazine Applications: It has been in used for about 25 years for the treatment of hypertension. This is converted to its hydrazine called as hydralazine. (b) Minoxidil: It is synthesis involves series of reactions wherein ethylcyanoacetate js condensed with guanidine under base catalysis to give the diaminopyrimidinol (I) which is chlorinated. Reaction of (III) with piperidine gives minoxidil (IV). Any agent used for counteracting this condition i.4-diamine pyrimidine 1-oxide O 2. and the resultant chloropyrimidine (II) is converted to the N-oxide (III) by reaction with m-chloroperbenzoic acid (MCPBA). reducing blood pressure and its accompanying symptoms are known as antihypertensive or hypotensive drugs. flushing and rash. 3.. It is generally given along with hydrochlorothiazide. blood pressure increases.Applications: It is used as a vasodilator. Side effects of this drug are initially headache.e. HN OEt O NH2 guanidine NH2 base H2N N ethylcyanoacetate OH N N POCl3 NH2 H2N N N Cl MCPBA N NH2 H2N N NH2 Cl N H H2N N N NH2 N + C 2. O COOH + Cl NHNH2 NH N H2 N NH 2 NH2 NH2 NH N N N CHO phthalaldehydic acid hydrazine phthalazin-1(2H )-one 1-chloro-1. gastrointestinal disturbances. reserpine.6-diamino-4-chloro pyrimidine-2. It has the action typical of nitrite but its action is developed more slowly and is of longer duration. Many persons suffer from high blood pressure or hypertension. In such patients. Pentritol) and Theophylline ethylenediamine (aminophylline). Other Vasodilators are Khellin (Visammin). or hydrochlorothiazide-r-reserpine.6-diamino-4-(piperidin-1-yl) pyrimidine 1-oxide (Minoxidil) Applications: It is a potent.

mental depression. diarrhoea and impotence. The drugs used to control cholesterol level are. increase in facial Jiair growth. The range of serum cholesterol in normal individuals is 190 to 250 mg %. Its side effects are tachy cardia. nausea.Aluminium nicotinate. thus causing high blood pressure and heart attack. dryness of mouth. vomiting. Clofibrate etc. coma etc. (d) Methyldopa. Chemically. This may interfere with the supply of blood. respiratoiy depressions. muscle twitch. with approximately 30 % in the free state and 70 % as cholesterol esters. CH3 NH2 CH3 ClCH2COCl CH3 NHCOCH2Cl CH3 CH3 HN(C2H5)2 diethylamine NHCOCH2N(C2H5)2 CH3 2-chloroacetyl chloride 2. Sodium salicylate.hypertension fresulting from increased vascular resistance.6-dimethylphenyl) acetamide (II) which reacts with diethylamine to give lidocaine (III). (c) Lidocaine: It is synthesized from 2. Antihypercholesterolemic drags: Cholesterol plays an important role in the development of atherosclerosis (deposition of fat in the inner linings of arteries) in human beings. its side effects are sedation. etc. it is 3-hydroxy- -methyl-L-tyrosine. However. (iii) Inhibit the synthesis of cholesterol within the liver. convulsions.6-dimethylaniline (I) by chloroacetylation to give 2chloro-N-(2. It is synthesised from 3methoxy-4-hydroxyphenyl acetone (I) and following series of reaction. These are used for the elimination of varicose (dilated) veins. HO H3CO CH2COCH3 (1) KCN NH2 (2) HCl (3) NH4OH H3CO (II) HO CH2C CN (1) NH3 NH2 HO H3CO CH2C COOH CH3 (2) 45% HCl CH3 4-hydroxy-3-methoxyphenyl acetone (I) Methyldopa (III) Applications: Methyldopa is mainly used for the treatment of moderate-hypertension.6-dimethylaniline (I) 2-chloroN -(2. Its adverse reactions are drowsiness. Ex.6-dimethylphenyl)acetamide (lidocaine) (III) Applications: It is a drug of choice for immediate control of ventricular premature extra systoles and ventricular tachycardia.6-dimethylphenyl) acetamide (II) 2-(diethylamino)N-(2. sodium chloride etc Antiarrhythmic Agents 3 . (ii) Increase the metabolism and biliary excretion of cholesterol. It is given in combination with. Three following methods are used to bring serum cholesterol levels within this range : (i) Diminish the absorption of cholesterol from the gastrointestinal tracts. Sclerosing agents These arc the drugs which have been found to irritate the inner most layer of the vessel wall and start a thrombus and occlude the vessels. propranolol and hydro--chlorothiazide.

Chemically it is 2-(diethylamino)ethyl 4-aminobenzoate hydrochloride. too slow (bradycardia). age of the patients. procaine is a vasodilator. Prior to the discovery of procaine. and coworkers reported the Antiarrhythmic Properties of Lidocaine and Procaine Amide (1965).C. Whenever. This may be due to diseases and the use of certain drugs. Vasoconstriction helps to reduce bleeding and prevents the drug from reaching systemic circulation in large amounts. The antiarrhythmic agent to be used and the route have been found to depend on the type of arrhythmia. Novocaine or Scuro-caine). electrolyte value and also the nature of other drugs taken.The drugs. Harrison D. ventricular rate. However. using the route shown below: O O OH + Cl H2O/KOH/Alcohol O + NH2 O NH OH α-naphthol epichlorhydrin 2-((naphthalen-1 -yloxy)methyl) isopropylamine oxirane propranolol Applications: Propranolol is the most useful nonselective adrenergic antagonist (β1. Propranolol is used in the treatment of angina and hypertension. nearly 50 per cent of the patients are known to develop vascular collapse or pulmonary congestion. Like other local anesthetics (with the exception of cocaine) and mepivacaine. Ex. with increased rate. By antagonizing the β2-receptor. which are used for the modification of cardiac rate and rhythm. are known as antiarrhythmic agents. The synthesis is described as followsHO N O2N COOH PCl5 O2N COCl diethylethanolamine 4-nitrobenzoic acid 4-nitrobenzoyl chloride O O O N O N Reduction Fe/H2O O2N H2N procaine Applications:Procaine is used less frequently today since more effective (and hypoallergenic) alternatives such as lidocaine (Xylocaine) exist. Procaine: (It is also called as Ethocaine hydrochloride. and is often coadministered with epinephrine for the purpose of vasoconstriction. Propranolol and Procaine Propranolol: Propranolol presents an aryloxypropanolamine structure and has been synthesized in two steps from α-naphthol. heartbeats are more than 180 beats per minutes. propranolol possesses serious problems to asthmatic patients. 4 . this may lead to death. cocaine was the most commonly used local anesthetic. β2blocker). such as beating too fast (tachycardia). An arrhythmia is a disorder of the heart rate (pulse) or heart rhythm.

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