2nd unit anti-anginal agents

Introduction.
Symptoms
Types of Angina Pectoris
Classification
Vasodilators
Calcium Channel Blockers
Mechanism of action .
SAR.
Structure , Synthesis.
Adverse Drug Reactions , Uses.
References

1. Prepared by G. Nikitha, M.Pharmacy Assistant Professor Department of Pharmaceutical Chemistry Sree Dattha Institute Of Pharmacy Hyderabad 2 nd UNIT ANTI-ANGINAL AGENTS 1 Subject: Medicinal Chemistry-II Year: B.Pharmacy 3 rd Year Semister: 1 st Semister

2. Contents Introduction. Symptoms Types of Angina Pectoris Classification Vasodilators Calcium Channel Blockers Mechanism of action . SAR. Structure , Synthesis. Adverse Drug Reactions , Uses. References 2

3. Introduction 3 Angina Pectoris is a symptom of Ischemic heart disease occurs due to imbalance between demand and supply of oxygen. It is characterized severe pain in the middle of chest which spreads towards the left arm, throat, jaws, and teeth and sometimes towards right arm. Angina is a manifestation of myocardial ischemic which may occur due to any of the reason like heart valve disease, thickening of heart muscles, coronary heart disease, hypertension, smoking etc.

4. Symptoms 4 Sweating Weakness Discoloration of skin Shortness of breath Nausea, vomiting Indigestion etc.

5. Types of Angina Pectoris 5 Stable/ Typical/common Angina: It is the classical form of angina Pectoris where in the cause of pain is predictable. It occurs during severe exercise, emotional stress, hence it is also termed exertional angina. Unstable/ Uncommon Angina: It is new or sudden worsening previous angina. Rare form of angina where in chest pain may occurs even when the person is at rest. However the anginal attacks may be more severe prolonged or occur with increased frequency. It required immediate hospitalization. The cause might be the same as seen in myocardial infraction where in a thrombus formed would associate with the rupture plaque and block the myocardial blood flow.

6. 6 Variant or Prinzimetal Angina: Characterized by pain at chest. It occurs more commonly in women caused due to coronary vasospasm and occurs during night. Micro vascular agents: It is a recently discovered type of angina. In these patient experiences chest pain but there is no apparent coronary artery blockage.

7. Classification 7 Agents are used to prevent the attack of angina by decreasing the consumption of oxygen by heart known as Antianginal agents.

8. 8 1. Vasodilators: a. Organic nitrates and nitrites/ short acting compounds: Amylnitrile Nitro glycerine

9. 9 b. Long acting compounds: Isosorbide dinitrate Pentaerythrial tetranitrate Isosorbide mononitrate

10. 10 c. Peripheral coronary vasodilators: i . Potassium channel activators: Nicorandil Minoxidil Diazoxide

11. 11 ii. Other Peripheral vasodilators: Dipyridamole Papaverine

12. 12 2. Calcium Channel antagonist: a. Phenyl alkyl amine derivative: bepridil Verapamil

13. 13 b. Benzothiazepine derivaties : Diltiazem

14. 14 C. Dihydropyridine derivatives Drugs R 1 R 2 R 3 X First Generation: nefedipine -CH 3 -CH 3 CH 3 2-NO 2

15. 15 Second Generation Amlodipine - C 2 H 5 CH 3 2-Cl Felodipine CH 3 - C 2 H 5 -CH 3 - 2,3-Cl nicardipine CH 3 -CH 3 2-NO 2 nimodipine CH 3 -[CH 2 ] 2 -O-CH 3 -CH 3 3-NO 2

16. 16 3. β-blockers/ β-receptor antagonist: Propranolol nadalol Atenolol

17. 17 4. Miscellaneous drugs: Aspirin Clopidogrel Ticlopidine

18. Vasodilators 18

19. 19 Vasodilators are the agents used to treat various conditions like hypertension, angina pectoris, and cardiac failure. They act by dilating the blood vessels, increasing the blood flow to the constricted blood vessels there by decreases the arterial and venous pressure, because of this decrease in pressure the work done by myocardium decreases as a result of which the oxygen demand by heart also decreases. Hence Vasodilators are effective in the treatment of angina as they balance the oxygen demand by heart. Compounds included under coronary vasodilators act by dilating the coronary vessels.

20. 20 These are further sub-divided into Three categories, namely a. Organic nitrates and nitrites/ short acting compounds b. Long acting compounds c. Peripheral coronary vasodilators

21. 21 a. Organic nitrates and nitrites These esters formed due to the reactions between organic alcohols with nitric acid are known as organic nitrates. Chemically they are considered as nitrate esters. All the compound included under the reaction of isoamyl alcohol with nitrous acid. Organic nitrates and nitrites are successful in relaxing angina pain because of their ability to release nitric oxide which is primarily responsible for producing vasodilating activity. These drugs cannot be used in the pure and concentrate forms for the treatment of angina because of their explosive nature so diluted preparation are recommended. The drugs which comes under short acting compounds : Amylnitrile , Nitro glycerine

22. 22 General Mechanism of action:

23. 23 Organic nitrates converts into nitrites in the body and release nitric oxide which is responsible for the direct and non specific relaxation of vascular smooth muscle. Organic nitrites provide reactive free radical nitric oxide through enzymatic denitration. They released nitric oxide activates the cytosolic guanyl cyclase enzyme that causes an increase in the production of cyclic GMP. Cyclic GMP causes dephosphorylated interaction and myosin light chain kinase enzyme that is essential for the activation of myosin pigment. As MLCK is dephosphorylated interaction between action and myosin does not occur which ultimately results in relaxation of smooth muscles.

24. 24 SAR: Presence of an ester group makes the compound effective in relieving angina pain because the ester group binding Lipophilic will easily penetrate the lipodial barriers and thus effectively reduce the angina attacks presence of this ester group renders the compounds volatile. Therapeutic activity of the compound decreases in the presence of moisture due to the ester bond hydrolysis. Compounds with high partition coefficient are known to be more potent than compounds with low values.

25. 25 Common Adverse Drug Reactions: Weakness Dizziness Palpitation Facial flushing Decrease in blood pressure Continuation use of drug may leads to drug dependence. Sudden deaths Common Uses: Use in the treatment of angina pectoris, congestive heart failure, myocardial infarction, left ventricular fibrillation, interventional cardiac procedures, prophylaxis of pain in bile duct, prophylaxis of cyanide poisoning, to provide relief from esophageal spasm.

26. 26 Amyl Nitrite Structure: IUPAC: Pentyl nitrite/ 2-Methyl butyl nitrite Properties: Amyl nitrite is a clear yellow liquid, Penetrating fragrant, somewhat fruity odor, Pungent, aromatic taste, Very slightly soluble in water, miscible with alcohol, acetone, chloroform. Molecular formula: C 5 H 11 NO 2

27. 27 Pharmacokinetics: Oral route of administration is low, so it is administered through nasal route, metabolized by the liver to form inorganic nitrites, which are much less potent vasodilators than the parent drug. One-third of the inhaled dose is excreted in urine. Adverse Drug Reactions: headache, dizziness, flushing of the face, lightheadedness or fainting, involuntary urination or defecation, low blood pressure, nausea, vomiting, shortness of breath, cold sweat, pale skin, rapid heart rate, restlessness, weakness, or slowed breathing

28. 28 Therapeutic Uses: Amyl nitrite is employed medically to treat heart diseases as well as angina. Amyl nitrite is sometimes used as an antidote for cyanide poisoning.

29. 29 Dose: Liquid for inhalation: 0.3 ml (0.85-103%) crushable glass ampule Acute Relief of Angina: 0.3 ml by inhalation of crushed ampule , may repeat q3-5min Wave crushed ampule under nose multiple times for 2-6 nasal inhalations Cyanide Poisoning: 0.3 ml ampoule crushed and contents poured onto a gauze and placed in front of patient's mouth or endotracheal tube, if patient intubated , to inhale over 15-30 sec; repeat q Min until IV sodium nitrite available Each ampul lasts ~3 min; separate administration by at least 30 sec to allow patient to adequate oxygenate

30. 30 Nitro glycerine Structure: IUPAC: 1,2,3-Propanetriol trinitrate Properties: Pale-yellow, oily liquid, Sweet, burning taste, poor solubility in water, Sparingly sol in petroleum ether, liquid petrolatum, glycerol, Miscible with glacial acetic acid, nitrobenzene, pyridine, ethylene bromide,  dichloroethylene ,  ethyl acetate. Molecular formula: C 3 H 5 N 3 O 9

31. 31 Synthesis:

32. 32 Mechanism of Action: Nitroglycerin is converted by mitochondrial aldehyde dehydrogenase ( mtALDH ) to nitric oxide (NO), an active substance which then activates the enzyme guanylate cyclase . The activation of this enzyme is followed by the synthesis of cyclic guanosine 3',5'-monophosphate ( cGMP ), activating a cascade of protein kinase-dependent phosphorylation events in smooth muscles. This process eventually leads to the dephosphorylation of the myosin light chain of smooth muscles, causing relaxation and increased blood flow in veins, arteries and cardiac tissue. The above processes lead to decreased work of the heart decreased blood pressure, relief of anginal symptoms, and increased blood flow to the myocardium. One in vitro study using mouse aorta suggests that nitric oxide (an activated metabolite of nitroglycerin) targets the natriuretic peptide receptors.

33. 33 Pharmacokinetics: Oral, sublingual, transdermal route of administration. Nitroglycerin is metabolized to nitrite, 1,2-glyceryl dinitrate, and 1,3 glyceryl dinitrate.  Nitrite is then metabolized to nitric oxide or S- nitrosothiol .  The 1,2-and 1,3-dinitroglycerols are less potent in strength than nitroglycerin, but they have longer half-lives, explaining some prolonged effects of nitrates. Both dinitrates are subsequently metabolized to mononitrates that are not active on the blood vessels, and to glycerol and carbon dioxide in the final step of metabolism. Metabolism is the main route by which nitroglycerin is eliminated from the body.

34. 34 Adverse Drug Reactions: headache, weakness, dizziness, lightheadedness, nausea, and Flushing as your body adjusts to this medication. mild burning or tingling with the tablet in your mouth, and Flushing (warmth, redness, or tingly feeling under your skin). Therapeutic Uses: Nitroglycerin is used for the treatment of angina, acute myocardial infarction, severe hypertension, and acute coronary artery spasms. Dose: 2.5-6.5 mg PO q6-8hr.

35. 35 b. Long acting compounds The drugs which comes under Long acting compounds Isosorbide dinitrate, Pentaerythritol tetranitrate, Isosorbide mononitrate

36. 36 Pentaerythrial tetranitrate Structure: IUPAC: 2,2-Bis[( nitrooxy )methyl]propane-1,3-diol dinitrate Properties: White crystalline solid, mild odor, Soluble in acetone, sparingly soluble in alcohol, ether, Very soluble in acetone, Soluble in benzene,  pyrene , Soluble in toluene; slightly soluble in methanol. Molecular formula: C 5 H 8 N 4 O 12

37. 37 Pharmacokinetics Oral route of administration, extensively metabolized in the liver  Metabolites: pentaerythritol trinitrate , pentaerythritol dinitrate, pentaerythritol mononitrate , & pentaerythritol (inactive), eliminated through urine. Adverse Drug Reactions: skin irritation head ache dry mouth blurred vision Elder patient requires the caution in receiving nitrates, Renal failures Liver problem

38. 38 Therapeutic Uses: It is used medically as a vasodilator in the treatment of heart conditions. These drugs work by releasing the signaling gas nitric oxide in the body. It is used exploser, in the preparation of bombs. Dose: Angina Pectoris (Treatment and Prevention) 10-20 mg orally four times daily, may increase to 40 mg orally four times daily. Erythrityl Tetranitrate ( Cardilate ) 10 mg orally/SL as needed to no more than 100 mg/day

39. 39 Isosorbide dinitrate Structure: IUPAC: 3,7-dihydro-2,6- dioxynitrate   -D-glucitol Properties: Hard colorless crystals, odorless, soluble in water, freely soluble in organic solvent such as acetone, alcohol, ether. Molecular Formula: C 6 H 8 N 2 O 8

40. 40 Synthesis: Step-I: D-glucose undergoes hydrogenation with platinum as catalyst to yield D- sorbital

41. 41 Step-II: D- sorbital upon treating with sulphuric acid loses one molecule of water to yield Isosorbide

42. 42 Step-III: Isosorbide on nitration yields Isosorbide dinitrate

43. 43 Mechanism of Action: Isosorbide dinitrate is converted to the active nitric oxide to activate guanylate cyclase . This activation increases levels of cyclic guanosine 3',5'-monophosphate ( cGMP ). cGMP activates protein kinases and causes a series of phosphorylation reactions which leads to dephosphorylation of myosin light chains of smooth muscle fibers. Finally there is a release of calcium ions which causes smooth muscle relaxation and vasodilation .

44. 44 Pharmacokinetics: Oral route of administration, metabolized in the liver, eliminated through urine Adverse Drug Reactions: Headache dizziness  lightheadedness Fast, slow, pounding, or uneven heart rate; worsening angina pain; blurred vision or dry mouth; Nausea, vomiting, sweating, pale skin, feeling like you might pass out; or. Blue-colored skin, tiredness, and feeling short of breath. Flushing may occur as your body adjusts to this medication.

45. 45 Therapeutic Uses: Isosorbide dinitrate is used to prevent chest pain (angina) in patients with a certain heart condition (coronary artery disease). This medication belongs to a class of drugs known as nitrates. It works by relaxing and widening blood vessels so blood can flow more easily to the heart. Dose: 5 to 20mg orally 2 to 3 times a day- Intermediate release 40 to 60 mg/day orally

46. 46 c. Peripheral coronary vasodilators These are further sub-divided into two categories, namely i . Potassium channel activators: Nicorandil Minoxidil Diazoxide ii. Other Peripheral vasodilators: Dipyridamole Papaverine

47. 47 Dipyridamole Structure: IUPAC: 2,2',2'',2'''-{[4,8-Di(piperidin-1-yl) pyrimido [5,4-d]pyrimidine-2,6-dinitro} tetraethanol Properties: Bright yellow color, almond and methanol flavor Molecular formula: C 24 H 40 N 8 O 4

48. 48 Pharmacokinetics: Oral, i.v route of administration, metabolized in the liver ( glucuronidation ), eliminated through urine Adverse Drug Reactions: dizziness, stomach upset, diarrhea, vomiting, Headache, and. Flushing (warmth, redness, or tingly feeling under your skin), particularly at first as your body adjusts to the medication.

49. 49 Therapeutic Uses: Dipyridamole is used to dilate blood vessels in people with peripheral arterial disease and coronary artery disease. Dipyridamole has been shown to lower pulmonary hypertension without significant drop of systemic blood pressure It inhibits formation of pro-inflammatory cytokines (MCP-1, MMP-9) in vitro and results in reduction of hsCRP  in patients. It inhibits proliferation of smooth muscle cells in vivo and modestly increases unassisted patency of synthetic arteriovenous hemodialysis grafts. It increases the release of tissue plasminogen activator from brain microvascular endothelial cells.

50. 50 It results in an increase of 13-hydroxyoctadecadienoic acid and decrease of 12-hydroxyeicosatetraenoic acid in the subendothelial matrix and reduced thrombogenicity of the subendothelial matrix. Pretreatment it reduced reperfusion injury in volunteers. It has been shown to increase myocardial perfusion and left ventricular function in patients with ischemic cardiomyopathy . It results in a reduction of the number of thrombin and PECAM-1 receptors on platelets in stroke patients. Dose: The recommended dose is 75-100 mg four times daily as an adjunct to the usual warfarin therapy. Please note that aspirin is not to be administered concomitantly with coumarin anticoagulants.

51. Calcium Channel Blockers 51

52. 52 These drug include a heterogeneous class of compound which act by preventing the entry of ca +2 ions the cells which are required for the contraction of muscles. The drugs act on the ca +2 ions cause blockage of ca +2 channels. The ultimate effect of these drugs would be relaxation of muscular system or decreases in muscular activity and negative inotropic, chronotropic effects on heart.

53. 53 These are further sub-divided into Three categories, namely a. Phenyl alkyl amine derivative b. Benzothiazepine derivaties c. Dihydropyridine derivatives

54. 54 General Mechanism of action: ca +2 channels blockers act by inhibiting the voltage sensitive calcium channel and there by prevent the entry of extracellular calcium into the myocardial and vascular smooth muscle cells. This leads to decrease in availability of intracellular calcium and consequent decrease in calcium dependant coupling of action and myosin filaments in the muscle leading to relaxation of the muscle Therapeutic uses: Used in the treatment of hypertension, Angina, Cardiac arrhythmias, Hypertrophic cardiomyopathy .

55. 55 a. Phenyl alkyl amine derivative The drugs which comes under Phenyl alkyl amine derivative 1. Verapamil 2. Bepridil

56. 56 Verapamil: Structure: IUPAC: 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxy phenyl) ethyl] (methyl) amino}-2-(propan-2-yl) pentanenitrile Properties: It is viscous pale yellow oil having a boiling point of 246 O C insoluble in water, sparingly soluble in Hexane, soluble in benzene and ether, freely soluble in the acetone, alcohol, ethyl acetate and chloroform. It is available as Verapamil Hcl which is a white crystalline powder soluble in water, methanol. molecular formula: C 27 H 38 N 2 O 4

57. 57 Pharmacokinetics: Verapamil is well absorbed on oral administration but its bioavailability is less due to extensive first pass hepatic metabolism. The onset of action is quick. It is highly bound to plasma proteins. The plasma half-life is about 5-6 hours. The metabolite of Verapamil is also active. It is primarily excreted in urine. Adverse Drug Reactions: Constipation, headache, dizziness, hypotension, bradycardia . Congestive heart failure, nausea, tiredness, flushing, shortness of breath Skin itching, rapid weight gain, stomach pain, sweating, liver problems.

58. 58 Therapeutic Uses: Used in the treatment of hypertension, angina, arrhythmia. It helps to prevent the stroke, heart attacks and kidney problems, prevent chest pain. Dose: 40-80 mg t.i.d orally.

59. 59 Bepridil hydrochloride Structure: IUPAC: N-benzyl-N-[3-(2-methylpropoxy)-2- (pyrrolidin-1-yl) propyl ] aniline Molecular Formula: C 24 H 37 ClN 2 O 2

60. 60 Properties: White or half white crystalline powder with bitter taste, slightly soluble in water, soluble in acetone, very slightly soluble in chloroform, alcohol. Pharmacokinetics: Oral route of administration, metabolized in liver by cytochrome enzyme, undergoes renal elimination. Adverse Drug Reactions: fatigue or tiredness, nausea, upset stomach, diarrhea, constipation, dyspepsia, dry mouth Headache, nervousness, dizziness, trouble sleeping (insomnia), or tremor (shaking), drowsiness. Flu syndrome, palpitation, Dyspnea , respiratory infection Abdominal pain, Tremors, insomnia, nervousness.

61. 61 Therapeutic Uses: It is a ca + 2 channel blockers used to prevent hypertension, angina. Dose: The usual starting dose of Vascor is 200 mg once daily.

62. 62 b. Benzothiazepine derivatives The drugs which comes under Benzothiazepine derivatives Diltiazem

63. 63 Diltiazem hydrochloride Structure: IUPAC: 5-[2-( dimethylamino )ethyl]-2-(4-methoxyphenyl)-4-oxo-1,5-benzothiazepin-3-yl acetate Properties: White crystalline powder, freely soluble in water, methanol, methylene chloride, slightly soluble in ethanol, odorless, bitter taste, insoluble in benzene. Molecular formula: C 22 H 27 ClN 2 O 4 S

64. 64 Pharmacokinetics: Oral, I.V roué of administration, it is subject to extensive first-pass metabolism, which explains its relatively low absolute oral bioavailability. It undergoes metabolism primarily mediated by CYP3A4, due to its extensive metabolism, only 2% to 4% of the unchanged drug can be detected in the urine. Adverse Drug Reactions: Dizziness, lightheadedness, weakness, nausea, Flushing, constipation, and headache may occur. Hypotension, nausea, GI disturbances, hepatitis, dermatitis, allergic reactions Tinnitus, Thrombocytopenia, not recommended for pregnant women, breast feeding women.

65. 65 Therapeutic Uses: Diltiazem  is used to prevent chest pain (angina). It may help to increase your ability to exercise and decrease how often you may get angina attacks. Diltiazem is called a calcium channel blocker. It works by relaxing blood vessels in the body and heart and lowers the heart rate. Blood can flow more easily and your heart works less hard to pump blood. Dose: 30-60 mg b.i.d , orally.

66. 66 c. Dihydropyridine derivatives The drugs which comes under Dihydropyridine derivatives First Generation 1. Nefedipine Second Generation 1. Amlodipine 2. Felodipine 3. Nicardipine 4. Nimodipine

67. 67 Nifedipine Structure: IUPAC: 3,5-dimethyl,2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine -3,5-dicarboxylate Molecular formula: C 17 H 18 N 2 O 6

68. 68 Properties: Yellow crystalline odorless powder, soluble in acetone, chloroform, ethyl acetate, methanol, methylene chloride. Pharmacokinetics: It is well absorbed on oral administration. The onset of action is quick but the duration of action is short. It is highly bound to plasma proteins. It is primarily excreted in urine. Adverse Drug Reactions: Dizziness, headache, drowsiness, nausea Tachycardia, cough, shortness of breathing, Heart failure, hypotension Flushing, oedema, feeling tired.

69. 69 Therapeutic Uses: It is used in the treatment of hypertension. However nifedipine is not recommended for the long term treatment of hypertension. It is used in the treatment of some peripheral vascular diseases like Raynaud’s syndrome. It is used as an alternative tocolytic agent. It can also be used in angina. Dose: 10-20 mg t.i.d , orally.

70. 70 Amlodipine Structure: IUPAC: 3-ethyl-5methyl-2-(2-aminoethoxymethyl)-4-(2-chloroPhenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Molecular formula: C 20 H 25 ClN 2 O 5

71. 71 Properties: White powder, slightly soluble in water, soluble in methanol, ethanol, propanol . Pharmacokinetics: Oral roué of administration, it undergoes metabolism primarily mediated by CYP3A4, it is excreted via kidneys. Adverse Drug Reactions: Nausea, headache, dizziness, depression, Flushing, oedema, palpitations, dyspepsia, dyspnoea, mood changes, pancreatitis, Visual disturbances, rashes, hepatitis.

72. 72 Therapeutic Uses: Used as antihypertensive agent can be used alone or in combination with other drugs like ACE inhibitor, adrenergic blockers or diuretics to treat hypertension. It is also used as anti anginal drug. Used in the treatment of diabetic kidney disease, chest pain, heart failure, silent heart attack. Dose: 2.5-10 mg OD Daily.

73. 73 Felodipine Structure: IUPAC: 3-ethyl5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Molecular formula: C 18 H 19 Cl 2 NO 4

74. 74 Properties: White or yellow crystalline powder, practically insoluble in water, freely soluble in acetone, ethanol, methanol, methylene chloride. Pharmacokinetics: Oral route of administration, hepatic metabolism primarily via cytochrome P450 3A4. Six metabolites with no appreciable vasodilatory effects have been identified. Although higher concentrations of the metabolites are present in the plasma due to decreased urinary excretion, these are inactive. Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta. Adverse Drug Reactions: Head ache, dizziness, drowsiness, nervousness Weakness, nausea, difficulty in breathing, sneezing Constipation, diarrhea, stomach pain, Joint pain, redness, skin rashes, redness of skin, muscle cramps, Irregular heartbeat, chest pain, sweating Swelling of hands, legs, face

75. 75 Therapeutic Uses: Used to treat hypertension, angina pectoris. It will prevent the stroke, heart attacks, and kidney problems. It is known as ca + 2 channel blockers by blocking calcium this medication relaxes and widens blood vessels so blood can flow more easily. Dose: 2.5–10 mg once daily.

76. 76 Nicardipine Structure: IUPAC: 3-{2-[benzyl(methyl) amino]ethyl} 5-methyl 2,6 dimethyl -4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Molecular formula: C 26 H 29 N 3 O 6

77. 77 Properties: White crystalline powder, soluble in water Pharmacokinetics: Oral, I.V route of administration, it is metabolized extensively by the liver, eliminated through kidneys. Adverse Drug Reactions: Headache, dizziness or lightheadedness, numbness upset stomach, constipation, dry mouth excessive tiredness, flushing fast heartbeat, muscle cramps heartburn, increased sweating It may cause damage to brain, heart, blood vessels, kidney and other body parts Loss of vision

78. 78 Therapeutic Uses: Nicardipine is used to treat high blood pressure and to control angina (chest pain). Nicardipine is in a class of medications called calcium channel blockers. It lowers blood pressure by relaxing the blood vessels so the heart does not have to pump as hard. It controls chest pain by increasing the supply of blood and oxygen to the heart. Dose: 20-40 mg q8h oral route. 0.5- 2 mg/hr I.V route.

79. 79 Nimodipine: Structure: IUPAC: 3-(2-methoxyethyl) 5-propan-2-yl2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Molecular formula: C 21 H 26 N 2 O 7

80. 80 Properties: Yellow crystalline powder, soluble in ethyl acetate, sparingly soluble in ethanol, insoluble in water. Pharmacokinetics: Oral, I.V route of administration. Hepatic metabolism via CYP 3A4. Nimodipine is eliminated through urine, and feces. Adverse Drug Reactions: Flushing, headache nausea, dizziness Palpitation, constipation, vomiting Sweating, unusually fast or slow heartbeats Fainting, low blood pressure (hypotension). Thrombocytopenia, decrease platelet count Sweating, muscle pain, liver disease.

81. 81 Therapeutic Uses: Used to decrease problems due to certain type of bleeding in the brain. Used in the treatment of high blood pressure. It is not regularly used to treat the head injury, used to prevent the seizures in women. Dose: The oral dose is 60 mg (two 30 mg capsules) every 4 hours for 21 consecutive days, preferably not less than one hour before or two hours after meals.

82. 82 Reference books Text book of Medicinal chemistry volume-1-3 rd edition by V.Alagarasamy. Text book of Medicinal chemistry volume-2-3 rd edition by V.Alagarasamy. Medicinal chemistry by Rama Rao Nadendla. Essentials of Medicinal chemistry 2 nd edition by Andrejus Korol Kovas. Faye’s Principles of Medicinal Chemistry- 7 th edition by Thoms L.Lemke , Victoria F.Roche , S. Willam Zito . Medicinal Chemistry- 4 th edition by Ashutosh Kar . Medicinal and Pharmaceutical Chemistry by Harkishan Singh, V.K Kapoor . Wilson and Gisvolid’s Textbook of Organic Medicinal and Pharmaceutical chemistry-12 th edition by John M. Beale, John. H. Block.

83. 83 Thank YOU