Nephron sites of action of diuretics
Osmotic Diuretics <ul><li>Mannitol , urea, glycerine, isosorbide </li></ul><ul><li>Properties of osmotic diuretics:  </li>...
Mechanism of Action <ul><li>OD is filtrated and increases osmotic pressure in tubular lumen </li></ul><ul><li>Hence, incre...
Carbonic Anhydrase Inhibitor   Acetazolamide,  Dichlorphenamide, Metazolamide   <ul><li>Mechanism of Actions </li></ul><ul...
Synthesis of acetazolamide Methazolamide Dichlorphenamide
Thiazides <ul><li>Hydrochlorothiazide (HCT), Chlorothiazide, Bendroflumethiazide, Chlorthalidone, Metolazone, Indapamide) ...
Effects on Electrolytes <ul><li>Increases Na+ and Cl- excretion </li></ul><ul><li>K +  excretion also increase associated ...
Loop Diuretics <ul><li>Furosemide, torasemide, bumetanide, ethacrynic acid </li></ul><ul><li>Site of action: thick ascendi...
Potassium Sparing Diuretics <ul><li>Na +  channel inhibitor  (Amiloride, triamterene) </li></ul><ul><ul><li>   Inhibit Na...
 
Cardiovascular Drugs
MAJOR CLASSIFICATION :- <ul><li>ANTI-HYPERTENSIVES </li></ul><ul><li>CARDIAC GLYCOSIDES </li></ul><ul><li>ANTI-ARRHYTHMIC ...
ANTI-HYPERTENSIVES : Classification <ul><li>centrally acting -   -agonists, others </li></ul><ul><li>ganglionic blocking ...
Direct Acting Agents  (Vasodilators) <ul><li>Nitric Oxide </li></ul><ul><li>Nitroprusside </li></ul><ul><li>Nitroglycerine...
STRUCTURE OF VASODILATORS Sodium Nitroprusside Hydralazine Purine
ACE Inhibitors <ul><li>Angiotensinogen </li></ul><ul><li> renin </li></ul><ul><li>Angiotensin I  Bradykinin </li></ul><...
ACE Inhibitors <ul><li>Captopril – active with active metabolites </li></ul><ul><li>Enalapril – prodrug via hepatic metabo...
Captopril Enalapril Lisinopril Ramipril STRUCTURE OF ACE INHIBITORS
Potassium Channel Openers <ul><li>Minoxidil </li></ul><ul><li>Diazoxide </li></ul><ul><li>Pinacidil </li></ul><ul><li>ATP ...
 -Adrenergic Blockers <ul><li>Phenyoxybenzamine </li></ul><ul><li>Phentolamine </li></ul><ul><li>Prazosin </li></ul><ul><...
Calcium Channel Blockers <ul><li>Verapamil </li></ul><ul><li>Nimodipine, Nifedipine, Nicardipine </li></ul><ul><li>Amlodip...
Verapamil Nimodipine Nicardipine Amlodipine Diltiazem STRUCTURES
Chemical classes & Actions of calcium channel blockers <ul><li>phenylalkylamines -  verapamil </li></ul><ul><ul><li>act on...
 -adrenergic agonists <ul><li>Include: </li></ul><ul><ul><li>Adrenaline </li></ul></ul><ul><ul><li>Noradrenaline </li></u...
Structure of Beta- adrenergic agonists Adrenaline Isoprenaline Dopamine Dobutamine Dopexamine
Cardiac Glycosides <ul><li>combination of an aglycone, or  genin , with 1-4 sugar molecules </li></ul><ul><ul><li>pharmaco...
<ul><li>Digitoxin </li></ul><ul><li>Gitoxin </li></ul><ul><li>Digoxin </li></ul><ul><li>Ouabain(strphanthin-G) </li></ul><...
ANTI-ARRHYTHMIC AGENTS : Arrhythmia <ul><li>an arrhythmia is, </li></ul><ul><ul><li>an abnormality of the  rate ,  regular...
<ul><li>Class-1 : quinidine,lignocaine, flecainide </li></ul><ul><li>Class-2 : propranolol,sotalol. </li></ul><ul><li>Clas...
Amiodarone <ul><li>class III antiarrhythmic agent effective orally & IV in the treatment of ventricular and atrial arrhyth...
Amiodarone Flecainide
ANTICOAGULANT  AND  ANTIPLATELET DRUGS
<ul><li>Haemostasis  is the arrest of blood loss from a  </li></ul><ul><li>damaged vessel. This usually involves:  </li></...
Intrinsic pathway Extrinsic pathway XII XIIa XIa XI IX Ca 2+ IXa PF-3 Ca 2+ VIII Xa Ca 2+ PF-3 V X X III Ca 2+ VIIa    VI...
<ul><li>ANTICOAGULANTS </li></ul><ul><li>Two types of drugs are employed in  </li></ul><ul><li>preventing blood coagulatio...
<ul><li>Heparin </li></ul><ul><li>Heparin is a rapidly- acting anticoagulant.  </li></ul><ul><li>Heparin occurs normally c...
<ul><li>Mechanism of Action   </li></ul><ul><li>Heparin increases activity of antithrombin III  </li></ul><ul><li>which in...
<ul><li>Therapeutic   uses </li></ul><ul><li>preoperative prophylaxis against deep  </li></ul><ul><li>vein thrombosis </li...
<ul><li>Warfarin </li></ul><ul><li>Warfarin is a coumarin derivative.  </li></ul><ul><li>Another  example is dicoumarol.  ...
<ul><li>Adverse effects </li></ul><ul><li>bleeding </li></ul><ul><li>hemorrhagic infarction in the breast,  intestine and ...
<ul><li>ANTIPLATELET   DRUGS </li></ul><ul><li>These include: </li></ul><ul><li>Cyclooxygenase  inhibitors –  aspirin  etc...
<ul><li>Inhibitors of ADP receptor activity  – eg </li></ul><ul><li>ticlopidine, clopidogrel. </li></ul><ul><li>Ticlopidin...
BIBLIOGRAPHY:- <ul><li>HKS & V.K.Kapoor – Medical & pharmaceutical      chemistry  2 nd  edition reprint. </li></ul><ul><l...
<ul><li>SOUMYAKANTA  MISHRA </li></ul><ul><li>0281961106 (Roll no.) </li></ul><ul><li>8 th semester </li></ul><ul><li>M.S....
 
SYNTHESIS
SYNTHESIS OF ACETAZOLAMIDE
CONVERSION OF L-MANNITOL
SYNTHESIS OF UREA 2NH3 + CO2  NH2COONH4 ammonium carbamate NH2COONH4  NH2CONH2 + H2O urea
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Diuretics, cardiovascular drugs, antiplatelets n anticoagulant.

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  • Diuretics, cardiovascular drugs, antiplatelets n anticoagulant.

    1. 2.
    2. 3. Nephron sites of action of diuretics
    3. 4. Osmotic Diuretics <ul><li>Mannitol , urea, glycerine, isosorbide </li></ul><ul><li>Properties of osmotic diuretics: </li></ul><ul><ul><li>Freely filtrated by glomerulus </li></ul></ul><ul><ul><li>Negligible tubular reabsorption </li></ul></ul><ul><ul><li>Chemically inert </li></ul></ul><ul><ul><li>Usually non metabolized </li></ul></ul>HO-C-H HO-C-H CH 2 OH CH 2 OH H-C-OH H-C-OH - - - - - Mannitol
    4. 5. Mechanism of Action <ul><li>OD is filtrated and increases osmotic pressure in tubular lumen </li></ul><ul><li>Hence, increases excretion of water and electrolytes </li></ul><ul><li>Almost all of electrolyte are excreted: Na + , K + , Ca ++ , Mg ++ , HCO 3 - , phosphate </li></ul>
    5. 6. Carbonic Anhydrase Inhibitor Acetazolamide, Dichlorphenamide, Metazolamide <ul><li>Mechanism of Actions </li></ul><ul><li>Kidney: </li></ul><ul><ul><li>Inhibition of Bicarbonate (HCO3-) reabsorption </li></ul></ul><ul><ul><li>Reduces Na-H-exchange  NaHCO 3 is excreted along w/ H2O </li></ul></ul><ul><li>Eye: </li></ul><ul><ul><li>Inhibits formation of aqueous humor  decreases intra ocular pressure </li></ul></ul><ul><li>CNS: anti convulsive effects </li></ul><ul><ul><li>due to pH decrease </li></ul></ul><ul><ul><li>direct effect </li></ul></ul>
    6. 7. Synthesis of acetazolamide Methazolamide Dichlorphenamide
    7. 8. Thiazides <ul><li>Hydrochlorothiazide (HCT), Chlorothiazide, Bendroflumethiazide, Chlorthalidone, Metolazone, Indapamide) </li></ul><ul><li>Mechanism of Actions </li></ul><ul><ul><li>Thiazides are secreted by proximal tubules but works in distal convoluted tubules </li></ul></ul><ul><ul><li>Inhibit Na + -Cl - symporter from the lumen to tubular cells  increase Na + , Cl - excretion (and water) </li></ul></ul><ul><ul><li>Some thiazides have weak CA-I effect </li></ul></ul>
    8. 9. Effects on Electrolytes <ul><li>Increases Na+ and Cl- excretion </li></ul><ul><li>K + excretion also increase associated with increased Na+ in distal tubules. </li></ul><ul><li>Inhibits uric acid secretion  hyper uricemia and gout </li></ul><ul><li>Decreases Ca 2+ excretion (unknown mechanism)  tends to increase plasma Ca++ </li></ul><ul><li> Delays osteoporotic process </li></ul><ul><li>Increases Mg 2+ excretion </li></ul>
    9. 10. Loop Diuretics <ul><li>Furosemide, torasemide, bumetanide, ethacrynic acid </li></ul><ul><li>Site of action: thick ascending limb of Henle. </li></ul><ul><li>Mechanism: </li></ul><ul><ul><li>Loop diuretics should be excreted into the lumen </li></ul></ul><ul><ul><li>Inhibits Na + , K + , 2Cl - symporter  significantly increases the excretion of Na + , K + , Cl - </li></ul></ul><ul><ul><li>Osmotic gradient for water reabsorption is also decreased  increasing water excretion </li></ul></ul><ul><ul><li>Ca2+ and Mg2+ are excreted as well. </li></ul></ul>Furosemide Bumetanide
    10. 11. Potassium Sparing Diuretics <ul><li>Na + channel inhibitor (Amiloride, triamterene) </li></ul><ul><ul><li> Inhibit Na+ reabsorption  Na+ excretion </li></ul></ul><ul><ul><li> Reduced K+ secretion  K+ retention </li></ul></ul><ul><li>Aldosterone antagonist (Spironolactone, eplerenone) </li></ul><ul><ul><li>Aldosterone induces the expression of Na/K- ATPase and Na + channel </li></ul></ul><ul><ul><li>Spironolactone and eplerenone blocks aldosterone receptor  reduces Na + reabsorption and K + secretion </li></ul></ul>
    11. 13. Cardiovascular Drugs
    12. 14. MAJOR CLASSIFICATION :- <ul><li>ANTI-HYPERTENSIVES </li></ul><ul><li>CARDIAC GLYCOSIDES </li></ul><ul><li>ANTI-ARRHYTHMIC DRUGS </li></ul><ul><li>ANTI-ANGINAL </li></ul>
    13. 15. ANTI-HYPERTENSIVES : Classification <ul><li>centrally acting -  -agonists, others </li></ul><ul><li>ganglionic blocking agents </li></ul><ul><li> -adrenergic blocking agents </li></ul><ul><li> &  -adrenergic blocking agents </li></ul><ul><li>angiotensin converting enzyme inhibitors </li></ul><ul><li>angiotensin antagonists </li></ul><ul><li>potassium channel &quot;openers&quot; </li></ul><ul><li>calcium channel blockers </li></ul><ul><li>nitrovasodilators & direct agents </li></ul><ul><li>inodilators </li></ul><ul><li>diuretics </li></ul>survey
    14. 16. Direct Acting Agents (Vasodilators) <ul><li>Nitric Oxide </li></ul><ul><li>Nitroprusside </li></ul><ul><li>Nitroglycerine & Organic Nitrates </li></ul><ul><li>Purines / Adenosine </li></ul><ul><li>Hydralazine </li></ul>
    15. 17. STRUCTURE OF VASODILATORS Sodium Nitroprusside Hydralazine Purine
    16. 18. ACE Inhibitors <ul><li>Angiotensinogen </li></ul><ul><li> renin </li></ul><ul><li>Angiotensin I Bradykinin </li></ul><ul><li> ACE   </li></ul><ul><li> Angiotensin II inactive fragments </li></ul><ul><li> </li></ul><ul><li> Angiotensin III </li></ul>
    17. 19. ACE Inhibitors <ul><li>Captopril – active with active metabolites </li></ul><ul><li>Enalapril – prodrug via hepatic metabolism </li></ul><ul><li>Linisopril – active , renal excretion </li></ul><ul><li>Ramipril – prodrug via hepatic metabolism to diacid moiety </li></ul>
    18. 20. Captopril Enalapril Lisinopril Ramipril STRUCTURE OF ACE INHIBITORS
    19. 21. Potassium Channel Openers <ul><li>Minoxidil </li></ul><ul><li>Diazoxide </li></ul><ul><li>Pinacidil </li></ul><ul><li>ATP dependent K + channel </li></ul><ul><ul><li>membrane hyperpolarisation and relaxation </li></ul></ul>Minoxidil Diazoxide Pinacidil
    20. 22.  -Adrenergic Blockers <ul><li>Phenyoxybenzamine </li></ul><ul><li>Phentolamine </li></ul><ul><li>Prazosin </li></ul><ul><li>Trimazosin, Doxazosin </li></ul><ul><li>dual  &  -adrenergic blocking agents </li></ul><ul><ul><li>Labetalol </li></ul></ul><ul><ul><li>Carvedilol </li></ul></ul>
    21. 23. Calcium Channel Blockers <ul><li>Verapamil </li></ul><ul><li>Nimodipine, Nifedipine, Nicardipine </li></ul><ul><li>Amlodipine </li></ul><ul><li>Felodipine </li></ul><ul><li>Diltiazem </li></ul>
    22. 24. Verapamil Nimodipine Nicardipine Amlodipine Diltiazem STRUCTURES
    23. 25. Chemical classes & Actions of calcium channel blockers <ul><li>phenylalkylamines - verapamil </li></ul><ul><ul><li>act on inner phosphorylation gate of Ca channel </li></ul></ul><ul><li>benzothiazepines - diltiazem </li></ul><ul><ul><li>Mechanism unclear </li></ul></ul><ul><li>dihydropyridines - nifedipine </li></ul><ul><ul><li>act on outer gate of calcium channel </li></ul></ul>
    24. 26.  -adrenergic agonists <ul><li>Include: </li></ul><ul><ul><li>Adrenaline </li></ul></ul><ul><ul><li>Noradrenaline </li></ul></ul><ul><ul><li>Isoprenaline </li></ul></ul><ul><ul><li>Dopamine </li></ul></ul><ul><ul><li>Dobutamine </li></ul></ul><ul><ul><li>Dopexamine </li></ul></ul>
    25. 27. Structure of Beta- adrenergic agonists Adrenaline Isoprenaline Dopamine Dobutamine Dopexamine
    26. 28. Cardiac Glycosides <ul><li>combination of an aglycone, or genin , with 1-4 sugar molecules </li></ul><ul><ul><li>pharmacological activity resides in the genin </li></ul></ul><ul><ul><li>attached sugars modify the water/lipid solubility and potency of the glycoside </li></ul></ul><ul><li>genins are related to the bile acids, steroids, sex & adrenocortical hormones, </li></ul><ul><ul><li>cyclopentanoperhydrophenanthrene nucleus </li></ul></ul><ul><ul><li>to which is attached an unsaturated lactone ring at C 17 </li></ul></ul><ul><ul><li>all naturally occurring genins possessing a C 14 -OH </li></ul></ul>
    27. 29. <ul><li>Digitoxin </li></ul><ul><li>Gitoxin </li></ul><ul><li>Digoxin </li></ul><ul><li>Ouabain(strphanthin-G) </li></ul><ul><li>Thevetin </li></ul>Cyclopentanoperhydro ring
    28. 30. ANTI-ARRHYTHMIC AGENTS : Arrhythmia <ul><li>an arrhythmia is, </li></ul><ul><ul><li>an abnormality of the rate , regularity , or site of origin of the cardiac impulse, or </li></ul></ul><ul><ul><li>a disturbance in conduction that causes an alteration of the normal sequence of activation of the atria and ventricles </li></ul></ul><ul><li>these may arise from abnormal impulse generation , altered conduction , or both </li></ul>
    29. 31. <ul><li>Class-1 : quinidine,lignocaine, flecainide </li></ul><ul><li>Class-2 : propranolol,sotalol. </li></ul><ul><li>Class-3 : amiodarone </li></ul><ul><li>Class-4 : verapamil </li></ul>
    30. 32. Amiodarone <ul><li>class III antiarrhythmic agent effective orally & IV in the treatment of ventricular and atrial arrhythmias </li></ul><ul><li>analogue of thyroid hormone </li></ul><ul><ul><li>200 mg tablet containing 75 mg of organic iodine </li></ul></ul><ul><li>prolongs APD and ERP, of atrial, nodal and ventricular tissues </li></ul><ul><ul><li>explains its broad spectrum of activity </li></ul></ul><ul><li>decreases automaticity in the SA node by reducing the slow phase 4 depolarisation </li></ul>
    31. 33. Amiodarone Flecainide
    32. 34. ANTICOAGULANT AND ANTIPLATELET DRUGS
    33. 35. <ul><li>Haemostasis is the arrest of blood loss from a </li></ul><ul><li>damaged vessel. This usually involves: </li></ul><ul><li>localized vasoconstriction </li></ul><ul><li>platelet adhesion and activation </li></ul><ul><li>blood coagulation. </li></ul>
    34. 36. Intrinsic pathway Extrinsic pathway XII XIIa XIa XI IX Ca 2+ IXa PF-3 Ca 2+ VIII Xa Ca 2+ PF-3 V X X III Ca 2+ VIIa  VII Common pathway Prothrombin (factor II) Thrombin XIII XIIIa Fibrinogen Fibrin Stable fibrin polymer
    35. 37. <ul><li>ANTICOAGULANTS </li></ul><ul><li>Two types of drugs are employed in </li></ul><ul><li>preventing blood coagulation, heparin and </li></ul><ul><li>the vitamin K antagonists. </li></ul><ul><li>Their mechanisms of action </li></ul><ul><li>differ, as do their clinical uses. </li></ul>
    36. 38. <ul><li>Heparin </li></ul><ul><li>Heparin is a rapidly- acting anticoagulant. </li></ul><ul><li>Heparin occurs normally complexed to </li></ul><ul><li>histamine in mast cells. </li></ul><ul><li>It is strongly acidic. </li></ul>
    37. 39. <ul><li>Mechanism of Action </li></ul><ul><li>Heparin increases activity of antithrombin III </li></ul><ul><li>which inhibits activated serine proteases </li></ul><ul><li>such as IIa (thrombin) IXa, Xa, XIa, XIIa </li></ul><ul><li>and XIIIa, in the clotting cascade. </li></ul>
    38. 40. <ul><li>Therapeutic uses </li></ul><ul><li>preoperative prophylaxis against deep </li></ul><ul><li>vein thrombosis </li></ul><ul><li>in acute myocardial infarction </li></ul><ul><li>to prevent pulmonary embolism in patients </li></ul><ul><li>with established thrombosis </li></ul><ul><li>to prevent clotting in extracorporeal </li></ul><ul><li>circulation devices. </li></ul>
    39. 41. <ul><li>Warfarin </li></ul><ul><li>Warfarin is a coumarin derivative. </li></ul><ul><li>Another example is dicoumarol. </li></ul><ul><li>These anticoagulants act by antagonizing </li></ul><ul><li>Vit K which is essential for the synthesis </li></ul><ul><li>of a number of clotting factors including </li></ul><ul><li>Factors II, VII, IX. </li></ul>
    40. 42. <ul><li>Adverse effects </li></ul><ul><li>bleeding </li></ul><ul><li>hemorrhagic infarction in the breast, intestine and fatty tissues </li></ul><ul><li>crosses placenta. </li></ul>
    41. 43. <ul><li>ANTIPLATELET DRUGS </li></ul><ul><li>These include: </li></ul><ul><li>Cyclooxygenase inhibitors – aspirin etc </li></ul><ul><li>They are used in unstable angina and </li></ul><ul><li>myocardial infarction </li></ul>
    42. 44. <ul><li>Inhibitors of ADP receptor activity – eg </li></ul><ul><li>ticlopidine, clopidogrel. </li></ul><ul><li>Ticlopidine </li></ul><ul><li>Dextran </li></ul>Clopidogrel Ticlopidine
    43. 45. BIBLIOGRAPHY:- <ul><li>HKS & V.K.Kapoor – Medical & pharmaceutical chemistry 2 nd edition reprint. </li></ul><ul><li>Ashutoshkar- Medicinal Chemistry- 4 th edition. </li></ul><ul><li>Wilson & Gisvold. </li></ul><ul><li>Google.com </li></ul><ul><li>Wikipedia.com </li></ul><ul><li>Science Direct </li></ul>
    44. 46. <ul><li>SOUMYAKANTA MISHRA </li></ul><ul><li>0281961106 (Roll no.) </li></ul><ul><li>8 th semester </li></ul><ul><li>M.S.I.P </li></ul>
    45. 48. SYNTHESIS
    46. 49. SYNTHESIS OF ACETAZOLAMIDE
    47. 50. CONVERSION OF L-MANNITOL
    48. 51. SYNTHESIS OF UREA 2NH3 + CO2 NH2COONH4 ammonium carbamate NH2COONH4 NH2CONH2 + H2O urea
    49. 52. Survey
    50. 53. SURVEY

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