31 Dec 2012

Mechanism of action : All drugs in pharmacology - Part 3

Mechanism of action : All drugs in pharmacology - Part 3

Cardiovascular system

  • ACE Inhibitors :

    ( Captopril , Enalopril , Lisinopril .... )

    It blocks the enzyme that cleaves angiotensin I to form angiotensin II . Thus , circulating angiotensin II levels are reduced and decreases secretion of aldosterone resulting in decreased sodium and water retention . It also diminishes the rate of bradykinin inactivation.

  • Angiotensin Receptor Blockers ( ARBs ) :

    ( Losartan , Valsartan , Candesartan .... )

    It competes strongly with angiotensin for angiotensin type I receptors. This leads to complete blockade of angiotensin action.


  • Direct Vasodilators :

    ( Nitrate , Hydralazine , Isosorbide dinitrate.... )

    It cause dilation of venous ( or arterial ) blood vessels leads to reduced system venous (or arterial ) resistance and decrease preload ( or afterload ).

  • Digitalis ( Digoxin ) :

    It inhibits Na/K ATPase and this increases the concentration of intracellular Na and decreases the concentration of gradient across the membrane.
    Consequently, the ability of Na/Ca exchanger to move calcium out of the cell is decreased. So that , more Ca is retained intracellularly and small increase in the free Ca available at the next contraction cycle of the cardiac muscle , thereby increasing cardiac contractility.

  • Organic Nitrates :

    ( Nitroglycerine , Isosorbide dinitrate , .... )

    It inhibits coronary vasoconstriction so increasing perfusion of the myocardium and thus relieving vasospastic angina. It relaxes the veins so decreasing preload and myocardial oxygen consumption and thus treating classic angina.

    (Nitroglycerine + )

    It is converted to nitrite ions then to nitric oxide which increases cGMP and leads to dephosphorylation of myosin light chains resulting in vascular smooth muscle relaxation.
      

  • Thiazide Diuretics :

    ( Hydrochlorothiazide, Chlorothalidone, .... )

    It increases sodium and water excretion. This causes a decrease in extracellular volume resulting in a decrease in cardiac output and renal blood flow. This leads to lowering of blood pressure. 

  • Loop Diuretics :

    ( Furosemide , Bumetanide , Torsemide.... )

    It causes decreased renal vascular resistance and increased renal blood flow.

  • Platelete aggregation inhibitors :

    ( Aspirin )

    Aspirin inhibits thromboxane A2 synthesis from arachidonic acid in platelets by irreersible acetylation of a serine preventing arachidonic acid from binding to active site , thus , inhibition of COX-1 which is required for conversion of arachidonic acid to prostaglandin H2 which is converted to thromboxane A2 which promotes the dum[ing process that is essential for the rapid formation of hemostatic plug.

    ( Ticlopidine , Clopidogrel , Others ... )

     It irreversibly inhibit the binding of ADP to its receptors on platelets and thereby inhibit the activation of Gp IIb/IIIa receptors required for platelets to bind to fibrinogen and to each other.

  • Thrombin Inhibitors :

    ( Heparin )

    Heparin binds to anti-thrombin III and accelarates its rate of action about 1000 folds. Anti-thrombin III inhibits serine proteases including several of the clotting factors and thrombin.

  • Vitamin K antagonists :

    ( Warfarin, Dicumarol, Bishydroxycoumarin .... )

    It inhibits vitamin K epoxide reductase enzyme that is required for vitamin K regeneration. This leads decrease in vitamin K levels which is an essential co-factor for synthesis of coagulation factors by the liver. This leads to production of clotting factors with diminished activity.

  • Thrombolytic agents :

    ( Alteplase, Streptokinase, Urokinase .... )

    It converts plasminogen into plasmin which cleaves fibrin thus lysing thrombi.

  • HMG CoA reductase inhibitors ( STATINS ) :

    ( Lovastatin, Simvastatin, Provastatin .... )

    It competes with HMG CoA reductase enzyme and inhibit it which is the rate-limiting step in cholesterol synthesis. This leads to depletion of the intracellular supply of cholesterol.> Lower serum lipoprotein concentration.

  • Niacin ( Nicotinic Acid ) :

    Niacin strongly inhibits lipolysis in adipose tissue. This leads to reduction of free fatty acids production. This results in reduction in VLDL concentration and also results in a decreased plasma LDL concentration. Thus both plasma triacylglycerol and cholesterol are lowered. It also increases HDL levels.

  • The fibrates :

    ( Fenofibrate, Gemfibrozil, .... )

    It leads to decreased triacylglycerol concentration by increasing the gene expression of lipoprotein lipase and decreasing apo C II concentration. It also increases the level of HDL cholesterol by increasing the expression of apo A I and apo A II .

  • Bile acid-binding resins :

    ( Cholestyramine, Colestipol, Colesevelam.... )

    It binds bile acids and bile salts in the small intestine forming complex which is excreted in feces ,thus, preventing the bile acids from returning to the liver and this causes hepatocytes to increase conversion of cholesterol to bile acids.
    Consequently, intracellular cholesterol concentration decreases leading to a fall in plasma LDL. The final outcome is : a decreased total plasma cholesterol concentration. 

  • Potassium-sparing Diuretics :

    ( Spironolactone, Amiloride, .... )

    It antagonizes aldosterone at intracellular cytoplasmic receptors sites. The spironolactone-receptor complex is inactive. This results in a failure to produce proteins that normally stimulate Na/K exchange sites of the collecting tubules. This prevents Na re-absorption and , therefor , K and H secretion.

    NEXT PART : MECHANISM OF ACTION FOR ALL DRUGS ACTING ON ENDOCRINE SYSTEM

0 comments:

Post a Comment