Anti-anginal:

Vasodilators: Amyl nitrite, Nitroglycerin*, Pentaerythritol tetranitrate, Isosorbide dinitrite*, Dipyridamole.

Calcium channel blockers: classification of entire and SAR of only “dipine” class: Verapamil, Bepridil
hydrochloride, Diltiazem hydrochloride, Nifedipine, Amlodipine, Felodipine, Nicardipine, Nimodipine.

Diuretics: Classification mechanistic and chemical both and SAR of highlighted classes

Carbonic anhydrase inhibitors: Acetazolamide*, Methazolamide, Dichlorphenamide.

Thiazides: Chlorthiazide*, Hydrochlorothiazide, Hydroflumethiazide, Cyclothiazide

Loop diuretics: Furosemide*, Bumetanide, Ethacrynic acid.

Potassium sparing Diuretics: Spironolactone, Triamterene, Amiloride. Osmotic Diuretics: Mannitol

Vasodilators

Organic Nitrates and nitrites :

isopentyl nitrite

All above are esters of nitrate except amyl nitrite ,

Mechanism of nitrates :

Vasodilator drugs relax the smooth muscle in blood vessels, which causes the vessels to dilate. Dilation of
arterial vessels leads to a reduction in systemic vascular resistance, which leads to a fall in arterial blood
pressure. Dilation of venous vessels decreases venous blood pressure.

The nitrates and nitrites are simple organic compounds that metabolize to a free radical nitric oxide
(NO) at or near the plasma membrane of vascular smooth muscle cells. NO is the most potent
endogenous vasodilator . NO is a highly reactive species with a very short half-life of few seconds. It
is an endothelium derived relaxing factor (EDRF) that influences vascular tone. Nitric oxide induces
vasodilation by stimulating soluble guanylate cyclase to produce cyclic GMP (cGMP) as shown
in Figure .
Anti-hyperlipidemic agents

Classification mechanistic Clofibrate, Lovastatin, Cholestyramine and Cholestipol

BILE ACID SEQUESTRANTS (chelating agents) : Cholestyramine , colestipol,

Cholestyramine was originally developed in the 1960s to treat pruritus (itching ) secondary to elevated plasma
concentrations of bile acids in patients with cholestasis. Its ability to bind (i.e., to hold or to sequester) bile
acids and to increase their fecal elimination was subsequently shown to produce beneficial effects in lowering
serum cholesterol levels.

Colestipol and colesevelam, which retain the key structural features required to bind bile acids.

Cholestyramine, colestipol, and colesevelam are chemically classifi ed as anion-exchange resins

Mechanism of Action

Cholestyramine, colestipol, lower plasma LDL levels by indirectly increasing the rate at which LDL is cleared
from the bloodstream. Under normal circumstances, approximately 97% of bile acids are reabsorbed into the
enterohepatic circulation. these compounds are returned to the liver where they regulate their own
production. Bile acid sequestrants are not orally absorbed but, rather, act locally within the gastrointestinal
tract to interrupt this process. They bind the two major bile acids, glycocholic acid and taurocholic acid, and
greatly increase their fecal excretion. As a result, decreased concentrations of these compounds are returned
to the liver. This removes the feedback inhibition of 7α-hydroxylase and increases the hepatic conversion of
cholesterol to bile acids

The decreased return of bile acids to the liver also will produce an increase in triglyceride synthesis and a
transient rise in VLDL levels. Subsequent compensatory mechanisms will increase VLDL removal, most likely
through the increased LDL receptors, and return VLDL levels to predrug levels.

Structure–Activity Relationships

Cholestyramine is a copolymer consisting primarily of polystyrene, with a small amount of divinylbenzene as

the cross-linking agent. In addition, it contains approximately 4 mEq of fixed quaternary ammonium groups
per gram of dry resin. These positively charged groups function as binding sites for anions. Virtually all of these
sites are accessible to bile acids. Increasing the amount of divinylbenzene from 2% to 4% to 8% increases the
cross-linkage and reduces the porosity of the resin. This prevents binding of bile acids to interior sites and
decreases the efficacy of the compound.

Colestipol is a copolymer of tetraethylenepentamine and epichlorhydrin and is commercially marked as its

hydrochloride salt. The key functional groups on colestipol are the basic secondary and tertiary amines.
Although the total nitrogen content of colestipol is greater than that of cholestyramine, the functional anion-
exchange capacity of the resin depends on intestinal pH and may be less than cholestyramine. Comparative in
vitro studies indicate that cholestyramine has a higher adsorption capacity than colestipol for bile salts

Cholestyramine, colestipol, and colesevelam are not orally absorbed and are not metabolized by
gastrointestinal enzymes. They are excreted in the feces as an insoluble complex with bile acids.

Therapeutic Application
Bile acid sequestrants are indicated for the treatment of hypercholesterolemia in patients who do not
adequately respond to dietary modifi cations. They may be used either alone or in combination with HMGRIs
or niacin.

HMGCoA REDUCTASE INHIBITORS: Lovastatin

All of these compounds effectively block the conversion of HMG-CoA to mevalonic acid
and have similar effects on plasma cholesterol levels. The compounds differ somewhat in their indications,
potencies, and pharmacokinetic profi les. They often are referred to as statins or vastatins. Because of the
potential confusion of the terms “statin” and “statine” (i.e., a stable dipeptide mimic ) it is suggested here that
classifying an HMGRI as a vastatin is preferable to classifying it as a statin

FIBRATES

The use of this class of drugs to treat hyperlipoproteinemias can predates the use of bile acid sequestrants
and HMGRIs. A random screening test on a series of aryloxyisobutyric acids demonstrated that these
compounds could lower both plasma cholesterol and total lipid levels . The compound that produced the best
balance between activity and toxicity was ethyl p-chloroaaaphenoxyisobutyrate . Later renamed clofibrate,
this compound was subsequently shown to be a prodrug for p-chlorophenoxyisobutyric acid (clofibric acid)
trials indicated that despite a 9% lowering of cholesterol, patients taking clofibrate showed no reduction of
cardiovascular events and actually had an increase in overall mortality. Although clofibrate is no longer
available in the United States, it has served as the prototype for the design of safer and more effective
fibrates. Structural modifications, focused primarily on ring substitutions and the addition of spacer groups,
have produced a number of active compounds.

Mechanism of Action

Overall, fibrates decrease plasma triglyceride levels much more dramatically than they decrease plasma
cholesterol levels. They significantly decrease VLDL levels, cause a moderate increase in HDL levels, and have
variable effects on LDL concentrations. As an example of this latter point, gemfibrozil will raise LDL levels in
patients with hypertriglyceridemia but lower LDL levels in patients with normal triglyceride levels. The exact
mechanisms for these actions have not been fully elucidated; however, studies have shown that this class of
compounds can produce a variety of beneficial effects on lipoprotein metabolism.

Decreases in plasma VLDL primarily result from the ability of these compounds to stimulate the activity of
lipoprotein lipase, the enzyme responsible for removing triglycerides from plasma VLDL . Additionally, fibrates
can lower VLDL levels through PPAR gamma -mediated stimulation of fatty acid oxidation, inhibition of
triglyceride synthesis, and reduced expression of apoC-III. This latter effect enhances the action of lipoprotein
lipase because apoC-III normally serves as an inhibitor of this enzyme

Coagulant & Anticoagulants

Mechanistic classification

Warfarin

Warfarin sodium is rapidly and completely absorbed (∼100% bioavailability) following oral, intramuscular,
intravenous, or rectal administration. Peak plasma concentrations occur at approximately 3 hours. Its
anticoagulant effect is not immediately present, however, following initiation of therapy. Instead, a delay in
onset of anticoagulation occurs while the clotting factors with normal activity are cleared and those that have
not been carboxylated because of the actions of warfarin reach physiologically significant levels. On average,
this delay is approximately