Anti-anginal drugs: Vasodilators – Nitrates (Nitroglycerin, Isosorbide dinitrate, Penta erythritol tetranitrate), Nitrites (Amyl nitrite), Miscellaneous (Dipyridamole).
Hi viewers welcome to chem easy in this video let us discuss about vasodilators this is one of the drug class under anti-anginal drugs to know the complete classification of antioxidant drugs watch classification of anti-anginal drugs video already uploaded in this channel and before watching this video subscribe kmz to learn chemistry easily this is a brief
Introduction about tobacco dilators the vasodilators dilate the blood vessels it means the term itself dilators is included you can understand easily it dilates blood vessels and it affects the muscles in the walls of the arteries and veins so that it prevents the muscles from tightening and also prevents the walls from narrowing as a result of this blood flows
More easily through the vessels so that the heart doesn’t have to pump as hard and reduces the blood pressure the subclasses under vasodilators are nitrates nitrites and miscellaneous that is non-nitrate again the nitrates are classified into short-acting nitrates and long-acting nitrates short-acting nitrates example glycerol trinitrate that is nitroglycerin
And under long-acting nitrates isoscerbide di nitrate isoscerbid mono nitrate erythritol tetra nitrate panto erythritol tetra nitrate then under nitrites the available drugs are abyl nitrite sodium nitrite and sodium nitro president then the non-nitrate includes dibridamol this is a general mechanism of action of nitrates organic nitrates lead to the formation
Of the reactive gaseous free radical nitric oxide and related nitric oxide containing compounds nitric oxide can activate guanelite cyclase then increases the cellular level of cyclic gmp activate protein kinase g and modulate the activities of cyclic nucleotide phosphor diastosis in smooth muscle the net result is reduced phosphorylation of myosin light chain
Reduced calcium ion concentration in the cytosol and relaxation now let us discuss all the important drugs one by one in detail first one is glycerol tri nitrate that is nitro glycerin here the structure of nitroglycerin given and chemically this glycerol trinity is one two three propane trion tri nitrate nitroglycerin can be synthesized by nitration of glycerol
With nitric acid in presence of sulfuric acid the reaction is shown here glycerol with nitric acid and sulfuric acid which is nitrated and gives nitro glycerin nitroglycerin acts by this mechanism that is the nitroglycerin is converted to nitric oxide this nitric oxide is an active intermediate compound it activates the enzyme guanilite cyclase this guanilite
Cyclase stimulates the synthesis of cyclic guanosine monophosphate gmp which then activate a series of protein kinase dependent phosphorylation in the smooth muscle cells results in the d phosphorylation of the myosin light chain of the smooth muscle fiber subsequent release of calcium iron results in the relaxation of smooth muscle cells and vasodilation now
Let us see the structure activity relationship that is yes here of nitroglycerin in a cell free system the potency of organic nitrate for gonalite cyclase activation is mainly determined by the number of nitrate groups it means in glycerol trinity there are three nitrate groups since nitrate induced activation of bonnet cyclase involved the formation of nitric
Oxide free radicals potency therefore increases as nitric group increased in the group increase in lipophilicity due to esterification of the free oh group in isosarbid mononitrate had no major influence on the guanolate cyclase activation next one is metabolism of nitroglycerin it undergoes aquatic metabolism cytochrome p450 is a key enzyme of organic nitrate
Biotransformation nitroglycerin is degraded in the liver by reductive hydrolysis reaction and partially in plasma by spontaneous hydrolysis majority of urinary metabolites of nitroglycerin include glycerol mononitrate one commodore glyceral dye nitrate and one comma three glycerol di nitrate reductive hydrolysis in the liver by hepatic inorganic nitrate reductase
Leads to the formation of nitric oxide radical these are the structures of major urinary metabolites of nitroglycerin that is glycerol mononitrate one comma two glyceral dinitrate one comma three glycerine di nitrate next one is adverse drug reactions of nitroglycerin that is adr common adr includes headache hypotension tachycardia dyspnea dizziness blood vision
Lightheadedness flushing nervousness and serostomium serious adr includes methymoglobinemia this condition is rare then syncope prolonged bleeding time exfoliative dermatitis unstable angina rebound hypotension and thrombocytopenia then therapeutic uses of nitroglycerin includes this nitroglycerin is administered to relieve anginal chest pain and to manage blood
Pressure through vasodilation different preparations of nitroglycerin may also be administered for treatment of renal issues liver issues and even as alignment for anal fissures second drug under nitrates are isoscerbide dinitrate that is isdn here the structure of isdn is given we can draw like this or in this form both are same only to synthesize isosorbite
Dinitrate first the d’s orbital treated with paratoline sulfonic acid it gives iso sorbite in next step the prepared isosarbide undergoes nitration with nitric acid sulfuric acid mixture and gives finally isosarbite dinitrate mechanism of action of isdn isoscerbide dye nitrate which is a nitric oxide donor relaxes smooth muscles via dose dependent dilation
Of arterial and venous beds to reduce both preload and after load as well as myocardial oxygen demand this also improves the coronary collateral circulation lowering blood pressure increasing heart rate and causing occasional paradoxical bradycardia structure activity relationship of iso carbide dinitrate isoscele by dinitrate relaxes vascular smooth muscle by
Formation of the free radical nitric oxide and this nitric oxide activates guanola cyclase thereby increases the synthesis of cyclic gmp within smooth muscle resulting deep phosphorylation of light chain myosin and relaxation of peripheral arteries and veins in addition this drug really relaxes coronary arteries thereby increasing the blood circulation through
Ischemic area next one is metabolism of isosorbite dinitrate biotransformation of organic nitrates is result of reductive hydrolysis which is catalyzed by hepatic enzyme glutathione organic nitrate reductase enzyme converts lipid soluble nitrate esters into more water soluble denitrated metabolites and inorganic nitrite organic nitrates after intravenous or oral
Administration primary metabolite in plasma is five isosorbide mono nitrate so here the structure of five isos orbiter that is the metabolite is given edwards drug reaction of iso carbide dinitrate includes in cardiovascular system rebound hypertension which is uncommon syncope unstable angina flushing hypotension or orthostatic hypotension light-headedness
Palpitations and tachyarrhythmia in case of central nervous system dizziness headache restlessness and weakness in gastrointestinal tract nausea the therapeutic uses of isdn includes this drug is used to prevent chest pain that is an angina in patients with a certain heart condition that is coronary artery disease and this drugs works by relaxing and widening
Blood vessels so blood can flow more easily to the heart this is the third drug under nitrate that is penta erythritol tetra nitrate and this is a structure of penta erythema tetra nitrate mechanism of action of penta erythritol tetra nitrate includes this drug releases free nitric oxide after the denitration reaction this release in nitric oxide triggers nitric
Oxide dependent signaling transduction involving soluble guanolate cyclase nitric oxide binds reversibly to the ferrous heme center of sjc that is soluble granulate cyclase causing conformational change and activating the enzyme this enzyme results in increased cellular concentrations of cyclic guanosine monophosphate that is cyclic gmp within the vascular
Smooth muscle resulting in vasodilation mediated by cyclic gmp dependent protein kinases panto erythritol tetra nitrate is extensively metabolized in the liver and the metabolites includes panto erythritol tri nitrate panto erythritol dinitrate penta erythritol mono nitrate and finally penta erythritol therapeutic uses of penta erythritol tetra nitrate is this
Drug is used propyl actively to reduce the severity and frequency of anginal attacks and usually this drug is administered in sustained release preparations to increase its duration of action next drug is amyl nitrite so this under nitrite category and this is a structure of amyl nitrate which is nothing but one nitro pentane mechanism of action of amine nitrite
Amine nitrite causes a non-specific relaxation of smooth muscle with the most prominent accents occurring in vascular smooth muscle this effect on vascular smooth muscle results in coronary vasodilation and decreased systemic vascular resistance and left ventricular preload and afterload myocardial ischemia is relieved in patients with antenna factories with an
Abutment of chest pain and possible other related symptoms amine nitrite inhalant or absorbed rapidly through the pulmonary alveoli shows therapeutic effects within one minute after inhalation amine nitrite is metabolized hepatically and the drug is metabolized rapidly and probably by hydrolytic denitration reaction approximately one third of the inhaled amine
Nitrate is excreted in the urine the therapeutic uses of forming nitrite is this drug is used to treat the symptoms of acute relief of anxiety and cyanide poisoning and the drug may be used alone or with other medications the last drug is dipredamore this is one of the non-nitrate coronary vasodilator and here you can find the structure of dipetamol mechanism
Of action of dipredamol dipridumon inhibits the cellular reuptake of adenosine into platelets red blood cells and endothelial cells leading to increased extracellular concentrations of adenosine which is a potent vasodilator and diprotomol metabolism takes place hepatically it is slightly bound to plasma proteins and is metabolized in the liver where it is
Conjugated to a glucuronide and this is excreted in the bile therapeutic uses of dipedamol is it is approved for secondary prevention of stroke when it is combined with low dose aspirin and this drug is a long acting vasodilator its vasodilating action is selective for the coronary system and the drug is indicated for long term therapy of chronic enzyme
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Transcribed from video
Anti-anginal drugs: Vasodilators [Medicinal Chemistry} By Chem Eazy
