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Pharmacology CVS: Anti-anginal drugs.

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Class by: gauthami ( government medical college, kannur)

Hi all so today we are going to learn about anti-anginal drugs what are anti-anginal drugs these are drugs used to prevent abort or terminate attacks of angina pectoris so last year we had learned briefly about angina pectoris and myocardial infarction let’s learn about it in detail so angina pectoris is a pain syndrome due to induction of an adverse oxygen

Supply or demand situation in a portion of the myocardium so there is myocardial ischemia which results in accumulation of metabolites and further elicits the pain there are three types of angina first is the classical variety this is the most common form and attacks are provoked by exercise emotion eating and coitus what is the underlying pathology here there is

Arteriosclerotic affliction of larger coronary arteries this results in fixed coronary obstruction the blood flow fails to increase despite the increased demand the inadequacy of the ischemic left ventricle will raise the end diastolic left ventricular pressure from 5 to 25 millimeters of mercury this causes sub endocardial crunch and hence further aggravates the

Ischemia the second type is variant or prince metal or vasospastic angina it is an uncommon and unpredictable form the attacks occur even at rest or during sleep the underlying pathology is recurrent localized coronary vasospasm superimposed on arteriosclerotic coronary artery disease the third type is unstable angina there is a rapid increase in the frequency

And severity of the attacks the attacks occur even during rest and sleep the pathology is there is rupture of an atheromatous plaque which results in platelet deposition occludes the coronary artery reduces the blood supply results in cardiac muscle atrophy and hence there is fibrous replacement which further results in cardiac arrhythmias coming to the clinical

Classification of anti-anginal drugs it can be divided into two groups first is the drugs used to abort or terminate the attack that is sublingual preparation of glycerol tri nitrate and isosorbide dye nitrate the other group is used for chronic prophylaxis now here’s a chart of the classification of anti-anginal drugs pharmacologically the first is the group

Of nitrates so among nitrates glycerol trinitrate is the prototype drug nitrates are divided into two types that is short acting and long acting so let us see how glycerol tri nitrate causes vascular smooth muscle relaxation there are four mechanisms one is preload and afterload reduction then comes redistribution of the coronary flow and it relieves the pain

Symptoms preload reduction is by veno dilatation which results in peripheral pooling of blood reduces the venous return and hence the end diastolic size and pressure are reduced according to laplace law when the ventricular radius decreases the tension or pressure onto the ventricular wall also decreases this causes decrease in the oxygen consumption and cardiac

Output after after load reduction this is by arteriolar dilatation reduces the total peripheral resistance the aft load on the heart also decreases the systolic bp falls more than the diastolic bp and hence reduces the cardiac work redistribution the nitrates preferentially relax the big conducting coronary arteries than the resistance vessels hence there is

Favorable redistribution of blood flow to the ischemic region mechanism of relief the primary effect is reducing the cardiac work by action on peripheral vasculature and increased blood supply then the peripheral vasculature that is bronchi biliary tract and esophagus are also mildly relaxed now coming to the mechanism mechanism of action at the cellular level in

The smooth muscle cells the organic nitrates undergo denitration this releases a free radical called nitrous oxide which activates gluonyl cyclase increases the levels of cyclic gmp which reduces the calcium entry and d phosphorylates mlck that is myosin light chain kinase through a cyclic gmp mediated protein kinase this reduces the availability of active mlck

Which interferes with myosin activation hence myosin will not bind with actin contraction is prevented and causes relaxation coming to the pharmacokinetics the drugs are lipid soluble well absorbed from the buccal mucosa intestine and skin extensive and variable first pass metabolism in the liver exception is isosorbide mononitrate they have got longer t half

And acid above classified into two types that is short acting and long acting some of the adverse effects are fullness in head throbbing headache flushing fainting palpitation and dizziness then very few rare adverse effects are meth hemoglobinemia and rashes tolerance the sublingual type of gtn no tolerance develops against this but when gtn is given orally

The reactive oxygen species produced during denitration of organic nitrates inhibit the mitochondrial aldehyde dehydrogenase and nitrogen oxide or nitrous oxide generation is interfered so the free radicals are not produced this does not cause arteriolar dilatation hence this can result in tolerance but it can be prevented by providing a nitrate-free intervals

Every day dependence sudden withdrawal of the drug after prolonged exposure can result in coronary and peripheral blood vessels spasm this can cause mi and sudden deaths drug interactions sedina fil and other pde5 inhibitors cause dangerous potentiation of the nitrate action that is severe hypotension and when a patient who is receiving other vasodilators when

This person is given nitrates it results in additive hypotension coming to the clinically used nitrates first is gtn that is a prototype or nitroglycerin it can be given as three different preparations sublingual transdermal and intravenous the sublingual preparation is given to terminate or abort an attack when anginal pain is relieved the remaining part of the

Tablet may be spit or swallowed transdermal patch it has got high bio availability it provides a steady delivery for 24 hours the effect fades within 8 to 10 hours of administration hence it is advised that the patch be taken off for 8 to 10 hours daily iv infusion rapid steady titrable plasma concentration for as long as desired the use is an unstable angina mi

Hypotension and lvf accompanying mi others used are isosorbide dinitrate isosobide mononitrate penta erythritol tetra nitrate and erythritol tetra nitrate the other uses of nitrates are classical and variant angina acute coronary syndromes myocardial infarction ch of an acute left ventricular failure biliary colic esophageal spasm and in cyanide poisoning so the use

Of nitrates to treat cyanide poisoning is quite important so here goes the mechanism hemoglobin it first binds with a nitrate compound that is sodium nitrite to form meth hemoglobin this when combined with cyanide forms cyanomethamoglobin which further interacts with sodium thiosulfate to form meth hemoglobin and sodium thiocyanate which is excreted in the urine

Now let’s go on to the next group of drugs that is beta blockers it reduces the coronary flow by blocking the beta-2 receptors heart rate is reduced this results the heart being in an ionos inotropic state the mean bp and cardiac work are reduced oxygen consumption also reduces it is useful in decreasing the frequency and severity of the attacks this increases the

Exercise tolerance in classical angina it is used in unstable angina as well as nstmi coming to calcium channel blockers there are three types one is phenylalkylamine benzothiazepine and dihydropyridines so the pharmacological action is basically smooth muscle relaxation with negative chronotropic ionotropic and romotropic actions on the heart on smooth muscle it

Depolarizes by an inward calcium movement through the l-type channel which is voltage sensitive so this causes relaxation by decreasing the amount of calcium intracellularly there is arteriolar dilatation there is milder effect on the veins dhps have the most marked smooth muscle relaxant and vasodilator action on the heart it causes negative ionotropic action

Except dhps all other calcium channel blockers have a negative chronotropic as well as a dromotropic effect on the heart so in brief how is the mechanism l type of calcium channels they activate as well as inactivate at a very slow rate so the calcium depolarized cells will have a lesser steep zero phase and refractory period the recovery process results in a

State from which it can be re activated is blocked okay the state is blocked by diltiazem and verapamil and varapamil it has another effect that it slows the sinus rate as well as the av conduction but nephedepin cannot do this dhps are more selective for smooth muscle l channels let’s learn about varapanel it causes arterial artery dilatation it has got some

Alpha blocking activity and reduces the total peripheral resistance heart rate is reduced av conduction is slowed but the cardiac output is maintained adverse effects include bradycardia nausea hypotension and it can accentuate the conduction defects interactions varapamil shouldn’t be given with beta lockers because it can result in additive sinus depression

Conduction defects and a systole it increases the plasma digoxin level and can result in digoxin toxicity so it cannot be administered in a person who is receiving digoxin it shouldn’t be used with cardiac depressants like quinodine now coming to deltasm it is a less potent vasodilator than verapamil it has got a negative inotropic action it causes depression of

The sa node and av conduction it dilates the coronaries the adverse effects are it is milder as compared to varapamil but it cannot be given to patients pre-existing sinus av nodal or myocardial disease it increases the plasma digoxin levels hence it cannot be given in a patient who is receiving digoxin now coming to nephidipin it is the first and prototype dhp

It has got a direct depressant action on the heart the arteriolar dilatation results in decrease in the total peripheral resistance hence bp falls rapid and short duration of action that is three to six hours reflects sympathetic stimulation of the heart can result in tachycardia and increase the cardiac contractility as well as cardiac output the adverse effects

Include palpitation ankle edema hypotension drowsiness etc it has got higher mortality among post mi patients and can be safely administered along with beta blockers and digoxin now the fourth one is amlodipine this is also a dhp it has got complete and slow oral absorption high overall bioavailability vasodilation effects are lesser volume of distribution and t

Half is long nemo dipin it is a short-acting dhb it penetrates the blood-brain barrier because it is highly lipid soluble it selectively relaxes the cerebral vasculature hence it is given in case of subarachnoid hemorrhage side effects include headache flushing palpitation etc uses are angina pectoris hypertension cardiac arrhythmia hypertrophic cardiomyopathy

And premature labor in case of premature labor we give nephidipin coming to the drug combinations in case of angina pectoris first is beta blocker along with the long acting nitrate in case of classic angina because tachycardia due to nitrate can be blocked by beta blocker and the tendency of beta blocker to produce ventricular dilatation as well as to reduce

Total coronary flow can be blocked by nitrate the second combination is of a slow acting bhp with beta blocker it has got the same advantages as the above combination now the third combination is nitrates along with calcium channel blockers nitrates can reduce the preload whereas calcium channel blockers reduce after load as well as increase the coronary flow

The beta blockers will help reduce cardiac work as well coming to the fourth group of drugs that is potassium channel opener nicorandal it activates the atp sensitive potassium channels in smooth muscle membrane thereby hyper polarizing or relaxing it it acts as a no donor and hence causes arteriolar dilatation it increases the levels of cyclic gmp venous

Veno dilation is there preload and afterload are also reduced the coronary flow is increased it reduces the frequency of angina and improves exercise tolerance there is a cardio protective action that is there is ischemic preconditioning that is activation of the mitochondrial atp sensitive potassium channels this results in brief period of ischemia followed

By reperfusion now there are few important anti-anginal drugs apart from the given classification that is dipyridamole and trimethazine dipyridamole it is a powerful coronary dilator the total coronary flow is increased prevention of uptake and degradation of adenosine is what results in increased coronary flow dilates the resistance vessels and abolishes the

Autoregulation but it has no effect on the large coronary arteries cardiac work isn’t increased venous return is not reduced and the anginal symptoms are not relieved hence dipyridamole it exhibits a pharmacological success but a therapeutic failure there is a phenomenon called coronary steel phenomenon here dipyridamole dilates the resistance vessels in the

Non-ischemic zone so this diverts the already reduced blood flow away from the ischemic zone further accentuating or aggravating the ishchemia coming to the second type that is trimethylamine it is a non-hemodynamic mechanism it reduces the fatty acid oxidation and promotes glucose oxidation in the myocardium so this is having metabolic effect on the myocardium

It reduces the frequency of angina and improves the exercise tolerance thank you

Transcribed from video
Pharmacology CVS: Anti-anginal drugs. By GOOD DOCTOR