Drugs used for the treatment of myocardial ischemia

• 1. Drugs used for the treatment ofmyocardial ischemia Presented bySk.yasmeen I/II M.PharmacyDepartment of pharmacologyHindu college of pharmacyGuntur Under the Guidance of Mrs.G. Sumalatha,M.Pharm(PhD) Department of pharmacology Hindu college of pharmacy Guntur

2. myocardial ischemia Myocardial ischemia:o Myocardial ischemia also known angina is a heartcondition caused by a temporary lack of oxygen-richblood to the heart.o The sudden severe, pressing chest pain occurs, startingfrom substernal and radiate to left arm.o The inadequate blood flow is caused by narrowedcoronary arteries, which are the vessels that supplyblood to the heart 3. Myocardial ischemia 4. Myocardial infraction 5. Understanding the heart and coronary arteries Like any muscle, the heart needs a constant supply ofoxygen and nutrients Which are carried to it by the blood in the coronaryarteries similar to other muscle. The harder the heart is working the more oxygen&nutrients it needs The coronary arteries can become narrowed orclogged, which can decrease the amount of blood thatgoes to the heart muscle 6. Types of myocardial ischemia Stable (typical angina) Unstable (crescendo angina) Varient (prinzmetals angina)Stable MI It is a most common type Occurs when heart is working harder than usual Regular pattern to this condition After several episodes, patient learns to recognize &predict Pain goes away in a few min by taking rest & medicine 7. variant MI It is rare and occurs at rest Pain associated with this can be severe and usuallyoccurs between midnight and early morning Pain relieved by medicines unstable MI it is dangerous condition & requires emergencytreatment it is a sign that heart attack could occur soon it does not follow a pattern occurs without physical exertion & not relieved by rest& medicine 8. Conditions that increases o2 supply1. Stress2. Exercise3. During increased heart rateConditions that decrease o2 supply1. Coronary arteries diseases Accumulation of plaques Platelets aggregation Stenosis or spasm or constriction or narrowing2. Reduction in blood flow to heart Due to constriction of blood vessels3. Reduction in o2carrying capacity of blood Decrease Hb levels (in anemic conditions) Normal blood flow and supply but decrease in o2 carrying capacity 9. Symptoms Some people have silent ischemia MI with sign & symptoms include 1. Chest pain (left side) 2. Neck or jaw pain 3. Shoulder or arm pain 4. Clammy skin 5. Nausea &vomitingCauses1. Coronary artery diseases2. Blood clot3. Coronary spasm4. Sever illness 10. Risk factors1.Tobacco 2. Diabetis 3. High B.P 4. High blood cholesterol or triglyceride levels 5. Lack of physical activity 6. Obesity 7. Family historyComplications Irregular heart rhythms (arrhythmia) Heart attack (myocardial infarction) 11. Classification coronary vasodilators1. Nitrites & nitratesaccording to duration of action Shot acting (3 to 60 min) Amyl nitrite, nitroglycerin(sublingual), isosorbide dinitrate Intermediate acting(3 to 6hrs) Isosorbide dinitrate ,nitroglycerin(ointment) Long acting(6 to 10 hrs) Erythirtyl tetranitrate, nitroglycerin (trans-cutaneous 12. Beta adrenergic blocking agents Atenolol Propranolol NadololCalcium Channel Blockers Amlodipine , Bepridil Diltiazem , Felodipine Isradipine, Nicardipine, Nifedipine Nimodipine, Verapamil 13. Potassium Channel Activators: Nicorandil, PinacidilAntiplatelet Drugs : Aspirin ClopidogrelAngiotensin-Converting enzyem Inhibitor:captopril, enalapril, lisinoprilCholesterol Lowering Medication :Atorvastatin, Fenofivrate 14. Further treatment surgical procedures for MI1. Angioplasty and stenting2. Coronary artery bypass surgery 15. stenting Angioplasty 16. Organic nitrates 17. Biochemical role of nitrates Release of Nitric oxide radical Activation of Guanylate cyclase Accumulation of cGMPActivation of cGMP dependent KinasesDephosphorylation of myosin light chainVasodilatation of Venules and Arterioles 18. 1. Hemodynamic role of nitrates1. Venodilatation Preload2 . Arteriolar dilatation After load3. Redistribution of blood in myocardinm4. Increase PGE1, PGI2 Decrease in platelet aggregation 19. Pharmacokinetics -Extensive first pass metabolism. - Metabolized by denitration & conjugation -Low bioavailability only 20% -Unchanged nitrate has half life of 2-8min-Excretion : renal route.Clinical uses of Nitrates:For treatment & prophylaxis of classical anginapectorisTreatment of Variant AnginaTreatment of Unstable Angina 20. Adverse effects of Nitrates In therapeutic doses:-1. Throbbing Headache2. Flushing3. Syncope In high doses:-4. Drug rash1. Reflex sympathetic over activity5. Toleranceleading to tachycardia which6. Constipation.increases work load on heart.2. Fall in blood pressure3. Methemoglobinemia 21. Ca+2 Channel Blockers 22. Ca+2 Channel Blockers Ca+2 channel blockers protect tissue by inhibitingthe entrance of Ca+2 into cardiac and smoothmuscle cells of the coronary and systemic arterialbeds. All Ca+2 channel blockers produce somevasodilatation ( PVR) Some agents also slow cardiac conductionparticularly through the AV node thus serving tocontrol cardiac rhythm. Some agents have more effect on cardiac musclethan others but all serve to lower blood pressure. They are useful in Prinzmetal angina inconjunction with nitrates. 23. pharmacokineticsAdministration: orally well absorbedUndergoes first pass metabolismHalf life : 3 to 5 hrsSide effectsSwelling of legsExcess lowering of heart rate and blood pressureDepressing heart muscle function 24. -Blockers These decrease O2 demands by lowering the heart rate &contractility (decrease CO) particularly the increaseddemand associated with exercise.They also reduce PVR by direct vasodilation of botharterial & venous vessels reducing both pre- and after load.These effects are caused by blocking 1 receptors, selective1 antagonistso atenolol,o metoprolol andoacebutolollose their selectivity at high doses and at least partiallyblock 2 receptors (a concern for bronchospastic disease). 1 antagonists reduce the frequency and severity of anginalepisodes particularly when used in combination withnitrates. 25. -Blockers 26. There are a number of contraindications for blockers:asthma, diabetes, bradycardia. Pharmacokinetics: GI 30-50% metabolized in the first-pass in liver. T1/2: 3-5 hours,Side effectsWorsening of asthmaDepression, fatigueImpotenceIncreased cholesterol levelsShortness of breath due to diminished heart muscle function 27. Potassium channel openers mechanism Potassium channel openers Activate potassium channelincrease potassium permeability in cell lHyperpolarisation occurs Closer of L-type calcium channelsReduced intracellular free calciumLeads to vasodilatation 28. NicorandilAdministration : orallyBioavailability : 75 to 80%Protein binding : 25%Metabolism : hepaticHalf life : 1hrExcretion : renal Adverse effect Headaches Nausea Vasodilatation Vomiting Decrease B.P Stomach pain 29. Antiplatelet drugsMechanism of action prostacyclin (PGI2) & thromboxane (TXA2) are derived from archedonicacid.PGI2 is formed from vascular endotheliumTXA2 is generated by platelets is a vasoconstrictorPGI2 is important for natural resistance to arterial thrombosisTXA2 and vascular PGI2regulates the the platelet aggreabilityCollagen form sub endothelial matrix of damaged vessel initiates theattachmentTXA2 inhibits the adenylyl cyclase and lowers the cAMP concentrationLow concentration of cAMP accelerates platelets aggregation-Aspirin inhibits cyclo-oxygenase-Inhibits the TXA2 synthesis-Prevention of platelet aggregations 30. PharmacokineticsAdministration : orallyBioavailability : rapidly and completely absorbedProtein binding : 99.6%Metabolism : hepaticHalf life : 5-9hrExcretion : renalAdverse effectsNauseaRashes and diarroheaPeptic ulceration 31. Angiotensin converting enzyme inhibitorsMechanism: inhibit ACElow circulating Ang IIdecreased PVRPharmacokineticsBioavailability : 60% (oral)Metabolism : hepaticHalf life : 11 hrsExcretion : renalMain effects: decreased PVR decreased BPAdverse effects: skin rash, taste, cough, hyperkalemia 32. Cholesterol lowering drugsMechanism of actionCompetitively inhibiting HMG-CoA reductase firstenzyme of HMG-CoA reductase pathwayStatins are similar to HMG-CoAThey take the place of HMG-CoA in the enzymeand reduce the rate by which it is able to producemevalonate which is used in production ofcholesterolReduce LDL levels by 30% to40%Reduce HDL levels by 2% to 15%Reduce triglycerides by 10% to30% 33. Atrovastatinabsorption :rapid oral absorptionT max 1 to 2 hoursHigh intestinal clearance &first pass metabolismProtein binding >98%Excretion: hepatic biliary excretion Fenofivrate absorbtion : oral absorbtion Half life :20 hrs Protein binding >99%Adverse effectsExcretion: renalexcretionMild transient GI disturbancesRash headacheMyopathy (muscle pain)Elevation of liver diseases 34. ContraindicationInteraction with anti arrhythmic drugs Antidepressantso Failure of sublingual tablets of nitrates to dissolveInteractions with corticosteroids NSAIDSo Hypotensive action is antagonizedInteraction with beta blockers and calcium channel blockersoThey can cause the excessive hypotension 35. Additional MI treatment Stop smoking Eliminate alcohol Manage any underlying disorders, such as, high B.P high levels of serum cholesterol, 36. Newer antianginal drugsBecause of high prevalence of angina ,new drugs are actively sought for its treatmentSome of the drugs or groups currently under investigation are listedDrugsPotassium channel activators : nicorandilMetabolic modulators : trimetazidine, ronolazineDirect bradycardic agents : ivabradineProtein kinase Gfacilitators : detanonoateSulfonyl ureas : glybenclamideNitric oxide donors : L-arginineCapsaicinamilorideThiazolidinedionesVasopepdidase inhibitors 37. REFERENCERANG &DALES pharmacology 6th editionBERTRAM G.KATZUNG BASIC AND CLINICALPHARMACOLOGYROBBIN AND COTRON PATHOLOGIC BASIS OF DISEASEPRINCIPLES OF PHARMACOLOGY HL.SHARMAKK.SHARMAPHARMACOLOGY AND PHARMACOKINETICSR.S.Satoskar S.D.Bhandarkar 38. Thank you