Angina pectorisSudden,severe,pressing chest painstarting substernal &radiate to leftarm.Due to imbalance betweenmyocardium oxygen requirementand oxygen supply.Risk factors :Age,sex,obesity.smoking,diabetes.
Classification of angina1. Exertional angina,Stable,Atherosclerotic,Classic,Due to obstruction of coronaries byatheroma.2. Variant, Vasospastic anginadue to Spasm of coronaries.3- Unstable angina.Due to spasm and partial obstruction ofcoronaries.
Nitrates & NitritesPreparations :1- Short acting:Start within few minutes and total durationof action 15-30 minutes.A) Nitroglycerine (Glyceryl trinitrate)Used as sublingual tablets.B) Isosorbide dinitrateAs sublingual spray.C) Amyl nitriteInhalation
2- Long actingNitroglycerine, Isosorbide dinitrate,Isosorbide mononitrate,Erythrityl –Tetranitrate.Action of all start withen hours andcontinue for hours .They are given :Orally,Ointment,Buccal,Transdermalpatch,Parenteral.
AbsorptionWell absorbed according to the route:GIT for the long actingshort acting SublingualTransdermal for long actinginhaLation
MetabolismThrough first pass hepatic metabolism .Short acting have a low oral bioavailability(10-20%),so not given orally to avoid firstpass metabolism.Nitroglycerine metabolites( two dinitro Andtwo mononitro forms).The dinitro forms are active metabolitesand have significant vasodilator effect.
MetabolismIsosorbide dinitrate metabolite (5-mononitrate) is an active metaboliteused clinically.ExcretionAs metabolites through kidney.
Mechanism of actionGlutathione S-transferaseNitroglycerine ————————→No.guanylyl cyclase and NO activatesincrease c GMPc GMP dephosphorelate myosin lightchain (Myosin-LC-po4 ) to myosin- LCCausing muscle relaxation.
Pharmacological actionsNitrates relax all types of smooth musclesvascular or non vascular .Relax both arteries and veins but moreeffective on veins.They have no direct effect on cardiac orskeletal muscles.NO released stimulate guanylyl cyclaseIn platelets causing increase cGMP thatdecrease platelet aggregation.
Clinical usesShort acting for acute attacksLong acting for prophylactic.Treatment of all types of angina .
Adverse effectsOrthostatic hypotensionThrobbing headacheTachycardiaFacial or cutaneous flushingTolerance (Tachyphylaxis)Salt and water retentionCarcinogenicityMethaemoglobinemia only with nitrities
ContraindicationNitrates are contraindicated inincrease intracranial pressure.Nitrates can be used safely inincrease of intraocular pressure(Glucoma).
2-Block calcium entry in vascularsmooth muscles (arterioles) causinga)decrease in peripheralresistance( after load)------ decreasein oxygen requirement.• b)Relief of coronary spasm.
Clinical usesIn all types of angina but veryeffective in variant angina .Used mainly in prophylactic therapy.
β-Adrenoceptor blockingdrugsThey are not vasodilatorsThey are used in treatment ofangina :They decrease both heart rate &myocardial contractility thatdecrease in myocardial oxygenrequirement at rest & in exercise soimprove exercise tolerance.
Clinical usesThey are effective in the prophylactictreatment of classic & unstable angina.They are not used in variant angina.They are effective in treatment of silent orambulatory angina (no pain ).Decrease mortality of patients with recentmyocardial infarction.
Potassium channel openers(Nicorandil )Activation of potassium channels.Nitric oxide release.Arterio & venodilators.Used as prophylactic therapy .May cause :Headache,flushing,dizziness.
Drug treatment of angina1- Acute attack :Short acting nitrates or nitritis.2- Prophylactic therapy ;Long –acting nitrates.Calcium channel blockers.β- adrenoceptors blockers.Potassium channel openers.
Combination therapyNitrates and β-adrenoceptorsblockers.Calcium channel blockers and β-adrenoceptor blockers .? ?Calcium channel blockers andnitrates.Calcium channel blockers, β-adrenoceptor blockers, nitrates.