More Related Content
What's hot
What's hot (20)
Similar to Angina PPT.ppt
Similar to Angina PPT.ppt (20)
More from Jhansi Uppu
Recently uploaded
Recently uploaded (20)
Angina PPT.ppt
- 1. DRUGS USED FOR ANGINA PECTORIS
- 2. Angina is chest pain or discomfort caused when your heart muscle doesn't get enough oxygen-rich blood. Angina is not a disease. It is a symptom of an underlying heart problem, usually coronary heart disease (CHD). Angina happens when one or more of the coronary arteries is narrowed or blocked, also called ischemia.
- 4. Mechanism include: Atherosclerosis (plaque-related epicardial coronary obstruction) focal or diffuse spasm of normal or atheromatous arteries microvascular dysfunction left ventricular dysfunction secondary to previous acute myocardial necrosis/hibernation (ischaemic cardiomyopathy) left ventricular hypertrophy (hypertension, aortic stenosis, hypertrophic cardiomyopathy).
- 6. •Four types of Angina Stable angina Unstable angina Microvascular angina Prinzmetal’s angina
- 7. Mechanisms of atherosclerosis The pathophysiology of atherosclerosis, development of symptomatic angina and subsequent acute coronary syndrome (ACS) is well characterised.2,3 The microscopic development of atherosclerotic plaque involves: endothelial dysfunction sub-endothelial accumulation and oxidation of low-density lipoprotein (LDL) increased expression of adhesion molecules and chemokine secretion immune cell infiltration and development of foam cells development of fibroatheromatous plaque involving positive remodelling, neovascularisation, and development of necrotic core with overlying fibrous cap formation and calcification.
- 8. Endothelial dysfunction and nitric oxide The endothelium is a single layer of cells lining blood vessels and performs multiple functions, including: the regulation of coronary blood flow a barrier to toxic substrates regulation of thrombosis and inflammation control of angiogenesis.
- 9. Endothelial dysfunction is characterised by a reduction in the bioavailability of vasodilators, such as NO, as a result of reduced production and increased consumption of NO, and an increase in endothelium-derived contracting factors, such as endothelin and angiotensin II (AII) (figure 1). This is seen as the blood vessel being unable to dilate. In addition, endothelial dysfunction promotes platelet and leukocyte activation and the release of cytokines, which increase vessel permeability. This enables the sub-endothelial infiltration of oxidised lipoproteins and inflammatory cells.
- 10. Endothelial dysfunction has been referred to as “the risk of the risk factors”,4 since it has been shown to occur in the presence of conventional, modifiable risk factors (e.g. cigarette smoking, high blood pressure, hyperlipidaemia and diabetes). These risk factors are, in turn, associated with a state of increased oxidative stress and the overproduction of reactive oxygen species. This all contributes to the complex interplay of endothelial dysfunction since reactive oxygen species can themselves lead to abnormal NO metabolism (figure 2).
- 11. Fatty streaks: A fatty streak marks the earliest macroscopic atherosclerotic lesion. Beginning in early life, these fatty streaks comprise a focal build-up of various substrates e.g. lipid-rich macrophages (foam cells), extracellular matrix, smooth muscle cells, intracellular and extracellular lipid deposits, and T lymphocytes, to form a minor thickening of the intimal surface.
- 13. Plaque formation
- 19. Unstable angina: •Also called “Crescendo angina” •Acute coronary syndrome in which angina worsens •Occurs at rest •Severe and of acute onset •Crescendo pain- pain increases every time
- 20. Unstable angina: •Increased frequency , severity or duration of pain in a apatient of stable angina. •Pain occurs with less exertion or at rest. •Myocardial contraction may occur in 10-20% patients
- 22. Microvascular angina: •Also called Syndrome X •Cause unknown •Probably due to poor functioning of the small blood vessels of the heart, arms and legs •No arterial blockage •Difficult to diagnose because it does not have arterial blockage •Good prognosis
- 23. Prinzmetal’s angina or variant angina •Prinzmetal’s angina is a variant form of angina with normal coronary vessels or minimal atherosclerosis •It is probably caused by spasm of coronary artery
- 30. Immediate pre exertional prophylaxis of angina: Sublingual Nitroglycerine 0.5mg or Isosorbide dinitrate 5mg should be taken within 5 minutes. For long term prophylaxis: Long acting nitrates, calcium channel blockers, beta blockers or combination of these drugs. Antiplatelet therapy: Aspirin small dose 75mg – 150mg once daily orally or Dipyridimole 75mg orally.
- 31. CORONARY ARTERY REVASCULARIZATION For patients not responding to medical therapy Percutaneous Transluminar Coronary Angioplasty (PTCA). Coronary Artery bypass grafting (CABG)
- 34. Pharmacologic management of acute coronary syndromes
- 35. Classification 1. Nitrates a)Short acting: Glyceryl trinitrate (GNT, Nitogycerine) b)Long acting: Isosorbide dinitrate, Isosorbide mononitrate, Erythrityl tetranitrate 2.β- blockers: Propranolol, Metoprolol, Atenolol 3.Calcium channel blockers a)Phenyl alkylamine: Verapamil b)Benzothiazepine: Diltiazem c)Dihyropyridines: Nifedipine, Nimodipine, Lacidipine, Lercanidipine, Benidipine 4.Potassium channel opener: Nicorandil 5.Others: Dipyridamole, Trimetazidine, Ranolazine, Ivabradine, Oxyphendrine
- 36. NITRATES MODE OF ACTION : ACTS DIRECTLY ON VASCULAR SMOOTH MUSCLE TO PRODUCE ARTERIAL AND VENOUS DILATATION EFFECT DURING ANGINA 1.REDUCES MYOCARDIAL OXYGEN DEMAND (LOWERS PRE-LOAD AND AFTER LOAD) 2. INCREASES MYOCARDIAL OXYGEN SUPPLY (CORONARY VASODILATATION)
- 38. Mode of action of organic nitrates
- 39. NITRATE PREPARATIONS 1.SUBLINGUAL GLYCERYL TRINITRATE (GTN) 2.BUCCAL GLYCERYL TRINITRATE 3.TRANSDERMAL GLYCERYL TRINITRATE 4.ORAL ISOSORBIDE DINITRATE 5.ORAL ISOSORBIDE MONONITRATE 6.INTRAVENOUS GTN- FOR ACUTE MYOCARDIAL INFARCTION/LEFT VENTRICULAR FAILURE -10 -200 µg /MIN INTRAVENOUS INFUSION, TITRATING TO CLINICAL RESPONSE AND BLOOD PRESSURE.
- 40. DURATION OF ACTION OF SOME NITRTATE PREPARATIONS PEAK ACTION DURATION OF ACTION Sublingual GTN(Tablet 300- 500µg or metered dose aerosol 400µg/spray) 4-8 minutes 10-30 minutes Buccal GTN (1-5 mg tablet 6 hourly) 4-10 minutes 30-300 minutes Transdermal. GTN (5-10 daily) 1-3 hours Up to 24 hours Oral isosorbidedinitrate.(10- 20 mg 8 hourly) 45-120 hours 2-6 hours Oral isosorbide mononitrate ( 20-60 mg once or twice a day) 45-120 hours 6-10 hours
- 41. SUBLINGUAL GTN- Administered a.as a tablet – 300-500 µg to disolve under the tongue b.As metered-dose aerosol (400 µg per spray) RELIEVES AN ATTACK OF ANGINA IN 2-3 MINUTES UNWANTED EFFECTS HEADACHE SYMPTOMATIC HYPOTENSION –DIZZINESS, POSTURAL GIDDINESS, BLURRING OF VISION RARELY SYNCOPE – FAINTING ASK PATIENT TO SPIT TABLET IF ABOVE EFFECTS OCCUR NOT HABIT FORMING TEACH PATIENTS TO USE PROPHYLACTICALLY e.g. Before exerting VIRTUALLY INEFFECTIVE IF SWALLOWED DUE TO EXTENSIVE FIRST PASS METABOLISM IN THE LIVER CONTINUOUS USE CAUSES PHARMACOLOGICAL TOLERANCE THERFORE ATTEMPT TO INCLUDE A ‘NITRATE-FREE’ PERIOD OF 6-8 HOURS A DAY
- 43. Beta Blockers are effective in Stable and Unstable Angina. In contrast they are not useful in variant angina may worsen the condition. This deleterious effect is likely due to the increase in the coronary resistance caused by the unopposed effects of catecholamines acting at alpha adrenoreceptors.
- 44. • Heart rate • Contractility • Preload • Afterload • Coronary flow • Regional myocardial blood flow O2 D e m a n d O2 S u p p l y -Blockers/Ca2+ channel blockers Nitrates/Ca2+ channel blockers Nitrates/Ca2+ channel blockers/antithrombotics/ statins HEART
- 46. Adverse Drug reactions: Bronchospasm Hypotension Bradycardia Increase in Lipid profile test Mask signs of Hypoglycemia Contraindications: Asthma, Diabetes, Hypotension
- 47. CALCIUM CHANNEL BLOCKERS MODE OF ACTION 1.DECREASES MYOCARDIAL OXYGEN DEMAND BY REDUCING BLOOD PRESSURE AND MYOCARDIAL CONTRACTILITY Mechanism of Action 1.Calcium channel blockers block voltage-gated L-type calcium channels, the calcium channels most important in cardiac and smooth muscle. By decreasing calcium influx during action potentials in a frequency and voltage dependent manner, these agents reduce intercellular calcium concentration and muscle contractility. USED IN ALL TYPES OF ANGINA Verpamil 80-160mg/8hr Diltiazem 60-120mg/8hr Nifedipine 10-40mg/8hr Amlodipine 5mg/day
- 49. VERAPAMIL AND DILITIAZEM-SUITABLE FOR PATIENTS WHO ARE NOT RECEIVING BETA BLOCKERS AS THEY DECREASE THE HEART RATE ( DANGEROUS ADDITIVE EFFECT Adverse Drug reactions: Facial puffiness Pedal edema Flushing Headache Contraindications: Heart failure, Bradycardia
- 50. POTASSIUM CHANNEL ACTIVATORS MODE OF ACTION: DILATES ARTERIES AND VEINS DOES NOT EXHIBIT TOLERANCE SEEN WITH NITRATES NICORANDIL- 10-30 mg 12 hourly Caution in: hypovolaemic patients Patients with pulmonary oedema Side effects: a.Headache b.Flushing c.Dizziness d.Weakness e.May cause a dose dependent increase in heart rate f.Myalgia g.Angioedema
- 51. Potassium channel openers: Types of potassium channels: Voltage gated, calcium activated, ATP acyivated Nicorandil is a newer agent activates ATP sensitive potassium channel and hyperpolarises vascular smooth muscles. Decreases pre and after load and produce coronary dilation
- 52. Ranolazine Reserve agent for chronic, resistant angina Inhibits cardiac late Na Current influx , there by reducing calcium flow into the cells thus help the heart to relax improve the blood flow Decreases cardiac contractility No change in Heart rate and BP Prolongs QT interval so it is containdicated with drugs that prolong QT interval. Dose: 500mg, 1000mg
- 54. IVABRADINE Direct Bradycardic agent or pure HR lowreing agent Blocks hyperpolarazation activated if current through Na channel present in SA node which get activated during early part of slow diastolic depolarization durring ischemic episodes. Heart rate decreased and Oxygen demand decreased No fall in BP Dose: 5mg
- 55. ANTIPLATELET DRUGS ASPIRIN CLOPIDOGREL THROMBOLYTIC AGENTS STREPTOKINASE ALTEPLASE RETEPLASE-
- 56. ASPIRIN ANTIPLATELE T EFFECT BY INHIBITION OF THROMBOXANE A 2 NSAID, INHIBITS COX-1 AND COX -2 WHICH LEADS TO DECREASED PROSTAGLANDIN SYNTHESIS USES THROMBO-EMBOLIC CVA, ISCHAEMIC HEART DISEASE- PROPHYLAXIS (75MG/DAY) AND ACUTE TREAMENT (375 MG) CONTRAINDICATIONS 1.THOSE UNDER AGE OF 16Y-CAN INCREASE INCIDENCE OF REYE’S SYNDROME, LIVER/BRAIN DAMAGE 2.GASTRO-INTESTINAL ULCERS 3.BLEEDING DISORDERS 4.GOUT 5.HYPERSENSITIVITY TO ANY NSAID 6.GFR <10ML/MIN
- 58. ASPIRIN CAUTION 1.ASTHMA 2.UNCONTROLLED HYPERTENSION 3.ANY ALLERGIC DISEASE 4.G6PD DEFICIENCY 5.DEHYDRATION OTOTOXIC IN OVERDOSE MAY INCREASE EFFECTS OF SULPHONYL UREAS AND OF METHOTREXATE FOR ANALGESIA- 300-900 MG 4-6 HPOURLY –MAXIMUM DOSE4G/DAY STOP 7 DAYS BEFORE SURGERY IF SIGNIFICANT BLEEDING IS EXPECTED IF CARDIAC SURGERY OR PATIENT HAS ACUTE CORONARY SYNDROME- CONSIDER CONTINUING
- 59. CLOPIDOGREL ANTIPLATELET AGENT- The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet P2Y12 receptor and the subsequent ADP- mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. This action is irreversible USE PROPHYLAXIS OF ANTI-THROMBOTIC EVENTS IN NON—ST ELEVATIONMYOCARDIAL INFARCTION AND IN ST ELEVATION MYOCARDIAL INFARCTION-IN COMBINATION WITH ASPIRIN MYOCARDIAL INFARCTION (WITHIN A ‘FEW’ TO35 DAYS) ISCHAEMICCEREBROVASCULAR ACCIDENT- WITHIN 7 DAYS TO 6 MONTHS PERIPHERAL ARTERIAL DISEASE CONTRAINDICATION ACTIVE BLEEDING NOT RECOMMENDED WITH WARFARIN
- 60. CLOPIDOGREL SIDE EFFECTS HAEMORRHAGE (ESPECIALLY GASTRO-INTESTINAL OR INTRA-CRANIAL GASTRO-INTESTINAL UPSET PEPTIC ULCER PANCREATITIS HEADACHE FATIGUE DIZZINESS PARAESTHESIA RASH/PRURITUS MONITOR FULL BLOOD AND FOR SIGNS OF OCCULT BLEEDING
- 61. STREPTOKINASE THROMBOLYTIC AGENT INCREASES PLASMINOGEN CONVERSION TO PLASMIN WHICH INCREASES FIBRIN BREAKDOWN USES 1.ACUTE MYOCARDIAL INFARCTION -1.5 MILLION UNITS INTRAVENOUS INFUSION OVER 60 MIN 2.THROMBOEMBOLISM OF ARTERIES 3.PULMONARY EMBOLISM 4.CENTRAL RETINAL ARTERY THROMBOSIS 5.DEEP VEIN THROMBOSIS OTHER DOSES-250,000 UNITS INTRAVENOUS INFUSION OVER 30 MIN, THEN 100,000 UNITS EVERYHOUR FOR UPTO12-72 HOURS
- 62. ALTEPLASE (RECOMBINANT) TISSUE-TYPE PLASMINOGEN ACTIVATOR. RECOMBINANT FIBRINOLYTIC USE ACUTE MYOCARDIAL INFARCTION (TOTAL DOSE 100MG- REGIMEN DEPENDS ON TIME SINCE ONSET OF PAIN 0-6HOURS: 15 MG INTRAVENOUS BOLUS,FOLLOWED BY 50 MG INTRAVENOUS INFUSION OVER 30 MINUTES AND 35 MG INTRAVENOUS INFUSION OVER 60 MINUTES 6-12 HOURS-10 MG INTRAVENOUS BOLUS FOLLOWED BY 50 MG INTRAVENOUS INFUSION OVER 60 MIN, AND FOUR FURTHER 10 MG INTRAVENOUS INFUSIONS, EACH OVER 30 MIN) DECREASE DOSE IF PATIENT WEIGHS LESS THAN 65 KG RETEPLASE RECOMBINANT PLASMINOGEN ACTIVATOR; THROMBOLYTIC USED ONLY FOR MYOCARDIAL INFARCTION DOSE-10 UNITS AS SLOW INTRAVENOUS INJECTION OVER 2 MINUTES, REPEAT AFTER 30 MIN
- 63. Newer Drugs A) Ranolazine appears to act mainly by reducing a late, prolonged sodium current in myocardial cells. 1.The decrease in intracellular sodium causes an increase in calcium expulsion via the Na/Ca transporter and a reduction in cardiac force and work. 2.Ranolazine is moderately effective in angina prophylaxis. B) Dipyridamole 1.It is a powerful coronary dilator; increases total coronary flow by preventing uptake and degradation of adenosine. 2.It dilates resistance vessels and abolishes autoregulation. 3.Inhibit platelet aggregation. 4.Not useful as an anti-anginal drug but used for prophylaxis of Coronary and cerebral thrombosis in post-MI and post stoke patients.
Editor's Notes
- The principal mechanism by which the endothelium modulates coronary perfusion is by regulating coronary vascular tone through the production of nitric oxide (NO). NO is synthesised from the amino acid L-arginine by means of the enzyme endothelial NO synthase (e-NOS). Endothelial cells express e-NOS, producing a low level of NO, which is under the control of regulatory factors. NO has paracrine effects by readily permeating cell membranes where it activates the synthesis of cyclic guanylate cyclase (cGMP). Through this intracellular signalling pathway, it has a number of effects including vasodilation, angiogenesis, and reducing platelet adhesion and vascular smooth muscle proliferation.
- Relieving pain is one of the main goals of treating coronary microvascular disease (MVD). Treatments also are used to control risk factors and other symptoms. Treatments may include medicines, such as: ACE inhibitors and beta blockers to lower blood pressure and decrease the heart’s workload Aspirin to help prevent blood clots or control inflammation Nitroglycerin to relax blood vessels, improve blood flow to the heart muscle, and treat chest pain Statin medicines to control or lower your blood cholesterol.
- Causes of Variant (Prinzmetal) Angina: The pain from variant angina is caused by a spasm in the coronary arteries (which supply blood to the heart muscle). The coronary arteries can spasm as a result of:Exposure to cold weather Stress Medicines that tighten or narrow blood vessels Smoking Cocaine use Symptoms of Variant (Prinzmetal) Angina: The pain or discomfort:Usually occurs while resting and during the night or early morning hours Are usually severe Can be relieved by taking medication Treatment of Variant Angina | Prinzmetal's Angina Medicines can help control the spasms. Drugs such as calcium antagonists and nitrates are the mainstays of treatment.