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Angina pectoris
- 1. DRUGS USED IN ANGINA PECTORIS & MYOCARDIAL INFARCTION WIWIK RAHAYU, dr., M.Kes Depart.of.Pharmacology & Therapy Faculty Of Medicine – Riau University
- 2. ANGINA PECTORIS A syndrome of inadequate oxygen delivery to the myocardium relative to the oxygen requirement of this tissue • Symptom Severe, transient retrosternal pain radiated to the left arm, back or jaw • Duration: 0,5 – 30 minute • ECG:
- 3. ANGINA PECTORIS ↓ O2 Supply Ischemic PAIN
- 4. TYPE OF ANGINA PECTORIS 1. CLASSIC ANGINA – Atherosklerosis – Precipitating factor (+) 2. PRINZMETALS – Vasospasm – Precipitating factor (-) 3. UNSTABLE A rapid increase in frequency and intensity of anginal pain occurs, which is thought to herald imminent myocardial infection.
- 5. Angina Pectoris PATHOPHYSIOLOGY (I) RISK FACTOR • Age • Hypertension • Smoking • Hypercholesterolemia • DM • Oral contraception • Genetic ? atherosklerosi s OBSTRUCTION (a.coronary) Decreased 02 supply
- 6. Angina Pectoris PATHOPHYSIOLOGY II O2 supply & O2 demand Precipitating factors ISCHEMIA PAIN
- 7. PRINCIPLES IN THE TREATMENT OF ANGINA PECTORIS • O2 supply to the tissue • O2 demand of the tissue 3. Risk Factor
- 8. ANTI ANGINAL DRUGS 1. ORGANIC NITRATES – AMIL NITRIT – NITROGLYCERIN – ISOSORBIDE DINITRATE • Ca ++ CHANNEL BLOCKERS (CCB) – NIFEDIPINE, AMILODIPINE – DILTIAZEM – VERAPAMIL • β ADRENERGIC BLOCKERS – PROPANOLOL cs
- 9. NITROGLYCERINE Nitroglycerine – the prototype nitrate drug. All nitrates have the same mechanism of Action. MECHANISM OF ACTION Administrated nitrates ↑ Nitrites ↑ Nitric oxide (NO) ↑ cGMP ↑ Dephosphorylation of myosin light chain Vascular smooth muscle relaxation
- 10. Nitroglycerin EFFECT Venodilatation Relief of Preload coronary a spasm Collateral flow O2 demand O2 supply O2 supply Inotropic ? Chronotropic ?
- 12. Nitroglycerin EFFECT High Dose Vasodilatation BP tachycardia Paradoxal effect O2 demand
- 13. Nitroglycerin EFFECT • Increased O2 supply • Decreased O2 demand Preload Afterload • Contractility (N) • Heart rate • Decreased in platelet aggregation (?)
- 14. Dosage
- 15. Nitroglycerin INDICATION • ANGINA PECTORIS • Acute • Prophylaxis • ACUTE MYOCARDIAL INFARCTION • CONGESTIVE HEART FAILURE
- 16. Nitroglycerin ADVERSE DRUG REACTIONS • Common side – effects Headaches • Serious SE – Hypotension – Syncope ( cause cerebral ischemia) tachycardia • Others Edema Methemoglobinemia SL: Burning sensation • Withdrawal symptoms • Tolerance
- 17. Nitroglycerin ADVERSE DRUG REACTIONS Tolerance • Appears within 12 hours • Long acting preparation Continuous infusion Caused: - BM depletion • Avoid by a nitrate free interval • Cross tolerance
- 18. Nitroglycerin CONTRAINDICATION • Hypotension • Severe anemia • Brain injury • Tachyaritmia
- 19. CALCIUM CHANNEL BLOCKERS (CALCIUM ANTAGONIST) I. NIFEDIPINE AMLODIPINE, FELODIPINE, NICARDIPINE, NIMODIPINE, ETC II. DILTIAZEM III. VERAPAMIL
- 20. CCB MECHANISM OF ACTION • Inhibit the influx of Calcium into CARDIAC & VASCULAR cells MUSCLE TONE
- 21. CCB EFFECTS (I) Vascular Effects Cardiac Effects Vasodilatation Heart Rate ↓ Conduction ↑ O2 supply After load↓ BP ↓ Contraction ↓ O2 demand ↓ O2 demand
- 22. CCB EFFECTS (II) Phenylalkylamines Dihydropyridines Benzothiazepines A (Verapamil) D (Diltiazem) B(Nifedipine) C(Nimodipine) Vasodilatation Peripheral ++ +++ + + Coronary ++ +++ + +++ Cerebral + + +++ + Heart Rate ↓ ↑ - ↓ SA Node ↓ - - ↓↓ AV Node ↓↓ - - ↓ Contractility ↓↓ ↑ - ↓
- 23. Pharmacokinetics Drug Absorption Bioavailability Active Half Onset Peak Metabolites Life of Effect (hr) Action after after oral Oral Dosing Dosing Verapamil >90% 10%-35% + 5 <1hr 1-2hr Nifedipine >90% 60%-70% - 2 <20min 30min (2-3 min)* <1hr Diltiazem >80% 40% + 3,5 2-3hr
- 24. CLINICAL PROBLEMS AND SIDE EFFECTS VERAPAMIL Problems in 8% to 10% of patients Major Cardiodepression Moderate Hypotension AV node block Peripheral edema Minor Headache Constipation NIFEDIPINE Problems in 17% to 20% of patients Major Hypotension Headache Peripheral edema DILTIAZEM Problems in 2% to 5% of patients Minor Hypotension -AV Node Block Peripheral edema -Cardiodepression
- 25. NIFEDIPINE • Effects (?) • SE: VD flushing, dizziness, headache, palpitation, peripheral edema rare myalgia, hypokalemia, gingival swelling • Drug Interaction Cimetidine Prazosin
- 26. Nifedipine • Indication 1.PRINZMETAL,S (VASOSPASTIC) ANGINA Monotherapy, 40-80 mg More effective when combined with Isosorbid 4.CHRONIC STABLE ANGINA Combined with Beta Blocker 6.UNSTABLE ANGINA Monotherapy is contraindication Combined with Beta Blocker
- 27. Nifedipine SECOND GENERATION DHP AMLODIPIN: Dosage: 5-10 mg, once daily NICARDIPINE: Dosage: 20-40 mg, every 8 hours NIMODIPINE : Subarachnoid Hemorrhage Migraine
- 28. BETA BLOCKER • CARDIOSELECTIVE – Acebutolol – Atenolol * – Metoprolol * • NON CARDIOSELECTIVE – Propanolol * – Nadolol * – Carteolol – Sotalol • VASODILATOR NONSELECTIVE – Labetolol – Pindolol – Carvedilol
- 29. PROPANOLOL Is the prototype β adrenergic blocker ↓Inotropic chronotropic ↓ O2 demand β Adrenergic domotropic blocker ↓Renin → Ag → peripheral →BP ↓ resistance aldosteron ↓ Sodium, water BP ↓ retention
- 30. INDICATION I. ANGINA PECTORIS For Chronic management of stable angina III. MYOCARDIAL INFARCTION Reduces infarct size and has tens recovery Reduce the incidence f sudden arrhythmic death after myocardial infarct VI. HYPERTENSION VII. ARRYTHMIA VIII.MIGRAINE IX. GLAUCOMA X. HYPERTHYROIDISM
- 32. SELECTION OF DRUGS Drugs ESR Liposoluble FPE Elimination T 1/2 Propanolol +++ ++ L 1-6 Nadolol 0 0 0 K 20-24 Atenolol + 0 0 K 6-7 Metoprolol + + ++ L 3-7
- 33. CONTRAINDICATION • Severe bradycardia, heart block • Asthma or bronchospasm • Severe depression • Peripheral vascular (gangrene, skin, necrosis, Raynaud’s phenomenon) • DM • Renal failure
- 34. ACUTE MYOCARD INFARCT ↓ O2 Supply Infarct PAIN
- 35. THERAPY 1. Oksigen 2. Morfin 3. Metaklopramide 4. Nitrogliserin 5. Aspirin 6. Streptokinase 7. Heparin 8. Laksativ (bila perlu)
- 36. Other Drugs ACE INHIBITOR Reduce: 1. Remodeling ventricle 2. Haemodinamic 3. Reduce heart failure BETA BLOCKER – Reduce O2 myocard demand – Reduce size of infarct
- 38. Kasus: Seorang laki-laki 56 tahun, datang dengan keluhan sering nyeri dada (khas) PD: TD= 200/100 mmHg Diagnosis: Angina Pectoris Klasik Pertanyaan: - Bagaimana terapi akut, kronis, lainnya
- 39. Seorang wanita 62 tahun, datang dengan keluhan nyeri dada terutama pagi hari. PD: TD=180/90, Riwayat DM (+) Diagnosis: Angina Pectoris Vasospastik Pertanyaan: - Bagaimana terapi akut, kronis, lainnya ?
- 40. Seorang laki-laki, 60 tahun datang ke UGD dengan keluhan nyeri dada hebat, muntah, keringat dingin PD: TD= 180/100 Diagnosis: Acute Myocard Infarct Pertanyaan: - Bagaimana penanganan pasien tersebut?
- 41. Wassalam,