MAIN EXIT NEXT Definition Types of Angina Management of Angina Antianginal drugs BY: DR. MARWA SHAALAN

Transient Myocardial ischemia Severe Chest pain Myocardial Blood Flow Myocardial O2 Demands Angina Pectoris 2 BACK MAIN EXIT INDEX NEXT

Chest pain caused by transient myocardial ischemia due to an imbalance between myocardial oxygen supply and demand. Chest pain caused by transient myocardial ischemia due to an imbalance between myocardial oxygen supply and demand. 3 BACK MAIN EXIT INDEX NEXT

Types of Angina 1. Stable Angina. 4 BACK MAIN EXIT INDEX NEXT 2. Unstable Angina. 3. Variant Angina.

HOME Stable Angina. Retrosternal pain Radiating to left arm & shoulder The commonest cause isADVANCED ATHEROSCELEROSIS The commonest cause is ADVANCED ATHEROSCELEROSIS Lasting less than 15 min. 5 BACK MAIN EXIT INDEX NEXT

Exertion Emotion Heavy meals Exposure to cold weather Predisposing factors Relieving factors Rest sublingual nitroglycerin Stable Angina 6 BACK MAIN EXIT INDEX NEXT

Exercise ECG showing typical severe down sloping ST segment : Anginal pain is often associated with Depression of ST segment Standing 1 min. 3 min. 7 min. 9 min. Stable AnginaIn between attacks :ECG is entirely entirely NORMAL 7 BACK MAIN EXIT INDEX NEXT

2. 2. Unstable Angina. Increased frequency, severity or duration of pain in a patient of Stable Angina Myocardial infarction may occur in 10-20% of patients. N.B. Pain occurs with less exertion or at rest 8 BACK MAIN EXIT INDEX NEXT

The underlying cause is Atheroscelerotic changesAtheroscelerotic changes Fissuring of atheroscelerotic plaques Platelet aggregation Thrombosis Coronary artery spasm 9 BACK MAIN EXIT INDEX NEXT

3. 3. Variant Angina. (Prinzmetal) Chest pain at rest due to coronary artery spasm ECG changes: Acute elevation of ST segment The baseline ECG With chest pain, marked ST segment elevation Return of the ST segment to the baseline after nitroglycerin administration 10 BACK MAIN EXIT INDEX NEXT

Management of Angina Management of Stable Angina Management of Unstable Angina Management of Unstable Angina Management of Variant Angina 11 BACK MAIN EXIT INDEX NEXT

A-Management of Stable Angina 1- General measures. 2- Drug Treatment. 3- Coronary artery revascularization. 12 BACK MAIN EXIT INDEX NEXT

Stop smoking Reduce weight Treat Hypertension, Hypercholestrolimia and Diabetes AVOIDSevereexertion Heavy mealEmotionsCold Weather General measures 13 BACK MAIN EXIT INDEX NEXT Graduated exercise may open new collaterals

a. For an acute attack b. For immediate pre-exertional prophylaxis prophylaxis c. For long-term prophylaxis d. Antiplatelet therapy. 14 BACK MAIN EXIT INDEX NEXT

Treatment of an acute attack of angina 1-Sublingual nitroglycerin (0.5 mg ) or isosorbide dinitrate (5 mg ) 1-Sublingual nitroglycerin (0.5 mg ) or isosorbide dinitrate (5 mg ) or Oral spray nitroglycerin (0.4 mg/metered dose), isosorbide dinitrate(1.25 mg/metered dose) Relief within 1-3 min. Persistence of pain Repeat nitroglycerin at 5 min. interval (3 tab. max.) Relief not relieved Infarction HOSPITALIZATION 15 BACK MAIN EXIT INDEX NEXT

2-Immediate pre-exertional prophylaxis of Angina Sublingual nitroglycerin (0.5 mg) or isorbide dinitrate (5 mg) should be taken 5 min. before effort. 3-For Long term prophylaxis: Long acting nitrates, Ca ++ channel blockers,  -blockers or combinations of these drugs. 4-Antiplatelet therapy: Aspirin in small dose ( mg daily orally) or Dipyridamole (75 mg t.d.s orally) 16 BACK MAIN EXIT INDEX NEXT

Coronary artery bypass grafting (CABG) Percutaneous Transluminal coronary Angioplasty (PTCA) For patients not responding to adequate medical therapy 17 BACK MAIN EXIT INDEX NEXT

B-Management of Unstable Angina Nitrate+  -blocker + Aspirin (low dose) and/or Heparin or Heparin or Thrombolytic (stryptokinase) to minimize risk of infarction 18 BACK MAIN EXIT INDEX NEXT

C-Management of Variant Angina Nitrates and/or and/or Ca++ Channel blockers For the acute attack & prophylaxis 19 BACK MAIN EXIT INDEX NEXT

What are the antianginal drugs? 1-Organic nitrates. 3-Calcium channel blockers. 2-  - adrenoceptor blockers. 20 BACK MAIN EXIT INDEX NEXT

NITRATES Veins Arteries 21 BACK MAIN EXIT INDEX NEXT Relaxation of smooth muscles Dilatation

Cellular Mechanism of Vasodilatation Nitrates Formation of Nitric oxide (NO) Activation of Guanylate cyclase Synthesis of cyclic GMP Relaxation of Vascular smooth muscles 22 BACK MAIN EXIT INDEX NEXT N.B. (-SH) groups are required for formation of NO.

Effect of Nitrates : On Stable Angina : Venodilatation Arteriolar dilatation PreloadAfterload Myocardial Oxygen demand 2- Redistribution of coronary flow towards subendocardium 3- Dilatation of coronary collateral vessels. 1-

On Variant Angina : Relax smooth muscles of the epicardial coronaries  relieve coronary artery spasm On Unstable Angina : Dilatation of epicardial coronary arteries + reducing O 2 demands 24 BACK MAIN EXIT INDEX NEXT

Preparations : Short acting For acute attacks Long acting For antianginal prophylaxis For antianginal prophylaxis Nitroglycerin (sublingual, buccal spray) Isosorbide dinitrate(sublingual, buccal spray) Nitroglycerin oral SR ( mg) 2-4 times/day - 2% ointment (1-1.5 inch/4hrs) - patches (1 patch=25mg)/day Isosorbide dinitrate (oral) mg t.d.s. Isosorbide mononitrate (oral) 20mg/12 hrs. 26 BACK MAIN EXIT INDEX NEXT

Duration of Action of Various Preparations of Organic Nitrates

Adverse Reactions : 1- Postural Hypotension & Syncope 2- Tachycardia 5- Throbbing Headache 4- Facial Flushing 3- Drug Rash 6- Prolonged high dose Methaemoglobinaemia 28 BACK MAIN EXIT INDEX NEXT

How does it occur? The main limitation of chronic nitrate therapy is TOLERANCE It develops as SH groups in vessel wall become oxidized by constant exposure to nitrates, this prevents the production of NO & hence stimulation of Guanylate cyclase which is believed to be fundamental to smooth muscle relaxation produced by the drugs. Tolerance to the antianginal effect occurs as a result of chronic administration 29 BACK MAIN EXIT INDEX NEXT “NITRATE FREE INTERVAL” of 8-10 hrs reduces or prevents development of nitrate tolerance.e.g. isosorbide dinitrate is given at 7am, noon and 5pm; trnsdermal patches should be used for about 12 hrs daily

What are nitrosamines & what is their medical importance ? What is the effect of nitroglycerin on platelet aggregation ? 30 BACK MAIN EXIT INDEX NEXT These are small molecules formed from the combination of nitrates and nitrites with amines. They are also found in tobacco and cigarette smoke. Some of them may cause cancer in humans, but there is no evidence that the small doses of nitrates used in treatment of angina result in significant body levels of nitrosamines. It decreases platelet aggregation.

 -blockers are effective in STABLE & UNSTABLE angina In contrast they are not useful for vasospastic angina (Variant) {Prinzmetal} & may worsen the condition. This deleterious effect is likely due to an increase in coronary resistance caused by the unopposed effects of catecholamines acting at  -adrenoceptors.

The effectiveness of  -adrenoceptor  -adrenoceptor blockers in the treatment of exertional angina is attributable to a fall in myocardial O2 O2 O2 O2 requirement at rest & during exertion due to : 1- A -ve chronotropic effect (particularly during exercise). 2- A -ve inotropic effect. 3- A reduction in arterial blood pressure (particularly systolic pressure) during exercise. Mechanism of antianginal action: 32 BACK MAIN EXIT INDEX NEXT

33 BACK MAIN EXIT INDEX NEXT However the net effect of  -blockers is to  myocardial O 2 requirement particularly during exercise; their potentially deleterious effects can be balanced by concomitant use of nitrates 33 Rate & contractility Undesirable effects of  -blockers in treatment of angina: Systolic ejection period & left ventricular end diastolic vol. Myocardial O 2 requirements

Dosage and Route of Administration DrugRouteDosage PropranololOral mg/day in 2-4 divided doses NadololOral40-80 mg ONCE daily AtenololOral mg ONCE daily MetoprololOral mg TWICE daily

Adverse Reactions : CHF A-V block Bronchospasm Cold extremities Worsening symptoms of PVD Hypotension 35 BACK MAIN EXIT INDEX NEXT

Fatigue & weakness Mask signs of Hypoglycemia Nightmares, Hallucinations, Depression. Nightmares, Hallucinations, Depression. Plasma Triglycerides & HDL Cholesterol Discontinuation after long ttt exacerbates Angina 36 BACK MAIN EXIT INDEX NEXT Adverse Reactions :

CHF A-V block Peripheral Vascular disease Hypotension Contraindications : Bronchial asthma 37 BACK MAIN EXIT INDEX NEXT

Verapamil ( mg) /8 hr Diltiazem ( mg) /8 hr Dihydropyridine group Nifedipine (10-40mg) /8 hr Amlodipine 5mg/day Used in treatment of all types of angina. 38 BACK MAIN EXIT INDEX NEXT

Block Voltage -dependent calcium channels (L-type) in cardiac and smooth muscles. CALCIUMCALCIUMCALCIUMCALCIUM

Mechanism of anti-anginal action : 1 - Coronary artery dilatation and relief of coronary spasm (variant angina) (Verapamil & Diltiazem) Decrease HR. Decrease contractility Decrease AV conductivity Arteriolar dilatation Vascular resistance Afterload 2 -Decrease myocardial O 2 demand due to:

Dosage and Route of Administration

Adverse reactions : Dizziness Ankle edema HypotensionHeadache Flushing Constipation A-V block & HF only with Verapamil & Diltiazem Reflex Tachycardia with Nifedipine

3 - Bradycardia. Contraindications of Verapamil & Diltiazem: 1 - HF 2 - Sinus or A-V node disease.

 -blocker + Long acting Nitrate  -blocker + Nifedipine Verapamil or Diltiazem + Nitrate  -blocker + Nitrate + Nifedipine ???? ???? ???? ????

 -blockers block reflex tachycardia produced by nitrates Nitrates attenuate the increased left ventricular end-diastolic volume associated with  -blockers

 -blockers decrease reflex tachycardia produced by nifedepine.

Verapamil or Diltiazem decrease tachycardia produced by nitrates. In patients with stable angina not controlled by two types of antianginal drugs the use of three agents may provide improvement.

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