Angina pectoris

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Antianginal Drugs
Prof.AzzaEL-Medany
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Angina pectoris

• Sudden,severe,pressing chest pain starting
  substernal radiate to left arm.
• Due to imbalance between myocardium oxygen
  requirement and oxygen supply.

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Risk Factors

• Age
• Sex
• Obesity
• Smoking
• Diabetes

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• Classification of angina
• Exertional angina,
• Stable, Atherosclerotic or Classic,
• Due to obstruction of coronaries by
  atheroma.
• Prinzmetal(Variant or vasospastic )
• Due to Spasm of coronaries.

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• 3- Unstable angina
• Due to spasm and partial obstruction of
  coronaries
• 4- Silent angina

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Nitrates Nitrites

• Preparations
• 1- Short acting
• Start within few minutes and total duration of
  action 15-30 minutes.
• A) Nitroglycerine (Glyceryl trinitrate)
• Used as sublingual tablets.
• B) Isosorbide dinitrate
• As sublingual spray.
• C) Amyl nitrite
• Inhalation

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• 2- long acting
• Nitroglycerine, Isosorbide dinitrate,Isosorbide
  mononitrate.
• Delayed onset of action and continue for hours .
• Given Orally,Ointment,Transdermal patch,
  Intravenous.

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Pharmacokinetics

• Absorption
• Well absorbed according to the route of
  administration

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• Metabolism
• Through first pass hepatic metabolism.
• Short acting not given orally to avoid first
  pass metabolism.
• Nitroglycerine Isosorbide dinitrate have
  active metabolites.

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• Excretion
• Through the kidney.

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Mechanism of action

• Glutathione
  S-transferase
• Nitroglycerine ? Nitric oxide ( NO).
• NO activates guanylyl cyclase and increase c
  GMPc GMP dephosphorylate myosin light chain
• Causing smooth muscle relaxation.

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Pharmacological actions

• Nitrates relax all types of smooth muscles
  vascular or non vascular .
• Potent venodilator.
• Have no effect on cardiac or skeletal muscles.
• NO released stimulate guanylyl cyclase
• in platelets causing increase cGMP that decrease
  platelet aggregation.

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Clinical uses

• Effective in all types of angina
• Short acting for acute attacks Long acting
  for prophylactic.
• Severe heart failure.

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Angina of effort

• Decrease preload ( increase venous capacitance )
• Decrease afterload
• decrease myocardial oxygen requirement.
• Redistribution of coronary blood flow.
• Prevent platelet aggregation

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Variant angina

• Relax smooth muscle of epicardial coronary artery
  and relief coronary spasm.

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Unstable angina

• Decrease myocardial oxygen requirement.
• Relief coronary spasm.
• Decrease platelet aggregation.

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Adverse effects

• Orthostatic hypotension syncope
• Palpitation Tachycardia
• Salt water retention
• Throbbing headache
• Facial flushing
• Tolerance
• Carcinogenicity
• Methemoglobinemia only with nitrites

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Contraindication

• Nitrates are contraindicated in increase
  intracranial pressure.
• Notice
• Nitrates can be used safely in increase of
  intraocular pressure (Glucoma).

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Calcium channel blockers

• Block calcium entry in myocardium causing
• decrease in myocardium contractility heart
  rate
• Causing decrease in myocardium oxygen
  requirement.

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• Block calcium entry in vascular smooth muscles (
  arteries arterioles) causing
• Decrease in peripheral resistance (after
  load)------ decrease in oxygen requirement.
• Relief of coronary spasm.

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Classification of calcium channel blockers

• Dihydropyridine
• Nifedipine
• More selective as vasodilator
• Verapamil Diltiazem
• More selective as cardiac depressant

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Pharmacokinetics

• Given orally
• Verapamil Diltiazem can be given intravenously
• Excreted in urine

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Clinical uses

• In all types of angina but very effective in
  variant angina .
• Used in prophylactic therapy.
• Hypertension
• Supraventricular tachycardia
• Peripheral vascular disease

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Adverse effects

• Cardiac arrest, bradycardia
• ( verapamil diltiazem )
• Reflex tachycardia
• ( nifedipine)
• Fatigue headche
• Ankle edema
• Constipation ( verapamil)

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Drug interaction

• Verapamil or diltiazem with ß-blockers causing
  bradycardia or cardiac arrest

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ß-Adrenoceptor blocking drugs

• Not vasodilators
• Used in prophylactic treatment of angina through
  
• Decrease in both heart rate myocardial
  contractility that decrease myocardial oxygen
  requirement at rest in exercise so improve
  exercise tolerance.

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• Effective in the prophylactic treatment of all
  types of angina Except in variant angina.
• Decrease mortality of patients with recent
  myocardial infarction, heart failure
  hypertension.

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Potassium channel openers
Nicorandil

• Activation of potassium channels.
• Nitric oxide release.
• Arterio venodilator.
• Used as prophylactic therapy .
• Side effects Headache, flushing, dizziness.

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Fatty Acid Oxidase Inhibitors

• Oxidation of fatty acids as a source of energy
  needs more oxygen than oxidation of carbohydrate.
• Drugs that shift myocardial metabolism toward use
  of glucose (fatty acid oxidase inhibitors) have
  the potential of reducing the oxygen demand
  without change hemodynamics , e.g. trimetazidine

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Anticoagulants Antiplatelets

• Aspirin Heparin decreasing the risk in unstable
  angina acute coronary syndrome.

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Drug treatment of angina

• Acute attack
• Short acting nitrates or nitrites.
• Prophylactic therapy
• Long acting nitrates.
• Calcium channel blockers.
• ß- adrenoceptor blockers.
• Potassium channel openers.
• Fatty acid oxidase inhibitors

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Combination therapy

• Nitrates and ß-adrenoceptor blockers.
• Calcium channel blockers( dihydropyridine) and
  ß-adrenoceptor blockers .
• Calcium channel blockers and nitrates.
• Calcium channel blockers, ß-adrenoceptor
  blockers, nitrates , antiplateles or
  anticoagulants.

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Surgical therapy

• Ballon
• Coronary by pass.

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