Treatment of Angina Pectoris by E.Z
Syndrome Chest pain Symptoms: pain in your arms, neck, jaw, shoulder or back accompanying chest pain; nausea; fatigue; shortness of breath; sweating; dizziness Diagnosis: Chest radiography, graded exercise stress testing, ECG, selective coronary angiography Risk factors: smoking, diabetes, high blood pressure, obesity, genetics, etc
Stable angina Coronary artery disease Develops when your heart works harder Lasts a short time Disappears sooner
Unstable angina Acute coronary syndrome Occurs even at rest Usually more severe and lasts longer May not disappear with rest or use of angina medication
Prinzmetal angina Reversible spasms of arteries Occurs at any time Is often severe May be relieved by angina medication
Determinants of O2 requirement Diastolic factors Blood volume Venous tone Systolic factors Peripheral resistance Heart rate Heart force Ejection time
Strategies To increase O2 delivery To reduce O2 requirement To increase O2 utilization (new theory)
Drugs
Nitrates&Nitrites *In 1867, Lauder Brunton described the antianginal properties of nitrites *were first used as an antianginal agent in 1879 *3 types: short-acting, intermediate, long *nitroglycerin
Nitrates&Nitrites
Pharmacokinetics Oral bioavailavility is low Total duration of effect is 30 min Pentaerythritol tetranitrate is for long use
Pharmacokinetics Amyl nitrate is for inhalation Isosorbide mononitrate (100 % bioavailability)
In smooth muscles: glutathione S-transferase Mitochondrial enzyme: aldehyde dehydrogenase isoform 2
Effects *relaxation of vessels *compensatory responses: -baroreceptors mechanisms -hormonal mechanisms
Effects *relaxation of bronchi, GU, GI tracts *decrease in platelet aggregation
Cyanide poisoning Nitrite ion + hemoglobin = methemoglobin Cyanide poisoning: cytochrome iron complexing by CN- Methemoglobin has high affinity for CN-
Toxicities Orthostatic hypotension Tachycardia Throbbing headache Contraindicated if intracranial pressure is elevated Tolerance: -tachyphylaxis -Monday disease
Clinical use Immediate treatment of angina prophylaxis
Calcium channel-blocking drugs The important one is L-type channel Ca2+ for contraction
Calcium channel-blocking drugs Dihydropyridines (nifedipine) Nondihydropyridines (verapamil, diltiazem) Orally active
Effects Relaxation of smooth muscles Reduction in PVR Reduction of coronary artery spasm BP is reduced Impulse generarion in the SA and conduction is reduced Reduced cardiac contractility
Effects Nimodipine reduce morbidity after a subarachnoid hemorrhage Nicardipine prevents cerebral vasospasm + verapamil: *inhibits release of insulin *reverse the resistance of cancer cells +interfere with platelet aggregation
Toxicity Cardiac depression Nifedepine increases the risk of MI Flushing Dizziness Nausea Constipation Peripheral edema
Clinical uses Hypertension Angina Tachyarrhythmias Migraine Raynaud's phenomenon
Beta-blocking drugs Nonselective blockers: propranolol Selective blockers: atenolol, metaprolol Orally and parenterally Only for prophylactic therapy Effects: -decreased hr -decreased bp -decreased contractility
Toxicity Fatigue Insomnia Erectile dysfunction Worsening of claudication Contraindications: Asthma Severe bradycradia Severe unstable left ventricular failure
Other drugs Ranolazine: - reduces a late Na current - reduces diastolic tension, cardiac contractility, work - prolongs QT - for angina
Other drugs Trimetazidine: -pFOX inhibitor -inhibits the fatty acid oxidation -for ischemia
Other drugs Perhexiline: -shift myocardial metabolism to glucose oxidation -but! Hepatotoxicity, peripheral neuropathy Ivabradine: -inhibits Na channels in the SA node -reduces hr - for angina and heart failure Fasudil: -inhibits smooth muscle Rho kinase = relaxation -reduces coronary vasospam; for angina
5 reasons to eat pomegranate It's tasty It's beautiful It prevents anemia It improves digestion It lowers blood pressure
Don't forget about: beetroots cashews potatoes Green tea Dark chocolate
Thanks!
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