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Pharma seminar new version
The document discusses various drugs used to treat angina pectoris and myocardial infarction. It describes the classes of drugs which include nitrates, beta blockers, calcium channel blockers, nicorandil, aspirin, ACE inhibitors, and captopril. It explains the mechanisms of action, pharmacokinetics, indications, contraindications and side effects of these drug classes and examples like nitroglycerin, atenolol, nifedipine, verapamil, aspirin, and captopril.
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Pharma seminar new version
- 1. Supervised by ZHIYAR MUHAMMADNAZIFIBRAHIM PARWEEN DLOVAN MUHAMMAD Dr. chro TABAN FADHIL NABI SUPERVISED BY : Dr. suzan BASNA KAMAL MUHAMMAD
- 2. What is anginapectoris??
- 3.
- 4. Myocardial infarction Myocardial celldeath due to prolonged ischemia
- 5. Antianginal Drugs Principle ofaction: • Angina can be viewed as a problem of oxygen supply and demand , so these drugs will either increase supply of oxygen and nutrients of reduce myocardial oxygen demand or both.
- 6. Supply can beincreased by : 1*dilating coronary artery 2*slowing the heart (coronary flow, uniquely occurs in diastole, which lengthens as heart rate falls). Demand can be reduced by : 1*reducing afterload (i.e. reducing peripheral resistance) Reducing the work of heart in perfusing the tissues. 2*reducing preload( i.e. venous filling pressure ) according to starling's law of the heart, workload and oxygen demand varies with stretch of cardiac muscle fibers 3*slowing the heart
- 7. Classification: 1- NITRATES: a)Short acting:glyceryl trinitrate( GTN, nitrogylerine) b)Long acting : isosorbide dinitrate (if given sublingually its short acting), isosorbide mononitrate,erythrityl tetranitrate, pentaerythritol tertanitrate. 2- B BLOCKERS: propranolol, metoprolol, atenolol , carvidelol and others 3- CALCIUM CHANNEL BLOCKERS: a)Dihydropyridines : nefidepine, nicardepine, felodepine, amlodepine, nitrendepine, lercanidepine, benidepine. b)Non dihydropyridines: verapamil, diltiazem 4-POTASSIUM CHANNEL OPENER: nicorandil 5-Antiplatelet Drugs: Aspirin , Warfarin (Coumadin Clopidogrel 6- OTHERS: Dipyridamole,trimetazidine,ranolazine,oxyphedrine
- 8. 1-NITRATES AND NITRITES Aresimple nitric and nitrous acid esters of glycerol Classification of nitrates: 1. Rapidly acting nitrates * used to terminate acute attack of angina * e.g.- Nitroglycerin and Amyl nitrate * usually administered sublingually 2. Long acting nitrates * used to prevent an attack of angina * e.g. -Erythrytyl tetranitrate, Isosorbide dinitrate, Pentaerythrytol tetranitrate * administered orally or topically
- 9. • The onsetof action varies from 1 minute as in nitroglycerine to one hour as in isosorbide mononitrate • Nitroglycerine undergoes significant first pass metabolism in the liver so its given sublingually or as transdermal patches • The stability of isosorbide mononitrate against liver break down gives it its long duration of action and high bioavailability • Isosorbide dinitrate gives 2 molecules of isosorbide mononitrate in the body
- 11. Coronary artery dilatation Decrease coronary bed resistance (Relieved coronary vasospasm) Increase coronary blood flow Increase oxygen supply
- 12. Reduction on peripheral resistance (Secondary to dilatation of aorta) Decrease blood pressure Decrease after load Decrease workload Decrease oxygen consumption
- 13. Reduced venous return (Dueto dilatation of the veins) Decrease left ventricular volume Decrease preload Decrease workload Decrease oxygen consumption
- 14. ADVERSE EFFECT 1. Throbbing headache 2. Flushing of the face 3. Dizziness – especially at the beginning of treatment 4. Postural Hypotension – due to pooling of blood in the dependent portion of the body
- 15. Tolerance • Tolerance tothe action of nitrates develop rapidly in which blood • vessels will be desensitized to the vasodilatory effect of the drug. • Tolerance can be overcome by a daily nitrate free interval which is typically of 8 to 12 hours. • Nitrate free interval is usually at night as the oxygen demand increase • But in variant angina which worsen during early morning due to the circadian catecholamin attack the nitrate free interval should be at late afternoon.
- 16. Tolerance to theAntianginal and hemodynamic effects of nitrates develops: higher doses Drugs have longer half-lives. It is common in patients being treated with topical, transdermal or continuous i.v. infusions
- 17.
- 18. ROUTES OF ADMINISTRATION 1. Sublingual route 2. Oral route 3. Intravenous Route 4. Topical route
- 20. NITROGYLECERINE -Prototypical nitrate -Large first-passeffect with PO forms -Used for symptomatic treatment of ischemic heart conditions (angina) -IV form used for • BP control in perioperative hypertension. • treatment of CHF. • ischemic pain. • pulmonary edema associated with acute MI.
- 21. Drug interaction withcGMP-dependent phosphodiesterase inhibitors (e.g., sildenafil ). The reason for this adverse reaction is that nitrodilators stimulate cGMP production and drugs like sildenafil inhibit cGMP degradation. When combined, these two drug classes greatly potentiate cGMP levels, which can lead to hypotension and impaired coronary perfusion.
- 22. CONTRAINDICATION 1. Renal ischemia 2.Acute myocardial infarction 3. Patients receiving other antihypertensive agent
- 23. 2-B BLOCKERS 2types : non selective and cardioselective atenolol (Tenormin) metoprolol (Lopressor) propranolol (Inderal) nadolol (Corgard)
- 24. pharmacokinetics B blockersare orally active. Propranolol undergoes significant first pass metabolism They may take several weeks to develop full effect
- 25. B-Blockers Decrease heart rate & Contractility Increase duration of diastole Decrease workload Increase coronary blood flow Decrease O2 consumption Increase oxygen supply
- 26. Side effects Bradycardia CNS side effects as fatigue, lethargy, insomnia and hallucination. Hypotension Decrease in libido Decreases serum HDL and increases TG Withdrawal syndrome : rebound hypertension
- 27. CONTRAINDICATION 1. Congestive heartfailure 2. Asthma and COPD 3. Complete heart block 4. Patients with bradycardia 5. patients with history of cocaine use or in cocaine-induced tachycardia or MI.
- 28. ATENOLOL (TENORMIN) Atenolol isa selective β1 receptor antagonist
- 29. PHARMAKOKINETICS tcmax =2 to 4 hours after oral The mean elimination half-life is 6 hours. However, the action of the usual oral dose of 25 to 100 mg lasts over a period of 24 hours. Atenolol is a hydrophilic drug. The concentration found in brain tissue is approximately 15% of the plasma concentration only. The drug crosses the placenta barrier freely. In the milk of breastfeeding mothers, approximately 3 times the plasma concentrations are measured. Atenolol is almost exclusively eliminated renally and is well removable by dialysis. A compromised liver function does not lead to higher peak-activity and/or a longer half-life with possible accumulation.
- 30. Ca - ChannelBlockers a)Dihydropyridines : nefidepine, nicardepine, felodepine, amlodepine, nitrendepine, lercanidepine, benidepine. b)Non dihydropyridines: verapamil, diltiazem
- 31. Effects 1. Coronary artery dilatation 2. Reduction on peripheral arterial resistance – decrease after load
- 32. Coronary artery dilatation Decrease coronary bed resistance (Relieved coronary vasospasm) Increase coronary blood flow Increase oxygen supply
- 33. Reduction on peripheral resistance (Secondary to dilatation of aorta) Decrease blood pressure Decrease after load Decrease workload Decrease oxygen consumption
- 34. Pharmacokinetics: Calcium channel blockersare well absorbed form GIT and their bioavailability depends on the extent of first pass metabolism in the gut wall and liver which varies between the drugs. Interaction: - Both diltiazem and verapamil cause increase to exposure to carbamazepine ,quinidine and metoprolol. -Verapamil increase plasma concentration of digoxin.
- 35. Most commonly usedCa Channel Blockers: verapamil (Calan) diltiazem (Cardizem) nifedipine (Procardia
- 36. NEFIDEPINE • Nifedipine, adihydropyridine derivative, functions mainly as an arteriolar vasodilator. This drug has minimal effect on cardiac conduction or heart rate. • Other members of this class, amlodipine, nicardipin e, and felodipine, have similar cardiovascular characteristics except for amlodipine, which does not affect heart rate or cardiac output.
- 37. • Nifedipine isadministered orally, usually as extended-release tablets. • It undergoes hepatic metabolism to products that are eliminated in both urine and the feces. • The vasodilation effect of nifedipine is useful in the treatment of variant angina caused by spontaneous coronary spasm.
- 38. verapamil The diphenylalkylamine verapamil slows cardiac atrioventricular (AV) conduction directly, and decreases heart rate, contractility, blood pressure, and oxygen demand. Verapamil causes greater negative inotropic effects than nifedipine, but it is a weaker vasodilator.
- 39. _The drug isextensively metabolized by the liver; therefore, care must be taken to adjust the dose in patients with liver dysfunction.
- 40.
- 41. Contraindication Cardiogenic shock. Recent myocardial infarction. Heart failure. Atrioventricular block. in patients with preexisting depressed cardiac function or AV conduction abnormalities. In hypotensive patients.
- 42. Combination Therapy Nitratesand b blockers : to prevent the reflex tachycardia produced by nitrates Ca channel blockers with b blockers for same reason Ca channel blockers and Nitrates Nitrates reduce preload and after load Ca channels reduces the after load Net effect is on reduction of oxygen demand
- 43. STABLE ANGINA NITRATES ,CALCIUM CHANNEL BLOCKER AND B BLOCKERS UNSTABLE ANGINA NITRATES & CALCIUM CHANNEL BLOCKER VARIANT ANGINA NITRATES & CALCIUM CHANNEL BLOCKER
- 44. 4- POTASSIUM CHANNELOPENER NICORANDIL : an effective vasodilator through 2 actions: 1-it acts as nitrates by activating cGMP. 2- opens ATP dependent potassium channels. Leading to hyperpolarization and relaxation of vascular smooth muscle. Its given orally as an alternative to nitrates incase of tolerance . Adverse effect : similar to those of nitrates with headache in 35% of patients.
- 45. Pharmacokinetic Nicorandil is wellabsorbed with no significant first pass metabolism, metabolism is mainly by denitration into nicotinamide pathway and less than 20% is excreted into urine. contraindication People with low blood pressure. People with cardiogenic shock. People with heart failure with low filling pressure. People using drugs for impotence such as sildenafil & tadalafil. In pregnancy. In breastfeeding.
- 46. 5-ANTIPLATELETS 1-Aspirin- inhibits synthesis of prostacyclin and ASPIRIN thromboxane A2- prevent platelet aggregation- decrease thrombosis Indications- several. For angina- primarily used to prevent MI in patients with unstable angina 2-Other agents Clopidogrel (Plavix)- in place of WARFARIN aspirin Warfarin (Coumadin)
- 47. Myocardial infarction Goals oftreatment The most important goal of drug therapy early in the course of acute myocardial infarction is to improve the oxygen supply/demand ratio for the heart. The reduction in this ratio that occurs when coronary flow is compromised is the primary reason cardiac function is impaired, which leads to the clinical signs associated with myocardial infarction. There are two strategies to improve the coronary supply/demand ratio, 1) restore normal coronary blood flow. 2) decrease myocardial oxygen consumption.
- 48. Further treatment isbased on the following: Restoration of the balance between the oxygen supply and demand to prevent further ischemia Pain relief Prevention and treatment of any complications that may arise
- 49. Classes of DrugsUsed to Treat Myocardial Infarction 1•Vasodilators (dilate arteries and veins) - nitrodilators - angiotensin converting enzyme inhibitors (ACE inhibitors) - angiotensin receptor blockers (ARBs) 2•Cardiac depressant drugs (reduce heart rate and contractility) - beta-blockers 3•Antiarrhythmics (if necessary) 4•Anti-thrombotics (prevent thrombus formation) - anticoagulant - anti-platelet drugs 5•Thrombolytics (dissolve clots - i.e., "clot busters") - plasminogen activators 6•Analgesics (reduce pain) - morphine
- 50. ACEI(angiotensin converting enzyme inhibitors) CardiorenalEffects of ACE Inhibitors Vasodilation (arterial & venous) - reduce arterial & venous pressure - reduce ventricular afterload & preload Decrease blood volume - natriuretic - diuretic Depress sympathetic activity Inhibit cardiac and vascular hypertrophy
- 52. Specific Drugs • benazepril • captopril • enalapril • fosinopril • lisinopril • moexipril • quinapril • ramipril Note that each of the ACE inhibitors named above end with "pril."
- 53. captopril Captopril isa potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin- angiotensin-aldosterone system (RAAS).
- 54. Pharmacokinetics About 70% oforally administered captopril is absorbed. Bioavailability is reduced by presence of food in stomach. It is partly metabolized and partly excreted unchanged in urine.
- 55. Adverse reactions CNS:headache, dizziness, drowsiness, fatigue, weakness, insomnia CV: angina pectoris, tachycardia, hypotension EENT: sinusitis GI: nausea, diarrhea, anorexia GU: proteinuria, erectile dysfunction, gynecomastia, renal failure Hematologic: anemia, agranulocytosis, leukopenia, pancytopenia, thrombocytopenia Metabolic: hyperkalemia Respiratory: cough, asthma, bronchitis, dyspnea, eosinophilic pneumonitis Skin: rash, angioedema Other: altered taste, fever
- 56. contraindication Hypersensitivity todrug or other ACE inhibitors Angioedema (hereditary or Idiopathic) Pregnancy
- 57.
- 58. Specific Drugs • candesartan • eprosartan • irbesartan • losartan • olmesartan • telmisartan • valsartan Note that each of the ARBs named above ends with "sartan."
- 59. Losartan Losartan isan oral medication that belongs to a class of drugs called angiotensin receptor blockers (ARBs) Losartan (more specifically, the chemical formed when the liver converts the inactive losartan into its active form) blocks the angiotensin receptor. By blocking the action of angiotensin, losartan relaxes muscle cells and dilates blood vessels thereby reducing blood pressure. Losartan was approved by the FDA in April 1995.
- 60. Adverse effect CNS:dizziness, insomnia, headache, asthenia, fatigue CV: hypotension EENT: sinus disorders GI: nausea, vomiting, diarrhea, dyspepsia, abdominal pain Metabolic: hyperkalemia Musculoskeletal: joint pain, back pain, muscle cramps Respiratory: symptoms of upper respiratory infection, dry cough Other: hypersensitivity reactions including angioedema Contraindications • Hypersensitivity to drug or its components
- 61. INTERACTION Drug-drug. Diuretics,other antihypertensives: increased risk of hypotension Fluconazole: inhibited losartan metabolism, increased antihypertensive effects Indomethacin: decreased losartan effects Phenobarbital, rifamycins: enhanced losartan metabolism, decreased antihypertensive effects Potassium-sparing diuretics, potassium supplements: hyperkalemia Drug-diagnostic tests. Albumin: increased level Drug-food. Salt substitutes containing potassium: hyperkalemia
- 62. B BLOCKERS INMI Beta-adrenergic receptor blocking agents (beta- blockers) are drugs with multiple actions on the heart. Blockade of beta-1 receptors results in slowing of heart rate, reduction in myocardial contractility, and lowering of systemic blood pressure. In the context of acute myocardial infarction (AMI), which represents a state of reduced oxygen supply to the affected portion of the heart, these effects may be beneficial as they result in reduced myocardial workload and oxygen demand. Furthermore, beta- blockers may reduce the risk of ventricular arrhythmias, which are an important cause of death following AMI.
- 63.
- 64. carvidelol Reduces morbidity andmortalility rate due to myocardial infarction its called third generation b locker because of its effects: Inhibits lipid peroxidation Inhibits release of free radicals from neutrophils Scavenger of free radicals
- 65. Side effects slowor uneven heartbeats; feeling light-headed, fainting; feeling short of breath, even with mild exertion; swelling of your ankles or feet; nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing...
- 66. Antiarrhythmic Drugs • The aim is to restore normal rhythm and conduction. And prevent arrhythmias that follow MI Quinidine Procainamide Disopyramide • Used to: Decrease/increase conduction velocity. Alter the excitability of cardiac cells by changing the duration of the effective refractory period. Suppress abnormal automaticity.
- 67. Quinidine Antiarrythmic drug Na Channel Blocker Decreases speed of electrical current that travels through heart muscle. Prolongs period during which heart muscle cells become electrically stimulated to contract. Prolongs recovery period after contraction.
- 68. Given: Orally Side Effects: • Vomiting • Headache • Dizziness • Chest Pain Drug Interactions: Saquinavir Increase Quinidine levels by inhibiting removal of Quinidine by liver. Contraindications: Patients with Heart Failure
- 69. Thrombolytic Drugs Usedto dissolve blood clots. The thrombolytic drugs include: tissue plasminogen activator t-PA: alteplase (Activase) reteplase (Retavase) tenecteplase (TNKase) anistreplase (Eminase) streptokinase (Kabikinase, Streptase) urokinase (Abbokinase)
- 70.
- 71. • Given by:Injection • Side Effects • Low Blood Pressure • Nausea • Headache • Easy Bruising Drug Interaction: • Aprotinin • Reverses effect of Streptokinase Contraindications: • Injury & Trauma
- 72. Analgesics Used to reduce pain.
- 73. CLASSES: Paracetamol andNSAIDs COX-2 inhibitors Opiates and morphinomimetics Flupirtine Combinations
- 74. Morphine Powerful Narcotic Analgesic. Mechanismof Action: Acts on Opioid receptors in brain. Binds to & inhibits GABA inhibitory interneurons. Inhibits pain.
- 75. Given: Orally/ Injection Side Effects: • Slow breathing • Slow heartbeat • Sedation • Confusion Drug Interactions: Sedatives that make you sleepy and slow your breathing. Contraindications: In alcoholic patients which can lead to increased sedation & death.
- 77. references Richard D.howland , Mary J. Mycek.2000. pharmacology.USA. Williams & wilkins. Rand,Dale,Ritter,Moore.2004. pharmacology.Uk.churchil livingstone, Elsevier limited. Bertram Katzung.2007.basic and clinical pharmacology.singapore.McGRawHill. http://www.cvpharmacology.com/clinical%20topics/angina. htm http://www.cvpharmacology.com/Angina/antianginal.htm http://www.cvpharmacology.com/vasodilator/vasodilators.h tm http://www.cvpharmacology.com/vasodilator/ACE.ht m
- 78.