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Pharma seminar new version


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Pharma seminar new version

  2. 2. What is angina pectoris??
  3. 3. Types of angina?
  4. 4. Myocardial infarctionMyocardial cell death due to prolonged ischemia
  5. 5. Antianginal DrugsPrinciple of action:• 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. 6. Supply can be increased by :1*dilating coronary artery2*slowing the heart (coronary flow, uniquelyoccurs in diastole, which lengthens as heartrate falls).Demand can be reduced by :1*reducing afterload (i.e. reducing peripheralresistance)Reducing the work of heart in perfusing thetissues.2*reducing preload( i.e. venous fillingpressure ) according to starlings law of theheart, workload and oxygen demand varieswith stretch of cardiac muscle fibers3*slowing the heart
  7. 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 others3- CALCIUM CHANNEL BLOCKERS:a)Dihydropyridines : nefidepine, nicardepine, felodepine, amlodepine,nitrendepine, lercanidepine, benidepine.b)Non dihydropyridines: verapamil, diltiazem4-POTASSIUM CHANNEL OPENER: nicorandil5-Antiplatelet Drugs: Aspirin , Warfarin (CoumadinClopidogrel6- OTHERS:Dipyridamole,trimetazidine,ranolazine,oxyphedrine
  8. 8. 1-NITRATES AND NITRITESAre simple nitric and nitrous acid esters of glycerolClassification of nitrates:1. Rapidly acting nitrates * used to terminate acute attack of angina * e.g.- Nitroglycerin and Amyl nitrate * usually administered sublingually2. Long acting nitrates * used to prevent an attack of angina * e.g. -Erythrytyl tetranitrate, Isosorbide dinitrate, Pentaerythrytol tetranitrate * administered orally or topically
  9. 9. • The onset of 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
  10. 10. Coronary artery dilatation Decrease coronary bed resistance (Relieved coronary vasospasm)Increase coronary blood flow Increase oxygen supply
  11. 11. Reduction on peripheral resistance(Secondary to dilatation of aorta) Decrease blood pressure Decrease after load Decrease workload Decrease oxygen consumption
  12. 12. Reduced venous return(Due to dilatation of the veins)Decrease left ventricular volume Decrease preload Decrease workload Decrease oxygen consumption
  13. 13. 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
  14. 14. Tolerance• Tolerance to the 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.
  15. 15. Tolerance to the Antianginal andhemodynamic 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. 17. ROUTES OF ADMINISTRATION 1. Sublingual route 2. Oral route 3. Intravenous Route 4. Topical route
  18. 18. NITROGYLECERINE-Prototypical nitrate-Large first-pass effect 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.
  19. 19. Drug interaction with cGMP-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.
  20. 20. CONTRAINDICATION1. Renal ischemia2. Acute myocardial infarction3. Patients receiving other antihypertensive agent
  21. 21. 2-B BLOCKERS 2 types : non selective and cardioselectiveatenolol (Tenormin)metoprolol (Lopressor)propranolol (Inderal)nadolol (Corgard)
  22. 22. pharmacokinetics B blockers are orally active. Propranolol undergoes significant first pass metabolism They may take several weeks to develop full effect
  23. 23. B-Blockers Decrease heart rate & ContractilityIncrease duration of diastole Decrease workloadIncrease coronary blood flow Decrease O2 consumption Increase oxygen supply
  24. 24. 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
  25. 25. CONTRAINDICATION1. Congestive heart failure2. Asthma and COPD3. Complete heart block4. Patients with bradycardia5. patients with history of cocaine use or in cocaine-induced tachycardia or MI.
  26. 26. ATENOLOL (TENORMIN)Atenolol is a selective β1 receptor antagonist
  27. 27. 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.
  28. 28. Ca - Channel Blockersa)Dihydropyridines : nefidepine, nicardepine, felodepine, amlodepine, nitrendepine, lercanidepine, benidepine.b)Non dihydropyridines: verapamil, diltiazem
  29. 29. Effects1. Coronary artery dilatation2. Reduction on peripheral arterial resistance – decrease after load
  30. 30. Coronary artery dilatationDecrease coronary bed resistance (Relieved coronary vasospasm)Increase coronary blood flowIncrease oxygen supply
  31. 31. Reduction on peripheral resistance(Secondary to dilatation of aorta) Decrease blood pressure Decrease after load Decrease workload Decrease oxygen consumption
  32. 32. Pharmacokinetics:Calcium channel blockers are well absorbed form GIT and theirbioavailability depends on the extent of first pass metabolismin the gut wall and liver which varies between the drugs.Interaction:- Both diltiazem and verapamil cause increase to exposure tocarbamazepine ,quinidine and metoprolol.-Verapamil increase plasma concentration of digoxin.
  33. 33. Most commonly used Ca Channel Blockers:verapamil (Calan)diltiazem (Cardizem)nifedipine (Procardia
  34. 34. NEFIDEPINE• Nifedipine, a dihydropyridine 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.
  35. 35. • Nifedipine is administered 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.
  36. 36. 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.
  37. 37. _The drug is extensively metabolized bythe liver; therefore, care must be takento adjust the dose in patients with liverdysfunction.
  39. 39. Contraindication Cardiogenic shock. Recent myocardial infarction. Heart failure. Atrioventricular block. in patients with preexisting depressed cardiac function or AV conduction abnormalities.In hypotensive patients.
  40. 40. Combination Therapy Nitrates and b blockers : to prevent the reflex tachycardia produced by nitrates Ca channel blockers with b blockers for same reason Ca channel blockers and NitratesNitrates reduce preload and after loadCa channels reduces the after load Net effect is on reduction of oxygen demand
  42. 42. 4- POTASSIUM CHANNEL OPENER 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 relaxationof 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.
  43. 43. PharmacokineticNicorandil is well absorbed with no significant first passmetabolism, metabolism is mainly by denitration into nicotinamidepathway 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.
  44. 44. 5-ANTIPLATELETS1-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 angina2-Other agents Clopidogrel (Plavix)- in place of WARFARIN aspirin Warfarin (Coumadin)
  45. 45. Myocardial infarctionGoals of treatmentThe most important goal of drug therapy early in thecourse of acute myocardial infarction is to improve theoxygen supply/demand ratio for the heart. Thereduction in this ratio that occurs when coronary flow iscompromised is the primary reason cardiac function isimpaired, which leads to the clinical signs associatedwith myocardial infarction. There are two strategies toimprove the coronary supply/demand ratio,1) restore normal coronary blood flow.2) decrease myocardial oxygen consumption.
  46. 46. Further treatment is based on thefollowing: 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
  47. 47. Classes of Drugs Used to Treat Myocardial Infarction1•Vasodilators (dilate arteries and veins)- nitrodilators- angiotensin converting enzyme inhibitors (ACE inhibitors)- angiotensin receptor blockers (ARBs)2•Cardiac depressant drugs (reduce heart rate andcontractility)- beta-blockers3•Antiarrhythmics (if necessary)4•Anti-thrombotics (prevent thrombus formation)- anticoagulant- anti-platelet drugs5•Thrombolytics (dissolve clots - i.e., "clot busters")- plasminogen activators6•Analgesics (reduce pain)- morphine
  48. 48. ACEI(angiotensin converting enzymeinhibitors)Cardiorenal Effects 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
  49. 49. Specific Drugs• benazepril• captopril• enalapril• fosinopril• lisinopril• moexipril• quinapril• ramiprilNote that each of the ACE inhibitors named above end with"pril."
  50. 50. captopril Captopril is a 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).
  51. 51. PharmacokineticsAbout 70% of orally administered captopril is absorbed. Bioavailability is reduced by presence of food in stomach. It is partly metabolized and partly excreted unchanged in urine.
  52. 52. 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
  53. 53. contraindication Hypersensitivity to drug or other ACE inhibitors Angioedema (hereditary or Idiopathic) Pregnancy
  54. 54. Angiotensin receptor blockers
  55. 55. Specific Drugs• candesartan• eprosartan• irbesartan• losartan• olmesartan• telmisartan• valsartanNote that each of the ARBsnamed above ends with"sartan."
  56. 56. Losartan Losartan is an 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.
  57. 57. 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 angioedemaContraindications• Hypersensitivity to drug or its components
  58. 58.  INTERACTIONDrug-drug. Diuretics, other antihypertensives: increasedrisk of hypotensionFluconazole: inhibited losartan metabolism, increasedantihypertensive effects Indomethacin: decreased losartan effects Phenobarbital, rifamycins: enhanced losartan metabolism, decreased antihypertensive effects Potassium-sparing diuretics, potassium supplements: hyperkalemiaDrug-diagnostic tests. Albumin: increased levelDrug-food. Salt substitutes containingpotassium: hyperkalemia
  59. 59. B BLOCKERS IN MIBeta-adrenergic receptor blocking agents (beta-blockers) are drugs with multiple actions on theheart. Blockade of beta-1 receptors results in slowingof heart rate, reduction in myocardial contractility,and lowering of systemic blood pressure. In thecontext of acute myocardial infarction (AMI), whichrepresents a state of reduced oxygen supply to theaffected portion of the heart, these effects may bebeneficial as they result in reduced myocardialworkload and oxygen demand. Furthermore, beta-blockers may reduce the risk of ventriculararrhythmias, which are an important cause of deathfollowing AMI.
  60. 60. nadololpropranololtimololatenololMetoprololcarvidelol
  61. 61. carvidelolReduces morbidity and mortalility ratedue to myocardial infarction its calledthird generation b locker because ofits effects:Inhibits lipid peroxidationInhibits release of free radicals from neutrophilsScavenger of free radicals
  62. 62. Side effects slow or 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...
  63. 63. 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.
  64. 64. 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.
  65. 65. Given:OrallySide Effects:• Vomiting• Headache• Dizziness• Chest PainDrug Interactions:SaquinavirIncrease Quinidine levels by inhibitingremoval of Quinidine by liver.Contraindications:Patients with Heart Failure
  66. 66. Thrombolytic Drugs Used to 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)
  67. 67. Streptokinase & Mechanismof Action
  68. 68. • Given by: Injection• Side Effects• Low Blood Pressure• Nausea• Headache• Easy BruisingDrug Interaction:• Aprotinin• Reverses effect of StreptokinaseContraindications:• Injury & Trauma
  69. 69. Analgesics Used to reduce pain.
  70. 70. CLASSES: Paracetamol and NSAIDs COX-2 inhibitors Opiates and morphinomimetics Flupirtine Combinations
  71. 71. MorphinePowerful Narcotic Analgesic.Mechanism of Action: Acts on Opioid receptors in brain. Binds to & inhibits GABA inhibitory interneurons. Inhibits pain.
  72. 72. Given:Orally/ InjectionSide Effects:• Slow breathing• Slow heartbeat• Sedation• ConfusionDrug Interactions:Sedatives that make you sleepy and slow your breathing.Contraindications:In alcoholic patients which can lead to increased sedation &death.
  73. 73. 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. htm tm m
  74. 74. http:/