Atenolol Presentation Clin 210 50


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Atenolol Presentation Clin 210 50

  1. 1. Beta Blocker Presentation <ul><li>Clin 210 – 50 </li></ul><ul><li>Humber College </li></ul><ul><li>2008 </li></ul><ul><li>Beta blocker - Atenolol By </li></ul><ul><li>Rajeev Kashyap </li></ul>
  2. 2. Beta blocker <ul><li>Beta blockers block the action of epinephrine and norepinephrine on the β-adrenergic receptors in the body (primarily in the heart, peripheral blood vessels, bronchi, pancreas, and liver). The hormones and neurotransmitters stimulate the sympathetic nervous system by acting on these receptors. </li></ul>
  3. 3. Beta blocker <ul><li>Beta blockers block the action of epinephrine and norepinephrine on the β-adrenergic receptors in the body (primarily in the heart, peripheral blood vessels, bronchi, pancreas, and liver). The hormones and neurotransmitters stimulate the sympathetic nervous system by acting on these receptors. </li></ul>
  4. 4. Beta blockers <ul><li>May also be referred to as </li></ul><ul><li>ß adrenergic blocking agents. </li></ul><ul><li>ß adrenergic antagonists . </li></ul><ul><li>or </li></ul><ul><li>ß antagonists . </li></ul>
  5. 5. Receptor_antagonist <ul><li>A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses. (&quot;Pharmacology Guide: In vitro pharmacology: concentration-response curves.&quot; GlaxoWellcome. Retrieved on December 6, 2007.) </li></ul><ul><li>The term antagonist was originally coined to describe different profiles of drug effects. Negus SS (2006). &quot;Some implications of receptor theory for in vivo assessment of agonists, antagonists and inverse agonists&quot;. Biochem. Pharmacol. 71 (12): 1663–70. </li></ul>
  6. 6. Beta blockers <ul><li>A class of drugs used for various indications </li></ul><ul><li>Particularly for the management of cardiac arrhythmias </li></ul><ul><li>Cardio protection after myocardial infarction (heart attack) </li></ul><ul><li>and </li></ul><ul><li>hypertension. </li></ul>
  7. 7. Types of beta receptors <ul><li>β 1 -receptors located mainly in the heart. </li></ul><ul><li>β 2 -receptors located all over the body, but mainly in the lungs, muscles and arterioles. </li></ul><ul><li>β 3 -receptors are less well characterized, but have a role in fat metabolism. </li></ul>
  8. 8. Beta blockers <ul><li>Activation of β 1 -receptors by epinephrine increases the heart rate </li></ul><ul><li>Drugs that block β 2 receptors generally have a calming effect and are prescribed for anxiety </li></ul><ul><li>Beta blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels. </li></ul>
  9. 9. Beta blocker <ul><li>Beta blockers generally only block the type 1 receptor. They gradually become less selective at higher doses. </li></ul><ul><li>Examples of selective beta blockers in common use include Atenolol and Metoprolol. </li></ul>
  10. 10. Two main types of Hypertension <ul><li>Essential (primary) hypertension Potential causes include genetic and environmental factors . </li></ul><ul><li>Secondary hypertension </li></ul><ul><li>Causes include kidney problems (Reno vascular hypertension), Adrenal gland tumors, thyroid disease, and narrowing of the aorta (the main artery that takes blood from the heart to the rest of the body) </li></ul><ul><li>Other types of hypertension </li></ul><ul><li>Isolated systolic hypertension (top number ↑ ) </li></ul><ul><li>Isolated diastolic hypertension (bottom number ↑ ) </li></ul><ul><li>White coat hypertension </li></ul>
  11. 11. Treatment of Hypertension <ul><li>ACE Inhibitors : such as: Enalapril, ramipril, Lisinopril, Fosinopril. </li></ul><ul><li>Angiotensin ii receptor antagonists: Loasartan , valsartan, irbesartan, telmisatran. </li></ul><ul><li>Alpha Blockers :Prazosin, Doxazosin has been shown to increase risk of heart failure , and to be less effective than a simple diuretic, so is not recommended. </li></ul><ul><li>Beta Blockers : Atenolol , Metaprolol, Propranol , </li></ul><ul><li>Calcium channel Blockers : Nifedipine, Amlodepine (Norvasc), </li></ul><ul><li>Direct Renin Inhibitor : Alskiren </li></ul><ul><li>Diuretics : Bendroflumethiazide, Hydrocholorhiazide (HCTZ) </li></ul><ul><li>Combination Products : which usually contain HCTZ and one other drug. </li></ul>
  12. 12. Atenolol (Introduced in 1976 ) (Trade name Tenormin) Beta_blocker or ß-blocker Developed as a replacement for Propranolol the treatment of hypertension
  13. 13. Propranolol 1-(isopropylamino)- 3-(naphthalen-1-yloxy)propan-2-ol
  14. 14. Atenolol 2-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide                                                                                                                                                                                                                                                              
  15. 15. Atenolol <ul><li>The chemical works by slowing down the heart and reducing its workload. </li></ul><ul><li>There is no evidence to suggest that it is addictive. Wu A (November 2007) Ann. Acad. Med. Singap. 36 (11): 962–4. </li></ul><ul><li>Unlike Propranolol, atenolol does not pass through the blood-brain barrier thus avoiding various CNS side effects. ( Agon P, Goethals P, Van Haver D, Kaufman JM J. Pharm. Pharmacol. 43 (8): 597–600.) </li></ul>
  16. 16. Dosage <ul><li>The daily dose is 25 to 50 mg for the management of hypertension </li></ul><ul><li>Dosage can vary from as little as 25 mg to 200mg a day </li></ul><ul><li>In cases of doses over 100mg, the dosage is usually divided and taken twice daily. Injection    5 mg/10ml Tablet    100 mg ,  25 mg ,  50 mg. </li></ul>
  17. 17. Desired activity <ul><li>The desired activity of a drug is mainly due to one of the following: </li></ul><ul><li>Cellular membrane disruption </li></ul><ul><li>Chemical reaction. </li></ul><ul><li>Interaction with enzyme proteins </li></ul><ul><li>Interaction with structural proteins </li></ul><ul><li>Interaction with carrier proteins </li></ul><ul><li>Interaction with ion channels </li></ul><ul><li>Ligand binding to receptors </li></ul><ul><li>Hormone receptors </li></ul><ul><li>Neuro-modulator receptors </li></ul><ul><li>Neurotransmitter receptors. </li></ul>
  18. 18. Beta blockers <ul><li>Beta blockers, in addition to their sympatholytic B1 activity in the heart, influence the renin/angiotensin system at the kidneys . </li></ul><ul><li>Beta blockers cause a decrease in renin secretion, which in turn reduce the heart oxygen demand by lowering extracellular volume and increasing the oxygen carrying capacity of blood. </li></ul><ul><li>Beta blockers sympatholytic activity reduce heart rate, thereby increasing the ejection fraction of the heart despite an initial reduction in ejection fraction. </li></ul><ul><li>Trials have shown that Beta blockers reduce the absolute risk of death by 4.5% over a 13 month period. (Pritchett AM, Redfield MM (2002). &quot;Beta-blockers: new standard therapy for heart failure&quot; (PDF). Mayo Clin. Proc. 77 (8): 839–45; quiz 845–6) </li></ul>
  19. 19. Renin-angiotensin system <ul><li>The renin-angiotensin system (RAS) or the renin-angiotensin-aldosterone system (RAAS) is a hormone system that regulates blood pressure and water (fluid) balance. </li></ul>
  20. 21.                                                                                                                                                                                                                                                                                                  
  21. 22. Atenolol is a so-called ß 1 -selective or ( 'cardioselective') drug <ul><li>That means that it exerts greater blocking activity on myocardial ß 1 -receptors than on ß 2 ones in the lung. </li></ul><ul><li>The ß 2 receptors are responsible to keep the bronchial system open. If these receptors are blocked, bronchospasm with serious lack of oxygen in the body can result. However, due to its cardioselective properties, the risk of bronchospastic reactions if using atenolol is reduced compared to nonselective drugs as propranolol. </li></ul><ul><li>Extreme caution should be exerted if atenolol is given to asthma patients </li></ul>
  22. 23. Pharmacokinetic data <ul><li>t cmax = 2 to 4 hours after oral dosing </li></ul><ul><li>mean elimination half life is 6 hours </li></ul><ul><li>Atenolol is a hydrophilic drug. The concentration found in brain tissue is approximately 15% of the plasma concentration only </li></ul><ul><li>The drug crosses the placenta barrier freely </li></ul><ul><li>(In the milk of breastfeeding mothers, approximately 3 times the plasma concentrations are measured ). </li></ul><ul><li>Atenolol is almost exclusively eliminated renally , (pre existing renal insufficiency of higher degree makes dose-reductions necessary ). </li></ul>
  23. 24. Absorption pharmacokinetics of atenolol in patients with the Marfan syndrome <ul><li>Negative inotropic and chronotropic effects of beta-blocker therapy have been reported to reduce morbidity and mortality in patients with Marfan syndrome . </li></ul><ul><li>Little is known about the pharmacokinetics of atenolol after oral administration of multiple doses to patients with the Marfan syndrome( a connective tissue disorder) (prevention of infection of the heart or heart valves following dental and other selected procedures) </li></ul><ul><li>Ref: SJ Phelps, BS Alpert, JL Ward, JA Pieper, and JJ Lima </li></ul>
  24. 25. Atenolol Quantification in Human Plasma : Application to Bioequivalence Study <ul><li>β-blocking and antihypertensive effects persist for at least 24 hours (Following oral doses of 50 mg or 100 mg) </li></ul><ul><li>Renal function is impaired, elimination of ATN is closely related to the gromerular filtration rate. </li></ul><ul><li>Significant accumulation occurs when the creatinine clearance falls below 35 mL/min/1.73m. </li></ul><ul><li>Present study shows that atenolol 50-mg tablets was bioequivalent to Atenol tablets 50 mg, with regard to both the rate and extent of absorption. </li></ul><ul><li>Plasma samples were taken before and 1, 2,3, 4, 6, 12 and 24 h after administration in order to determine /3-adrenoceptor-antagonist concentrations. </li></ul><ul><li>Urine was collected for 24 h after drug intake. </li></ul><ul><li>REF : AAPS PharmSci 2003; 5 (2) Article 21 ( </li></ul>
  25. 27. Clinical Trials with Atenolol <ul><li>Benefits of beta-blockers have been investigated in patients surviving acute myocardial infarction (AMI) for three decades. Ref: Craig M. Pratt, MD, FACC </li></ul><ul><li>Europe (Atenolol—First International Study of Infarct </li></ul><ul><li>Survival [ISIS-I]) ISIS-1. Lancet 1986;2:57-66. </li></ul><ul><li>Scandinavia (timolol) </li></ul><ul><li>North America (propranolol—Beta-Blocker Heart Attack Trial [BHAT]) </li></ul><ul><li>I nclusion criteria for these trials were </li></ul><ul><li>stable AMI patients </li></ul><ul><li>Patients with overt congestive heart failure (CHF) were excluded </li></ul><ul><li>Total mortality was reduced in all three trials </li></ul>
  26. 31. Should Beta Blockers Be 1 ST Choice For Primary Hypertension? Mata Analysis. (Department of Public Health and Clinical Medicine, Sweden) <ul><li>A preliminary analysis has shown that Atenolol is not very effective in hypertension. </li></ul><ul><li>The Cochrane Library and PubMed were searched for beta blocker treatment in patients with primary hypertension. </li></ul><ul><li>Data were then entered into the Cochrane Collaboration Review Manager package and were summarized in meta-analyses. </li></ul><ul><li>in a meta-analysis comparing treatment with beta blockers with other antihypertensive drugs. </li></ul><ul><li>Seven studies (n=27 433) were included in a comparison of beta blockers and placebo or no treatment. </li></ul><ul><li>Relative risk of stroke was 16% higher for beta blockers (95% CI 4-30%) than for other drugs. </li></ul><ul><li>When the effect of beta blockers was compared with that of placebo or no treatment, the relative risk of stroke was reduced by 19% for all beta blockers (7-29%), about half that expected from previous hypertension trials. </li></ul><ul><li>There was no difference for myocardial infarction or mortality. </li></ul><ul><li>REF : Lancet. 2005 Oct 29-Nov 4;366(9496):1545-53 </li></ul>
  27. 32. Oral beta-blockers for mild to moderate hypertension during pregnancy. (Review) REF : Cochrane Database Syst Rev. ;(3):CD002863 . <ul><li>Hypertension is a common complication of pregnancy </li></ul><ul><li>Beta-blockers are a popular choice of antihypertensive agent during pregnancy ; other choices include methyldopa and calcium channel blockers </li></ul><ul><li>Twenty-seven trials, involving just under 2400 women, are included in this review. Fourteen trials (1516 women) compared beta-blockers with placebo/no beta blocker. Oral beta-blockers decrease the risk of severe hypertension (relative risk (RR) 0.37, 95% confidence interval (CI) 0.26-0.53) and the need for additional antihypertensive drugs (RR 0.44, 95% CI 0.31-0.62). There are insufficient data for any conclusions about the effect on perinatal mortality or preterm delivery. </li></ul><ul><li>Effect of beta-blockers on perinatal outcome is uncertain </li></ul>
  28. 33. Pediatric Heart Disease Clinical Research Children's Memorial Hospital ,Chicago. <ul><li>This study is being done at up to 30 medical centers in the U.S., Canada, and Europe to compare two drugs (Atenolol and losartan) </li></ul><ul><li>Studies have shown that Atenolol slows the rate of aortic root enlargement in people with Marfan syndrome but does not prevent the need for surgery on the aorta. </li></ul><ul><li>Losartan is a drug that is commonly used to treat high blood pressure, and is approved for use in children 6 years and older </li></ul><ul><li>Atenolol is a drug that is commonly used to treat high blood pressure and is also used in children with Marfan syndrome. </li></ul>
  29. 34. Role for ß -blockers <ul><li>Role for ß -blockers in hypertension was downgraded in June 2006 in the United Kingdom to fourth-line </li></ul><ul><li>As they perform less well than other drugs, particularly in the elderly. </li></ul><ul><li>And </li></ul><ul><li>There is increasing evidence that the most frequently used ß-blockers at usual doses carry an unacceptable risk of provoking type 2 diabetes. Sheetal Ladva (2006-06-28). &quot;NICE and BHS launch updated hypertension guideline </li></ul>
  30. 35. Side effects <ul><li>Dry mouth </li></ul><ul><li>Dizziness or faintness (especially cases of postural hypotension) </li></ul><ul><li>Indigestion or Constipation </li></ul><ul><li>Cold extremities </li></ul><ul><li>Hair loss </li></ul><ul><li>Problems with sexual function </li></ul><ul><li>Runny/blocked nose </li></ul><ul><li>Depression and confusion </li></ul><ul><li>Difficulty sleeping, nightmares </li></ul><ul><li>Fatigue, weakness or lack of energy </li></ul>
  31. 36. Interactions <ul><li>Beta blockers, including propranolol, have an additive effect with other drugs which decrease blood pressure, or which decrease cardiac contractility or conductivity. Clinically-significant interactions particularly occur with </li></ul><ul><li>Verapamil : is to block voltage-dependent Calcium channels. </li></ul><ul><li>Epinephrine : into the bloodstream, it rapidly prepares the body for action in emergency situations. </li></ul><ul><li>ß 2 -adrenergic receptor agonists: smooth muscle relaxation resulting in dilation of bronchial passages ( Solbutamol and terbutalin in case of Asthma) </li></ul><ul><li>clonidine </li></ul><ul><li>ergot alkaloids </li></ul><ul><li>isoprenaline </li></ul><ul><li>non-steroidal anti-inflammatory drugs </li></ul><ul><li>quinidine </li></ul><ul><li>cimetidine </li></ul><ul><li>lidocaine </li></ul><ul><li>phenobarbital </li></ul><ul><li>rifampicin </li></ul>
  32. 37. Contraindications <ul><li>Bradicardia (pulse less than 50 beats per minute) </li></ul><ul><li>Cardiogenic shock </li></ul><ul><li>Asthma(may cause broncho-constriction), although unlikely as Atenolol is cardioselective </li></ul><ul><li>Symptomatic hypotension (blood pressure of less than 100/60 mm Hg with dizziness, vertigo etc.) </li></ul><ul><li>Angina of the Prinzmetal type (vasospastic angina) </li></ul><ul><li>Metabolic acidosis (a severe condition with a more acid blood than normal) </li></ul><ul><li>Severe disorders in peripheral arterial circulation </li></ul><ul><li>AV-Blockage of second and third degree (a particular form of arrhythmia) </li></ul><ul><li>Acutely decompensated congestive heart failure (symptoms may be fluid retention with peripheral edema and/or abdominal fluid retention (ascites), and/or lung edema) </li></ul><ul><li>Hypersensitivity and/or allergy to Atenolol </li></ul><ul><li>Phaeochromocytoma (a rare type of tumor above the kidneys) </li></ul>
  33. 38. References <ul><li>1 . </li></ul><ul><li>  </li></ul><ul><li>2. . </li></ul><ul><li>  </li></ul><ul><li>3. Dwivedi, Girish & Dwivedi, Shridhar (2007). History of Medicine: Sushruta – the Clinician – Teacher par Excellence . National Informatics Centre (Government of India) . </li></ul><ul><li>  </li></ul><ul><li>3. . </li></ul><ul><li>  </li></ul><ul><li>4. “Toxicity, Beta-blocker”, Adhi Sharma, MD, Assistant Professor, Department of Emergency Medicine, Mount Sinai School of Medicine; Chairman, Department of Emergency Medicine, Good Samaritan Hospital Medical Center; Medical Toxicology Consultant, New York City Department of Health and Poison Control Center. </li></ul><ul><li>  </li></ul><ul><li>5. Mayo Foundation for Medical Education and Research (MFMER). 1998-2008. </li></ul><ul><li>  </li></ul><ul><li>6. The Cleveland Clinic Foundation. 1995-2006. </li></ul><ul><li>  </li></ul><ul><li>7. Pharmacy Author: Omudhome Ogbru , PharmD , Jay W. Marks, MD . </li></ul><ul><li>  </li></ul><ul><li>8. “ The Stress of Life” , Hans Selye, 1956. </li></ul><ul><li>  </li></ul><ul><li>9. www.upload / </li></ul><ul><li>  </li></ul><ul><li>10. Bodily changes in pain, hunger, fear, and rage. New York: Appleton </li></ul><ul><li>11. DENNIS T. M ANGANO , PH.D., M.D., ELIZABETH L. L AYUG,M.D., ARTHUR WALLACE , PH.D., M.D.,AND IDA TATEO,M.S.,FOR THE MULTICENTER STUDY OF PERIOPERATIVE ISCHEMIA RESEARCH GROUP* “EFFECT OF ATENOLOL ON MORTALITY AND CARDIOVASCULAR MORBIDITY AFTER NONCARDIAC SURGERY” </li></ul>