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Presented by: Manar Lashkar Samah Al-shehri Pharm.D candidates

Case Presentation. King Faisal Specialist Hospital and Research Center (2007-1428). Presented by: Manar Lashkar Samah Al-shehri Pharm.D candidates. Supervised by: Dr. Seema. Outline. Hypertension JNC VII Guidelines Resistant hypertension Pheochromocytoma Case Scenario

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Presented by: Manar Lashkar Samah Al-shehri Pharm.D candidates

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  1. Case Presentation King Faisal Specialist Hospital and Research Center (2007-1428) Presented by: Manar Lashkar Samah Al-shehri Pharm.D candidates Supervised by: Dr. Seema Manar & Samah

  2. Manar & Samah

  3. Outline • Hypertension • JNC VII Guidelines • Resistant hypertension • Pheochromocytoma • Case Scenario • Points of Discussion Manar & Samah

  4. Hypertension affects more than 20% of the adult Saudi population with expected increasing prevalence • It is an important modifiable risk factor for cardiovascular diseases • Despite overwhelming evidence that lowering BP reduces morbidity and mortality, its management remains frequently sub-optimal Manar & Samah

  5. Hypertension • It is defined as persistent elevation of systolic blood pressure SBP ≥ 140 mm Hg and/or diastolic blood pressure DBP ≥ 90 mm Hg in adults not on anti-hypertensive medications • It can be classified as either essential(primary) or secondary • Essential hypertension indicates that no specific medical cause can be found to explain a patient's condition • Secondary hypertension indicates that the high blood pressure is a result of (i.e. secondary to) another condition Manar & Samah

  6. IdentifiableCausesofHypertension • Chronic kidney disease • Coarctation of the aorta • Cushing’s syndrome and other glucocorticoid excess states including chronic steroid therapy • Drug induced or drug related • Obstructive uropathy • Pheochromocytoma • Primary aldosteronism and other mineralocorticoid excess states • Renovascular hypertension • Sleep apnea • Thyroid or parathyroid disease Manar & Samah

  7. ClassificationofBloodPressureforAdults Manar & Samah

  8. Resistant Hypertension Resistant hypertension is defined as the failure to achieve goal BP in patients who are adhering to full doses of an appropriate three-drug regimen that includes a diuretic Manar & Samah

  9. ■ Nonadherence ■ Inadequate doses ■ Inappropriate combinations ■ Nonsteroidal anti-inflammatory drugs; cyclooxygenase 2 inhibitors ■ Cocaine, amphetamines, other illicit drugs ■ Sympathomimetics (decongestants, anorectics) ■ Oral contraceptive hormones ■ Adrenal steroid hormones ■ Cyclosporine and tacrolimus ■ Erythropoietin ■ Licorice (including some chewing tobacco) ■ Selected over-the-counter dietary supplements and medicines (e.g., ephedra, bitter orange) ■ Excess sodium intake ■ Volume retention from kidney disease ■ Inadequate diuretic therapy ■ Obesity ■ Excess alcohol intake CausesofResistantHypertension Volume overload Drug-induced or other causes Associated conditions Manar & Samah

  10. Manar & Samah

  11. Manar & Samah

  12. Drugs Used in Hypertension Manar & Samah

  13. Diuretics Manar & Samah

  14. Adrenergic Blockers Manar & Samah

  15. ACE-I, ARBs, CCB, and Direct Vasodilator Manar & Samah

  16. After age 50, high systolic blood pressure (> 140 mm Hg) is much more important than high diastolic pressure as a risk factor for cardiovascular events People with a systolic blood pressure of 120 to 139 mm Hg or a diastolic pressure of 80 to 89 mm Hg should be considered prehypertensive and should undertake health promoting lifestyle modifications to prevent cardiovascular disease. Most patients with hypertension need two or more antihypertensive medications to achieve their goal pressure (<140/90 mm Hg or < 130/80 mm Hg for patients with diabetes or chronic kidney disease). If blood pressure is more than 20/10 mm Hg above goal, one should consider starting therapy with two agents, one of which usually should be a thiazide-type diuretic Thiazide-type diuretics should be used to treat most patients with uncomplicated hypertension, either alone or combined with drugs from other classes, but certain high risk conditions constitute compelling indications for the initial use of other types of antihypertensive drugs People who are normotensive at age 55 still have a 90% lifetime risk for developing hypertension. Manar & Samah

  17. Pheochrmocytoma • Pheochromocytoma is a rare catecholamine-secreting tumor derived from chromaffin cells (medulla) • Because of excessive catecholamine secretion, pheochromocytomas may precipitate life-threateninghypertension or cardiac arrhythmias Manar & Samah

  18. SymptomsandSigns • Clinicalsigns • Hypertension(50% paroxysmal) • Postural hypotension • Hypertensive retinopathy • Pallor • Fever • Tachyarrhythmias • Pulmonary edema Symptoms • Headache • Diaphoresis • Palpitations • Tremor • Nausea • Weakness • Anxiety Manar & Samah

  19. RiskFactors • Precipitants of a hypertensive crisis • Anesthesia induction • Opiates • Dopamine antagonists • Cold medications • Radiographic contrast media • Drugs that inhibit catecholamine reuptake, such as tricyclic antidepressants and cocaine • Childbirth Manar & Samah

  20. Case Scenario Manar & Samah

  21. A 75-year-oldfemale with a history of: Past Medical History: Hypertension Left Bundle Branch Block Diabetes Mellitus Chronic renal impairment (Serum Cr = 127umol/L) Bronchial Asthma Osteoporosis Interventions: CAD CABG (2002, KFMH) PCI LCX (5/2006) PCI RCA (12/2006) Labs: (7/2007) Ejection Fraction= 40-45% Negative Thallium Social History: Quit smoking 3 years ago Manar & Samah

  22. Past Medication History • Aspirin 81 mg PO OD • Clopidogrel 75 mg PO OD • Carvedilol 12.5 mg PO BID • Atorvastatin 40 mg PO OD • Amlodipine 10 mg PO OD • Irbesartan 300 mg PO OD • Furosemide 60 mg PO BID • Isosorbide dinitrate retard 40 mg PO OD Manar & Samah

  23. On 10/12/2007 • Came to arrhythmia clinic complaining of recurrence syncope and blood pressure of 206/100 mm Hg • Admitted to N2 (cardiology ward) Manar & Samah

  24. During whole admission period she was on • Aspirin 81 mg PO OD • Gabapentin 400 mg PO BID • Clopidogrel 75 mg PO OD • Atorvastatin 40 mg PO OD • Insulin regular SC (Sliding Scale) Q6h • <8.3 ------------- none • 8.4-11.1 --------2 units • 11.2-13.9-------4 units • 14-16.7----------6 units • 16.8-19.4-------8 units • 19.5-22.2------10 units • >22.3-----------notify MD and do STAT blood sugar, urine ketone Manar & Samah

  25. 13\12 13\12 13\12 11\12 11\12 11\12 18\12 18\12 18\12 12\12 12\12 12\12 14\12 14\12 14\12 15\12 15\12 15\12 16\12 16\12 16\12 17\12 17\12 17\12 Recurrence Syncope She started to have tremor Hypertension Surgery for single chamber pacemaker implantation Asthma Others Manar & Samah

  26. 13\12 13\12 13\12 13\12 11\12 11\12 11\12 11\12 18\12 18\12 18\12 18\12 12\12 12\12 12\12 12\12 14\12 14\12 14\12 14\12 15\12 15\12 15\12 15\12 16\12 16\12 16\12 16\12 17\12 17\12 17\12 17\12 SrCr 160 umol/L Hypertension Irbesartan 300 mg PO OD Isosorbide dinitrate retard 20 mg PO BID Amlodipine PO OD carvedilol 12.5 mg PO BID Furosemide 40 mg IV 40 mg PO OD 10 mg 5 mg COPD/ Asthma Others Manar & Samah

  27. 13\12 13\12 13\12 11\12 11\12 11\12 18\12 18\12 18\12 12\12 12\12 12\12 14\12 14\12 14\12 15\12 15\12 15\12 16\12 16\12 16\12 17\12 17\12 17\12 Asthma Attack Irbesartan 300 mg PO OD Isosorbide dinitrate retard 20 mg PO BID Amlodipine PO OD carvedilol 12.5 mg PO BID Furosemide 40 mg IV 40 mg PO OD 10 mg 5 mg Hypertension Fluticasone/salmeterol 250/25 mcg/ puff BID Budesonide nebulizer 500 mcg TID Ipratropium nebulizer 500 mcg TID Asthma Others Manar & Samah

  28. SrCr 107 umol/L 19/12 19/12 2/1 2/1 20/12 20/12 3/1 3/1 21/12 21/12 22/12 22/12 23/12 23/12 24/12 24/12 25/12 25/12 26/12 26/12 27/12 27/12 28/12 28/12 29/12 29/12 30/12 30/12 31/12 31/12 1/1 1/1 4/1 4/1 20 mg 40 mg 40 mg 60 mg 40 mg Hypertension ? Irbesartan 300 mg PO OD Isosorbide dinitrate retard PO BID Amlodipine 10 mg PO OD Nifedipine LA 60 mg PO STAT Captopril 6.25 mg PO TID carvedilol 12.5 mg PO BID Metoprolol 12.5 mg PO BID Clonidine 100 mcg PO OD Furosemide IV BID 20 mg PO 40 mg PO Manar & Samah

  29. 19/12 19/12 19/12 2/1 2/1 2/1 20/12 20/12 20/12 3/1 3/1 3/1 21/12 21/12 21/12 22/12 22/12 22/12 23/12 23/12 23/12 24/12 24/12 24/12 25/12 25/12 25/12 26/12 26/12 26/12 27/12 27/12 27/12 28/12 28/12 28/12 29/12 29/12 29/12 30/12 30/12 30/12 31/12 31/12 31/12 1/1 1/1 1/1 4/1 4/1 4/1 40 mg 30 mg 20 mg 50 mg 15 mg 10 mg 5 mg 60 mg Hypertension Methylprednisolone 60 mg IV OD Prednisolone PO OD Magnesium Sulphate 2 g IV Different inh/neb COPD Asthma K 5.5 mmol/L K 5.4 mmol/L K 5.3 mmol/L Ca polystyrene Sulphonate 30 g PO OD Heparin Sodium 5000 U S.C BID Others Manar & Samah

  30. Patient was distress, tachypnic, wheezing, complaining of shortness of breath, orthopnea, bilateral chest crepitation Manar & Samah

  31. Transferred to ICU Manar & Samah

  32. 7\1 7\1 7\1 5\1 5\1 5\1 6\1 6\1 6\1 8\1 8\1 8\1 9\1 9\1 9\1 10\1 10\1 10\1 Hypertension COPD/ Asthma Others Manar & Samah

  33. 7\1 7\1 5\1 5\1 6\1 6\1 8\1 8\1 9\1 9\1 10\1 10\1 Hypertension Irbesartan 300 mg PO OD Amlodipine 10 mg PO OD Nitroglycerin 5 mg SLstat 200 mcg/ml INF Clonidine 100 mcg PO OD Enalapril 5 mg PO OD Furosemide IV BID 60 mg 40 mg 40 mg 80 mg 80 mg 40 mg Manar & Samah

  34. 7\1 7\1 7\1 5\1 5\1 5\1 6\1 6\1 6\1 8\1 8\1 8\1 9\1 9\1 9\1 10\1 10\1 10\1 Irbesartan 300 mg PO OD Amlodipine 10 mg PO OD Nitroglycerin 5 mg SLstat 200 mcg/ml INF Clonidine 100 mcg PO OD Enalapril 5 mg PO OD Furosemide IV BID Hypertension 60 mg 40 mg 40 mg 80 mg 80 mg 40 mg Hydrocortisone IV stat IV TID Different Neb/Inh Aminophylline IV 250 mg stat 40 mg 80 mg COPD Hospital Acquired Pneumonia K 3.5 mmol/L K 2.9 mmol/L Piperacillin/Tazobactam 2.25 mg IV Q6h Potassium Chloride IV over 2h 40 mEq PO Heparin (PROTECT study) 20 mEq 40 mEq Others Manar & Samah

  35. Returned to Cardiology Ward Manar & Samah

  36. 11/1 11/1 12/1 12/1 13/1 13/1 14/1 14/1 15/1 15/1 16/1 16/1 17/1 17/1 18/1 18/1 19/1 19/1 20/1 20/1 21/1 21/1 22/1 22/1 Hypertension Irbesartan 300 mg PO OD Amlodipine 10 mg PO OD Nifedipine LA 60 mg PO OD Nitroglycerin 200 mcg/ml INF Isosorbide dinitrate 40 mg PO BID Spironolactone 25 mg PO OD Hydralazine 25 mg PO BID Enalapril PO Furosemide 40 mg IV BID 40 mg PO OD 10 mg QD 10 mg BID Manar & Samah

  37. 11/1 11/1 11/1 12/1 12/1 12/1 13/1 13/1 13/1 14/1 14/1 14/1 15/1 15/1 15/1 16/1 16/1 16/1 17/1 17/1 17/1 18/1 18/1 18/1 19/1 19/1 19/1 20/1 20/1 20/1 21/1 21/1 21/1 22/1 22/1 22/1 5 mg 20 mg 10mg Irbesartan 300 mg PO OD Isosorbide dinitrate 40 mg PO BID Amlodipine 10 mg PO OD Nifedipine LA 60 mg PO OD Spironolactone 25 mg PO OD Hydralazine 25 mg PO BID Enalapril PO Nitroglycerin 200 mcg/ml INF Furosemide 40 mg IV BID 40 mg PO OD Hypertension Hypertension 10 mg QD 10 mg BID Prednisolone PO QD Different Neb/Inh COPD K 2.8 mmol/L K 3.2 mmol/L Heparin Sodium 5000 U S.C BID Potassium Chloride 40 mEq IV 40 mEa PO OD Others Manar & Samah

  38. Was not managed before Same Medications Was not managed before carvedilol 12.5 mg PO BID Irbesartan 300 mg PO OD Furosemide 60 mg PO BID Isosorbide dinitrate retard 40 mg PO OD Aspirin 81 mg PO OD Clopidogrel 75 mg PO OD Atorvastatin 40 mg PO OD Amlodipine 10 mg PO OD was on was on • Insulin NPH SC 32 Units BID • Gabapentin 400 mg PO BID • Alfacalcidol 0.5 mcg PO OD • Calcium carbonate 500 mg PO BID Daibetes/ Complications Osteoporosis Discharge Medications Problems List/ Medications • Prednisolone 5 mg PO OD (for 15 days) • Fluticasone/ Salmetrol inhaler 2 puffs TID • Albuterol 2 puffs inhaler PRN Hypertension/ CV Problems carvedilol 12.5 mg PO BID Spironolactone 25 mg PO OD Irbesartan 300 mg PO OD Furosemide 40 mg PO BID Nifedipine LA 60 mg PO BID Enalapril 10 mg PO BID Hydralazine 25 mg PO BID Isosorbide dinitrate retard 20 mg PO BID Aspirin 81 mg PO OD Clopidogrel 75 mg PO OD Atorvastatin 40 mg PO OD COPD Manar & Samah

  39. Points of Discussion Manar & Samah

  40. I) Prednisolone Side Effect and Tapering Manar & Samah

  41. CorticosteroidsSide Effects • Adverse reactions: • Dose and duration related side effects include fluid and electrolyte disturbance (e.g. hypokalemia with possible edema and hypertension), hyperglycemia, peptic ulcer disease, osteoporosis, euphoria, psychosis, myopathy, and infections Prolonged therapy can lead to suppression of pituitary-adrenal function Too rapid withdrawal of long-term therapy can cause acute adrenal insufficiency (e.g. fever, myalgia, arthralgia and malaise) • In our case the patient suffered from: • Myopathy • Uncontrolled hypertension • Hypokalemia • Hospital acquired pneumonia • The patient is predisposed to osteoporosis Manar & Samah

  42. Corticosteroids Tapering Off There are many regimens for tapering off corticosteroids. Example of prednisone tapering schedule: However, corticosteroids can be rapidly tapered and discontinued abruptly if used for less than 2 to 3 weeks Manar & Samah

  43. 19/12 19/12 19/12 2/1 2/1 2/1 20/12 20/12 20/12 3/1 3/1 3/1 21/12 21/12 21/12 22/12 22/12 22/12 23/12 23/12 23/12 24/12 24/12 24/12 25/12 25/12 25/12 26/12 26/12 26/12 27/12 27/12 27/12 28/12 28/12 28/12 29/12 29/12 29/12 30/12 30/12 30/12 31/12 31/12 31/12 1/1 1/1 1/1 4/1 4/1 4/1 40 mg 30 mg 20 mg 50 mg 15 mg 10 mg 5 mg 60 mg This is not a prednisolone tapering off. The goal of decreasing the dose was to seek for the lowest effective and tolerated dose that can manage her COPD with minimum myopathy and fluid retention Hypertension myopathy Methylprednisolone 60 mg IV OD Prednisolone PO OD Magnesium Sulphate 2 g IV Different inh/neb COPD Asthma Ca polystyrene Sulphonate 30 g PO OD Heparin Sodium 5000 U S.C BID Guaifenesin/ Dextromethorphan 10 ml PO BID Others Manar & Samah

  44. II) b-Blocker Withdrawal Manar & Samah

  45. b-Blocker Withdrawal Withdrawing b-blockers may produce b-adrenergic supersensitivity. Both abrupt cessation and gradual withdrawal over 4 to 8 days have caused overshoot hypertension and cardiovascular complications within within 48 to 72 hours after the last b-blocker dose To prevent b-adrenergic supersensitivity, the b-blocker dosage should be reduced over 7 to 10 days to the equivalent of 30 mg/day of propranolol and then maintained at this low dosage for 2 additional weeks b-blocker Withdrawal in patient who are free of CHD resulted in fourfold increase in onset of CHD Manar & Samah

  46. 19/12 19/12 2/1 2/1 20/12 20/12 3/1 3/1 21/12 21/12 22/12 22/12 23/12 23/12 24/12 24/12 25/12 25/12 26/12 26/12 27/12 27/12 28/12 28/12 29/12 29/12 30/12 30/12 31/12 31/12 1/1 1/1 4/1 4/1 20 mg 40 mg 40 mg 60 mg 40 mg Hypertension Irbesartan 300 mg PO OD Isosorbide dinitrate retard PO BID Amlodipine 10 mg PO OD Nifedipine LA 60 mg PO STAT Captopril 6.25 mg PO TID carvedilol 12.5 mg PO BID Metoprolol 12.5 mg PO BID Clonidine 100 mcg PO OD Furosemide IV BID 20 mg PO 40 mg PO Titration of the cavedilol 12.5 mg to metoprolol 12.5 mg Then D/C b-blocker after 8 days Manar & Samah

  47. Thank you Manar & Samah

  48. References • Chobanian AV, Bakris GL, Black HR, et al and the National High Blood Pressure Education Program Coordinating Committee.The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The JNC 7 report. JAMA 2003; 289:2560–2572. • Vidit D, Borazanian R. Treat high blood pressure sooner: Tougher, simpler JNC 7 guidelines. Cleveland Clinic Journal of Medicine 2003; 70(8):721-728 • Saudi Hypertension Management Society. Saudi hypertension guidelines. 2007; 1-46 • Helms R, Quan D, Herfindal E eds. Textbook of therapeutics. Drug and disease management. Eighth Edition. Philadelphia, PA. Lippincott Williams & Wilkins; 2006: 451-471 • Herfindal E and Gourley D. Textbook of therapeutics. Drug and disease management. Seventh Edition. Philadelphia, PA. Lippincott Williams & Wilkins; 2000: 795-823 • http://www.emedicine.com/MED/topic1106.htm Manar & Samah

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