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

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1 Presented by: Manar Lashkar Samah Al-shehri Pharm.D candidates
Case Presentation King Faisal Specialist Hospital and Research Center ( ) 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 It is an important modifiable risk factor for cardiovascular diseases
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 Renal failure, pregnancy, renal artery stenosi
Hyperkalemia, cough, hypotension, angioedema, loss of taste, renal failure, neutropenia, cholestasis, rash, blood dyscrasias. Renal failure, pregnancy, renal artery stenosi Similar to ACEI but do not cause cough Headache, flushing, hypotension, dizziness, palpitation, rash Dihydropyridines (edema, tachycardia) Diltiazem (Lupus-like rash) Verapamil (Constipitation, bradycardia, AV block) Congestive heart failure, heart block Headache, dizzines, sodium and fluid retention, positive antinuclear antibody, lupus-like syndrome, hepatitis, nasal congestion, GI disturbance. Manar & Samah

7 Less bradycardia and dyslipidemia, drug-induced Lupus Erythematosus
Fatigue, insomnia, nightmare, depression, sexual dysfunction, dyslipidemia, rash, withdrawal rebound coronary heart disease, bradycardia, GI upset, mask symptoms of hyperglycemia Asthma, COPD, Decompensated CHF, heart block, DM, peripheral vascular disease. Less bradycardia and dyslipidemia, drug-induced Lupus Erythematosus Orthostatic hypotension, hepatotoxiciy No dyslipidemia Syncope after first dose or dose increase, orthostatic hypotension, headache, dizziness, drowsiness, tachycardia, sodium and fluid retention. Advanced age, first dose Sedation, dry mouth, sexual dysfunction, withdrawal rebound hypertension, impaired mental concentration Methyldopa (hepatitis, Coombs-positive hemolytic anemia, colitis, drug-induced lupus erythematosus) Depression, taper dosage when discontinue to avoid rebound. Manar & Samah

8 Triamterene urinary sediment, nephrolithiasis
Renal dysfunction, Diabetes, ACEI Gynecomastia, impotence, hirsutism, menstrual irregularities, GI symptoms. Manar & Samah

9 Identifiable Causes of Hypertension
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

10 Classification of Blood Pressure for Adults
Blood Pressure Classification SBP mm Hg DBP mm HG Normal < 120 and < 80 Prehypertension or 80-89 Stage 1 Hypertension or 90-99 Stage 2 Hypertension > 160 or > 100 Manar & Samah

11 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

12 Causes of Resistant Hypertension
Volume overload ■ Excess sodium intake ■ Volume retention from kidney disease ■ Inadequate diuretic therapy ■ 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) Drug-induced or other causes Associated conditions ■ Obesity ■ Excess alcohol intake Manar & Samah

13 Manar & Samah

14 Manar & Samah

15 Drugs Used in Hypertension
Manar & Samah

16 Usual Dose Range (mg/d)
Diuretics Class Adverse Effects Special Precautions Potassium Sparing Diuretics Triamterene urinary sediment, nephrolithiasis Renal dysfunction, Diabetes, ACEI Aldosterone receptor blocker Gynecomastia, impotence, hirsutism, menstrual irregularities, GI symptoms. Adverse Effects Special Precautions Loop diuretics Similar to thiazide diuretics except hypocalcemia Effect in patients with renal insufficiency Class Drug Usual Dose Range (mg/d) Daily Frequency Thiazide Diuretics Hydrochlorothiazide Indapamide Metolazone 2.5-5 OD Loop Diuretics Furosemide 20-80 BID Potassium Sparing Diuretics Amiloride Triamterene 5-10 50-100 OD/BID OD/ BID Aldosterone receptor blocker Spironolactone 25-50 Adverse Effects Special Precautions hyperurecimia, glucose intolerance, dyslipidemia, sexual dysfunction, dehydration, increase Ca, decrease (K, Na, Mg), skin rash and photosensitivity Gout, renal failure, digoxin, lithium Manar & Samah

17 Usual Dose Range (mg/d)
Adrenergic Blockers Class Drug Usual Dose Range (mg/d) Daily Frequency b-Blockers Atenolol Bisoprolol Metoprolol Propranolol 25-100 2.5-10 50/100 40/160 OD OD/BID BID b-Blockers with ISA Acebutolol Combined a/b Blocker carvedilol Labetalol a1 Blocker Doxazocin Prazocin 1-16 2-20 BID/TID Central a2 agonist Clonidine Methyldopa Reserpine Class Adverse Effects Special Precautions a1-Blocker Syncope after first dose or dose increase, orthostatic hypotension, headache, dizziness, drowsiness, tachycardia, sodium and fluid retention. Advanced age, first dose Central a2 agonist Sedation, dry mouth, sexual dysfunction, withdrawal rebound hypertension, impaired mental concentration Methyldopa (hepatitis, Coombs-positive hemolytic anemia, colitis, drug-induced lupus erythematosus) Depression, taper dosage when discontinue to avoid rebound. Adverse Effects Special Precautions Fatigue, insomnia, nightmare, depression, sexual dysfunction, dyslipidemia, rash, withdrawal rebound coronary heart disease, bradycardia, GI upset, mask symptoms of hyperglycemia Asthma, COPD, Decompensated CHF, heart block, DM, peripheral vascular disease. Less bradycardia and dyslipidemia, drug-induced Lupus Erythematosus Orthostatic hypotension, hepatotoxiciy No dyslipidemia Manar & Samah

18 Usual Dose Range (mg/d)
ACE-I, ARBs, CCB, and Direct Vasodilator Class Drug Usual Dose Range (mg/d) Daily Frequency Angiotensin Converting Enzyme Inhibitor Captopril Enalapril 25-100 2.5-40 BID OD/BID Angiotensin II Antagonist Candesartan Irbesartan Losartan Valsartan 8-32 80-320 OD Calcium Channel Blocker Amlodipine Nifedipine LA Verapamil LA Diltiazem LA 2.5-10 30-60 Direct Vasodilator Hydralazine Class Adverse Effects Special Precautions Calcium Channel Blocker Headache, flushing, hypotension, dizziness, palpitation, rash Dihydropyridines (edema, tachycardia) Diltiazem (Lupus-like rash) Verapamil (Constipitation, bradycardia, AV block) Congestive heart failure, heart block Direct Vasodilator Headache, dizzines, sodium and fluid retention, positive antinuclear antibody, lupus-like syndrome, hepatitis, nasal congestion, GI disturbance. Adverse Effects Special Precautions Hyperkalemia, cough, hypotension, angioedema, loss of taste, renal failure, neutropenia, cholestasis, rash, blood dyscrasias. Renal failure, pregnancy, renal artery stenosis Similar to ACEI but do not cause cough Manar & Samah

19 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 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). 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. 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 People who are normotensive at age 55 still have a 90% lifetime risk for developing hypertension. 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 Manar & Samah

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

21 Pathophysiology The clinical manifestations of a pheochromocytoma result from excessive catecholamine secretion by the tumor. Catecholamines typically secreted, either intermittently or continuously, include norepinephrine and epinephrine and rarely dopamine Stimulation of b-adrenergic receptors alpha-adrenergic receptors Increase in heart rate Increase cardiac contractility Elevated blood pressure Increased cardiac contractility Glycogenolysis Gluconeogenesis Intestinal relaxation Manar & Samah

22 Symptoms and Signs Symptoms Clinical signs Headache Diaphoresis
Palpitations Tremor Nausea Weakness Anxiety Clinical signs Hypertension (50% paroxysmal) Postural hypotension Hypertensive retinopathy Pallor Fever Tachyarrhythmias Pulmonary edema Manar & Samah

23 Symptoms and Signs Symptoms Clinical signs Headache
Diaphoresis Palpitations Tremor Nausea Weakness Anxiety Epigastric pain Flank pain Constipation Weight loss Clinical signs Hypertension (50% paroxysmal) Postural hypotension Hypertensive retinopathy Pallor Fever Tachyarrhythmias Pulmonary edema Cardiomyopathy Ileus Café au lait spots Patches of cutaneous pigmentation, which vary from 1-10 mm and occur any place on the body. Characteristic locations include the axillae and groin. They vary from light to dark brown Manar & Samah

24 Risk Factors 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

25 Diagnosis Sensitivity (96%) Specificity (85%) Sensitivity (87%)
Plasma metaphrine testing Sensitivity (96%) Specificity (85%) 24-hour urinary metanephrine and normetanephrine Sensitivity (87%) Specificity (99%) Manar & Samah

26 Medical Care The patient should undergo volume expansion with isotonic sodium chloride solution. Encourage liberal salt intake Initiate a b-blocker only after adequate alpha blockade If b-blockade is started prematurely, unopposed alpha stimulation could precipitate a hypertensive crisis Administer the last doses of oral alpha- and b-blockers on the morning of surgery Surgical resection of the tumor is the treatment of choice and usually results in cure of the hypertension Careful treatment with alpha- and b-blockers is required preoperatively to control blood pressure and prevent intraoperative hypertensive crises Start alpha blockade with phenoxybenzamine 7-10 days preoperatively Manar & Samah

27 Either surgical option requires prior treatment with the non-specific and irreversible alpha adrenoceptor blocker Phenoxybenzamine. Doing so permits the surgery to proceed while minimizing the likelihood of severe intraoperative hypertension (as might occur when the tumor is manipulated). Some authorities would recommend that a combined alpha/beta blocker such as labetalol also be given in order to slow the heart rate. Regardless, a 'pure' beta blocker such as atenolol must never be used in the presence of a pheochromocytoma due to the risk of such treatment leading to unopposed alpha agonism and, thus, severe and potentially refractory hypertension. The patient with pheochromocytoma is invariably volume depleted. In other words, the chronically elevated adrenergic state charactersitic of an untreated pheochromocytoma leads to near-total inhibition of renin-angiotensin activity. Volume depletion results. Hence, once the pheochromocytoma has been resected, thereby removing the major source of circulating catecholamines, a situation arises where there is both very low sympathetic activity and volume depletion. This can result in profound hypotension. Therefore, it is usually advised to "salt load" pheochromocytoma patients before their surgery. This may consist of simple interventions such as consumption of high salt food pre-operatively, direct salt replacement (perhaps in the form of bouillon cubes such as Oxo), or through the administration of intravenous saline solution. Manar & Samah

28 Case Scenario Manar & Samah

29 A 75-year-old female 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

30 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

31 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

32 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 < none units units units units units > notify MD and do STAT blood sugar, urine ketone Manar & Samah

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

34 Hypertension Asthma Others Manar & Samah 11\12 18\12 17\12 16\12 15\12
14\12 13\12 12\12 Hypertension 11\12 12\12 13\12 14\12 15\12 16\12 17\12 18\12 Asthma 11\12 12\12 13\12 14\12 15\12 16\12 17\12 18\12 Others Manar & Samah

35 Hypertension 10 mg 5 mg COPD/ Asthma Others Manar & Samah 11\12 18\12
17\12 16\12 15\12 14\12 13\12 12\12 SrCr 160 umol/L Hypertension 11\12 18\12 17\12 16\12 15\12 14\12 13\12 12\12 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 11\12 18\12 17\12 16\12 15\12 14\12 13\12 12\12 10 mg 5 mg COPD/ Asthma 11\12 18\12 17\12 16\12 15\12 14\12 13\12 12\12 Others Manar & Samah

36 10 mg 5 mg Hypertension Asthma Others Manar & Samah 11\12 18\12 17\12
16\12 15\12 14\12 13\12 12\12 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 Asthma Attack 11\12 18\12 17\12 16\12 15\12 14\12 13\12 12\12 Fluticasone/salmeterol 250/25 mcg/ puff BID Budesonide nebulizer 500 mcg TID Ipratropium nebulizer Asthma 11\12 18\12 17\12 16\12 15\12 14\12 13\12 12\12 Others Manar & Samah

37 Hypertension Asthma / COPD Others Manar & Samah 19/12 20/12 31/12
22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 Hypertension 19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 Asthma / COPD 19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 Others Manar & Samah

38 ? Hypertension 20 mg 40 mg Manar & Samah SrCr 107 umol/L Irbesartan
19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 SrCr 107 umol/L Hypertension ? 19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 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 Clonidine 100 mcg PO OD Furosemide IV BID 20 mg PO 40 mg PO 20 mg 40 mg 40 mg 60 mg Manar & Samah

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

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

41 Transferred to ICU Manar & Samah

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

43 Hypertension Manar & Samah 5\1 10\1 9\1 8\1 7\1 6\1 5\1 10\1 9\1 8\1
Irbesartan 300 mg PO OD Amlodipine 10 mg PO OD Nitroglycerin 5 mg SL stat 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

44 Hypertension COPD Others Manar & Samah 5\1 10\1 9\1 8\1 7\1 6\1 5\1
Irbesartan 300 mg PO OD Amlodipine 10 mg PO OD Nitroglycerin 5 mg SL stat 200 mcg/ml INF Clonidine 100 mcg PO OD Enalapril 5 mg PO OD Furosemide IV BID 60 mg 40 mg 80 mg 5\1 10\1 9\1 8\1 7\1 6\1 Hydrocortisone IV stat IV TID Different Neb/Inh Aminophylline IV 250 mg stat 80 mg 40 mg COPD Hospital Acquired Pneumonia 5\1 10\1 9\1 8\1 7\1 6\1 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

45 Returned to Cardiology Ward
Manar & Samah

46 Hypertension Manar & Samah Irbesartan 300 mg PO OD Amlodipine
11/1 12/1 14/1 15/1 16/1 17/1 18/1 19/1 20/1 21/1 22/1 13/1 Hypertension 11/1 12/1 14/1 15/1 16/1 17/1 18/1 19/1 20/1 21/1 22/1 13/1 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

47 Hypertension Hypertension COPD Others 5 mg 20 mg 10mg Manar & Samah
11/1 12/1 14/1 15/1 16/1 17/1 18/1 19/1 20/1 21/1 22/1 13/1 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 11/1 12/1 14/1 15/1 16/1 17/1 18/1 19/1 20/1 21/1 22/1 13/1 Prednisolone PO QD Different Neb/Inh 20 mg 10mg 5 mg COPD 11/1 12/1 14/1 15/1 16/1 17/1 18/1 19/1 20/1 21/1 22/1 13/1 K 3.2 mmol/L K 2.8 mmol/L Heparin Sodium 5000 U S.C BID Potassium Chloride 40 mEq IV 40 mEa PO OD Others Manar & Samah

48 Discharge Medications vs Past Medication History
Aspirin 81 mg PO OD Clopidogrel 75 mg PO OD Isosorbide dinitrate retard 40 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 Manar & Samah

49 Calcium carbonate 500 mg PO BID
Same Medications Insulin NPH SC 32 Units BID Gabapentin 400 mg PO BID Alfacalcidol 0.5 mcg PO OD Calcium carbonate 500 mg PO BID Was not managed before was on 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 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 not managed before 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 Hypertension/ CV Problems COPD was on Manar & Samah

50 Points of Discussion Manar & Samah

51 I) ACEI Induced Cough ACE inhibitor cough is an apparent class effect that may occur with all ACE inhibitors Manar & Samah

52 Clinical Presentation
The cough is described as being a troublesome dry cough, without wheezing, typically starting from 1-7 days after the onset of therapy to as late as several weeks after the initiation of treatment The cough usually subsides within 4-7 days after cessation of treatment, but may continue for as long as 3-4 weeks The symptoms are apparently common to all ACE inhibitors, including those primarily tissue-bound such as quinapril and others that are found predominantly in the serum such as lisinopril Chest x-ray and ENT examinations are normal Manar & Samah

53 Diagnosis At times, the diagnosis of ACE inhibitor induced cough may be difficult to establish, particularly if the patients have asthma, COPD, allergic rhinitis, or congestive heart failure since coughing is frequently a symptom which complicates these disorders Manar & Samah

54 Stop the ACE inhibitor for one week Restart the ACE inhibitor
Diagnosis Rather than having the patient undergo expensive testing, the simplest manoeuvre would be Stop the ACE inhibitor for one week If the cough stops If the cough continues Treat the cause Stop the ACE inhibitor If the cough resolves Try another class of medication Restart the ACE inhibitor Manar & Samah

55 Alternative Treatment
An alternative treatment of ACE inhibitors is angiotensen II receptor blockers Angiotensin II receptor blockers do not lead to cough and do not decrease the degradation of bradykinin as does the ACE inhibitor However, the beneficial effects of angiotensin II receptor blockers on myocardium, diabetic nephropathy or congestive heart failure have not yet been established Manar & Samah

56 Patients with congestive heart failure, diabetic nephropathy,
acute myocardial infarction, or diabetes may have the medical need to continue ACE inhibitor therapy despite the cough Drugs, such as sodium cromoglycate, theophylline, and baclofen, may be prescribed to alleviate the cough Manar & Samah

57 Larger trials are necessary to establish definitive conclusions
Sodium cromoglycate: given by inhalation at 20 mg four times a day Larger trials are necessary to establish definitive conclusions Theophylline: at a dosage of 8.5 mg/kg orally once a day while providing no bronchodilation resulted in a beneficial effect with reduction in cough Baclofen: starting with 5 mg three times a day and ending with 10 mg three times a day Manar & Samah

58 19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 Hypertension After single day use of captopril the patient developed cough that relieved by using Guaifenesin/ Dextromethorphan and captopril discontinuation 19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 Methylprednisolone 60 mg IV OD Prednisolone PO OD Magnesium Sulphate 2 g IV Different inh/neb 60 mg 50 mg 15 mg 30 mg 20 mg 10 mg 5 mg 40 mg COPD 19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 Ca polystyrene Sulphonate 30 g PO OD Heparin Sodium 5000 U S.C BID Guaifenesin/ Dextromethorphan 10 ml PO BID Others Manar & Samah

59 5\1 10\1 9\1 8\1 7\1 6\1 Hypertension Irbesartan 300 mg PO OD Amlodipine 10 mg PO OD Nitroglycerin 5 mg SL stat 200 mcg/ml INF Clonidine 100 mcg PO OD Enalapril 5 mg PO OD Furosemide IV BID 60 mg 40 mg 80 mg After treatment of hospital acquired pneumonia by the antibiotics the ACE-I was restarted with enalapril 5\1 10\1 9\1 8\1 7\1 6\1 Hydrocortisone IV stat IV TID Different Neb/Inh Aminophylline IV 250 mg stat 80 mg 40 mg COPD Hospital Acquired Pneumonia 5\1 10\1 9\1 8\1 7\1 6\1 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

60 I) Prednisolone Side Effect and Tapering
Manar & Samah

61 Corticosteroids Side 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 In our case the patient suffered from: Myopathy Uncontrolled hypertension Hypokalemia Hospital acquired pneumonia The patient is predisposed to osteoporosis 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) Manar & Samah

62 Corticosteroids Tapering Off
There are many regimens for tapering off corticosteroids. Example of prednisone tapering schedule: Dosage (mg) Duration (wks) 20 2 17.5 3 15 4 15 alternating with 12.5 2-4 15 alternating with 10 15 alternating with 7.5 15 alternating with 5 15 alternating with 2.5 20 alternating with 0 17.5 alternating with 0 15 alternating with 0 However, corticosteroids can be rapidly tapered and discontinued abruptly if used for less than 2 to 3 weeks Manar & Samah

63 19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 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 19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 myopathy Methylprednisolone 60 mg IV OD Prednisolone PO OD Magnesium Sulphate 2 g IV Different inh/neb 60 mg 50 mg 15 mg 30 mg 20 mg 10 mg 5 mg 40 mg Asthma COPD 19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 Ca polystyrene Sulphonate 30 g PO OD Heparin Sodium 5000 U S.C BID Guaifenesin/ Dextromethorphan 10 ml PO BID Others Manar & Samah

64 II) b-Blocker Withdrawal
Manar & Samah

65 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

66 Titration of the cavedilol 12.5 mg to metoprolol 12.5 mg
19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 Hypertension 19/12 20/12 31/12 22/12 23/12 24/12 25/12 26/12 27/12 28/12 29/12 30/12 21/12 1/1 4/1 2/1 3/1 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 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 20 mg 40 mg 40 mg 60 mg Manar & Samah

67 Thank you Manar & Samah

68 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): 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: Herfindal E and Gourley D. Textbook of therapeutics. Drug and disease management. Seventh Edition. Philadelphia, PA. Lippincott Williams & Wilkins; 2000: Manar & Samah


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