Hypertension Presented by Maha Islami Pharm D candidate

Hypertension Presented by: Maha Islami Pharm. D. candidate Supervised by : Prof. Osama M. Ibrahim Professor of clinical pharmacy 1

outlines • • • Definition. Classification. Etiology. Complication. Diagnosis. Treatment. 2

What is blood pressure? • Arterial BP = co x PVR • co = HR x SV (blood out flow after-load systolic BP). • p. VR resistance of arterioles resistance to blood flow pre-load diastolic BP. 3

Classification of BP category SBP mm. Hg DBP mm. Hg Normal <120 & <80 prehypertension 120 - 139 Or 80 - 89 Stage 1 HTN 140 -159 Or 90 -99 Stage 2 HTN >160 Or >100 4

Isolated systolic HTN • a systolic BP of > 140 mm Hg and diastolic BP < 90 mm Hg and staged. • Ex : BP 170/82 mm. Hg is stage 2 isolated systolic HTN. • Treatment : chlorthalidone. 5

Classification of HTN Primary (essential) HTN Secondary HTN No specific cause There is specific cause Accounts for about 95% of cases of HTN Accounts for about 5% of cases of HTN Usually develops at the age of 35 years old Usually develops between the ages of 30 and 50 years old curable chronic 6

Etiology of primary HTN • Primary HTN: may be affected by number of factors: 1. Age. 2. Genetics. 3. Body weight. 4. Stress : (mental and physical stress causes transient increase in BP ). 5. Smoking. 6. Sodium intake. 7. Sympathetic NS hyper-reactivity. 8. Renin-angiotensin system hyper-reactivity. 7

Etiology of secondary HTN 1) Renal diseases: a) Renal artery stenosis. b) Pyelonephritis. c) Polycystic kidneys. 2) Endocrinal disease: a) Cushing‘s disease. b) Pheochromocytoma. c) Conn‘s disease. d) Hyperthyrodism. 8

Etiology of secondary HTN cont…. 3) Drug induced: a)Oral contraceptives. b)corticosteroids. c)NSAIDs. d)cyclosporine. e) erythropoietin. f) venlafaxine. 4) pregnancy: Preclampsia(the development of HTN, albuminuria and edema between the 20 th week of pregnancy and the end of the first week postpartum). 9

Complications a) Cardiovascular complication: 1 - angina. 2 -heart failure. 3 -aneurysms. b) Cerebral complicaions: 1 -cerebral hemorrhage. 2 - hypertensive encephalopathy. c) Renal failure due to arteriolar nephrosclerosis. d) Retinal hemorrhage. 10

Diagnostic studies • 1 -urin analysis: a) Increase Urinary excretion of catecholamines or its metabolites (VMA) confirms pheochromocytoma. b) Presence of hematuria , proteinuria and casts suggests primary renal disease. • 2 - blood analysis: a) Increase BUN and creatinine suggest renal disease. b) Hypokalemia suggests primary hyperaldosteronism or cushing‘s syndrome. c) Increase serum cortisol confirms cushing‘s syndrome. 11

Diagnostic studies cont…. • 3 - ECG: may reveal left ventricular hypertrophy or ischemia. • 4 - CT scane or MRI: may be done to confirm the diagnosis of secondary or complicated HTN. 12

Treatment • BP GOAL <140/90 mm Hg. <130/80 mm Hg if DM or renal disease. • More than 2/3 of hypertensive patients can‘t be controlled on one drug and will require 2 or more agents from different classes. 13

Algorithm for Treatment of Hypertension Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mm. Hg) (<130/80 mm. Hg for those with diabetes or chronic kidney disease) Initial Drug Choices Without Compelling Indications With Compelling Indications Stage 1 Hypertension Stage 2 Hypertension (SBP 140– 159 or DBP 90– 99 mm. Hg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. (SBP >160 or DBP >100 mm. Hg) 2 -drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Not at Goal Blood Pressure Optimize dosages or additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist. 14 Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.

Lifestyle modification Average BP reduction range Weight reduction 5 -20 mm Hg /10 kg DASH diet 8 -14 mm Hg Na+ restriction 2 -8 mm Hg Physical activity 4 -9 mm Hg 15

Ischemic heart disease • BBs are DOC due to ↓ HR ( ↓ of MO 2). • If BBs are contraindicated such as high degree AV blook , sick sinus syndrome give CCB. • Treatment include smoking cessation , ttt DM , Lipid lowering , antiplatlets , wt reduction. • If BP is not controlled with BB alone, add CCB (dihydropyridine is preferred for combination ) DHP CCB ↓ total peripheral resistance but NDHP CCB will also ↓ HR more if added to BB sever bradycardia or heart blook may occur. • If BP is still not controlled on BB & CCB , add nitrate. 16

Heart failure stages treatment Stage A High risk , no symptoms or LV dysfunction ACEI (↓ Mortality ) and thiazide diuretics have been suggested to prevent dz progression Stage B Reduced LV function , EF< 40% but asymptomatic ACEI & BB are recommended Stage C Manifest LV dysfunction , overt symptoms ACEI , BB , aldosterone antagonist & loop diuretics ±digoxin. Stage D Critically ill pts Pacemaker , mechanical assist devices or transplantation in addition to ttt included in stage C 17

Diabetes /HTN • The coexistence of HTN in diabetes is particularly pernicious b/c of the strong linkage of the two condition with all ( CVD , Stroke , renal dz , and retinopathy). • American Diabetics Association(ADA) state that BP goal in DM is 130/80 mm Hg or lower. • Treatment: many agent are used (ACEI , BB , CCB , Diuretics)difficult to specify one b/c most diabetic pts require 2 or more drugs. • ACEI is important component to control BP in diabetic pts can be used alone or combined with other agents esp. diuretic. 18

Diabetes /HTN cont. . • The ADA has recommended ACEI for diabetics pts >55 years at high risk for CVD and BBs for those with known CAD. • The ADA recommended both ACEI and ARB for use in type 2 diabetic pts with CKD b/c these agents delay the deterioration in GFR and worsening of albuminuria. 19

Chronic kidney disease • Many studies found that ACEI or ARB are more effective in slowing progression of CKD. • Goal BP : <130/80 mm Hg. • ACEI+diuretic (loop is better) or ARB +loop diuretic. v central alpha -2 agonists as clonidine appear to the safest in dialysis population. v. Transdermal clonidine up to 1. 2 mg/day as monotherapy in one short term study was successful. 20

stroke • The management of BP during an acute stroke remain controversial b/c BP is high immediately post –stroke period as a compensatory physiologic response to improve cerebral perfusion. If you reduce BP may lead to neurologic deterioration. • American Stroke Association has a guideline SBP>220 mm Hg or DBP >120 -140 mm. Hg ↓ BP by approx 10 -15 % and monitor for neurologic deterioration. • If DBP>140 mm Hg give IV nitropusid carefully to ↓ BP by 10 -15%. • BP affect the use of thrombolytic agents in ischemic stroke. SBP>185 mm Hg or DBP>110 mm Hg is contraindication to use t. PA within first 3 h of attack, should ↓BP first to prevent intracerebral bleeding. 21

Black people • HTN is more common , more severe , develop at earlier age. • The pathogenesis of HTN in different racial subgroups may be due to contribution factors such as salt , stress , cv reactivity , hormonal system and socioeconomic condition. • CCB or thiazide is effective in these people. 22

Left ventricular hypertrophy • Most antihypertensive agents produces LVH regression. • New trend : the most consistent reduction in LV mass was achieved with ACEI. the intermediate benefits with diuretics and CCB. the least reduction with BB. v. Significant LV mass reduction was also achieved with Losartan. 23

HTN in older people • With age SBP continue to rise , DBP rises until age of 55 then it decreases due to central arterial stiffness. (ISH). • Increase in age ------- postural hypotension. • Geriatric > 65 yo the preferred agent is CCB. 24

Orthostatic hypotension • Present when there is a supine to standing BP ↓> 20 mm Hg systolic or > 10 mm Hg diastolic. • Causes: Sever volume depletion , baroreflex dysfunction , autonomic insufficiency. v venodilator such as alpha blockers , alpha-beta blockers , and nitrates may further aggravate orthostatic hypotension. 25

Urinary Outflow Obstruction (BPH) • Use alpha 1 blockers such as terazosin , doxazosin , or prazosin. • They indirectly dilate prostatic and urinary sphincter smooth muscle and also lower BP. v. Precautions : 1 - first dose phenmenon (a syncopal epiaode occur 30 -90 min of the first dose. 2 - palpitation & sweating to minimize this effect the first dose should be limited to 1 mg of each agent & given at bedtime. 26

treatment of chronic HTN in pregnancy agents comments methyldopa Preferred based on long term follow-up studied supporting safety BBs Reports of intrauterine growth retardation (atenolol) Generally safe labetalol Increasingly preferred to methyldopa due to reduced SE clonidine Limited data CCB Limited data Diuretics Not first line agents (probably safe ) ACEIs , ARBs Contraindicated (reported fetal toxicity and death) 27

HTN during lactation • All antihypertensive agents are excreted into human milk. • In mother with stage 1 HTN who wish to breast feed for a few months , it might be prudent to withhold antihypertensive with close monitoring of BP. resume drug after d/c of breast feeding. • No short term SE have been reported from exposure to methyldopa. • Propranolol & Labetalol are preferred if BB is indicated. • Avoided ACEI & ARB. • Diuretic may ↓ milk volume. 28

Renal transplantation • HTN is a relatively common occurence in organ transplantation. • In kidney allograft HTN prevalence approx 65%. • Mechanism: vasoconstriction and long term vascular structural changes caused by chronic immunosuppressive such as cyclosporine , Tacrolimus and corticosteroid. v the high risk of graft occlusion and CV events has suggested that BP should be lowered to 130/80 mm Hg or less. v No particular class is superior , combination agent is necessary. v Monitor K and Src particularly when ACEI or ARB are used. 29

Renal transplantation cont…. • In practice : I see CCB is effective in HTN in transplant. • National kidney foundation Guidelines : most transplant centers use dihydropyridine CCB for initial therapy , since these agents dilate the afferent arteriole, therapy ameliorating vasoconstricton afferent arteriole induced by calcineurin inhibitors (cyclosporin and tacrolimus). v a recent randomized study comparing nifedipine and lisinopril demonstrated improved kidney outcomes (lower creatinine and improved GFR at 2 years ) with use of nifedipine. 30

Hypertensive emergency • Characterized by sever elevation in BP >180/120 mm Hg complicated by evidence of impending or progressive target organ damage. • Target organ damage : a) Heart : LVH , angina or MI , HF. b) Brain : stroke or TIA , retinopathy. c) Kidney : GFR , chronic kidney disease. • Pts must be admitted to ICU for BP monitoring and administration IV antihypertensive agent. 31

Hypertensive emergency cont…. • Initial goal is to reduce BP no more than 25% within minutes to 1 hr, then if stable, to 160/110 mm Hg within the next 2 -6 hrs(avoid excessive fall in BP ---to avoid precipitation of renal , cerebral or coronary ischemia. If the pts tolerated this BP and clinically stable , further gradual reduction toward a normal BP within the next 24 -48 hrs. 32

33 Parental drugs for treatment of hypertensive emerencies Drug Dose Onset of action vasodilators Special indication Na nitroprusside o. 25 -10 µg/kg/min as IV infusion immediate Most use Caution with high ICP or azotemia nitroglycerin 5 -100 µg/min as IV infusion 2 -5 min Coronary ischemia Hydralazine hydrochloride 10 -20 mg IV 10 -40 mg IM 10 -20 min IV 20 -30 min IM eclampsia Labetalol hydrochloride 20 -80 mg IV bolus every 10 min 0. 5 -2 mg/min IV infusion 5 -10 min Most use except acute HF Esmolol hydrochloride 250 -500 µ/kg/min IV 1 -2 min bolus then 50 -100 µg/kg min by infusion Adrenergic inhibitor phentolamine 33 5 -15 mg IV bolus 1 -2 min Aortic dissection, Perioperative Catecholamine excess

Hypertensive urgency • Severe elevation of BP without target organ damage. E. g. , upper level of stage 2 HTN with severe headache , SOB , epistaxis or severe anxiety. • Either non compliant or inadequately treatment. • Treatment : oral , short acting agents such as captopril , labetalol , or clonidine followed by several hrs of observation at ED. If stable , reinstitute previous medications , combination. 34

Diuretics 1 – K sparing diuretics : • weak when used alone , combined with Thiaz/ loop to prevent ↓ K. • Avoided in ARF. 2 -thiaz diuretics: • initial therapy is more effective than loop. • Efficacy @ Cr CL > 30 ml/min. • Low dose 12. 5 mg HCTZ , not > 50 mg. 3 - loop diuretics: • Indicated : loss of THIAZ effect & Cr CL < 30 ml/min. • Expensive than THIAZ. 35

BBs v. Three pharmacodynamic diffrences : 1 - cardioselectivity =affinity for B 1 than B 2 (Atenolol , metoprolol , bisoprolol & acebutolol) dose dependent phenomenon , effect is lost at higher doses. 2 - intrinsic sympathomimetic activity (ISA)= these agents release catecholamines to maintains normal basal sympathetic tone. Not safer to use in HF , sinus bradycardia. (acebutolol , carteolol , penbutolol , pindolol ). 36

BBs cont…. 3 - membrane-stabilizing action (MSA) =(or quinidine like effect ) on cardiac cell if large enough doses are given (antidysrhythmic effect ) , the dose exceeds that used in HTN. • all BBs share this property. • Only (propranolol , sotolol , acebutolol ) indicated for arrythmias. • Precautions : no BB is totally safe in pts with bronchospasm. abrupt cessation may produce unstable angina , MI , taper dose over 14 days before d/c the drug. 37

conclusion • HTN is not a disease but an important risk factor for CV and cerebrovascular disease. • Education of the pt is necessary on longterm importance of treatment and lifestyle changes. • There is no ideal antihypertensive drug that reduces BP without causing SE. • It is imortant to match the antihypertensive to the patient‘s other coexisting disease states to gain the most benefit. 38

references • Daniel H. cooper. The Washington Manual Of Medical Therapeutics. Lippincolt Williams and Wilkins , Baltimore , MD. 32 nd ED , 2008 ; chapter 4 , page ; 72 -91. • http: //www. emedicinehealth. com/high_blood_p ressure/article_em. htm. Richard A Helms Pharm. D, BCNSP; David J Quan Pharm. D. Text Book of Therapeutics. Disease and Drug Management. LWW, 8 th Edition ( 2005 ), Chapter 20, hypertension pg : 565 - 485. 39