By : Dr. Hala M. Al- Khalidi, Pharm.D. By : Dr. Hala M. Al- Khalidi, Pharm.D. Faculty of Pharmacy,

King Abdulaziz University 2626thth , Oct., 2008. , Oct., 2008.

Hypertension & Hypertension & Guidelines UpdateGuidelines Update

Introduction Introduction

JNC 7 key messagesJNC 7 key messagesClassification of BPClassification of BP Diagnostic toolDiagnostic tool Causes of HTN/ Causes of HTN/ EtiologyEtiology CV risk factorsCV risk factorsPathophysiologyPathophysiologyPrinciples of HTN Principles of HTN treatmenttreatment Nifedipine warningNifedipine warning BP measurement BP measurement techniquestechniques

Life style modificationLife style modification

Pharmacologic Pharmacologic therapytherapy

Compelling indicationCompelling indication

Causes of resistance Causes of resistance HTNHTN

TODTOD

HTN in ESRDHTN in ESRDImproving patient Improving patient compliancecompliance

JNC7 Key messagesJNC7 Key messages Subjects > then 50 yo, systolic BP > 140 Subjects > then 50 yo, systolic BP > 140 mmHg is more of a risk factor the mmHg is more of a risk factor the diastolic BP.diastolic BP.

CVD risk begins at 115/75 mmHg doubles CVD risk begins at 115/75 mmHg doubles with increments of 20/10 mmHg; with increments of 20/10 mmHg; normotensive individuals at age 55 have a normotensive individuals at age 55 have a 90% risk for developing HTN.90% risk for developing HTN.

Prehypertensives with SBP of 120-139mmHg Prehypertensives with SBP of 120-139mmHg or a DBP 80-89mmHg, need to stress on or a DBP 80-89mmHg, need to stress on lifestyle modification to prevent CVD. lifestyle modification to prevent CVD.

JNC7 Key messagesJNC7 Key messages

Uncomplicated HTN treatment for Uncomplicated HTN treatment for most patients are Thiazide-type most patients are Thiazide-type diuretics, either alone or in diuretics, either alone or in combination with other classes. With combination with other classes. With high risk conditions that require use high risk conditions that require use other antihypertensive drug classes other antihypertensive drug classes (ACEI, ARB’s, B-B, and CCB).(ACEI, ARB’s, B-B, and CCB).

Tow or more classes of Anti-HTN’s are Tow or more classes of Anti-HTN’s are required to achieve goal BP (< 140/90 required to achieve goal BP (< 140/90 mmHg, or < 130/80 mmHg for mmHg, or < 130/80 mmHg for diabetics or chronic kidney disease). diabetics or chronic kidney disease).

JNC7 Key messagesJNC7 Key messages

Two agents should be initiated If BP is Two agents should be initiated If BP is >20/10 mmHg above goal BP , one of which >20/10 mmHg above goal BP , one of which should be a thiazide-type diuretic. should be a thiazide-type diuretic.

Motivation is a key aspect in BP control, and Motivation is a key aspect in BP control, and it is maintained with BP control, (+ve) it is maintained with BP control, (+ve) experience & trust in clinicians is built experience & trust in clinicians is built (empathy build trust).(empathy build trust).

In providing these guidelines, physicians In providing these guidelines, physicians judgment remains paramount.judgment remains paramount.

Taking BPTaking BP

Classification of HTN Classification of HTN

Category Category SBP SBP mmHgmmHg

DBP DBP mmHgmmHg

Normal Normal < 120< 120 & < 80& < 80

PrehypertensiPrehypertensionon 120 - 139120 - 139 Or 80-89Or 80-89

HHypertension, ypertension, stage 1stage 1 140 - 159140 - 159 Or 90-99Or 90-99

Hypertension, Hypertension, stage 2stage 2 ≥ ≥ 160160 OrOr ≥ 100≥ 100

Isolated Systolic Isolated Systolic HypertensionHypertension

Definition Definition A A systolic BP of ≥ 140mmHg and diastolic BP systolic BP of ≥ 140mmHg and diastolic BP

< 90 mmHg, and staged @ BP 170/82mmHg is < 90 mmHg, and staged @ BP 170/82mmHg is stage 2 isolated systolic HTN .stage 2 isolated systolic HTN .

Treatment used in the study is Treatment used in the study is chlorthalidone chlorthalidone

(SHEP trial 1999).(SHEP trial 1999).

Causes of Secondary Causes of Secondary HTNHTN

Renovscular disease Renovscular disease (abdomanal bruits, recent (abdomanal bruits, recent onset, & accelerated HTN = onset, & accelerated HTN = renal artery stenosis renal artery stenosis

Drug inducedDrug induced

- OC (develop over 1-2 - OC (develop over 1-2 years) years)

RF = age>35/ smoking/ RF = age>35/ smoking/ obesity/ FH -HTN obesity/ FH -HTN

- PPA, NSAIDs, nasal - PPA, NSAIDs, nasal decongestants, decongestants, Cyclosporine, Erythropoietin, Cyclosporine, Erythropoietin, MAO+ tyramin. MAO+ tyramin.

11ryry aldosteronism ( ↓K, aldosteronism ( ↓K, weakness, ↑urination, weakness, ↑urination, muscle cramps) muscle cramps)

Coarctation of aorta, Coarctation of aorta, Sleep apnea, Sleep apnea, Thyroid, & Thyroid, & parathyroid disease parathyroid disease (JNC-7)(JNC-7)

PheochromocytomaPheochromocytoma

Wt. loss/ HA/ Wt. loss/ HA/ diaphoresis/ flushingdiaphoresis/ flushing

Cushing’s syndromCushing’s syndrom

Cardiovascular Risk Cardiovascular Risk FactorsFactors

Hypertension Hypertension

Cigarette smokingCigarette smoking

Obesity (BMI ≥ 30 Obesity (BMI ≥ 30 kg/mkg/m22))

Physical inactivityPhysical inactivity

Microalbuminuria or Microalbuminuria or ~ GFR < 60ml /min~ GFR < 60ml /min

Age older then 55 Age older then 55 men, 65 womenmen, 65 women

Dyslipidemia Dyslipidemia

FH of premature CVDFH of premature CVD

Men < 55, woman < 65 Men < 55, woman < 65 yr oldyr old

Target Organ DamageTarget Organ Damage

HHearteart- - LVHLVH - - AAngina or Hx . MIngina or Hx . MI- Hx . coronary - Hx . coronary revascularizationrevascularization- HF- HF

BBrainrain - Stroke or TIA- Stroke or TIA

- Peripheral arterial - Peripheral arterial diseasedisease

- Retinopathy- Retinopathy

KKidneyidney - Glomerular filtration - Glomerular filtration raterate

- Components of the - Components of the metabolic syndrome metabolic syndrome

- Chronic kidney - Chronic kidney diseasedisease

Diagnostic ToolsDiagnostic Tools Assess RF and comorbidities Causes of HTNDetection of TODConduct hx and physical examinationObtain laboratory tests: UA, SCr, FBS, H+/H+, FLP, serum K,+ and Ca+

Optional: urinary albumin/creatinine

ratio EKG

BP Measurement BP Measurement TechniquesTechniques

MethodMethod NotesNotes

IN-officeIN-office

Two readings, 5 minutes Two readings, 5 minutes apart, sitting in a chair . apart, sitting in a chair . Confirm BP reading in Confirm BP reading in

contra lateral arm contra lateral arm

Ambulatory Ambulatory BP BP

monitoringmonitoring

White Coat HTN , absence White Coat HTN , absence of 10-20% BP ↓ during of 10-20% BP ↓ during sleep may ↑ CVD risksleep may ↑ CVD risk

Patient Patient self-checkself-check

Assess in response to TxAssess in response to Tx

Improve adherence to Improve adherence to therapytherapy

Useful for evaluating Useful for evaluating white coat HTNwhite coat HTN

Lifestyle ModificationLifestyle Modification

ModificatioModification n RecommendationRecommendation

Avg. BP Avg. BP Reduction Reduction

rangerange

Weight Weight

ReductionReduction

Maintain normal body Maintain normal body weight (BMI 18.5-weight (BMI 18.5-

24.9kg/m24.9kg/m22))

5-20 5-20 mmHg/10kmmHg/10k

gg

DASHDASH DIET DIET

A Diet rich in fruits, A Diet rich in fruits, vegetables, & low fat vegetables, & low fat

dairy product, low dairy product, low saturated & fatsaturated & fat

8-14 8-14 mmHgmmHg

Na+ Na+ restrictionrestriction

Reduce NaReduce Na++ in in diet 2.4-6 G/daydiet 2.4-6 G/day

2-8 2-8 mmHgmmHg

PhysicalPhysical

activityactivity

Aerobics e.g. Brisk Aerobics e.g. Brisk walking walking (at least (at least

30mints/day most days of 30mints/day most days of the week the week 4-9 4-9 mmHgmmHg

Alcohol Mod.Alcohol Mod. Male vs. Female & light Male vs. Female & light weightweight 2-4 2-4 mmHgmmHg

Treatment Recommendations Treatment Recommendations Thiazide diuretics are first-line agents for the managementThiazide diuretics are first-line agents for the management

of hypertension in most patients. supported by clinical trials of hypertension in most patients. supported by clinical trials showing reduced morbidity & mortality with these agents. showing reduced morbidity & mortality with these agents. Comparative data from the landmark clinical trial, the Comparative data from the landmark clinical trial, the ALLHAT, confirm the first-line role of thiazide diuretics.ALLHAT, confirm the first-line role of thiazide diuretics.

Older patients with isolated systolic hypertension are oftenOlder patients with isolated systolic hypertension are often

at risk for orthostatic hypotension when drug therapy is at risk for orthostatic hypotension when drug therapy is started. started.

Particularly prevalent with diuretics, ACE inhibitors, and Particularly prevalent with diuretics, ACE inhibitors, and ARBs. ARBs.

Although overall treatment should be the same, initial doses Although overall treatment should be the same, initial doses should be very low and dose titrations gradual to minimize should be very low and dose titrations gradual to minimize risk of orthostatic hypotension.risk of orthostatic hypotension.

Primary Antihypertensive Primary Antihypertensive AgentsAgents

Furosemide (Lasix) Dose 20–80mg bidFurosemide (Lasix) Dose 20–80mg bid Dose in the morning & afternoon to avoid nocturnal diuresisDose in the morning & afternoon to avoid nocturnal diuresis

higher doses may be needed for patients withhigher doses may be needed for patients with severely decreased glomerular filtration rate or heart failureseverely decreased glomerular filtration rate or heart failure

Spironolactone Dose 25–50 qd/ bidSpironolactone Dose 25–50 qd/ bid Dose morning or afternoon to avoid nocturnal diuresisDose morning or afternoon to avoid nocturnal diuresis Eplerenone CI in patients with Cr ClEplerenone CI in patients with Cr Cl< 50 mL/min, < 50 mL/min, elevated elevated

serum creatinine (serum creatinine (> 1.8 mg/dL in women,> 2 mg/dL in men), > 1.8 mg/dL in women,> 2 mg/dL in men), and type 2 diabetes with and type 2 diabetes with microalbuminuriamicroalbuminuria

Avoid spironolactone in Avoid spironolactone in chronic kidney disease CrClchronic kidney disease CrCl< 30 < 30 mL/min); may cause hyperkalemia, mL/min); may cause hyperkalemia, especially in combination especially in combination with an ACEI, ARB or potassium supplementswith an ACEI, ARB or potassium supplements

B-Adrenergic blockersB-Adrenergic blockers

Three pharmacodynamic diffrences; Three pharmacodynamic diffrences;

1- Cadioselectivity1- Cadioselectivity = > affinity for B = > affinity for B11-R then B-R then B22-R -R

(Atenolol, metoprolol, bisoprolol, & acebutolol) (Atenolol, metoprolol, bisoprolol, & acebutolol) dose dose dependent phenomenondependent phenomenon , effect is lost at higher , effect is lost at higher doses.doses.

2- Intrinsic sympathomimetic activity (ISA)2- Intrinsic sympathomimetic activity (ISA) = these = these agents can release catecholamines to maintains agents can release catecholamines to maintains normal basal sympathetic tone while blocking access normal basal sympathetic tone while blocking access adrenergic stimulation, this is manifested at all dosage adrenergic stimulation, this is manifested at all dosage levels, so theoretically wouldn’t be safer to use in HF, levels, so theoretically wouldn’t be safer to use in HF,

sinussinus bradycardia, PVD, bradycardia, PVD, but no confirmed studies, but no confirmed studies, (e.g. acebutolol, carteolol, penbutolol, pindolol) .(e.g. acebutolol, carteolol, penbutolol, pindolol) .

Cont. B-Adrenergic blockersCont. B-Adrenergic blockers

3- Membrane-stablilizing action (MSA)3- Membrane-stablilizing action (MSA) =(or =(or quinidine-like effect) on cardiac cells if large enough quinidine-like effect) on cardiac cells if large enough doses are given (antidysrhythmic effect), the dose doses are given (antidysrhythmic effect), the dose exceeds that used in tx HTN, or cardiac arrhythmias, exceeds that used in tx HTN, or cardiac arrhythmias, all B-B share this property. all B-B share this property.

only (e.g. propranolol, sotolol, acebutolol) indicated only (e.g. propranolol, sotolol, acebutolol) indicated for arrythmias. for arrythmias.

Primary Antihypertensive Primary Antihypertensive AgentsAgents

Atenolol (Tenormin) Atenolol (Tenormin) Dose 25–100mg qd Dose 25–100mg qd

Metoprolol (Lopressor) Metoprolol (Lopressor) DoseDose 50–200mg bid50–200mg bid

Propranolol (Inderal) Propranolol (Inderal) DoseDose 160–480mg bid160–480mg bid Abrupt discontinuation may cause, rebound HTN inhibit Abrupt discontinuation may cause, rebound HTN inhibit β1 β1

and β2 receptors at all doses; can and β2 receptors at all doses; can exacerbate asthma; have exacerbate asthma; have additional benefits in patients with essential tremor, migraine additional benefits in patients with essential tremor, migraine headache, thyrotoxicosisheadache, thyrotoxicosis

Carvedilol (Coreg) Carvedilol (Coreg) DoseDose 12.5–50 bid12.5–50 bid Abrupt discontinuation may cause rebound hypertension; Abrupt discontinuation may cause rebound hypertension;

additional additional αα blockade produces more orthostatic blockade produces more orthostatic hypotensionhypotension

Primary Antihypertensive AgentsPrimary Antihypertensive Agents

Dihydropyridines are more potent peripheral vasodilators Dihydropyridines are more potent peripheral vasodilators than nondihydropyridines and may cause more reflex than nondihydropyridines and may cause more reflex sympathetic discharge (tachycardia), dizziness, headache,sympathetic discharge (tachycardia), dizziness, headache,

flushing, and peripheral edemaflushing, and peripheral edema additional benefits in Raynaud’s syndromeadditional benefits in Raynaud’s syndrome Extended-release products are preferred for hypertension; Extended-release products are preferred for hypertension;

these agents block slow channels in the heart and reducethese agents block slow channels in the heart and reduce

heart rate; may produce heart blockheart rate; may produce heart block these products are not AB rated as interchangeable on a these products are not AB rated as interchangeable on a

equipotent mg-per-mg basis due to different release equipotent mg-per-mg basis due to different release mechanisms and different bioavailability parametersmechanisms and different bioavailability parameters

Alternative Antihypertensive AgentsAlternative Antihypertensive Agents

Clonidine (Catapres)Clonidine (Catapres) Dose 0.1–0.8mg bid Dose 0.1–0.8mg bid

Methyldopa (Aldomet) Methyldopa (Aldomet) Dose 250–1000 bidDose 250–1000 bid Central Central α2-α2-agonists -agonists -most effective if used with most effective if used with

adiuretic to diminish fluid retention; clonidineadiuretic to diminish fluid retention; clonidine Patch is replaced once per weekPatch is replaced once per week

Warning Associated with Warning Associated with Nifedipine (ProcardiaNifedipine (Procardia®®))

Not enough studies dun or sufficient numbers of subjects Not enough studies dun or sufficient numbers of subjects with patients > 65 yowith patients > 65 yo occasional y patient had excessive & poorly tolerated occasional y patient had excessive & poorly tolerated hypotensionhypotensionProcardia & immedate-release forms should not be used Procardia & immedate-release forms should not be used for the acute reduction of BP, several well-documented for the acute reduction of BP, several well-documented reports describereports describe

cases of profound hypotension, MI, & deathcases of profound hypotension, MI, & deathRandomized trials studied the use of immediate-release Randomized trials studied the use of immediate-release nifedipine in patients that just had an MI, showed no nifedipine in patients that just had an MI, showed no benefit & in some showed significantly worse outcome benefit & in some showed significantly worse outcome then placebo patients, so it was concluded that within the then placebo patients, so it was concluded that within the 11stst week or two after an MI procardia should be avoided. week or two after an MI procardia should be avoided.

Alternative Antihypertensive AgentsAlternative Antihypertensive Agents

Minoxidil (Loniten) Minoxidil (Loniten) 10–40mg qd/bid10–40mg qd/bid

Hydralazine (Apresoline) Hydralazine (Apresoline) 20–100 bid/qid20–100 bid/qid

Direct arterial vasodilators; should be used with diuretic Direct arterial vasodilators; should be used with diuretic and and β-blocker to β-blocker to diminish fluid retention and reflex diminish fluid retention and reflex tachycardiatachycardia

Compelling Indications for Compelling Indications for IndividualIndividual

Drug ClassesDrug Classes Compelling IndicationCompelling Indication Initial Initial

Therapy OptionsTherapy Options

Heart FailureHeart Failure THIAZ, BB, ARB, ALDO ANTTHIAZ, BB, ARB, ALDO ANT

POST MIPOST MI BB, ACEI, ALDO ANTBB, ACEI, ALDO ANT

High CVD riskHigh CVD risk THIAZ, BB, ACEI, THIAZ, BB, ACEI, CCBCCB

Diabetes Diabetes THIAZ, BB, ACEI, ARB, THIAZ, BB, ACEI, ARB, CCBCCB

Chronic kidney diseaseChronic kidney disease ACEI, ACEI, ARBARB

Recurrent stroke preventionRecurrent stroke prevention THIAZ, THIAZ, ACEIACEI

Recommendations in CKDRecommendations in CKD

Chronic kidney disease (CKD) with an Chronic kidney disease (CKD) with an estimated estimated

GFR < 60ml/min ~ 1.5mg/dl in men & GFR < 60ml/min ~ 1.5mg/dl in men & 1.3mg/dl in women, albuminuria > 1.3mg/dl in women, albuminuria > 300mg/day, or 200mg albumin /g creatinine.300mg/day, or 200mg albumin /g creatinine.Goal is to slow deterroration of renal Goal is to slow deterroration of renal function and prevent CVD.function and prevent CVD.Aggressive BP management with three or Aggressive BP management with three or more drugs to a goal BP < 130/80mmHg.more drugs to a goal BP < 130/80mmHg.

Recommendations in CKDRecommendations in CKDACEI’s or ARB’sACEI’s or ARB’s show favorable effects with show favorable effects with DM, and renal patients, and up to > 35% DM, and renal patients, and up to > 35% inc. in SCr , therefore with holding Tx would inc. in SCr , therefore with holding Tx would be due to hyperkelimia.be due to hyperkelimia.

GFR < 30ml/min, corresponding to SCr = GFR < 30ml/min, corresponding to SCr = 2.5-3 mg/dl, inc. ↑ dose of loop diuretics 2.5-3 mg/dl, inc. ↑ dose of loop diuretics are usually needed in combination with are usually needed in combination with other drug classes. other drug classes.

Thiazides efficacy is ↓, or ineffective to Thiazides efficacy is ↓, or ineffective to lower BP in renal function/CrCl < lower BP in renal function/CrCl < 30ml/min , therefore high dose loops is 30ml/min , therefore high dose loops is recommended , see JNC 6.recommended , see JNC 6.

HTN in ESRDHTN in ESRD

BP should be controlled prior starting epoetin BP should be controlled prior starting epoetin Bone marrow depression up to 10% in renal Bone marrow depression up to 10% in renal failure patients on captopril (sulfhydryl gp.) failure patients on captopril (sulfhydryl gp.) especially autoimmune disease, therefore especially autoimmune disease, therefore close monitor of WBC, and low dose captopril.close monitor of WBC, and low dose captopril.Central alpha-2 agonists as clonidine appear Central alpha-2 agonists as clonidine appear to be the safest in the dialysis population.to be the safest in the dialysis population.Trans dermal clonidine up to 1.2mg/day as Trans dermal clonidine up to 1.2mg/day as monotherapy in one short-term study was monotherapy in one short-term study was successfulsuccessful. .

Hypertension in Older Hypertension in Older PersonsPersons

More than two-thirds of people over 65 have HTN.This population has the lowest rates of BP control.Treatment, including those who with isolated systolic HTN, should follow same principles outlined for general care of HTN. Lower initial drug doses may be indicated to avoid symptoms; standard doses and multiple drugs will be needed to reach BP targets.

Followup and MonitoringFollowup and Monitoring

Patients should follow-up & adjust Patients should follow-up & adjust medications on a monthly basis until BP medications on a monthly basis until BP control is achieved, then f/u can be every 3-6 control is achieved, then f/u can be every 3-6 month intervals.month intervals.Stage 2 HTN & comorbid conditions well need Stage 2 HTN & comorbid conditions well need more frequent visits .more frequent visits .Serum K and SCr should be monitored 1-2 Serum K and SCr should be monitored 1-2 times/year.times/year.Tobacco abuse should be addressed Tobacco abuse should be addressed vigorously.vigorously.Low dose ASA is only considered when BP Low dose ASA is only considered when BP control is achieved , due to the increased risk control is achieved , due to the increased risk of hemorrhagic stroke in this population . of hemorrhagic stroke in this population .

Improving Patient Improving Patient ComplianceCompliance

I.I. Convince your patients that the treatment plan Convince your patients that the treatment plan is is

necessary and efficacious.necessary and efficacious.

II.II. Explain exactly what your patients should Explain exactly what your patients should expectexpect

- - What the drug does What the drug does

- How it should be taken - How it should be taken

- What are the major side effects - What are the major side effects

- What patients should do if they - What patients should do if they experience SE experience SE

- How the drug’s effect will be monitored.- How the drug’s effect will be monitored.

Causes of Resistant HTNCauses of Resistant HTN

Improper BP measurementImproper BP measurement

Excess NaExcess Na++ intake intake

Inadequate diuretic therapyInadequate diuretic therapy

MedicationMedication

- - Inadequate dosesInadequate doses

- Drug action & interaction (e.g. NSAIDs) , - Drug action & interaction (e.g. NSAIDs) , sympathomimetics, OCsympathomimetics, OC

- OTC drugs & herbal supplements- OTC drugs & herbal supplements

Excess alcohol intakeExcess alcohol intake

Improving Patient Improving Patient ComplianceCompliance

III.III. Listen carefullyListen carefully

IV.IV. Assess your patient’s mental stateAssess your patient’s mental state

V.V. Encourage the help of family and Encourage the help of family and friends friends

VI.VI. Keep medication regimens as simple as Keep medication regimens as simple as possiblepossible

VII.VII.Troubleshoot potential obstaclesTroubleshoot potential obstacles

VIII.VIII. Build reminders into the treatment plan Build reminders into the treatment plan

IX.IX. Include a plan to monitor complianceInclude a plan to monitor compliance

X.X. Ask your patients how they are doing Ask your patients how they are doing