hypertension - kau12/11/2010 dr. ahmed elberry, md 1 1 hypertension dr. ahmed a. elberry, mbbch,...

12/11/2010

Dr. Ahmed Elberry, MD 1

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HYPERTENSION

Dr. Ahmed A. Elberry, MBBCH, MSc, MDAssistant Professor of Clinical Pharmacy

Faculty of pharmacy,KAU

Hypertension

• It is a sustained of arterial bl. pr. ≥ 140/90

• Causes:1. 1ry: “Essential” or “Idiopathic”: 90-95% of cases

2. 2ry: about 5% of cases Disease:

Renal or renovascular disease Coarctation of the aorta Endocrine disease: eg:

Phaeochomocytoma Cushing syndrome Acromegaly

Drugs (Iatrogenic)

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Drug-Induced HT:

1- Hormones: Steroids Estrogens & OC Erythropoietin

2- Autonomic: Phenylpropanolamines Clonidine withdrawal Ergotamine

Sibutramine Methylphenidate

3- CNS: Anxiolytic: Buspirone Anesthetic:

Ketamine Desflurane

Antiparkinsonian: Bromocryptine Antiepileptic: Carbamazepine Antiemetic: Metoclopramide Antidepressants: Venlafaxine

4- Antiinflammatory: NSAIDs

5- Immunosuppressive:cyclosporine/tacrolimus

Risk factors for 1ry HT

Controllable RiskFactors

1- Salt intake2- Alcohol3- Stress4- Weight (Obesity)

5- exercise

Uncontrollable RiskFactors

1- Heredity2- Age

- Men: 35 – 50- Women: aftermenopause

3- Race :More inAfrican Americans

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JNC 7 Classification of BP: The 7th report of the Joint National Committee on Detection, Evaluation

& Treatment of High Bl Pr (JNC 7) classifies adult BP as shown

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Classification Systolic BP(mmHg)

Diastolic BP.(mmHg)

NormalPrehypertensionStage 1 hypertensionStage 2 hypertension

<120120–139140–159

≥160

<8080–8990–99≥100

NB.:• If systolic & diastolic lie in different stages, the highest is considered• Diastolic bl.pr. is generally more reliable, while, systolic is more important in elderly

Manifestations

Usually NO SYMPTOMS! “The Silent Killer” May have:

Headache Blurry vision Chest Pain Frequent urination at night

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Complications of HT

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Treatment of HT

• Nonpharmacological• Pharmacological

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Non pharmacological therapy

Include:

Indication: patients with prehypertension. Patients diagnosed with stage 1 or 2 hypertension should be

placed on lifestyle modifications & drug therapy concurrently.

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Approximate SBP Reduction1- Adopt DASH eating plan 8-14 mmHg2- Dietary sodium 2-8 mmHg3- Alcohol consumption 2-4 mmHg4- Weight 5-20 mmHg/ 10 kg weight loss5- Physical activity 4-9 mmHg

DASH Eating Plan

1. saturated fat, cholesterol & total fat2. red meat3. sweets & sugar containing

beverages

4. fruits, vegetables & fiber5. low fat diary products & plant protein6. magnesium, potassium & calcium

DASH Can reduce BP in 2 weeks(SBP, 8-14 mmHg)

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Pharmacological treatment

1st line 1ry options: (ABCD) Diuretics, ACE inhibitors (or ARBs)* , CCBs & β-Blockers**

Alternatives: Sympatholytics:

central α2-agonists, α1-Blockers, peripheral adrenergic neurone antagonists (guanithidine, reserpine,

α-methyldopa) direct renin inhibitors (Aliskiren)

Direct arterial vasodilators: (hydralazine, minoxidil, diazoxide)

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*ACE inhibitors (or ARBs) are contraindicated in pregnancy

**BBs are not indicated as first line therapy for elderly (age 60 and above)

The A B C D classes (1st line)

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DIURETICS

First and Best Choice

Can be combined with A, B, C

βBlockers

Good third Choice

Can be combined with A, D

Ca channelBlockers

Fourth Choice, Useful

Can be combined with D, A

ACEI and ARB

Second Best Choice

Can be combined with D, B, C

D

Diuretics

A

ACEI, ARB

B

β-Blockers

C

Ca-Blockers

D A

B C

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GOAL OF THERAPY

Stage 1: monotherapy Stage 2: combination therapy

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Hypertension

With Framinghamrisk factor ˂10%

-PLUS-

1-Framingham risk factor˃10%2- DM3- Renal Disease4- CAD

-PLUS-

HF

< 140/90mmHg

< 130/80mmHg

< 120/80mmHg

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Algorithm for Treatment of HT

Not at Goal Blood

Initial Drug Choices

Drug(s) for the compellingindications

With CompellingIndications

Lifestyle Modifications

Stage 2 HTN2-drug combination for most(usually thiazide diuretic and

ACEI, or ARB, or BB, or CCB)

Stage 1 HTNThiazide diuretics for most.May consider ACEI, ARB,BB, CCB, or combination.

Without CompellingIndications

Not at GoalBlood Pressure

Optimize dosages or add additional drugs

Compelling Indications

CompellingIndication

Initial Therapy Options Sequential therapy

Diabetes ACEI (or ARB) THIAZ, BB, CCB

Chronic kidneydisease (CKD)

ACEI (or ARB)

CAD BB + ACEI (or ARB) - THIAZ for BP control- CCB fro ischemia control

Recurrentstrokeprevention

ACEI (or ARB) + THIAZ

HF BB + THIAZ + ACEI (orARB)

- Aldosterone antagonist forsevere HF- Hydralazine or nitrates forblack patients

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Diuretics

1. Thiazides: As hydrochlorthiazide (HCTZ) or chlorthalidone

2. Loop Diuretics: Furosemide (lasix) twice daily Torsemide once daily

3. Potassium-Sparing Diuretics:1. Non-aldosterone antagonists: Triamterene & Amiloride.2. Aldosterone antagonists (more potent) : Spironolactone &

Eplerenone

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1- Thiazide Diuretics

• Indication: of choice for treating HT (it has both diuretic & direct VD effect) all are equally effective.

• Dosage: Starting dose of HCTZ (Esidrex) or chlorthalidone of 12.5 mg once daily. Maintenance dose of 25 mg once daily effectively lower BP with low

incidence of SE.

• SE: Hpokalemia , Hyponatremia , Hypomagnesemia, Hypochloremic

alkolosis Hyper uricemia , Hyper glycemia , Hyper lipidemia , Hyper sensitivity

Hypercalcemia

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Ca++

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2- Loop diuretics

• Indication: of choice for:

severe CKD (GFR<30 mL/min./1.73 m2) Lt ventricular dysfunction, or severe edema (because potent

diuresis is often needed in these patients).

• SE: Hpokalemia , Hyponatremia , Hypomagnesemia, Hypochloremic

alkolosis Hyper uricemia , Hyper glycemia , Hyper lipidemia , Hyper

sensitivity Hypocalcemia, Deafness, Dehydration

NB.: Loop diuretics have less effect on serum lipids & glucose19

Ca++

Hypokalemia

• Manifestation: Muscle fatigue or cramps. Serious cardiac arrhythmias may occur, esp. in patients:

receiving digitalis, with LV hypertrophy, with IHD.

• Monitoring: Serum K+ should be measured at baseline & within 4 w of

initiating therapy or after increasing diuretic doses.

• Management:1. Intermittent use of the least effective dose2. K+ rich food (bananas, potatoes, avocados)3. KCl supplement (20 – 40 mEq/day)4. Add K+ sparing diuretic

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K+

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3- K+-Sparing Diuretics

Indication: Patients who develop hypokalemia while on a thiazide diuretic.

SE: Hyperkalemia, especially in:

chronic kidney disease DM, concurrent treatment with an ACE.I, ARB, NSAID, or K+

supplement.

Gynecomastia with Spironolactone(in up to 10% of patients), but this effect occursrarely with eplerenone.

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ACEIs

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ACEIs1. S.H containing:

Captopril (capoten): [Active drug, given 2-3 timesdaily, absorption is affected by food]

2. Non-S.H containing: Active drug

Lisinopril (zestril) & Enalaprilate (given IV in emergencyhypertension)

Prodrugs Enalapril (renitec) - Perindopril - Benazepril -

Ramipril – Trandolapril - Fosinopril

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NB.: Enalaprilate (enalaprilic acid) is the active metabolite of Enalapril ACE.I is more effective in young white patients than in black or elderly

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ACEIsSide effects:1) Related to S.H:

1. Allergy2. Taste (Dysgeusia)3. Protinuria4. Neutropenia

2) Related to ACE1. Cough due to bradykinin2. 1st dose Hypotension (esp. in elderly & heart failure). So tart with

low dose with slow dose titration3. Hyperkalemia4. ARF esp. in bilateral renal art. stenosis

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ACEIs

Contraindications:1. Hypotension2. Pregnancy (They are fetopathic may cause

oligohydramnios – pulmonary hypoplasia – growthretardation – fetal death)

3. Bilateral renal artery stenosis

Drug interactions:1. Na+ depleting diuretics initial Hypotension2. K+ retaining diuretics hyperkalemia3. NSAID Hypotensive Effect Through Inhibition of

Bradykinin & PGs4. Antacids absorption

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AT-II Blockers (ARBs)

Candesartan - Losartan (Cozar) - Olmesartan –Valsartan – Eprosartan -Irbesartan – Telmisartan

Actions & Uses As ACEI Side effects As ACEI but with less cough

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CCB

Classification: Dihydropyridine:

Short acting: Nifedipine (Adalat, Epilat) Long acting: Amlodipine (Norvasc) – nisoldipine – felodipine –

isradipine

Non-dihydropyridine: Verapamil (isoptin) – Diltiazem (cardizem)

Side effects:1. Bl.V.: Headache – flush – Hypotension – ankle oedema2. Heart:

Bradycardia with Diltiazem & marked with verapamil Reflex Tachycardia with nifedipine

3. G.I.T.: Constipation is marked with verapamil.

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β-Blockers

Mechanism of antihypertensive effect:1. Block -1 of Heart COP.2. Block -1 of CNS Sympathetic outflow.3. Block -1 of Kidney Renin.4. Block Pre-synaptic Release of Nor-adr.5. Resetting the sensitivity of Baro-receptors.6. Prostacyclin (VD) synthesis

Classification:1. according to Selectivity2. according to Lipid solubility

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PGs

Classification according to Selectivity

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ISA L.A NotesA. Non- selective:

Pindolol + +Oxprenolol + +Propranolol (Inderal) No + Extensive hepatic 1st pass metabolismSotalol No NoNadolol No NoTimolol No No Eye drop in glaucoma.

B. Cardio-selective (B1)Acebutolol + +Atenolol (Tenormin) No NoBisoprolol (Concor) No NoBetaxolol No NoMetoprolol (Lopressor) No +Esmolol No No Ultrashort. I.V. Infusion.

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NB.: Vasodilator B- Blockers:

1. 2-Partial agonist: Celiprolol: (Selective 1 Block – No ISA – No LA)

2. Nitrogenic effect ( production of NO): Nebivolol

3. 1-blocking effect: Labetalol – Bucindolol – Carvedilol (dilatrend) - Medraxalol

Classification of according to Lipidsolubility

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Lipophilic Hydrophilic1. G.I.T. Absorption: - Well Absorbed. - Poorly absorbed.2. Passage across

B.B.B.:- Pass BBB- has CNS. effects.

- Not pass BBB- has little CNS effect

3. Metabolism: - Extensive hepatic. - Mainly Renal.4. Duration of Action: - Short (4-6 Hours) - Longer (12-24 Hs)5. Examples: - Propranolol.

- Oxprenolol.- Metoprolol.- Timolol

- Nadolol.- Atenolol.- Sotalol.- Bisoprolol

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SE & contraindications

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Side effects ContraindicationsI. CNS: - Sedation - depression - sleep disturbances

(only in lipophilic B.B. crossing BBB)Severe depression

(use hydrophilic B.B.)

II. CVS:1.Heart:

2.B.V.

3.B.P.

1.Heart failure - Heart block - Bradycardia ----

2.Cold extremities, Raynaud's phenomenon, numbness,tingling

3.Hypotension---------------------------------------

• H.F. - Hear block - severe bradycardia• With Verapamil: H.F. & H. Block• Variant angina .• Raynaud's phenomenon & P.V.D & alone

in pheochromocytoma• Hypotension

III. Respiration - Precipitate acute attack of B.A. in asthmatics - Bronchial asthma (use selective B1)

IV. Metabolism 1. Hypoglycemia (severe in patient receiving insulin ororal hypoglycemic [coma can occur without warning(silent death) ]

2. Hyperkalemia3. Atherosclerosis ( HDL & Triglycerides)

• Hypoglycemia in insulin or oralhypoglycemic treatment.

V. Others Sudden withdrawal withdrawal syndrome sympathetic over activity and precipitation of anginalattack even myocardial infarction

• Never stop suddenly.

α1-Receptor Blockers

Prazosin (Minipress), terazosin, and doxazosin (Cardura)

Side Effects:1. Initial Syncopal Attack (1st dose phenomenon). An αattack of

severe postural hypotension. Start by small dose while patientis recumbent (At Bed Time), then increase the dose gradually

2. Sexual dysfunction after long use in males & failure ofejaculation

3. Salt & H2O retention as it C.O. R.B.F. So, Diuretic isadded.

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Central α2-Agonists Include:

Clonidine, guanabenz, guanfacine, & methyldopa

Mechanism: Selective α2 & Imidazoline I1 Agonist (15 : 1) Hypotension by:

1. Sympathetic outflow from C.N.S.2. Presynaptic Release of N.A.3. Kidney: Release of Renin

Side effects of centrally acting drugs1. Sudden Withdrawal Rebound severe hypertension

Treat by Re-using Clonidine or by -Blocker + -Blocker.2. Sedation3. Dry mouth (xerostomia) & Dry nasal mucosa

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Moxonidine (physiotens) & Rilmenidine (Hyperium): They are selective I1 agonist used in ttt of

hypertension Less liable to cause sedation

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Peripheral adrenergic neuronedepressants

Include Guanethidine Reserpine Methyldopa (act centrally also)

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Guanethidine Reserpine -Methyldopa*Kinetic *Kinetic: *Kinetic- Incompletely absorbed- Not pass B.B.B- Slowly excreted in urine

- Well absorbed- Passes B.B.B- Slowly excreted in urine

- Well absorbed- Passes B.B.B- Transformed to -methyl

NAMechanism (Release) Mechanism: (Depletion) Mechanism ( synthesis &

Central)* Side effects: * Side effects: * Side effects:1) Parasymp. Predominance:

1. Nasal congestion2. Bradycardia3. Postural hypotension4. Diarrhea

2) Others:1. Parotid pain

2. Failure of ejaculation

1) Parasymp. Predominance:1.Nasal congestion{Stuffiness}

2.Bradycardia3.Hypotension4.Diarrhea

2) Others:1. Na & H2O retention2.Weight gain3.Peptic ulcer4.Endocrinal disturbance5.Breast cancer.6.Impotence

3) C.N.S:1. Psychic depression2. Nightmares3. Parkinsonism

1) Parasymp. Predominance:1.Nasal congestion2.Bradycardia3.Hypotension4.Diarrhea

2) Other:1.Na & H20 retention weight

gain2.Liver toxicity3.Bone marrow

Depression3) C.N.S:

1. Psychic depression2. Night mares3. Parkinsonism4. Sedation

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Direct renin inhibitors(Aliskirin (Tecturna®))

Inhibit directly the renin Similar to ACEIs & ARBs & contraindicated in

pregnancy Used once orally as an alternative antihypertensive

agent

Direct Arterial Vasodilators Include:

Hydralazine - Minoxidil - Diazoxide

Actions & effects :1. Direct Arterio-dilator Bl.Pr useful in Hypertension2. Bl.Pr symp & after load Co useful in H.F

Disadvantages & general SE:1. Bl.Pr sympathetic leading to: Tachycardia & Angina [Add - blockers] Rennin edema [Add diuretic](So, they are not used alone, but used in combinationwith - blockers & diuretics)

2. V.D Headache – congestion – flush

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(1)Hydralazine (2) Minoxidil (3) Diazoxide

Side effects1. Hypersensitivity in the form of:- Rash- Rheumatoid arthritis- Systemic lupus

erythematosus likesyndrome

2. GIT upset3. Peripheral neuritis

. Hypertrichosis 1. Hyperglycemia2. Hyperuricemia(as it is related to Thiazide

diuretic)

UsesOrally& I.V1. Hypertension & emergency2. H.F

Orally1. Hypertension2. H.F3. Locally in alopecia

I.VEmergency Hypertension

SPECIAL POPULATIONS

• Pregnancy: Methyldopa is the drug of choice Alternatives: ΒB & CCBs. ACEI & ARBs are contraindicated (teratogens).

• African Americans: Thiazides & CCBs are particularly effective. Response is significantly when either class is

combined with a BB, ACEI, or ARB.

• Older People: Diuretics & ACEI can be used safely, but in smaller-

than-usual initial doses, and titrations should occurover a longer period to minimize the risk ofhypotension.

Centrally acting agents & BB should be avoided orused with caution because they are associated withdizziness & postural hypotension.

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HYPERTENSIVE CRISIS

˃ 180/110 & may be classified into:

Hypertensive urgency: without target organ damage (TOD) (eg. Encephalopathy,

unstable angina, renal failure & papilledema) ttt: adjusting maintenance therapy by adding a new

antihypertensive and/or increasing the dose of a present drug.

Hypertensive emergency: with TOD ttt: require immediate BP reduction to limit new or progressing

target-organ damage.

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Goal in treatment of hypertensivecrisis

The goal: not to lower BP to normal; as rapid drops in BP may cause end-

organ ischemia or infarction.

The initial target is MAP 25% within minutes to hours. If BP is then stable, it can be reduced to 160/100 -110 mm Hg

within the next 2-6 hours. Additional gradual decrease toward the goal BP after 24 -48

hours.

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Treatment of hypertensive crises

Hypertensive urgency: Hypertensive emergency:Acute administration of short-actingoral drugs (captopril or labetalol)followed by careful observation forseveral hours to ensure gradual BPreduction.

• Captopril 25-50 mg may be givenat 1- to 2-hour intervals. The onsetof action is 15- 30 min.

• Labetalol 200-400 mg, followed byadditional doses every 2- 3 h.

Nitroprusside is the drug of choice inmost cases.

• Given as a IV infusion (0.25 to 10mcg/kg/min.)

• Onset of action is immediate &disappears within 1-2 min ofdiscontinuation.

• When infusion is continued ˃72 h.,serum thiocyanate levels should bemeasured, & infusion should bestopped if the level ˃12 mg/dL.

Other Parentral drugs used inemergency HT

Nitroprusside Nitroglycerin Nicardipine

Diazoxide Esmolol Enalaprilate Fenoldopam

Hydralazine Labetalol

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Causes of Resistant HT

1. Improper BP measurement2. Identifiable causes of HTN

3. Excess sodium intake4. Excess alcohol intake

5. Inadequate diuretic or medication therapy6. Drug actions and interactions:

• NSAIDs, sympathomimetics, oral contraceptives,OTC drugs & herbal supplements

12/11/2010


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hypertension - kau12/11/2010 dr. ahmed elberry, md 1 1 hypertension dr. ahmed a. elberry, mbbch,...

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