Anti-hypertensive Therapy

Introduction

50 million Americans age 6 and older have hypertension

90% suffer for primary (essential) hypertension

People with lower educational and income levels

Diagnosis

Repeated, reproducible and high BP measurements

Not patient symptoms!

Hypertension Treatment

Lifestyle Modifications Drug Therapy Substitute Drugs from different classes of

anti-hypertensives

Hypertension TreatmentLifestyle Modifications

Lifestyle Modifications Lose weight Reduce alcohol intake Reduce Na+ intake Reduce fat and

cholesterol intake DASH diet Exercise Stop smoking

Hypertension TreatmentDrug Therapy Overview

If lifestyle modifications do not work, initiate Drug Therapy!

Drug Classifications

1. Diuretics

2. Calcium Channel Blockers

3. Sympatholytic Drugs

4. Vasodilators

5. ACE inhibitors

6. Angiotensin II antagonists

1. DiureticsGeneral Information

Reduces pressure by 10-15 mmHg

Can be combined with other anti-hypertensives

May be used with potassium supplements

Not useful in patients with renal insufficiency

Mechanism of Action Na+ depletion Blood volume reduction Decreases peripheral

resistance

1. DiureticsClasses

A. Thiazides

B. Loop Diuretics

C. Potassium-Sparing Diuretics

1A. DiureticsThiazides

Used in patients with: mild to moderate HTN Normal cardiac and renal

function Most frequently used

anti-hypertensive in the USA

Hydrochlorothiazide (Hydrodiuril)

Chlorthalidone (Hygroton)

1A. DiureticsThiazides

Side Effects Hypokalemia impaired diabetes control Hyperuricemia muscle cramps increased LDL/HDL ratio

Contraindications Digitalis Lithium NSAIDS

1B. DiureticsLoop Diuretics

Shorter duration of action

Subjects refractory to thiazides

Furosemide (Lasix)

1B. DiureticsLoop Diuretics

Side Effects Dehydration Hypokalemia Impaired diabetes control Increases LDL/HDL ratio

Contraindications Digitalis Lithium

1C. DiureticsPotassium-Sparing Diuretics

Used in combination with other diuretics

Used to correct hypokalemia

Used to avoid potassium depletion in digitalis patients

Spironolactone (Aldactone) Aldosterone Antagonist

Triamterene (Dyrenium)

1C. DiureticsPotassium-Sparing Diuretics

Side Effects Hyperkalemia Gynecomastia G.I. disturbances

Contraindications Lithium NSAIDS ACE Inhibitors

2. Calcium Channel Blockers

2. Calcium Channel BlockersGeneral Information

Rarely associated with abnormalities in electrolyte, carbohydrate, or lipid metabolism

Useful in ischemic heart disease, chronic pulmonary disease, diabetes mellitis, and variant angina

Do not alter plasma levels of uric acid

2. Calcium Channel BlockersMechanism of Action

Inhibit Ca++ influx into VSM Relax peripheral arteriole SM Decrease Peripheral resistance Interferes with Ang II and Alpha-2 mediated

vasoconstriction

2. Calcium Channel BlockersDrugs

Nifedipine (Procardia) Dihydropyridine Selective vasodilator Less effect on heart

Diltiazem (Cardizem) Heart and Vessels

Verapamil (Calan) Mainly Heart

2. Calcium Channel BlockersSide Effects

Tachycardia Dizziness Edema Constipation Bradycardia Headache

3. Sympatholytic DrugsGeneral Information

Reduce sympathetic activity to heart and blood vessels

Must withdraw slowly Several classes

3. Sympatholytic DrugsClasses

A. Centrally acting agents

B. Adrenergic blocking agents

C. Alpha Antagonists

D. Beta Antagonists

3A. Sympatholytic DrugsCentrally acting agents

Reduce sympathetic output from vasopressor centers in brainstem

Decreases CO Decreases peripheral

resistance

Clonidine (Catapres) Methyldopa (Aldomet)

3A. Sympatholytic DrugsCentrally acting agents: Clonidine

Alpha-2 agonist at medullary cardiovascular centers

Decreases sympathetic outflow from CNS

Tablet and transdermal patch (reduced side effects?)

Little effect on plasma proteins

Side Effects Sedation Dry mouth Bradycardia (rare)

Contraindications Other CNS depressants

3A. Sympatholytic DrugsCentrally acting agents: Methyldopa

Methyldopa

Converted to Methyldopamine

Converted to Methylnorepinephrine

H3C-NE acts on central alpha-2 receptors

Sympathetic outflow from CNS is decreased

Blood pressure is decreased

3A. Sympatholytic DrugsCentrally acting agents: Methyldopa

Drug of choice for pre-eclampsia Side Effects

Sedation Nightmares Movement Disorders Hyperprolactinemia Hypersensitivity of skin and liver (very rare) Anemia

Contraindications MAOis Levodopa

3B. Sympatholytic DrugsAdrenergic Blocking Agents: General Information

Mechanism of Action Reduces NE release in

heart and blood vessels

Decrease CO and peripheral resistance

Reserpine (Serpasil) Guanethidine (Ismelin)

3B. Sympatholytic DrugsAdrenergic Blocking Agents: Reserpine

Disrupts NE vesicular storage

Both central and peripheral action

Used to treat mild-moderate HTN

Side Effects Sedation Diarrhea Depression Bradycardia Nasal Congestion

Contraindications CNS depressants MAOis

3B. Sympatholytic DrugsAdrenergic Blocking Agents: Guanethidine

Prevents NE release from nerve terminals

Effective, but side effects are severe

Reserved for severe HTN

Does not cross CNS

Side Effects Orthostatic hypotension Diarrhea Bradycardia Impotence

Contraindications TCAs

3C. Sympatholytic DrugsAlpha Antagonists: General Information

Mechanism of Action Act at post-synaptic

receptors to produce arteriole and venous vasodilatation

Decrease BP to a certain extent

Does not impair exercise tolerance

Prazosin (Minipress)

Less tachycardia Side Effects

Dizziness Headaches Weakness Decrease LDL/HDL

3C. Sympatholytic DrugsAlpha Antagonists: Prazosin

3D. Sympatholytic DrugsBeta Antagonists: General Information

Mechanisms of Action Decrease contractility

and CO Decrease renin secretion

Decrease Ang II

Must be withdrawn gradually

May mask insulin-induced hypoglycemia

1) Propanolol (Inderal)

2) Nadolol (Corgard)

3) Pindolol (Visken)

4) Metoprolol (Lopressor)

5) Labetolol (Trandate, Normodyne)

Nonselective Beta antagonist Mild to moderate HTN Used with vasodilators

Prevent tachycardia

3D. Sympatholytic DrugsBeta Antagonists: Propranolol

Nonselective Beta antagonist Long half-life Better patient compliance

3D. Sympatholytic DrugsBeta Antagonists: Nadolol

Nonselective Beta antagonist Partial agonist properties Less bradycardia

3D. Sympatholytic DrugsBeta Antagonists: Pindolol

Selective beta-1 antagonist

3D. Sympatholytic DrugsBeta Antagonists: Metoprolol

High incidence of side effects Sexual dysfunction Hypotension Useful in treatment of pheochromocytoma

3D. Sympatholytic DrugsBeta Antagonists: Labetolol

Mild-chronic fatique Low exercise tolerance Sedation Nightmares Increased airway resistance Bradycardia

3D. Sympatholytic DrugsBeta Antagonists: General Side Effects

4. VasodilatorsGeneral Information

Mechanism of Action Dilate small arteries Decrease peripheral

resistance

1) Hydralazine (Apresoline)

2) Minoxidil (Loniten)

3) Nitroprusside (Nipride)

4) Diazoxide (Hyperstat IV)

4. VasodilatorsHydralazine

Orally effective Emergencies Normal hypertensive

situations Mechanism:

Increases cGMP K channel opener

Side Effects Tachycardia Aggravation of Angina Fluid retention Nausea Sweating Flushing Lupus-like syndrome

4. VasodilatorsMinoxidil

Resistant HTN Mechanism:

Increases cGMP K channel opener

Side Effects Tachycardia Aggravation of Angina Fluid Retention Nausea Sweating Flushing Hypertrichosis

4. VasodilatorsNitroprusside

Emergencies Immediate onset Short duration

Side Effects Nausea Cyanide toxicity Muscle twitching

4. VasodilatorsDiazoxide

Emergencies Long duration of action Mechanism:

K channel opener

Side Effects Severe tachycardia Prolonged hypotension Nausea

5. ACE InhibitorsGeneral Information

Mechanism of Action Inhibits production of Ang

II Decreases peripheral

resistance

Contraindicated in 2nd and 3rd trimesters of pregnancy

5. ACE InhibitorsDrugs

Drugs Captopril (Capoten) Enalapril (Vasotec) Lisinopril (Zestril, Prinvol)

Side Effects Hyperkalemia Rash Dry cough Angioneurotic edema

6. Angiotensin II AntagonistsGeneral Information

Relax smooth muscle Increase salt and water

excretion Decrease plasma

volume

Drugs Saralasin Losartan (Cozaar) Side Effects Hyperkalemia Contraindicated in 2nd

and 3rd trimesters of pregnancy

Considerations

Pregnancy African Americans Elderly Diabetes Mellitus Hyperlipidemia COPD

ConsiderationsPregnancy

If taken before pregnancy, most anti-hypertensives can be continued

Methyldopa is most widely used Beta-blockers, ACE Inhibitors, and

Angiotensin II Antagonists are not recommended

ConsiderationsAfrican Americans

1st Choice: Diuretics Decrease M & M

Calcium channel blockers and alpha and beta blockers are effective

Combination therapy may be the best answer

ConsiderationsElderly

Smaller doses Closely monitor side

effects

ConsiderationsDiabetes Mellitus

ACE Inhibitors, Alpha blockers, and Calcium Channel blockers are effective

Possibly, because they have little effect on carbohydrate metabolism

ConsiderationsHyperlipidemia

Diuretics have little effect on cholesterol and triglycerides

Alpha blockers decrease LDL/HDL ratio Calcium channel blockers, ACE inhibitors,

and Angiotensin II antagonists have little effect on lipid profile

ConsiderationsCOPD

Avoid Beta blockers

Thank You

Questions?