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?