Antihypertensive Agents Drug Management of Hypertension

Antihypertensive Agents Drug Management of Hypertension

Hypertension: Definition
High blood pressure i.e. Elevation of arterial blood pressure above 140/90 mm Hg. Can be caused by idiopathic process or an underlying disease process Normal : Systolic < 130 mm Hg Diastolic < 85 mm Hg

Classification of Blood Pressure
Category Systemic BP (mm Hg) Diastolic BP (mm Hg) Normal <130 <85 High Normal 85-89 Hypertension:- Stage 1 90-99 Stage 2 Stage 3 Stage 4  210  120

Classification of Blood Pressure…
Primary Hypertension Also known as essential or idiopathic hypertension 90% of the cases Secondary Hypertension 10% of the cases

Essential or Idiopathic or Primary Hypertension
- most (90%) patients with persistent arterial hypertension genesis of hypertension unknown predisposing factors: -(obesity, stress, salt intake, lack of Mg2+, K+, Ca2+, ethanol  dose, smoking) (positive family history, insulin resistance, age, sex, defect of local vasomotoric regulation

Secondary Hypertension
Cause is known is secondary to some distinct disease like: Renal + renovascular disease (artery stenosis) Hormonal defects (Cushing´s syndrome, phaeochromocytoma) Mechanical defect (coarctation of aorta) Hypertension in pregnancy (eclampsia of pregnancy), hypertension (sympathomimetics, glucocorticoids) Neurological desease

Blood Pressure = CO x SVR
CO = Cardiac output SVR = Systemic vascular resistance Ways of lowering Blood pressure:- Reduce cardiac output (ß-blockers, Ca2+ channel blockers) Reduce plasma volume (Diuretics) Reduce peripheral vascular resistance ( Vasodilators)

Treatment Rationale Short-term goal of antihypertensive therapy:
Reduce blood pressure Primary (essential) hypertension Secondary hypertension

Treatment Rationale… Long-term goal of antihypertensive therapy:
Reduce mortality due to hypertension-induced disease Stroke Congestive heart failure Coronary artery disease Nephropathy Peripheral artery disease Retinopathy

Major Risk Factors That Increase Mortality in Hypertension
Smoking Dyslipidemias Diabetes Mellitus Age >60 Gender: men, postmenopausal women Family history

"Individualized Care" Risk factors considered
Monotherapy is instituted Non pharmacological therapy tried first Considerations for choice of initial monotherapy: Renin status Coexisting cardiovascular conditions Other conditions

Treatment Thresholds for Essential Hypertension
Stages Risk group A (no major risk factors, no target organ damage) Risk Group B One or more major risk factors (except diabetes), no organ damage Risk Group C Target organ damage and/or diabetes High Normal Lifestyle Modification Lifestyle Modification and Drug Therapy Stage 1 Lifestyle Modification (up to 12 months) Stages 2, 3 and 4

Antihypertensive Agents
Medications used to treat hypertension

Antihypertensive Agents: Categories
Adrenergic agents Angiotensin-converting enzyme inhibitors Angiotensin II receptor blockers Calcium channel blockers Diuretics Vasodilators

Antihypertensive Agents: Categories…
Adrenergic Agents Alpha1adrenoceptor blockers Beta–adrenoceptor blockers (cardioselective and nonselective) Centrally acting alpha blockers Combined alpha-beta blockers Peripheral-acting adrenergic agents

Antihypertensive Agents: Mechanism of Action
Adrenergic Agents Alpha1 Blockers (peripherally acting) Block the alpha1-adrenergic receptors The SNS is not stimulated Result: DECREASED blood pressure Stimulation of alpha1-adrenergic receptors causes HYPERtension Blocking alpha1-adrenergic receptors causes decreased blood pressure

Antihypertensive Agents:
Adrenergic Agents Alpha1 Blockers doxazosin (Cardura) prazosin (Minipress) terazosin (Hytrin)

Adrenergic Agents Central-Acting Adrenergics Stimulate alpha2-adrenergic receptors Sympathetic outflow from the CNS is decreased Result: decreased blood pressure

Adrenergic Agents Central-Acting Adrenergics clonidine (Catapres) methyldopa (Aldomet) (drug of choice for hypertension in pregnancy)

Adrenergic Agents Adrenergic Neuronal Blockers (peripherally acting) Inhibit release of norepinephrine Also deplete norepinephrine stores SNS (peripheral adrenergic nerves) is not stimulated Result: decreased blood pressure

Antihypertensive Agents: Adrenergic Agents
Adrenergic Neuronal Blockers (peripherally acting)… reserpine guanadrel (Hylorel) guanethidine (Ismelin)

Therapeutic Uses Alpha1 blockers (peripherally acting) Treatment of hypertension Relief of symptoms of BPH Management of severe CHF when used with cardiac glycosides and diuretics

Therapeutic Uses… Central-Acting Adrenergics Treatment of hypertension, either alone or with other agents Usually used after other agents have failed due to side effects Also may be used for treatment of severe dysmenorrhea, menopausal flushing, glaucoma Clonidine is useful in the management of withdrawal symptoms in opioid- or nicotine-dependent persons

Therapeutic Uses… Adrenergic neuronal blockers (peripherally acting) Treatment of hypertension, either alone or with other agents Seldom used because of frequent side effects

Side Effects: Most common: dry mouth, drowsiness sedation, constipation Other: headaches, sleep disturbances nausea, rash cardiac disturbances (palpitations) HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION

Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors): Large group of safe and effective drugs Often used as first-line agents for CHF and hypertension May be combined with a thiazide diuretic or calcium channel blocker

ACE Inhibitors… RAAS: Renin Angiotensin-Aldosterone System When the enzyme angiotensin I is converted to angiotensin II, the result is potent vasoconstriction and stimulation of aldosterone Result of vasoconstriction: increased systemic vascular resistance and increased afterload Therefore, increased BP

ACE Inhibitors… Aldosterone stimulates water and sodium resorption. Result: increased blood volume, increased preload, and increased BP

ACE Inhibitors… ACE Inhibitors block the angiotensin-converting enzyme, thus preventing the formation of angiotensin II. Also prevent the breakdown of the vasodilating substance, bradykinin Result: decreased systemic vascular resistance (afterload), vasodilation, and therefore, decreased blood pressure

ACE Inhibitors… Captopril (Capoten) Short half-life, must be dosed more frequently than others Enalapril (Vasotec) The only ACE inhibitor available in oral and parenteral forms Lisinopril (Prinivil and Zestril) and quinapril (Accupril) Newer agents, long half-lives, once-a-day dosing Several other agents available

Antihypertensive Agents: Therapeutic Uses
ACE Inhibitors… Hypertension CHF (either alone or in combination with diuretics or other agents) Slows progression of left ventricular hypertrophy after a MI (Myocardial Infarction) Renal protective effects in patients with diabetes Drugs of choice in hypertensive patients with CHF

Antihypertensive Agents: Side Effects
ACE Inhibitors… Fatigue Dizziness Headache Mood changes Impaired taste Dry, nonproductive cough, reverses when therapy is stopped NOTE: first-dose hypotensive effect may occur!!

Angiotensin II Receptor Blockers (A II Blockers or ARBs) Newer class Well-tolerated Do not cause coughing

Angiotensin II Receptor Blockers… Allow angiotensin I to be converted to angiotensin II, but block the receptors that receive angiotensin II Block vasoconstriction and release of aldosterone

Angiotensin II Receptor Blockers: Losartan (Cozaar) eposartan (Teveten) valsartan (Diovan) irbesartan (Avapro) candesartan (Atacand) telmisartan (Micardis)

Angiotensin II Receptor Blockers… Hypertension Adjunctive agents for the treatment of CHF May be used alone or with other agents such as diuretics

Angiotensin II Receptor Blockers Upper respiratory infections Headache May cause occasional dizziness, inability to sleep, diarrhea, dyspnea, heartburn, nasal congestion, back pain, fatigue

Calcium Channel Blockers Benzothiazepines Dihydropyridines Phenylalkylamines

Calcium Channel Blockers… Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction This causes decreased peripheral smooth muscle tone, decreased systemic vascular resistance Result: decreased blood pressure

Calcium Channel Blockers:- Benzothiazepines: diltiazem (Cardizem, Dilacor) Phenylalkamines: verapamil (Calan, Isoptin) Dihydropyridines: amlodipine (Norvasc), bepridil (Vascor), nicardipine (Cardene) nifedipine (Procardia), nimodipine (Nimotop)

Calcium Channel Blockers Angina Hypertension Dysrhythmias Migraine headaches

Calcium Channel Blockers… Cardiovascular hypotension, palpitations, tachycardia Gastrointestinal constipation, nausea Other rash, flushing, peripheral edema, dermatitis

Antihypertensive Agents: Diuretics
Decrease the plasma and extracellular fluid volumes Results: decreased preload decreased cardiac output decreased total peripheral resistance Overall effect: decreased workload of the heart, and decreased blood pressure

Antihypertensive Agents: Diuretics…
Examples of Diuretics used??? Therapeutic uses??? Side effects???

Vasodilators Directly relaxes arteriolar smooth muscle Result: decreased systemic vascular response, decreased afterload, and PERIPHERAL VASODILATION

Vasodilators…. diazoxide (Hyperstat) hydralazine HCl (Apresoline) minoxidil (Loniten, Rogaine) sodium nitroprusside (Nipride, Nitropress)

Vasodilators… Treatment of hypertension May be used in combination with other agents Sodium nitroprusside and diazoxide IV are reserved for the management of hypertensive emergencies

Vasodilators… Hydralazine: dizziness, headache, anxiety, tachycardia, nausea and vomiting, diarrhea, anemia, dyspnea, edema, nasal congestion Sodium nitroprusside: bradycardia, hypotension, possible cyanide toxicity

Antihypertensive Agents: Nursing Implications
Before beginning therapy, obtain a thorough health history and head-to- toe physical examination. Assess for contraindications to specific antihypertensive agents. Assess for conditions that require cautious use of these agents.

Educate patients about the importance of not missing a dose and taking the medications exactly as prescribed. Patients should never double up on doses if a dose is missed; check with physician for instructions on what to do if a dose is missed. Monitor BP during therapy. Instruct patients to keep a journal of regular BP checks.

Instruct patients that these drugs should not be stopped abruptly, as this may cause a rebound hypertensive crisis, and perhaps lead to CVA (Cerebral Vascular Accident) or Stroke. Oral forms should be given with meals so that absorption is more gradual and effective. Administer IV forms with extreme caution and use an IV pump.

Remind patients that medications is only part of therapy. Encourage patients to watch their diet, stress level, weight, and alcohol intake. Patients should avoid smoking and eating foods high in sodium. Encourage supervised exercise.

Instruct patients to change positions slowly to avoid syncope from postural hypotension. Patients should report unusual shortness of breath; difficulty breathing; swelling of the feet, ankles, face, or around the eyes; weight gain or loss; chest pain; palpitations; or excessive fatigue.

Men taking these agents may not be aware that impotence is an expected effect. This may influence compliance with drug therapy. If patients are experiencing serious side effects, or believe that the dose or medication needs to be changed, they should contact their physician immediately.

Hot tubs, showers, or baths; hot weather; prolonged sitting or standing; physical exercise; and alcohol ingestion may aggravate low blood pressure, leading to fainting and injury. Patients should sit or lie down until symptoms subside. Patients should not take any other medications, including OTC drugs, without first getting the approval of their physician.

Monitor for side/adverse effects (dizziness, orthostatic hypotension, fatigue) and for toxic effects. Monitor for therapeutic effects Blood pressure should be maintained at less than 140/90 mm Hg

THANK YOU FOR YOUR ATTENTION!

Antihypertensive Agents Drug Management of Hypertension

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