Hypertension and Drug Therapy

• Hypertension and Drug Therapy

Blood Flow Through the Heart

• Blood flows through the heart in the following sequence: Superior vena cava > Right atrium (1) > Tricuspid valve > Right ventricle (2) > Pulmonary valve Pulmonary artery > Lungs > Left pulmonary veins (3) > Left atrium (4) > Mitral valve > Left ventricle (5) > Aortic valve > Aorta (to body) (6)

Mechanical System

• Systole is the contraction of the myocardium.
• Diastole is the relaxation of the myocardium.
• Cardiac output refers to the amount of blood pumped by each ventricle in one minute.
• CO (cardiac output) = SV (stroke volume) x HR (heart rate).
• Cardiac index needs to be defined.

Factors Influencing Blood Pressure

• Blood Pressure = Cardiac Output x Systemic Vascular Resistance.
• Systemic Vascular Resistance is affected by dilation of blood vessels, and amount of blood pumping through the heart.

Evidence-Based Guidelines for Blood Pressure Management

• BP measurements are based on four stages. -They include Normal, Elevated, Stage 1, Stage 2 and Hypertensive crisis
• Elevated Systolic Blood Pressure (SBP) is strongly associated with heart failure, stroke, and renal failure.
• Prehypertensive blood pressures are no longer considered "high normal” and require lifestyle modifications to prevent cardiovascular disease.
• Thiazide-type diuretics are recommended as the initial drug therapy for most patients with hypertension because it reduces volume of blood being pumped.

Etiology of Hypertension

• Primary (essential/idiopathic) hypertension accounts for 90% to 95% of all cases and is elevated BP without a specific cause.
• Contributing factors to primary hypertension include increased sodium-retaining hormones and vasoconstrictors, diabetes mellitus, being above ideal body weight, increased sodium intake, and excessive alcohol intake.
• Secondary hypertension is elevated BP for which there is a specific cause, accounting for 5% to 10% of adult cases.
• Contributing factors to secondary hypertension include coarctation of the aorta, renal disease, endocrine disorders, neurologic disorders, cirrhosis, and sleep apnea.

Risk Factors for Primary Hypertension

• Risk factors include vessel rigidity with age, alcohol consumption, cigarette smoking, diabetes mellitus, elevated serum lipids, excess dietary sodium, gender, family history, obesity, ethnicity, sedentary lifestyle, socioeconomic status, and stress.

Pathophysiology of Primary Hypertension

• Genetic factors have little contribution to BP levels in the general population.
• Stress and increased SNS activity produce increased vasoconstriction, increased heart rate and increased Renin release.
• High sodium intake may activate pressor mechanisms, resulting in water retention.
• Salt sensitivity is associated with obesity, increasing age, and African American ethnicity.
• High insulin concentration stimulates SNS activity and impairs nitric oxide-mediated vasodilation.
• Insulin resistance and hyperinsulinemia results in elevated blood pressure.

Hypertension: Clinical Manifestations

• Development is insidious because patients are frequently asymptomatic until target organ disease occurs.
• Symptoms are often secondary to target organ disease and can include fatigue, reduced activity tolerance, dizziness, palpitations, angina, and dyspnea.

Hypertension: Complications

• Target organ diseases occur most frequently in the heart, brain, peripheral vasculature, kidney (preserve blood flow to heart and brain), and eyes.

Hypertension Complications

• Hypertensive heart disease includes coronary artery disease, left ventricular hypertrophy, and heart failure.

Hypertension Collaborative Care

• Overall goals include controlling blood pressure and reduce cardiovascular disease risk factors.
• Drug therapy's primary mechanism of action is to reduce SVR and the volume of circulating blood to treat hypertension.

Antihypertensive Drugs

• Categories of antihypertensive drugs include diuretics, adrenergic drugs, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), direct renin inhibitors, and vasodilators.

Diuretics

• Diuretics decrease plasma and extracellular fluid volumes.
• This results in decreased preload, decreased cardiac output, and decreased total peripheral resistance.
• The effect is decreased workload of the heart and decreased blood pressure.

Thiazide Diuretics

• Hydrochlorothiazide is a prototype, and a first-line treatment for hypertension.
• The mechanism of action involves action on the distal convoluted tubule of the kidney.
• Thiazide diuretics inhibit the reabsorption of sodium, potassium, and chloride.
• They result in osmotic water loss
• They also directly relax the small blood vessels which reduces peripheral vascular resistance (afterload).
• Indications for use include heart failure, hypertension, edema, hypercalciuria, and diabetes insipidus.
• Contraindications include drug allergy, anuria, and renal failure.

Thiazide Diuretics: Adverse Effects

• CNS: Dizziness, headache, blurred vision, paresthesia.
• GI: Anorexia, nausea, vomiting, diarrhea, pancreatitis, cholecystitis.
• GU: Decreased libido and impotence (sexual activity).
• Hematologic: Jaundice, leukopenia, purpura, thrombocytopenia.
• Integumentary: Urticaria, photosensitivity.
• Metabolic: Hypokalemia, glycosuria, hyperglycemia, hyperuricemia."
• Toxicity: Overdose can cause severe hypokalemia with symptoms such as lethargy, muscle weakness, confusion, and severe hypotension.

Adrenergic Drugs: 'Sympathomimetics'

• Adrenergic drugs bind to adrenergic receptors, but inhibit (block stimulation) of the sympathetic nervous system (SNS).
• They inhibit or lyse sympathetic stimulation.
• Classified as Alpha-blockers and beta-blockers
• Classified by the type of adrenergic receptor they block: Alpha1 and alpha2 receptors, or Beta1 and beta2 receptors.
• Multiple sub-groups with drowsiness/sedation
• Central acting Alpha2 agonists.
• Peripherally acting alpha adrenergic blockers.
• Beta Blockers.

Adrenoceptors

• α1 receptors induce vasoconstriction, increase peripheral resistance, increase blood pressure, and cause mydriasis and increased closure of the internal sphincter of the bladder.
• α2 receptors inhibit norepinephrine Vasoconstriction release, inhibit acetylcholine release, and inhibit insulin release to cause Vasodilation.
• β1 receptors induce tachycardia, increased lipolysis, increased myocardial contractility, and increased release of renin.
• β2 receptors induce vasodilation, slightly decreased peripheral resistance, bronchodilation, increased muscle and liver glycogenolysis, increased release of glucagon, and relaxed uterine smooth muscle.

Adrenergic Drugs: Centrally Acting alpha2 agonists

• Prototype: clonidine (Catapres).
• Other Medications: methyldopa (Aldomet).
• Stimulate alpha-2 adrenergic receptors in the brain.
• Decrease sympathetic outflow from the CNS.
• Decrease norepinephrine production.
• Stimulate alpha2-adrenergic receptors, thus reducing renin activity in the kidneys.
• Results in decreased blood pressure.
• Indications include Hypertension.
• Clonidine is useful in the management of withdrawal symptoms in opioid- or nicotine-dependent persons.
• Can be used for hypertension in pregnancy (Methyldopa).
• Contraindications: Use cautiously in patients who have had stroke, recent MI, major depressive disorder and chronic renal failure.
• Adverse Effects/Side Effects: Drowsiness and Sedation, Dry Mouth, Rebound Hypertension.
• Nursing Administration: Administered by oral, transdermal and epidural routes.
• Medication is usually administered twice daily; instruct patients to take larger dose at bedtime.
• Transdermal patches are applied every seven days.

Adrenergic Drugs: Peripherally Acting Alpha₁ Blocker

• doxazosin mesylate (Cardura).
• terazosin (Hytrin).
• Block alpha 1-adrenergic receptors that cause Vasoconstriction.
• Cause both arterial and venous dilation, reducing peripheral vascular resistance and BP.
• Results in decreased blood pressure.
• Indications includes treatment of hypertension and Tamulosin (Flomax).
• Flomax has and effect on receptors on the prostate gland and bladder; it decreases resistance to urinary outflow, thus reducing urinary obstruction and relieving effects of BPH.
• Contraindications: Hypotension, Angina, renal insufficiency.
• Nursing Administration: First dose often at night and teach safety measures.

Alpha-Blockers: Adverse Effects

• Cardiovascular: Palpitations, orthostatic hypotension, chest pain, tachycardia, edema, dysrhythmias, hypotension or bradycardia.
• CNS: Dizziness, headache, drowsiness, anxiety, depression, vertigo, weakness, numbness, fatigue.
• Gastrointestinal: Nausea, vomiting, diarrhea, constipation, abdominal pain.
• Other: Incontinence, nosebleeds, tinnitus, dry mouth, pharyngitis, rhinitis.

Adrenergic Drugs: Beta-Blockers

• Block stimulation of beta receptors in the SNS.
• Compete with norepinephrine and epinephrine.
• Can be selective or nonselective.
• Nonselective beta-blockers block both beta₁ and beta2 receptors.
• β1 receptors induce tachycardia, increased lipolysis, increased myocardial contractility, and increased release of renin.
• β2 receptors induce vasodilation, slightly decreased peripheral resistance, bronchodilation, increased muscle and liver glycogenolysis, increased release of glucagon, and relaxed uterine smooth muscle.

Beta Receptors

• Beta1 receptors have and affect primarily on the heart.
• Beta-blockers selective for these receptors are called cardioselective beta-blockers.
• Beta2 receptors affect primarily on smooth muscle of bronchio and blood vessels.

Beta-Blockers: Mechanism of Action

• Reduces BP by reducing heart rate through beta1-blockade.
• Reduces secretion of renin.
• Long-term use causes reduced peripheral vascular resistance.
• Result: decreased blood pressure

Non-selective and cardioselective Beta Blockers

• Cardio Selective (Beta 1): Reduce SNS stimulation of the heart, decrease heart rate, prolong SA node recovery, slow conduction rate through the AV node, and decrease myocardial contractility.
• Non-selective (Beta 1 and 2): cause same effects on heart as cardio selective beta-blockers, can constrict bronchioles which can result in narrowing of airways and shortness of breath, can produce vasoconstriction of blood vessels through smooth muscle, and reduce heart rate owing to B1-blockade.

Beta Blockers: Indications

• Indications include angina, cardiprotection, dysrhythmias, migraine headaches, and antihypertensive.
• Angina is decreased demand for myocardial oxygen.
• Cardioprotective inhibits stimulation from circulating catecholamines and reduces risk of post MI cardiac arrest
• Glaucoma has topical use.

Beta-Blockers: Examples

• Examples of beta-blockers: carvedilol (Coreg), labetalol (Normodyne), metoprolol (Lopressor), atenolol (Tenormin), esmolol (Brevibloc), and propranolol (Inderal).

Beta Blockers: Adverse Effects

• Blood thrombocytopenia, cardiovascular AV (heart) block, bradycardia (due to slowing heart rate), heart failure, peripheral vascular insufficiency.
• CNS includes dizziness, mental depression excitability decreases, lethargy, hallucinations, unusual dreams.
• Gastrointestinal: Nausea, dry mouth, vomiting, diarrhea, cramps, and Ischemic colitis.
• Other: Impotence, rash, alopecia, bronchospasm.

Beta-Blocking Drugs: Nursing Implications

• Rebound hypertension or chest pain may occur if this medication is discontinued abruptly.
• Instruct patients to notify their physician if they become ill and unable to take medication.
• Inform patients that they may notice a decrease in tolerance for exercise (dizziness and fainting may occur with increased activity), and have patients notify the physician if these problems occur.
• Due to fluid shifting patients should report weight gain of more than 2 pounds in 1 day or 5 pounds in 1 week, edema of the feet or ankles, shortness of breath, excessive fatigue or weakness, syncope or dizziness.

Adrenergic Drugs: Summary of Adverse Effects

• The most common adverse effects are high incidence of orthostatic hypotension, dry mouth, drowsiness/sedation (CNS effect), and constipation.
• Other adverse effects include: Headaches, sleep disturbances, nausea, rash (allergy), and cardiac disturbances (palpitations).

Adrenergic-Blocking Drugs: Nursing Implications

• Check patients for allergies and history of COPD, hypotension, cardiac dysrhythmias, or heart failure.
• Preexisting conditions might be a contraindication to their use.
• Alpha-blockers may precipitate hypotension.
• Beta-blockers may precipitate bradycardia, hypotension, heart block, heart failure and bronchoconstriction.
• Avoid over-the-counter medications because of possible interactions.
• Possible drug interactions may occur with: Antacids (aluminum hydroxide type), antimuscarinics/anticholinergics, diuretics and cardiovascular drugs, neuromuscular blocking drugs, and oral hypoglycemic drugs triggering sympathetic.
• Instruct patients to change positions slowly to minimize postural hypotension.
• Instruct patients to avoid caffeine, stimulants, alcohol ingestion and hazardous activities until blood levels become stable.
• Instruct patients to contact doctor if they have palpitations and Monitor BP HR control

Nursing Implications

• Monitor for adverse and therapeutic effects. BP should be under 130/90 or 130/80 if the patient has diabetes or kidney disease.

ACE Inhibitors

• Angiotensin-converting enzyme inhibitors treat heart failure and hypertension.
• Act on angiotensin I to prevent the production of agiotension II.
• They block angiotensin-converting enzyme, thus preventing formation of angiotensin II.
• These drugs may be combined with a thiazide diuretic or calcium channel blocker.
• They prevent the breakdown of bradykinin, which is a vasodilating substance
• Decreases systemic vascular resistance vasodilation and decreased blood pressure.
• Captopril, enalapril and lisinopril are examples.
• They are renally protective in patients with diabetes which extends the life of the Kidneys.
• May treat hypertensive or diabetic patients with heart failure.
• Slow progression of left ventricular hypertrophy.
• Adverse Effects: Fatigue, Dizziness, Headache, Mood changes, Impaired taste, Possible hyperkalemia, Dry, nonproductive cough, which reverses when therapy is stopped, Angioedema is a rare but potentially fatal.
• Administration: Monitor potassium levels, watch for first does orthostatic hypotension. These drugs maybe be combined with hydrochlorothiazide. Notify providers if the patient reports a cough.

Angiotensin II Receptor Blockers

• Allow angiotensin I to be converted to angiotensin II, but block receptors.
• Block vasoconstriction and release of aldosterone.
• Hypertension and Stroke Prevention is treated by ARBs.
• Used mostly alone.
• Only patients who are unable to tolerate ACE inhibitors are prescribed ARBs.
• Doesn't preserve kidneys, doesn't cause a dry cough, and hyperkalemia is unlikely.

Calcium Channel Blockers

• Veramapil is drug used from this category.
• Causes decreased peripheral muscle tone leading to decreased blood pressure.
• Administer IV overtime and monitor BP.

Dirtect Renin Inhibitors

• Binds with renin to inhibit angiotension one decreasing the profection of angiotension II. and aldosterone.
• Treat hypertension, pregnancy risk.
• Monitor high fat meals as they interfere..

Vasodilators

• Used to treat Hypertension.
• Treat high BP with drugs, hydralazine HCI, ninoxidal, sodium nirtoprussibe.
• Sodium nitroglycerin and intravenous diazopside are reserved for hypertensive emergencies.