Hypertension and Drug Therapy

• Hypertension and drug therapy.

Blood Flow Through the Heart

• Superior vena cava(from upper body) drains into the Right atrium (1).
• The tricuspid valve leads to the Right ventricle (2).
• The pulmonary valve carries blood to the pulmonary artery (6)
• The pulmonary artery leads to Left and Right lungs
• Blood returns from the lungs to the left atrium via the pulmonary veins (3).
• The mitral valve then brings blood to the left ventricle (4)
• The blood leave the heart through the aortic valve(5) to the aorta (to body)

Mechanical System

• Systole: Contraction of myocardium.
• Diastole: Relaxation of myocardium.
• Cardiac output is the amount of blood pumped by each ventricle in 1 minute.
• CO = SV(stroke volume) × HR (heart rate).

Factors Influencing Blood Pressure

• Blood Pressure = Cardiac Output × Systemic Vascular Resistance
• Systemic vascular resistance includes dilation of blood vessels and the amount of blood pumping through the heart

Evidence Based Guidelines for Blood Pressure Management

• Hypertension management involves categorization into four stages based on BP measurements.
• The stages are normal, elevated, stage 1, stage 2, and hypertensive crisis.
• Elevated systolic blood pressure (SBP) has strong correlation to heart failure, stroke, and renal failure.
• "Prehypertensive" BPs are no longer considered "high normal” and require lifestyle modifications to prevent cardiovascular disease.
• Thiazide-type diuretics can reduce blood volume being pumped, they should be the initial drug therapy for most patients with HTN.
• Joint National Committee on Prevention and Detection for Blood Pressure Management guidelines were updated in 2017.

Etiology of Hypertension

• Primary (essential/idiopathic) hypertension is elevated BP without an identifiable cause, accounting for 90% to 95% of cases.
• Contributing factors include:
  • Increased sodium-retaining hormones and vasoconstrictors
  • Diabetes mellitus
  • Greater than ideal body weight
  • Increased sodium intake
  • Excessive alcohol intake

Risk Factors for Primary Hypertension

• Risk factors include:
  • Age (vessels become more rigid with age)
  • Alcohol
  • Cigarette smoking
  • Diabetes mellitus (changes elasticity vessels)
  • Elevated serum lipids
  • Excess dietary sodium
  • Gender
  • Family history
  • Obesity
  • Ethnicity
  • Sedentary lifestyle
  • Socioeconomic status
  • Stress

Pathophysiology of Primary Hypertension

• Genetic factors have little contribution to BP levels in the general population.
• Increased Stress and SNS activity causes:
  • Increased vasoconstriction
  • Increased HR
  • Increased Renin release

Pathophysiology of Primary Hypertension

• Water and sodium retention causes:
  • High sodium intake may activate a number of pressor mechanisms, resulting in water retention.
  • Certain demographics are associated with "salt sensitivity", specifically patients with:
    • Obesity
    • Increased age
    • African American ethnicity
• Insulin resistance and hyperinsulinemia causes:
  • High insulin concentration stimulates SNS activity and impairs nitric oxide-mediated vasodilation
  • which Results in elevated blood pressure

Etiology of Hypertension

• Secondary hypertension involves Elevated BP with a specific cause, accounts for 5% to 10% of adult cases.
• Contributing factors for secondary hypertension include:
  • Coarctation of aorta
  • Renal disease
  • Endocrine disorders (hormone imbalances)
  • Neurologic disorders
  • Cirrhosis
  • Sleep apnea

Hypertension Clinical Manifestations

• Hypertension development is very insidious.
• 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
  • Dyspnea

Hypertension Complications

• Target organ diseases from hypertension occur most frequently in the:
  • Heart
  • Brain
  • Peripheral vasculature
  • Kidney (preserves blood flow to heart and brain)
  • Eyes

Hypertension Complications

• Resultant Hypertensive heart disease can cause:
  • Coronary artery disease
  • Left ventricular hypertrophy (thickening)
  • Heart failure.

Hypertension Collaborative Care

• Overall goals:
  • Control blood pressure
  • Reduce CVD risk factors
• Drug therapy primary mechanism of action includes drugs to treat hypertension.
  • Reduce SVR
  • Reduce volume of circulating blood

Antihypertensive Drugs

• Categories:
  • Diuretics
  • Adrenergic drugs
  • Angiotensin converting enzyme (ACE) inhibitors
  • Angiotensin II receptor blockers (ARBs)
  • Calcium channel blockers (CCBs)
  • Direct renin inhibitors
  • Vasodilators

Diuretics

• Decrease plasma and extracellular fluid volumes.
• Results includes Decreased preload, cardiac output, and total peripheral resistance.
• Overall effect involves decreased workload of the heart, and decreased blood pressure.

Thiazide Diuretics

• Prototype drug is Hydrochlorothiazide.
• First-line Treatment for Hypertension.
• Mechanism of Action:
  • Site of action is on the distal convoluted tubule of the kidney.
  • It inhibits the reabsorption of sodium, potassium, and chloride.
  • This results in osmotic water loss.
  • Directly relaxes the small blood vessels which reduces peripheral vascular resistance (afterload).
• Indications for Use:
  • Heart failure
  • Hypertension
  • Edema
  • Hypercalciuria
  • Diabetes insipidus
• Contraindications:
  • Drug allergy
  • Anuria
  • Renal failure

Thiazide Diuretics: Adverse Effects

• Body System 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 of medications can result in severe hypokalemia with symptoms such as lethargy, muscle weakness, confusion and severe hypotension.

Adrenergic Drugs ‘Sympathomimetics’

• Bind to adrenergic receptors, but inhibit (block stimulation) of the sympathetic nervous system (SNS).
• Inhibit or lyse sympathetic stimulation
• There are Alpha-blockers and beta-blockers
• Classified by the type of adrenergic receptor they block.
  • Examples are:
    • Alpha1 and alpha2 receptors- located in the cardiac muscle
    • Beta1 and beta2 receptors
• Multiple sub-groups may cause drowsiness/sedation
• There are Centrally acting alpha2 agonists
• Peripherally acting alpha adrenergic blockers
• Beta Blockers

Adrenoceptors

• Alpha 1:
  • Responsible for vasoconstriction and increased peripheral resistance.
  • Leads to increased blood pressure and mydriasis.
  • Also increases the closure of internal sphincter of the bladder.
• Alpha 2:
  • Results in inhibition of norepinephrine, which inhibits vasoconstriction.
  • Also is responsible for the inhibition of acetylcholine release.
  • Leads to inhibition of insulin release
• Beta 1:
  • Results in tachycardia and an increased myocardial contractility.
  • Also increases the release of renin.
• Beta 2:
  • Results in vasodilation, slightly decreased peripheral resistance, and bronchodilation.
  • Also increases muscle and liver glycogenolysis and release of glucagon.
  • Promotes relaxed uterine smooth muscle

Adrenergic Drugs: Centrally Acting alpha2 agonists

• The prototype drug is Clonidine (Catapres).

• Other Medications include methyldopa (Aldomet).

• Mechanism of Action includes stimulation of alpha2-adrenergic receptors in the brain.

  • This causes decreased sympathetic outflow from the CNS.
  • Leads to decreased norepinephrine production. -Stimulates alpha2-adrenergic receptors, thus reducing renin activity in the kidneys:

• Ultimately Results in decreased blood pressure

• Indications include treatment for:

  • Hypertension
  • Clonidine is useful in the management of withdrawal symptoms in opioid- or nicotine-dependent persons
  • Can be used for hypertension in pregnancy (Methyldopa)

Adrenergic Drugs: Centrally Acting alpha2 agonists

• Contraindications: should be used cautiously in patients who have had stroke, recent MI, major depressive disorder and chronic renal failure
• Adverse Effects/Side Effects includes:
  • Drowsiness and Sedation.
  • Dry Mouth.
  • Rebound Hypertension.
• Nursing Administration:
  • Can be 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

• The prototype drugs are doxazosin mesylate (Cardura) and terazosin (Hytrin).
• Mechanism of Action involves blocking alpha1-adrenergic receptors that cause vasoconstriction.
• This Causes both arterial and venous dilation, reducing peripheral vascular resistance and BP, ultimately reducing blood pressure
• Indications include:
  • Used to treat hypertension.
  • Tamulosin (Flomax) Effect on receptor on prostate gland and bladder decreases resistance to urinary outflow, reducing urinary obstruction and relieving effects of BPH.
• Contraindications include:
  • Hypotension.
  • Angina, renal insufficiency.
• Nursing Administration include:
  • First dose often at night
  • Teach safety measures.

Alpha-Blockers: Adverse Effects

• Body System and 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

• Beta blockers block stimulation of beta receptors in the SNS
• These medications Complete with norepinephrine and epinephrine
• Can be selective or nonselective
• Nonselective beta-blockers block both beta₁ and beta2 receptors

Beta Receptors

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

Beta-blockers Mechanism of Action

• They reduce BP by reducing heart rate through beta1-blockade.
• They cause reduced secretion of renin.
• Long-term use causes reduced peripheral vascular resistance.
• Results in decreased blood pressure

Adrenergic Drugs: Beta Blockers

• Cardioselective (Beta 1):
  • Reduce SNS stimulation of the heart.
  • Decrease heart rate.
  • Prolong SA node recovery.
  • Slow conduction rate through the AV node.
  • Decrease myocardial contractility = reducing myocardial oxygen demand.
• 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.
  • Reduce heart rate owing to B1-blockade.

Indications

• Angina: Decreases demand for myocardial oxygen.
• Cardioprotective: Inhibits stimulation from circulating catecholamines, gives post MI- reduces risk of post MI cardiac arrest.
• Dysrhythmias
• Migraine headaches
• Antihypertensive
• Heart failure
• Glaucoma (topical use)

Beta-Blockers: Examples

• carvedilol (Coreg)
• labetalol (Normodyne)
• metoprolol (Lopressor)
• atenolol (Tenormin)
• esmolol (Brevibloc)
• propranolol (Inderal)

Adverse Effects: Beta-Blockers

• Body System Adverse Effects:
  • Blood :Thrombocytopenia
  • Cardiovascular :AV (heart)block, bradycardia (due to slowing heart rate), heart failure, peripheral vascular insufficiency
  • CNS: Dizziness, mental depression (excitability decreases), lethargy, hallucinations, unusual dreams
  • Gastrointestinal Nausea, dry mouth, vomiting, diarrhea, cramps, 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

Beta-Blocking Drugs: Nursing Implications

• Inform patients to report the following to their physician:
  • Weight gain greater than 2 pounds in 1 day or 5 pounds in 1 week, due to fluid shifting.
  • 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 effect from use of adrenergic drugs is orthostatic hypotension.
• Other side effects:
  • Dry mouth
  • Drowsiness, sedation, produces this CNS effect.
  • Constipation
  • Headaches
  • Sleep disturbances
  • Nausea
  • Rash (allergy)
  • Cardiac disturbances (palpitations)

Adrenergic-Blocking Drugs: Nursing Implications

• Assess for allergies and history of COPD, hypotension, cardiac dysrhythmias, bradycardia or heart failure
• Assess for preexisting condition that might be exacerbated by the use of these drugs, might be a contraindication to their use
• Alpha-blockers may precipitate hypotension
• Beta-blockers may precipitate:
  • Bradycardia
  • Hypotension
  • Heart block
  • Heart failure
  • Bronchoconstriction

Adrenergic-Blocking Drugs: Nursing Implications

• 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
  • Oral hypoglycemic drugs
• Should trigger the sympathetic nervous system

Adrenergic-Blocking Drugs: Nursing Implications

• Teach patients to change positions slowly to prevent or minimize postural hypotension
• Instruct patients to avoid caffeine (stimulants) (excessive irritability)
• Instruct patients to avoid alcohol ingestion and hazardous activities until blood levels become stable
• Instruct patients to notify their physician if palpitations, dyspnea, nausea, or vomiting occurs
• Monitor for adverse effects
• Monitor for therapeutic effects with:
  • BP & HR control

Angiotensin Converting Enzymes ACE Inhibitors

• They are a large group of drugs, often used as first-line drugs for HF and hypertension.
• May be combined with a thiazide diuretic or calcium channel blocker.
• Prototype drug is captopril (Capoten) -very short half life.
• enalapril (Vasotec)and lisinopril (Prinivil and Zestril) are examples of ACE inhibitors.
• Mechanism of Action involves that they work on angiotensin I to prevent angiotensin II.
  • They Block angiotensin-converting enzyme, thus preventing the formation of angiotensin II.
  • Prevent the breakdown of the vasodilating substance, bradykinin
  • Result in decreased systemic vascular resistance (afterload), vasodilation, and therefore decreased blood pressure

ACE Inhibitors

• Indications:
  • Hypertension
  • Heart failure
    • May be used alone or in combination with diuretics or other drugs
    • Special considerations:
      • Slow progression of left ventricular hypertrophy after MI cardioprotective
      • Renal protective effects in patients with diabetes- extends life of kidneys
    • Drugs of choice:
      • Hypertensive patients with Heart failure
      • Diabetic patients

ACE Inhibitors: Adverse Effects

• Fatigue
• Dizziness
• Headache
• Mood changes
• Impaired taste
• Possible hyperkalemia!
• Dry, nonproductive cough, which reverses when therapy is stopped
• Angioedema: rare but potentially fatal

ACE Inhibitors Nursing Administration

• Administered orally, except for enalaprilat (Vasotec IV)
• Ace inhibitors may be combined with hydrochlorothiazide
• Notify providers if cough, rash, and or signs of infection occur.
• First dose orthostatic hypotension may occur
• Monitor potassium levels

Angiotensin II Receptor Blockers (ARBS)

• They are a newer class of drugs
• Well tolerated and does not typically cause a dry cough
• Examples are losartan (Cozaar, Hyzaar), valsartan (Diovan), and irbesartan (Avapro)
• These drugs may not preserve kidneys or heart
• Mechanism of Action:
  • Allow angiotensin I to be converted to angiotensin II but block the receptors that receive angiotensin II.
  • Block vasoconstriction and release of aldosterone
• Indications:
  • Hypertension
  • Stroke Prevention
  • Adjunctive drugs for the treatment of HF
  • May be used alone or with other drugs such as diuretics
  • Used primarily in patients who cannot tolerate ACE inhibitors

Angiotensin II Receptor Blockers (ARBS)

• Adverse Effects:
  • Upper respiratory infections
  • Headache
  • May cause occasional dizziness, inability to sleep, diarrhea, dyspnea, heartburn, nasal congestion, back pain, fatigue
  • Hyperkalemia much less likely to occur
• Nursing Administration:
  • Orally administered
  • May be combined with hydrochlorothiazide
  • Can be taken with or without food

Calcium Channel Blockers

• Examples: verapamil (Calan), diltiazem (Cardizem), Nifedipine (Aldat), amlodipine (Norvasc), felodipine (Plendil), nicardipine (Cardene)
• Mechanism of Action:
  • Smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction
• Decreased effects include:
  • Peripheral smooth muscle tone
  • Systemic vascular resistance
  • Blood pressure

Calcium Channel Blockers

• Indications:
  • Hypertension
  • Dysrhythmias
  • Angina
  • Migraine headaches
  • Raynaud's disease
• Adverse Effects:
  • Cardiovascular: Hypotension, palpitations, tachycardia-compensates for hypotension
  • Gastrointestinal: Constipation, nausea
  • Other: rash, flushing, peripheral edema -Nursing Administration:
  • Do not chew or crush extended release tablets
  • IV administration of verapamil should be over 2 to 3 minutes
  • Monitor blood pressure, and chest pain

Direct Renin Inhibitors

• Example: Aliskiren (Tekturna).
• Mechanism of action: Binds with renin to inhibit production of angiotensin I, thus decreasing production of both angiotensin II and aldosterone.
• Indications:
  • Hypertension
• Adverse Effects: -Allergic reaction -Hyperkalemia -Diarrhea
• Contraindications: -Pregnancy risk during 2 and 3 trimesters -Hyperkalemia
• Nursing Considerations: -High fat meals interfere with absorption -May be taken alone or in combination with other medications

Vasodilators: Indications

• Treatment of hypertension
• May be used in combination with other drugs
• Examples: -hydralazine HCI (Apresoline) -minoxidil (Loniten) -sodium nitroprusside (Nipride, Nitropress)
• Sodium nitroprusside and intravenous diazoxide are reserved for the management of hypertensive emergencies

Vasodilators: Mechanism of Action

• Directly relax arteriolar and/or venous smooth muscle
• Results in:
• Decreased systemic vascular response
• Decreased afterload
• Peripheral vasodilation

Vasodilators Contraindications

• Drug allergy
• Hypotension
• Cerebral edema/ head injury, vasodilation causes fluid leak
• Acute MI
• Coronary artery disease
• Heart failure

Vasodilators: Adverse Effects

• hydralazine
  • Dizziness
  • Headache
  • Anxiety
  • Tachycardia -compensates for hypotension
  • Nausea/vomiting
  • Diarrhea
  • Anemia
  • Dyspnea
  • Edema
  • Nasal congestion
• sodium nitroprusside
  • Bradycardia
  • Hypotension
  • Delirium
  • Possible cyanide toxicity (rare)

Vasodilator Toxicity

• Main symptom: Hypotension which is refractory and may be difficult to solve.
• Treatment:
  • Trendelenburg position- supports blood flow to head
  • Supportive and Symptomatic treatment
  • IV fluids
  • Sympathomimetics (dopamine and norepinephrine) usage to increase BP

SDOH

• Social determinants of health include:
  • Low education, low SES
  • Poverty
  • Poor neighborhoods
  • Diet high in processed foods
  • Stressful environments
  • Alcohol use, smoking, lack of physical activity
  • 36% of adults in Monroe County have HTN
  • 14605 is the poorest zip code in Rochester
• Costs of medications per month:
  • Metropolol (generic) - $5 per month
  • Hydrochlorothiazide - $17 per month
  • Captopril - $23 per month
  • Verapamil - $10 per month

Nursing Implications

• Before beginning therapy, obtain a thorough health history and head-to-toe physical examination
• Assess for contraindications to specific antihypertensive drugs
• Assess for conditions that require cautious use of these drugs
• Educate patients about the importance of not missing a dose and taking the medications exactly as prescribed
• Instruct patients to check with their physician for instructions on what to do if a dose is missed; patients should never double up on doses if a dose is missed
• Monitor BP during therapy; instruct patients to keep a journal of regular BP checks

Nursing Implications

• Instruct patients that these drugs should not be stopped abruptly because this may cause a rebound hypertensive crisis, and perhaps lead to 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
• Instruct patients to avoid smoking and eating foods high in sodium
• Encourage supervised exercise

Nursing Implications

• Teach patients to change positions slowly to avoid syncope from postural hypotension
• Instruct patients to 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
• Male patients who take these drugs may not be aware that impotence is an expected effect, and this may influence compliance with drug therapy
• If patients are experiencing serious adverse effects, or if they believe the dose or medication needs to be changed, they should contact their physician immediately

Nursing Implications

• 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 over-the-counter drugs, without first getting the approval of their physician
• Educate patients about lifestyle changes that may be needed
  • Weight loss
  • Stress management
  • Supervised exercise
  • Dietary measures

Nursing Implications

• Monitor for adverse effects
  • Dizziness
  • Orthostatic hypotension
  • Fatigue
  • Toxic effects
• Monitor for therapeutic effects
  • Blood pressure should be maintained at less than 130/90 mm Hg
  • If a patient with hypertension also has diabetes or renal disease, the BP goal is less than 130/80 mm Hg (JNC-7)

Gerontologic Considerations

• Age alters the cardiovascular response to physical and emotional stress.
• Heart valves become thick and stiff.
• Frequent need for pacemakers
• Less sensitive to ẞ-adrenergic agonist drugs
• Increase in SBP; decrease or no change in DBP

Cultural Considerations

• Beta-blockers and ACE inhibitors have been found to be more effective in white patients than in African American patients
• CCBs and diuretics have been shown to be more effective in African American patients than in white patients