Pharmacology Chapter 22- Antihypertensive Drugs

Prodrugs

A drug that is inactive in its administered form and must be metabolized to its active form in the body, generally by the liver, to be effective.

Nebivolol (Bystolic)

A newer beta blocker. Beta 1 selective (cardio-selective) beta blocker. *Used to treat* hypertension, investigational for heart failure. In addition to blocking beta 1 receptors, it also produces vasodilation, which results in a decrease in systemic vascular resistance (SVR).

Key point

(Page 360) Always assess for the presence of contraindications, cautions, and potential drug interactions before administering any of the antihypertensive drugs. Contraindications include a history of MI or chronic renal disease. Cautious use is recommended in patients with renal insufficiency or glaucoma. Drugs that interact with antihypertensive drugs include other antihypertensive drugs, anesthetics, and diuretics.

Adverse effects and interactions of the use of Calcium Channel Blockers

*Adverse effects*- orthostatic hypotension, constipation, peripheral edema, bradycardia, reflex tachycardia. *Interactions*- beta blockers, grapefruit juice, digoxin.

Contraindications and adverse effects of Angiotensin Receptor Blockers (ARBs)

*Contraindications*- drug allergy, pregnancy, lactation; use cautiously in older adults and in patients with renal dysfunction. *Adverse effects-* angioedema, fetal harm, renal failure, hyperkalemia, chest pain, fatigue, hypoglycemia, diarrhea, UTI, anemia, and weakness.

Categories of Antihypertensives

1. Adrenergics (many sub classes) 2. Angiotensin-converting enzyme inhibitors 3. Angiotensin II blockers 4. Direct renin inhibitors 5. Aldosterone antagonists 6. Calcium channel blockers 7. Direct acting vasodilators 8. Diuretics

Possibly nursing diagnoses for a patient with hypertension

1. Ineffective peripheral tissue perfusion r/t the impact of the hypertensive disease process and/or possible severe hypotensive adverse effects associated with antihypertensive drug therapy. 2. Sexual dysfunction r/t adverse effects of some antihypertensive drugs. 3. Constipation r/t adverse effects of some antihypertensive drugs. 4. Noncompliance with drug therapy r/t lack of familiarity with or acceptance of the disease process. 5. Risk for injury r/t possible antihypertensive drug-induced orthostatic hypotension with dizziness and syncope.

Angiotensin II

A potent vasoconstrictor activated by renin; also triggers release of aldosterone.

Aliskiren (Rasilez, Tekturna)

Direct Renin Inhibitor. Approved only for hypertension. Route- P.O., avoid high fat foods/meals. *Adverse effects-* angioedema, cough, diarrhea, hyperkalemia. *Black box alert*- fetal injury/harm.

When giving antihypertensive drugs, the nurse will consider giving the first dose at bedtime for which class of drugs? A. Alpha blockers such as doxazosin. B. Diuretics such as furosemide. C. ACE inhibitors such as captopril. D. Vasodilators such as hydralazine.

A. Alpha blockers such as doxazosin.

A beta 1 blocker is prescribed for a patient with heart failure and hypertension. Which adverse effects, if present, may indicate a serious problem is developing while the patient is taking this medication? (Select all that apply) A. Edema B. Nightmares C. Shortness of breath D. Nervousness E. Constipation

A. Edema C. Shortness of breath

A patient is being treated for a hypertensive emergency. The nurse expects which drug to be used? A. Sodium nitroprusside B. Losartan C. Captopril D. Prazosin

A. Sodium nitroprusside

Direct Renin Inhibitor

Acts on renin to inhibit the conversion of angiotensin to angiotensin I. Example drug- Aliskiren

Nursing implications

Always take BP and heart rate before giving any antihypertensive (parameters are usually set by the prescriber, HR should be > 60 and BP > 100 systolic. Always monitor for side effects. Monitor lab values.

Therapeutic effects of antihypertensives

An improvement in blood pressure and in the disease process. A return to a normal baseline level of blood pressure with improved energy levels and decreased signs and symptoms of hypertension, such as less edema, improved breath sounds, no abnormal heart sounds, capillary refill in less than 5 seconds, and less shortness of breath.

A 46-year-old man started antihypertensive drug therapy 3 months earlier and is in the office for a follow-up visit. While the nurse is taking his blood pressure, he informs the nurse that he has had some problems with sexual intercourse. Which is the most appropriate response by the nurse? A. "Not to worry. Eventually, tolerance will develop." B. "The physician can work with you on changing the dose and/or drugs." C. "Sexual dysfunction happens with this therapy, and you will learn to accept it." D. "This is an unusual occurrence, but it is important to stay on your medications."

B. "The physician can work with you on changing the dose and/or drugs."

A patient has a new prescription for an ACE inhibitor. During a review of the patient's list of current medications, which would cause concern for a possible interaction with this new prescription? (Select all that apply) A. A benzodiazepine taken as needed for allergies. B. A potassium supplement taken daily. C. An oral anticoagulant taken daily. D. An opioid used for occasional severe pain. E. An NSAID taken as needed for headaches.

B. A potassium supplement taken daily. E. An NSAID taken as needed for headaches.

The nursing is administering antihypertensive drugs to older adult patients. The nurse knows which adverse effect is of most concern for these patients? A. Dry mouth B. Hypotension C. Restlessness D. Constipation

B. Hypotension

A patient with type 2 diabetes mellitus has developed hypertension. What is the blood pressure goal for this patient? A. Less than 110/80 mmHg. B. Less than 130/80 mmHg. C. Less that 130/84 mmHg. D. Less that 140/90 mmHg.

B. Less than 130/80 mmHg.

Angiotensin Receptor Blockers (ARBs)

Block the *actions* of angiotensin II (ACE inhibitors block the *production* of angiotensin II). Effects are much like those of ACE inhibitors, but do not increase bradykinin (thus less incidence of a cough). *Therapeutic uses:* hypertension, heart failure, diabetic neuropathy, stroke prevention, prevent mortality following MI.

When a patient is being taught about the potential adverse effects of an ACE inhibitor, which of these effects should the nurse mention as possibly occurring when this drug is taken to treat hypertension? A. Diarrhea B. Nausea C. Dry, nonproductive cough D. Sedation

C. Dry, nonproductive cough

Calcium Channel Blockers

Block calcium channels in blood vessels (vascular smooth muscles), which causes vasodilation in arterioles (little to no effect in veins). *Therapeutic uses:* hypertension, angina, cardiac dysrhythmias.

Aldosterone Antagonist

Block receptors of aldosterone. Example drug- Eplerenon

Verapamil (Calan, Isotopin)

Blocks calcium channels in the heart and blood vessels. The following occurs- - vasodilation - increased coronary artery perfusion *Indicated for* hypertension, angina, cardiac dysrhythmias. Administered P.O. or IV, extensive first pass through the liver. *Adverse effects:* edema, constipation, bradycardia, flushing, decreased conduction, headache. *Interactions:* beta blockers, grapefruit juice, digoxin.

Cultural implications

Both thiazide-type diuretics and calcium channel blockers (CCBs) are recommended as first-line therapy for management of HTN in black patients. Asian patients receiving a CCB have been reported as achieving the highest rates of control of HTN. ARBs and ACEIs appear to have tolerability and/or adherence advantages. Asian patients have increased risk of occurrence of serious side effects with diuretic use.

The most common adverse effects of adrenergic drugs are-

Bradycardia with reflex tachycardia. Postural and postexercise hypotension. Dry mouth Drowsiness, dizziness. Depression Edema Constipation Sexual dysfunction Other- headache, sleep disturbances, nausea, rash, and palpitations.

A 46-year-old man has been taking clonidine for 5 months. For the past 2 months, his blood pressure has been normal. During this office visit, he tells the nurse that he would like to stop taking the drug. What is the nurse's best response? A. "I'm sure the doctor will the stop it — your blood pressure is normal now." B. "Your doctor will probably have you stop taking the drug for a month, and then we'll see how you do." C. "This drug should not be stopped suddenly; let's talk to your doctor." D. "It's likely that you can stop the drug if you exercise and avoid salty foods."

C. "This drug should not be stopped suddenly; let's talk to your doctor."

Given the nurse's knowledge of the side effects of alpha blockers, which instruction should the nurse provide to the patient with a new order for an alpha blocker to treat hypertension? A. Drink plenty of fluids. B. Wear sunscreen outside. C. Change positions slowly. D. Increase intake of potassium-rich foods.

C. Change positions slowly.

The nurse is obtaining a drug history on the patient being treated for hypertension. The prescriber has chosen the angiotensin receptor blocker losartan (Avapro) to treat the patient's hypertension. Which drug on the patient's current drug list would most concern the nurse? A. Furosemide B. Albuterol C. Ibuprofen D. Augmentin

C. Ibuprofen (An NSAID)

Examples of Angiotensin-Converting Enzyme (ACE) Inhibitors

Captopril Enalapril Fosinopril Lisinopril Moexipril Ramipril

Direct-acting vasodilators

Cause direct vasodilation of peripheral arteries and veins. Example drugs- Hydralazine, Sodium nitroprusside, Minoxidil.

Sodium Nitroprusside (Nipride)

Causes arterial and venous dilation. Administered via IV only; effect begins immediately. *Adverse effects:* reflex tachycardia, excessive hypotension, cyanide poisoning (delirium, hallucinations). *Black box alert*: should only be mixed with D5W. Fresh solutions may appear faint brown in color; solutions that are deeply colored should be discarded. Protect from light when administering. Max rate of 10 mcg/kg/min (max rate can only be for 10 min. Do not mix with other drugs.

Hydralazine (Apresoline)

Causes selective dilation of arterioles, has little or no effect on veins. Occurs from direct action on vascular smooth muscle. Metabolism occurs by acetylation and is highly variable among patients. *Used to treat:* essential hypertension, hypertensive crisis, heart failure. *Adverse effects:* lupus-like syndrome (fever, joint pain, rash), reflex tachycardia, fluid retention, neutropenia, hemoglobin. Available P.O. and IV (IV reserves for treating hypertensive crisis).

Clonidine (Catapres)

Centrally acting alpha 2 receptor agonist. Highly lipid soluble. *Approved for* hypertension (HTN), severe pain, and ADHD. Off-label or investigational uses: migraine prevention, opioid withdrawal, Tourette's. *Adverse effects:* dry mouth, constipation, nightmares, sedation, rebound hypertension (if abruptly d/c), sexual dysfunction. Usually administer twice a day (BID); available as a transdermal patch. *Safety measures:* take 2nd dose at bedtime, monitor blood pressure, change positions slowly; use hard candy, gum, and increase fluid intake.

The nurse is assessing a patient who will be starting antihypertensive therapy with an ACE inhibitor. Which condition, if present in the patient, would be a reason for cautious use? A. Asthma B. Rheumatoid arthritis C. Hyperthyroidism D. Renal insufficiency

D. Renal insufficiency

A patient in her eighth month of pregnancy has preeclampsia. Her blood pressure is 210/100 mmHg this morning. This type of hypertension is classified as which of the following? A. Primary B. Idiopathic C. Essential D. Secondary

D. Secondary

Nifedipine (Procardia)

Differs from verapamil and diltiazem in that it does not produce blockade of calcium channels in the heart, only in the periphery (therefore it is not used for dysrhythmias). Causes vasodilation by blocking calcium channels in the peripheral arterioles. Activates the baroreceptor reflex (reflex tachycardia)- can combine with a beta blocker to prevent it. Used for angina and hypertension. Adverse effects are similar to verapamil and diltiazem, except it causes *reflex tachycardia* instead of bradycardia or heart block.

Contraindications for use of adrenergic antihypertensives

Drug allergy Acute heart failure Concurrent use of monoamine oxidase inhibitors (MAOIs) Peptic ulcer Severe liver or kidney disease Asthma (with use of any non-selective beta blockers)

Contraindications to the use of Angiotensin-Converting Enzyme (ACE) Inhibitors

Drug allergy Patients with a high baseline potassium level. Lactating women Children Patients with bilateral renal artery stenosis.

Adverse effects of Angiotensin-Converting Enzyme (ACE) Inhibitors

Dry cough Taste impairment Rash Angioedema Hyperkalemia Agranulocytosis

Secondary hypertension

High blood pressure caused by another disease such as renal, pulmonary, endocrine, or vascular disease. May also result from the use of certain medications.

Essential hypertension

High blood pressure with no known cause. 90% of cases are this type. Also called primary or idiopathic hypertension.

Examples of Angiotensin Receptor Blockers (ARBs)

Losartan Candesartan Irbesartan Olmesartan Valsartan

Black box warning for Angiotensin-Converting Enzyme (ACE) Inhibitors

May cause fetal malformation if taken in the 2rd or 3rd trimester of pregnancy.

Interactions for use of Angiotensin-Converting Enzyme (ACE) Inhibitors

NSAIDs, other anti-hypertensives, diuretics, lithium, drugs that raise potassium levels, ETOH.

Propranolol (Inderal)

Non-selective beta blocker. Can decrease BP by blocking renin release from the kidney, and reducing heart rate (which decreases O2 demand on the heart). Highly lipid soluble. *Adverse effects*: bradycardia, AV heart block, heart failure, rebound cardiac excitation, bronchoconstriction, inhibition of glycogenolysis. *Cautious use with* diabetics, respiratory patients, and heart failure patients. *Interactions:* calcium channel blockers, insulin. *Black box warning*- taper slowly to avoid rebound cardiac excitation.

Minoxidil

Only used for patients with severe hypertension that is unresponsive to safer drugs, causes more intense vasodilation, but also has more severe side effects. *Adverse effects:* tachycardia, Na and H2O retention, hypertrichosis (hair growth), and rarely pericardial effusion. *Black box alert*- pericarditis. Cardiac tamponade. PO and topical formulations.

Drug interactions with Angiotensin Receptor Blockers (ARBs)

Other anti-hypertensives Picture (page 351)

Normal regulation of blood pressure and corresponding medications (picture)

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Adrenergic drugs: Drug interactions (picture)

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Doxazosin (Cardura, Cardura XL)

Peripherally acting alpha 1 receptor antagonist (blocker). Used for hypertension. *Adverse effects:* orthostatic hypotension, reflex tachycardia, first dose effect, nasal congestion, sexual dysfunction. P.O. only (immediate or extended release). Other anti-hypertensives can intensify hypotensive effects. Educate patients that when the drug is released from the extended-release form, the matrix of the capsule is expelled in the stool.

Carvedilol (Coreg)

Peripherally acting dual alpha 1 and beta receptor blocker. Dilates arterioles and veins, blocks beta 1's on the kidney and heart. *Used to treat* mild to moderate heart failure, hypertension, and angina. *Adverse effects:* mild. Similar to those of both alpha and beta blockers. Give with food. Full effects take 2-3 weeks. Contraindications: drug allergy, cardiogenic shock, severe bradycardia or heart failure, bronchospastic conditions such as asthma, and various cardiac problems involving the conduction system.

Angiotensin-Converting Enzyme (ACE) Inhibitors

Reduces levels of angiotensin II (a vasoconstrictor) and increases levels of bradykinin (a potent vasodilator). *Therapeutic uses:* hypertension, heart failure, nephropathy, high risk cardiovascular patients. All are P.O. (enalapril is the only one available in IV form). Many combination products are available.

Lab values to monitor

Renal labs- BUN (5-25 mg/dL) and creatinine (0.5-1.2 mg/dL). Liver enzymes. WBC (5-10,000/mm3)

Diltiazem (Cardizem)

Same effects as verapamil. First pass effect. Similar adverse effects, except less chance of constipation. *Interactions:* digoxin, grapefruit juice. *Indications:* hypertension, angina, anti-dysrhythmia.

Eplerenon (Inspra)

Selective aldosterone blocker (antagonist). Used for hypertension and heart failure. Well tolerated. Hyperkalemia is the greatest risk. Interacts with drugs that can raise potassium levels, erythromycin, protease inhibitors, verapamil, azole antifungals, lithium, NSAIDs.

Metoprolol (Lopressor, Toprol)

Selective beta 1 blocker (cardio-selective). *Adverse effects:* bradycardia, reduced cardiac output, AV heart block, heart failure., lethargy, fatigue Safer for respiratory and diabetic patients. *Black box warning-* rebound cardiac excitation when abruptly d/c.

Patient teaching

Take meds exactly as prescribed, never abruptly withdrawal (rebound hypertension). Compliance is key to effective management of hypertension. Stress safety precautions. Wear a medical alert bracelet. Teach how to take blood pressure before taking a BP med. Change positions slowly. Schedule periodic eye exams. Just because you feel good, does not mean you can stop taking the meds. Discuss side effects with provider (sexual dysfunction).

Blood pressure is determined by-

The product of cardiac output (4 to 8 L/min) x systemic vascular resistance (SVR). *Cardiac output* is the amount of blood that is ejected from the left ventricle. *SVR* is the resistance to blood flow that is determined by the diameter of the blood vessel and the vascular musculature.

Examples of Calcium Channel Blockers

Verapamil Nifedipine Diltiazem Other: amlodipine, felodipine, nicarpidine