Chapter 22: Antihypertensive Drugs
 Blood pressure (BP) = CO × SVR
 CO = cardiac output- the amount of blood ejected from the left ventricle per
minute (in liters/minute)
 SVR = systemic vascular resistance- the resistance to blood flow that is
determined by the diameter of the blood vessel and the vascular musculature
 60 years or older: systolic blood pressure (SBP) of greater than 150/90 mm Hg
 Younger than 60 years and those who have chronic kidney disease or diabetes: 140/90
 Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure (JNC-8)*
Four stages based on BP measurements
1.
Normal (Systolic <120 and Diastolic <80)
2.
Prehypertension (120-139 or 80-89)
3.
Stage 1 hypertension (140-159 or 90-99)
4.
Stage 2 hypertension (>160 or >100)
 Classification of Blood Pressure
 Unknown cause
 Essential, idiopathic, or primary hypertension: 90% of cases

Known cause
 Secondary hypertension: 10% of cases
 Pharmacology Overview
 Drug therapy for hypertension must be individualized.
 Seven main categories of drugs to treat hypertension
 Diuretics (only non-vasodilator)
 Adrenergic drugs
 Vasodilators
 Angiotensin-converting enzyme (ACE) inhibitors
 Angiotensin II receptor blockers (ARBs)
 Calcium channel blockers (CCBs)
 Direct renin inhibitors (Aliskiren black box pregnancy)
 Autonomic Nervous System
 Parasympathetic nervous system (PNS)
 Stimulates smooth muscle, cardiac muscle, glands
 Muscarinic or cholinergic and nicotinic receptors
 Stimulated: acetylcholine, cholinergic agonist
 Inhibited: anticholinergic drugs
 Sympathetic nervous system (SNS)
 Stimulates the heart, blood vessels, skeletal muscle
 Adrenergic or noradrenergic receptors and nicotinic sweat gland receptors
 Stimulated: adrenergic agonist, epinephrine and norepinephrine
 Inhibited: antiadrenergic (adrenergic blocker, alpha or beta blocker
Adrenergic Drugs: Five Subcategories (central=brain, peripheral=heart, blood vessels)
 Centrally Acting Adrenergic Drugs
 Clonidine and methyldopa
 Stimulate alpha2-adrenergic receptors in brain: reducing renin activity at kidneys
 Decrease sympathetic outflow from the CNS, norepinephrine production
 Result in decreased BP
 Methyldopa commonly used for HTN in pregnancy
 This class not used as first-line treatment due to high incidence of unwanted
side effects: orthostatic hypotension, fatigue, and dizziness
 Used with diuretics
 Peripherally Acting Alpha1 Blockers
 Block alpha1-adrenergic receptors = BP is decreased.
 Increase urinary flow rates and decrease outflow obstruction by preventing
smooth muscle contractions in the bladder neck and urethra.
 doxazosin (Cardura)
 Reduce peripheral vascular resistance and BP= dilate arterial and venous blood
vessels
 Teach clients that when extended-release form is used, the matrix of the
capsule is expelled in the stool
 tamsulosin (Flomax)
 not used to control BP
 Use: benign prostatic hyperplasia (BPH)
 Dual-Action Alpha1 and Beta Receptor Blockers
 Dual antihypertensive effects of reduction in heart rate (beta1 receptor
blockade) and vasodilation (alpha1 receptor blockade)
 Carvedilol (Coreg)
 Widely used drug that is well tolerated
 Uses: hypertension, mild to moderate HF in conjunction with digoxin, diuretics,
and ACE inhibitors
 Contraindications: known drug allergy, cardiogenic shock, severe bradycardia or
HF, bronchospastic conditions such as asthma, and various cardiac problems
involving the conduction system
 Beta Blockers
 Propranolol, metoprolol, and atenolol
 Reduction of the heart rate through beta1 receptor blockade
 Cause reduced secretion of renin
 Long-term use causes reduced peripheral vascular resistance.
 Nebivolol (Bystolic)
 Uses: hypertension and HF
 Action: blocks beta1 receptors and produces vasodilatation, which results in a
decrease in SVR
 Less sexual dysfunction
 Do not stop abruptly; must be tapered over 1 to 2 weeks. (severe rebound
hypertension)
 Adrenergic Drugs: Indications
 All used to treat hypertension
 Glaucoma
 BPH: doxazosin, prazosin, and terazosin
 Management of severe heart failure (HF) when used with cardiac glycosides and
diuretics
 Adrenergic Drugs: Adverse Effects
 High incidence of orthostatic hypotension
 Most common
 Bradycardia with reflex tachycardia
 Dry mouth
 Drowsiness, sedation
 Constipation
 Depression
 Edema
 Sexual dysfunction
 Adrenergic Drugs: Interactions
 Adrenergic drugs can cause additive CNS depression when taken with alcohol,
benzodiazepines and opioids
 Beta blockers may cause an additive effect and may potentiate bradycardia when used
with clonidine
Angiotensin-Converting Enzyme (ACE) Inhibitors
 Large group of safe and effective drugs
 Often used as first-line drugs for HF and hypertension
 May be combined with a thiazide diuretic or a calcium channel blocker (CCB)
 ACE Inhibitors: Mechanism of Action
 Block ACE, thus preventing the formation of angiotensin II
 Angiotensin II is a potent vasoconstrictor and causes aldosterone secretion from the
adrenal glands.
 Prevents the breakdown of the vasodilating substance bradykinin
 Result in decreased SVR (afterload), vasodilation, and therefore decreased BP
 Aldosterone stimulates sodium and water resorption, which can raise blood pressure
 Treat heart failure (Drug of choice) (Cardioprotective)
 Diuresis: decreases blood volume and return to the heart
 kidney protection (reduce glomerular filtration pressure)
 Cardiovascular drugs of choice for patients with diabetes (prevent nephropathy)
 ACE Inhibitors: Adverse Effects
 Possible hyperkalemia (potassium level >5, do not give)
 Dry, nonproductive cough, which reverses when therapy is stopped
 First-dose hypotensive effect may occur
 Black Box Warning= Pregnant Women
 Captopril (Capoten)
 First available ACE inhibitor
 Shortest half-life: Must be administered multiple times throughout the day
 Not a pro-drug so liver function does not matter (+lisinopril)
 Enalapril (Vasotec)
 Only ACE inhibitor available in both oral and parenteral preparations.
 Enalapril intravenous (IV) does not require cardiac monitoring
 Oral enalapril: prodrug
Angiotensin II Receptor Blockers
 Angiotensin II Receptor Blockers: Mechanism of Action
 Block the binding of A-2 to the type 1 A-2 receptors: vascular smooth muscle and
the adrenal gland
 ARBs block vasoconstriction and the secretion of aldosterone
 Comparison of ACE Inhibitors and Angiotensin II Receptor Blockers
 ACE inhibitors and ARBs appear to be equally effective for the treatment of
hypertension.
 ARBs do not cause cough
 Evidence that ARBs are better tolerated and are associated with lower mortality after
MI than ACE inhibitors
 Not yet clear whether ARBs are as effective as ACE inhibitors in treating HF
(cardioprotective effects) or in protecting the kidneys, as in diabetes
 Angiotensin II Receptor Blockers: Adverse Effects
 Hyperkalemia and cough are less likely to occur than with the ACE inhibitors.
 Fetal toxicity (Black Box Warning= Pregnant)
 Chest Pain= most common adverse effect
 Losartan (Cozaar)
 Caution: renal or hepatic dysfunction, renal artery stenosis
 Not safe for breastfeeding women and should not be used in pregnancy
Calcium Channel Blockers
 Calcium Channel Blockers: Mechanism of Action
 Cause smooth muscle relaxation by blocking the binding of calcium to its receptors,
preventing muscle contraction
 Calcium Channel Blockers: Indications
 Angina
 Hypertension: amlodipine (Norvasc)
 Dysrhythmias
 Migraine headaches
 Raynaud’s disease
 Prevent the cerebral artery spasms after subarachnoid hemorrhage: nimodipine
Diuretics
 First-line antihypertensives in the JNC 8 guidelines for the treatment of hypertension
 Decrease plasma and extracellular fluid volumes
 Decreased workload of the heart and decreased BP
 Thiazide diuretics= most commonly used
Vasodilators
 Vasodilators: Mechanism of Action
 Directly relax arteriolar or venous smooth muscle (or both)
 Results in:
 Decreased SVR
 Decreased afterload
 Peripheral vasodilation
 Vasodilators: Indications
 Treatment of hypertension
 May be used in combination with other drugs
 Sodium nitroprusside and IV diazoxide are reserved for the management of
hypertensive emergencies.
 Hydralazine (Apresoline)
 Orally: routine cases of essential hypertension
 Injectable: hypertensive emergencies, inability to tolerate oral therapy
 BiDil: specifically indicated as an adjunct for treatment of HF in African-American
patients
 Sodium Nitroprusside (Nitropress)
 Used in the intensive care setting for severe hypertensive emergencies; titrated to effect
by IV infusion
 Contraindications: known hypersensitivity to the drug, severe HF, and known
inadequate cerebral perfusion (especially during neurosurgical procedures)
 Adverse effects: Severe Hypotension
Miscellaneous Antihypertensive Drugs
 Epleronone (Inspra) (selective aldosterone blockers)
 Reduces BP by blocking the actions of aldosterone at its corresponding receptors in the
kidney, heart, blood vessels, and brain
 Indications: routine treatment of hypertension and for post-MI HF
 Treatment of Pulmonary Hypertension
 Bosentan (Tracleer)
 Specifically indicated only for patients with moderate to severe HF
 Action: blocks receptors of the hormone endothelin
 Treprostinil (Remodulin)
 Lowers blood pressure through a combined mechanism of action
 Dilating pulmonary and systemic blood vessels
 Inhibiting platelet aggregation
 Sildenafil and Tadalafil
 Commonly used for erectile dysfunction
 Sildenafil: Revatio
 Tadalafil: Adcirca
 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.
 Teach patients to change positions slowly to avoid syncope from postural hypotension.
 Male patients who take these drugs may not be aware that impotence is an expected
effect, and this may influence compliance with drug therapy.
 Hot tubs, showers, or baths; hot weather; prolonged sitting or standing; physical
exercise; and alcohol ingestion may aggravate low BP, leading to fainting and injury;
patients should sit or lie down until symptoms subside.
 Blood pressure should be maintained at less than 140/90