Chapter 33: Hypertension

• Thiazide Diuretic
• Initial decrease in ECF; sustained decrease in SVR
• Side Effects and Adverse Effects
• Fluid and electrolyte imbalances: volume depletion, hypokalemia, hyponatremia, hypochloremia,  hypomagnesemia, hypercalcemia, hyperuricemia, metabolic alkalosis; CNS effects; vertigo, headache, weakness.
• GI effects: anorexia, nausea, vomitting, diarrhea, constipation, pacreatitis
• Sexual problems: erectile dysfunction, decreased libido
• Dermatologic effects: photosensitivity, skin rash
• Blood dyscrasias; decreased glucose tolerance.

• Thiazide Diuretics
• Initial decrease in ECF; sustained decrease in SVR

• Side Effects and Adverse Effects
• Fluid and electrolyte imbalances: volume depletion, hypokalemia, hyponatremia, hypochloremia,  hypomagnesemia, hypercalcemia, hyperuricemia, metabolic alkalosis; CNS effects; vertigo, headache, weakness.
• GI effects: anorexia, nausea, vomitting, diarrhea, constipation, pacreatitis
• Sexual problems: erectile dysfunction, decreased libido
• Dermatologic effects: photosensitivity, skin rash
• Blood dyscrasias; decreased glucose tolerance.

• Thiazide and Related Diuretics
• Lower BP, moderately in 2-4 weeks

• Side Effects and Adverse Effects
• Fluid and electrolyte imbalances: volume depletion, hypokalemia, hyponatremia, hypochloremia,  hypomagnesemia, hypercalcemia, hyperuricemia, metabolic alkalosis; CNS effects; vertigo, headache, weakness.GI effects: anorexia, nausea, vomitting, diarrhea, constipation, pacreatitis
• Sexual problems: erectile dysfunction, decreased libido
• Dermatologic effects: photosensitivity, skin rash
• Blood dyscrasias; decreased glucose tolerance.

Monitor for orthostatic hypotension, hypokalemia, and alkalosis. Thiazides may potentiate cardiotoxicity of digoxin by producing hypokalemia. Dietary sodium restriction reduces the risk of hypokalemia. NSAIDs can decrease diuretic and antihypertensive effects of thiazide diuretics. Advise patient to supplement with potassium-rich foods. Current doses are lower than previously recommended.

• Loop Diuretics
• Inhibit NaCl reabsorption in the thick ascending  limb of the loop of Henle. Increase excretion of Na+ and Cl-. More potent diuretic than thiazides, but shorter duration of action. Less effective for hypertension.
• Side Effects and Adverse Effects
• Fluid and electrolyte imbalances as with thiazides, except no hypercalcemia.
• Ototoxicity: hearing impairment, deafness, vertigo, that are usually reversible
• Metabolic Effects: hyperuricemia, hyperglycemia, increased LDL cholesterol and triglycerides, decreased HDL cholesterol

• Monitor for orthostatic hypotension and electrolyte abnormalities.
• Loop diuretics remain effective despite renal insufficiency. Diuretic effect of drug increases at higher doses.

• Potassium-Sparing Diuretics
• Reduce K+ and Na+ exchange in the distal and collecting tubules. Reduce excretion of K+, H+, Ca+, and Mg+.
• Side Effects and Adverse Effects
• Hyperkalemia, nausea, vomiting, diarrhea, headache, leg cramps, dizziness.

Monitor for orthostatic hypotension and hyperkalemia. Contraindicated in patients with renal failure. Use with caution in patients on ACE inhibitors or angiotensin II blockers. Avoid potassium supplements.

• Aldosterone Receptor Blockers
• Inhibit the Na+ retaining and K+ excreting effects of aldosterone in the distal and collecting tubules.

• Side Effects and Adverse Effects
• Same as amiloride and triamterene.
• May cause gynocomastia, erectile dysfunction, decreased libido, menstrual irregularities.

• Central-Acting alpha-Adrenergic Antagonists
• Reduces sympathetic outflow from the CNS

• Side effects and Adverse Effects
• Dry mouth, sedation, erectile dysfunction, nausea, dizziness, sleep disturbance, nightmares, restlessness, depression.
• Symptomatic bradycardia in patients with conduction disorder.
•        For methyldopa:
•        Sedation, fatigue, orthostatic hypotension, decreased   libido, erectile dysfunction, dry mouth, hemolytic anemia, hepatotoxicity, sodium and water retention, depression.

• Central-Acting alpha-Adrenergic Antagonist
• Reduces peripheral sympathetic tone, produces vasodilation, decreases SVR and BP.

• Side Effects and Adverse 
• Dry mouth, sedation, erectile dysfunction, nausea, dizziness, sleep disturbance, nightmares, restlessness, depression.
• Symptomatic bradycardia in patients with conduction disorder.
• Patch may cause pruritis, redness, or darkening of skin.

• Sudden discontinuation may cause withdrawal syndrome including rebound hypertension, tachycardia, headache, tremors, apprehension, and sweating.
• Chewing gum or hard candy may relieve dry mouth. Alcohol and sedatives increase sedation.
• Transdermal patch (Catapres-TTS) may be related to  fewer side effects and better compliance.
•      For Methyldopa: Instruct patient about daytime sedation and avoidance of hazardous activities. Administration of a single daily dose at bedtime minimizes sedative effect.

• Peripheral-Acting alpha-Adrenergic Antagonists
• Prevents peripheral release of norepinephrine, resulting in vasodilation. Lowers cardiac output and reduces SBP more than DBP. 

• Side Effects and Adverse Effects
• Marked orthostatic hypotension, diarrhea, cramps, bradycardia, retrograde or delayed ejaculation, sodium and water retention.

• Peripheral-Acting alpha-Adrenergic Antagonists
• Prevents peripheral release of norepinephrine, resulting in vasodilation. Lowers cardiac output and reduces SBP more than DBP. Depletes central and peripheral stores of norepinephrine. Results in peripheral dilation (decreases SVR and BP).

• Side Effects and Adverse 
• Marked orthostatic hypotension, diarrhea, cramps, bradycardia, retrograde or delayed ejaculation, sodium and water retention. Sedation and inability to concentrate, depression, nasal stuffiness.

May cause severe orthostatic hypotension; not recommended for use in patients with cerebrovascular or coronary insufficiency or in older adults. Advise patient to rise slowly and wear support stockings. Hypotensive effect is delayed for 2-3 days and lasts 7-10 days after withdrawal.

Must be given twice daily. Contraindicated in patients with history of depression. Monitor mood and mental status regularly. Advise patients to avoid barbiturates, alcohol, and opiods.

• Alpha1 Adrenergic Blockers
• Block alpha1-adrenergic effects, producing peripheral vasodilation (decreases SVR and BP). Beneficial effects on lipid profile.

• Side Effects and Adverse Effects
• Variable amount of orthostatic hypotension depending on the plasma volume. May see profound orthostatic hypertension with syncope within 90 minutes after initial dose. Also, retention of salt and water.

• alpha1-adrenergic blockers
•      Blocks alpha1 adrenergic receptors, resulting in peripheral vasodilation (decreases SVR and BP). 

• Side Effects and Adverse Effects
• Acute, prolonged hypotension, cardiac dysrhythmias, tachycardia, weakness, and flushing. Abdominal pain, nausea, and exacerbation of peptic ulcer.

Used in short-term management of pheochromocytoma. Also used locally to prevent necrosis of skin and subcutaneous tissue after extravasation of adrenergic drug. No oral formulation.

Reduced resistance to the outflow of urine in benign prostatic hyperplasia. Taking drug a bedtime reduces risks associated with orthostatic hypotension.

• Beta Adrenergic Blockers
• Reduce blood pressure by antagonizing Beta Adrenergic effects. Cardioselective agents block B1 adrenergic receptors. Nonselective agents block B1 and B2 adrenergic receptors. Decrease CO and reduce sympathetic vasoconstrictor tone. Decrease renin secretion by kidneys.
• Side Effects and Adverse Effects
• Hypotension, bronchospasm, atrioventricular conduction block, impaired peripheral circulation.
• Nightmares, depression, erectile dysfunction, weakness, reduced exercise capacity.
• May induce or exacerbate heart failure in susceptible patients.
• Sudden withdrawal of Beta-adrenergic blockers may cause rebound hypertension and exacerbate symptoms of ischemic heart disease.

• Beta Adrenergic Blockers
• Reduce blood pressure by antagonizing Beta Adrenergic effects. Cardioselective agents block B1 adrenergic receptors. Nonselective agents block B1 and B2 adrenergic receptors. Decrease CO and reduce sympathetic vasoconstrictor tone. Decrease renin secretion by kidneys.
• Side Effects and Adverse Effects
• Hypotension, bronchospasm, atrioventricular conduction block, impaired peripheral circulation.
• Nightmares, depression, erectile dysfunction, weakness, reduced exercise capacity.
• May induce or exacerbate heart failure in susceptible patients.
• Sudden withdrawal of Beta-adrenergic blockers may cause rebound hypertension and exacerbate symptoms of ischemic heart disease.

• Beta Adrenergic Blockers
• Reduce blood pressure by antagonizing Beta Adrenergic effects. Cardioselective agents block B1 adrenergic receptors. Nonselective agents block B1 and B2 adrenergic receptors. Decrease CO and reduce sympathetic vasoconstrictor tone. Decrease renin secretion by kidneys.

• Side Effects and Adverse Effects
• Hypotension, bronchospasm, atrioventricular conduction block, impaired peripheral circulation.
• Nightmares, depression, erectile dysfunction, weakness, reduced exercise capacity.
• May induce or exacerbate heart failure in susceptible patients.
• Sudden withdrawal of Beta-adrenergic blockers may cause rebound hypertension and exacerbate symptoms of ischemic heart disease.

Beta-Adrenergic Blocker

• Reduces BP by antagonizing B1-Adrenergic effects. 
• IV administration; rapid onset and very short duration of action.

Beta-Adrenergic blockers vary in lipid solubility, selectivity, and presence of partial sympathomimetic effect, which explains different therapeutic and side effect profiles of specific agents. Monitor pulse and BP regularly. Use with caution in patients with diabetes mellitus because drug may depress the tachycardia associated with hypoglycemia. Nonselective agents may cause bronchospasm, especially in patients with a history of asthma.

• Beta-Adrenergic Blockers
• Alpha1, Beta1, and Beta2 adrenergic blocking properties producing peripheral vasodilation and decreased heart rate. Reduces CO, SVR, and BP.

• Side Effects and Adverse Effects
• Hypotension, bradycardia, orthostatic hypotension, dizziness, fatigue, nausea, vomiting, dyspepsia, paresthesia, nasal stuffiness, erectile dysfunction, edema. Also hepatic toxicity.

• Same as Beta-Adrenergic blockers. IV form available for hypertensive crisis in hospitalized patients.
• Patients must be kept supine during IV administration.
• Assess patient tolerance of upright position (severe orthostatic hypotension) before allowing upright activities (e.g. commode).