20 - Antihypertensives

Hypertension

1. What are the defined stages of hypertension? (LP p215)

Classification of Blood Pressure

Category SBP mmHg DBP mmHg
Normal <120 AND <80
Prehypertension 120-139 OR 80-89
Hypertension, Stage 1 140-159 OR 90-99
Hypertension, Stage 2 ≥160 OR ≥100
U.S. Department of Health and Human Services, NIH, National Heart, Lung, and Blood Institute

2. What are the risk factors for hypertension? (LP p215)

• Genetics • Diabetes
• ____________________ • ____________________
• Sex • Stressful lifestyle
• Age • High sodium diet
• ____________________ • ____________________

3. What are the consequences of hypertension? (LP p215)

• Atherosclerosis • Stroke
• _______________________________ (LVH) • Renal failure
• Congestive Heart Failure (_____) • __________________________
• Aortic dissection

4. What are the body’s two primary mechanisms for controlling blood pressure? (LP p216)
• Baroreceptors and the sympathetic nervous system
• Renin-Angiotensin-Aldosterone system

5. What are the stimulators of renin secretion? (LP p216)

• Reduced , sensed by the
• Sympathetic stimulation of renal
• Low sodium intake, or

6. What are the two main functions of angiotensin II? (LP p216)
• Vasoconstriction
• Stimulates production

7. Which class of drug is generally recommended as the first-line therapy for hypertension, unless there are
compelling reasons to start another? (LP p216)

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8. What are the preferred antihypertensives given the following patient? (LP p218)

Patient Characteristics Antihypertensives of Choice

Black Race

Elderly

Coronary Artery Disease / Angina

Diabetes

Chronic Renal Disease

Congestive Heart Failure

Diuretics

9. Which three classes of diuretics are typically used in the treatment of hypertension? (LP p219-220)

Thiazides
10. Which diuretic was used in the ALLHAT trial, and was proven to reduce the incidence of stroke and other
cardiovascular outcomes more than other antihypertensive drugs, including amlodipine, lisinopril, and
doxazosin?

11. What electrolyte disturbances do thiazide diuretics potentially cause? (LP p219)

Loop Diuretics
12. What are two common conditions treated with loop diuretics?

13. What is the duration of action of furosemide (Lasix)?

14. What effect do loop diuretics have on urinary calcium excretion?

Potassium-sparing Diuretics
15. What are the adverse effects of spironolactone?

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Quick Review 1

1. What lifestyle modifications should every patient with hypertension make?

• to decrease myocardial infarction (MI) risk
•
• Low sodium diet (Very important to try, but not always effective)
• Dietary Approach to Stop Hypertension (DASH Diet)
(4 fruits, > 4 veggies, and 3 servings of low fat diary daily)

2. What are four common reasons for hyponatremia?

•
•
• Cirrhosis
• Renal failure

3. Which class of diuretic is actually useful in treating hyponatremia?

4. In what scenario would you choose a thiazide as the antihypertensive of choice?

• with no other comorbidities
•
• Elderly
• Mild heart failure
• Hypercalciuria (hint: “Loops lose calcium; thiazides don’t”)
• Diabetes insipidus

5. Which drug category if used in combination with loop diuretics may cause ototoxicity?

6. What is the mechanism of action of the following antihypertensive diuretics?

Antihypertensive Mechanism of Action

Thiazides Decrease the reabsorption of _____________in the
_________________  more NaCl into the urine

Loop diuretics Inhibit the Na-K-Cl co-transporter in the

______________________________________

Amiloride and triamterene Inhibit sodium transport in the ___________________

and ____________________________ of the nephron

Spironolactone and eplerenone _______________________ receptor antagonists

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7. Why does spironolactone have gynecomastia as a side-effect?

8. What is the diuretic of choice in patients with renal failure (creatinine clearance < 50mL/min)?

9. What is the maximum dose of HCTZ that should be used to optimize BP control and minimize side-effects?

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β-Blockers

1. What is the mechanism by which beta-blockers reduce blood pressure? (LP p220)

2. Why is propranolol contraindicated in patients with asthma? (LP p220)

Propranolol is a , which acts on both β1 and β2
receptors. activity can provoke , which can be life-threatening in
asthmatics (and possibly patients with COPD).

3. Name four β1–selective β-blockers.

4. Which two selective β-blockers are most commonly used for the treatment of hypertension? (LP p220)

5. Beta-blockers are indicated in the treatment of chronic heart failure to reduce morbidity and mortality;
however, why should beta-blockers not be given to patients with an acute exacerbation of heart failure?

6. What are some of the non-cardiovascular uses of beta-blockers?

•
• Migraine Prophylaxis
•
• Social Anxiety (“Stage Fright”)

7. What are the adverse effects of beta-blockers? (LP p221)

• • Bronchoconstriction
• Fatigue/Lethargy •
• Insomnia • Hypoglycemia
• Arrhythmias •

8. Why should β-blockers be tapered slowly rather than stopped abruptly? (LP p 211)
Chronic β-blockade leads to of β-receptors. Sudden discontinuation of the β-blocker
can lead to .

9. What effect does β-blockade have on serum glucose? (LP p211)

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ACE Inhibitors

10. What does “ACE” stand for, and what does the enzyme do? (LP p221-222)

11. How do ACE inhibitors affect vascular tone? (LP p221-222)

• Less  less vasoconstriction
• More  more vasodilation

12. What hemodynamic effects do ACE inhibitors have on afterload and preload?

13. In what scenarios are ACE inhibitors the antihypertensive of choice? (LP p222)
• Congestive heart failure
• Prior myocardial infarction (MI)
• Renal disease, to reduce
• to slow progression of diabetic nephropathy

14. When should ACE inhibitors be avoided in patients?

15. What is the most common adverse effect of ACE inhibitors occurring in 10% of patients? What substance is
responsible for this side effect?

16. What labs should be monitored in patients on ACE inhibitors? (LP p222)

17. What rare but potentially life-threatening adverse effect can ACE inhibitors cause, and how do we treat it?
(LP p222)

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Angiotensin-Receptor Blockers

18. What effect do ARBs have on bradykinin levels, and how does this effect the drugs’ side effect profiles? (LP
p222-223)

19. Besides hypertension, in what other disease states can ARBs be beneficial? (LP p222-223)
•
• Post-MI
• who cannot tolerate ACE inhibitors

20. Why are ARBs and ACE inhibitors contraindicated in pregnant women? (LP p221-223)

Renin Inhibitor

21. What is the mechanism of action of Aliskarin? (LP p223)

Aliskarin prevents renin from cleaving into . This
blocks the renin-angiotensin-aldosterone system at an earlier stage.

22. Is Aliskarin more effective or less effective at lowering blood pressure than ACE inhibitors and ARBs? (LP
p223)

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Quick Review 2

1. A 50 year-old white male with DM, CAD, and HTN comes to your clinic to establish care as a new patient.
What medications should this patient be taking?

2. What are the cardioprotective beta-blockers?

3. Which two beta-blockers function not only as beta-antagonists but also as alpha-1 antagonists?

4. Why are thiazide diuretics commonly used in combination with ACE-Inhibitors or ARBs?

5. A patient with diabetic renal diease is started on an ACE inhibitor but then develops cough as a side effect. To
what class of medication should this patient be switched?

6. A patient with recently diagnosed hypertension was started on 25mg of HCTZ 3 months ago and now returns
for follow-up. The blood pressure measured at home and in clinic is consistently higher than 140/90. Which
second agent should be started on this patient with no other comorbidities?

7. What is the problem with using propranolol in the setting of a patient with pheochromocytoma?

8. What effect does phenoxybenzamine have on the treatment of pheochromocytoma?

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Calcium-channel Blockers

1. List the dihydropyridine calcium-channel blockers?

• • Isradipine
• Amlodipine •
• Felodipine • Nisoldipine

2. Which class of calcium-channel blockers is more commonly used in treating hypertension, because of higher
affinity for calcium channels in vascular smooth muscle? (LP p223)

3. Which calcium-channel blocker has the highest affinity for cardiac calcium channels? (LP p212)

4. In which patients are calcium-channel blockers the preferred antihypertensive?

• Black patients
•
•
• Patients with
• Patients with peripheral vascular disease

5. Which calcium-channel blockers are preferred for the management of atrial fibrillation and other
tachyarrythmias? (LP p212-213)

6. Give two reasons that calcium-channel blockers are contraindicated in patients with congestive heart failure.
(LP p212)

7. What are some of the other side-effects of the calcium-channel blockers?

Verapamil and diltiazem

(Non-dihydropyridines)

Dihydropyridines

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α1-Blockers

8. List the alpha-1 blockers used for hypertension. (LP p225)

9. Do α-Blockers act primarily on venous or arterial smooth muscle? (LP p225)

10. When might alpha-blockers be used as the antihypertensive of choice?

11. What α-Blocker is typically used in the treatment of benign prostatic hyperplasia? (LP p225)

12. What are the adverse effects of using an α-Blocker? (LP p225)
• Reflex
• First-dose
• Postural
• Retention of  worsening heart failure

Centrally-Acting Adrenergic Drugs

13. Complete the following table:

α2-Agonist Action Therapeutic Use Adverse Effect

(Centrally Acting)
Clonidine Agonist of ________ receptors in the
brain
Diminished central adrenergic
________
α-Methyldopa Analog of DOPA, taken in to the
________ , converted to
methylnorepinephrine
Inhibits _______________ discharge
• Refractory HTN •____________________
• HTN with •Rebound hypertension
_______________ •Sedation & dizziness
•____________________
•Dry mouth and nasal
mucosa
Hypertension in • Sedation and drowsiness
pregnancy • ____________________
• Dry mouth and nasal
mucosa

14. Why are clonidine and α-Methyldopa useful for hypertensive patients with renal disease? (LP p225-226)

15. What four drugs are commonly used to treat hypertension during pregnancy?
•
• Hydralazine
• (and other dihydropyridine CCBs)
• Labetalol

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Vasodilators

16. Which patients should avoid vasodilators in general due to increased heart by way of reflex tachycardia?

17. Complete and study the following list of commonly used drugs: (LP p219-226)

Vasodilators Action Therapeutic Use Adverse Effects

Hydralazine Exact mechanism • Reflex tachycardia
unknown • Increased renin 
______________________________
Primarily dilates • Headache, angina, nausea, sweating
_____________________ • Reversible drug-induced lupus
Minoxidil Opens ____ channels • Severe hypertension • Reflex tachycardia
• Refractory HTN • Incrased renin 
Hyperpolarizes and relaxes • Topical treatment for ______________________________
vascular smooth muscle male-pattern baldness • Hypertrichosis
Dilates arterioles but not
______________

18. Which medications are often used in combination with hydralazine to mediate the adverse effects?
• Use to reduce reflex tachycardia
• Use to reduce sodium and water retention

19. What drugs are associated with a reversible lupus-like syndrome which is associated with elevated anti-
histone antibodies?
• Sulfasalazine
•
• Isoniazid
• Procainamide
• Phenytoin
(hint: “SHIPP”)

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Hypertensive Emergency

20. What is the definition of hypertensive emergency? (LP p227)

• In an otherwise healthy patient: DBP > or SBP >
• In a patient with complications (i.e., encephalopathy, cerebral hemorrhage, left ventricular failure, aortic
stenosis): DBP >

21. Which antihypertensives are commonly used to treat hypertensive emergency?

• • Hydralazine
• Labetalol • Nitroglycerin
• •
• Clonidine

Sodium Nitroprusside
22. What is the mechanism by which nitrates reduce blood pressure?
Nitrates are converted to  nitric oxide activates guanylyl cyclase  increase in cGMP 
myosin light chain dephosphorylation  smooth muscle relaxation

23. Does sodium nitroprusside act primarily on venous or arterial smooth muscle? (LP p227)

24. Which antihypertensive drug can cause cyanide toxicity due to the production of thiocyanate? What is the
treatment for cyanide toxicity? (LP p227)

Other Common Drugs in Hypertensive Emergency

25. What adverse effects are associated with use of labetalol? (LP p 227)
• (from β2 blockade)
• (from β1 blockade)

26. What is the mechanism of action of fenoldopam? (LP p227)

Peripheral receptor agonist

27. Which calcium-channel blocker given in IV form is commonly used to treat hypertensive emergency? (LP
p227)

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Quick Review 3

1. Which calcium channel blocker has the highest incidence of causing constipation?

2. What antihypertensive might give you a positive Coombs test indicating that there might be a potential for a
hemolytic anemia?

3. Why might a vasodilator such as hydralazine not be a good choice as a single hypertensive agent?

4. Which antihypertensives act on only arterial pressure?

5. Which antihypertensive drug category is associated with first-dose orthostatic hypotension?

6. Which antihypertensive drugs are known for causing reflex tachycardia?

7. Which antihypertensive is known for severe rebound hypertension upon discontinuation?

8. For what other purpose is clonidine commonly used that is unrelated to its use in treating hypertension?

9. What medications or medication combinations are commonly used to reduce both afterload and preload in
patients with heart disease?
• or ARBs
•
• Combination +
• Clonidine (but not commonly used for this purpose)

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End of Session Quiz – Antihypertensives

1. What side-effects are commonly associated with β-blockers?

2. For most patients, what would be the first-line antihypertensive drug? (LP p219)

3. Which antihypertensives are safe to use in pregnancy?

4. Which antihypertensive drugs can increase uric acid and increase the risk of gout? (LP p219-220, 223)

5. What side effect is commonly seen following abrupt withdrawal of clonidine? (LP p226)

6. While on an ACE inhibitor, a patient develops a cough. What is a good replacement drug, and why doesn’t it
have the same side effects? (LP p222)

7. Which antihypertensive class or drug fits the following side effect?

First-dose orthostatic hypotension

Ototoxic (especially with aminoglycosides)
Hypertrichosis
Hyperkalemia
Cyanide toxicity
Dry mouth, sedation, severe rebound HTN
Bradycardia, impotence, asthma exacerbation
Reflex tachycardia
Cough
Avoid in patients with sulfa allergy
Possible angioedema
Hypercalcemia, hypokalemia

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8. Which antihypertensive drug can cause a reversible lupus-like syndrome at high doses? (LP p226)

9. Which antihypertensive drug might be a good choice for patients with diabetic nephropathy, and why?

10. In a patient with a history of coronary disease and MI, already taking a thiazide and an ACE inhibitor, what
class of antihypertensive drug would be a good choice for add-on therapy?

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