BP, the Kidneys and Diuretics as Anti-HTN Agents

1. (A Rapid Socratic Review) Prepared and presented by:
Marc Imhotep Cray, MD

2. Marc Imhotep Cray, M.D.
BP, Kidneys and Diuretics as Anit-HTN Agents
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According to JNC 7 guidelines, please define the following:
Normal blood pressure
<120/80 mm Hg
Prehypertension
120 to 139/80 to 89 mm Hg
Stage I hypertension
140 to 159/90 to 99 mm Hg
Stage II hypertension
≥ 160/100 mm Hg
Goal blood pressure (BP) in patients without diabetes mellitus (DM) or
chronic kidney disease?
<140/90 mm Hg
Goal BP in patients with DM or chronic kidney disease?
<130/80 mm Hg
Online: Seventh Report of the Joint National Committee
on Prevention, Detection, Evaluation, and Treatment.pdf
U .S. Department Of Health And Human Services
National Institutes of Health
National Heart, Lung, and Blood Institute

3. Marc Imhotep Cray, M.D.
BP, Kidneys and Diuretics as Anit-HTN Agents (2)
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1. Define essential hypertension (HTN)
2. True or False? The majority of HTN cases are essential.
3. What is the BP equation?
4. What is responsible for moment-to-moment changes in BP?
5. Where are the baroreceptors that are sensitive to the
moment-to-moment changes in BP located?
6. What organ is responsible for the long- term control of BP?

4. Marc Imhotep Cray, M.D.
Answers
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1. HTN of unknown etiology, that is, primary hypertension
2. True
3. Blood pressure (BP) = cardiac output (CO) × total peripheral
resistance (TPR)
4. Baroreceptor reflexes (autonomic nervous system)
5. Aortic arch; carotid sinuses
6. Kidney

5. Marc Imhotep Cray, M.D.
BP, Kidneys and Diuretics as Anit-HTN Agents (3)
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7. The kidney responds to reduced BP by releasing what peptidase?
8. Renin is responsible for what enzymatic reaction?
9. What enzyme is responsible for converting AT-I to AT-II?
10. Where is ACE found?
11. What function does AT-II have with regard to BP regulation?
12. Where is aldosterone synthesized?
13. What function does aldosterone have with regard to BP regulation?

6. Marc Imhotep Cray, M.D.
Answers
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7. Renin
8. Conversion of angiotensinogen to angiotensin-I (AT -I)
9. Angiotensin-converting enzyme (ACE) in the lungs
10. Vasoconstriction (increases TPR thereby increases BP);
stimulation of aldosterone release
11. Zona glomerulosa of the adrenal cortex
12. Increases reabsorption of sodium ion in exchange for
potassium ion; water osmotically follows sodium ion,
therefore, aldosterone leads to salt and water
13. retention thereby increasing BP

7. Marc Imhotep Cray, M.D.
BP, Kidneys and Diuretics as Anit-HTN Agents (4)
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14. What is the name of the most common thiazide diuretic used in the
treatment of HTN?
15. What are the immediate/acute effects of thiazide diuretics?
16. What are the chronic effects of thiazide diuretics?
17. What is the site of action of thiazide diuretics?
18. What transporter (in the distal convoluted tubule) is inhibited by thiazide
diuretics?
19. Give examples of thiazide diuretics:

8. Marc Imhotep Cray, M.D.
Answers
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14. Hydrochlorothiazide (HCTZ)
15. Increased sodium, chloride, and water excretion which leads
to decreased blood volume
16. Decreased TPR
17. Distal convoluted tubule of nephron
18. Na+/Cr transporter
19. HCTZ; chlorothiazide; chlorthalidone

9. Marc Imhotep Cray, M.D.
BP, Kidneys and Diuretics as Anit-HTN Agents (5)
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20.Thiazide diuretics may be ineffective in patients with
creatinine clearances of less than what?
21.With regard to blood concentrations, state whether each of
the following electrolytes will be increased or decreased in
patients on thiazide diuretic therapy: Calcium, Magnesium,
Potassium, Sodium
22.With regard to increased renal calcium reabsorption, what are
thiazide diuretics sometimes used for?
23.What are the adverse effects of HCTZ?

10. Marc Imhotep Cray, M.D.
Answers
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20. 50 mL/min
21. Increased, Decreased, Decreased, Decreased
22. Treatment of calcium stones in the urine
23. Hypercalcemia; hypokalemia; hypomagnesemia; hyperglycemia;
hyperuricemia; pancreatitis; metabolic alkalosis; Stevens Johnson syndrome;
hyperlipidemia

11. Marc Imhotep Cray, M.D.
BP, Kidneys and Diuretics as Anit-HTN Agents (6)
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24.Patients allergic to what class of antimicrobials may also be
sensitive to thiazide diuretics?
25.What is the site of action of loop diuretics?
26.Give examples of loop diuretics:
27.Which loop diuretic can be given safely to patients with
allergy to sulfonamide antimicrobials?
28.What transporter (in the thick ascending loop of Henle) is
inhibited by loop diuretics?

12. Marc Imhotep Cray, M.D.
Answers
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24. Sulfonamides
25. Loop of Henle (thick ascending limb)
26. Furosemide; bumetanide; ethacrynic acid; torsemide
27. Ethacrynic acid
28. Na+/KV2Cl~ transporter

13. Marc Imhotep Cray, M.D.
BP, Kidneys and Diuretics as Anit-HTN Agents (7)
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29.True or False? Loop diuretics increase calcium excretion.
30.What are the adverse effects of loop diuretics?
31.Which loop diuretic is the most ototoxic?
32.Which renal tubular segment is responsible for the majority of
sodium reabsorption?
33.What is the mechanism of action of mannitol?
34.What is mannitol used for?

14. Marc Imhotep Cray, M.D.
Answers
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29. True
30. Hypersensitivity; hypocalcemia; hypokalemia;
hypomagnesemia; metabolic alkalosis; hyperuricemia;
ototoxicity
31. Ethacrynic acid
32. Proximal convoluted tubule (>60%)
33. Acts as an osmotic diuretic, thereby drawing water via
increased osmolality, into the proximal convoluted tubule, loop
of Henle (thin descending limb), and the collecting ducts
34. Decreases intraocular and intracranial pressure; prevents
anuria in hemolysis and rhabdomyolysis

15. Marc Imhotep Cray, M.D.
BP, Kidneys and Diuretics as Anit-HTN Agents (8)
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35.Give two examples of carbonic anhydrase inhibitors (CAIs):
36.What is the mechanism of action of CAIs?
37.What metabolic disturbance may be caused by CAIs?
38.What are CAIs used for?
39.Name three potassium-sparing diuretics:
40.What is the mechanism of action of spironolactone?

16. Marc Imhotep Cray, M.D.
Answers
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35. Acetazolamide, Dorzolamide
36. Increased excretion of sodium and bicarbonate
37. Metabolic acidosis
38. Altitude sickness (decreases cerebral and pulmonary edema);
glaucoma (decreases aqueous humor formation thereby
decreasing intraocular pressure); metabolic alkalosis; to
enhance renal excretion of acidic drugs
39. Spironolactone, Triamterene , Amiloride
40. Aldosterone receptor antagonist

17. Marc Imhotep Cray, M.D.
BP, Kidneys and Diuretics as Anit-HTN Agents (9)
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41.Where in the kidney is the aldosterone receptor found?
42.Where in the kidney does triamterene and amiloride work?
43.What are the adverse effects of spironolactone?
44.Triamterene is often used in combination with what other
diuretic?
45.Spironolactone is used to treat what conditions?
46.Amiloride is used to treat what conditions?

18. Marc Imhotep Cray, M.D.
Answers
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41. Basolateral membrane of the principal cell in the collecting
duct
42. Sodium ion channel on the luminal side of the principal cell in
the collecting duct
43. Hyperkalemia; metabolic acidosis; gynecomastia
44. HCTZ
45. HTN; CHF; ascites
46. HTN; CHF; lithium-induced diabetes insipidus

19. Marc Imhotep Cray, M.D.
See next slide for sources and links to additional study tools and resources.
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20. Marc Imhotep Cray, M.D.
Sources and further study:
eLearning
Renal cloud folder tools and resources
MedPharm Guidebook:
Unit 9 Drugs Used to Affect Renal Function
Renal Pharmacology eNotes
Clinical Pharmacology Cases 7, 8, & 55 (Learning Triggers)
Textbooks
Brunton LL, Chabner BA , Knollmann BC (Eds.). Goodman and Gilman’s The Pharmacological
Basis of Therapeutics. 12th ed. New York: McGraw-Hill, 2011
Katzung, Masters, Trevor. Basic and Clinical Pharmacology, 12th ed. New York: McGraw-Hill,
2012
Mulroney SE. and Myers AK. Netter's Essential Physiology. Philadelphia: Saunders, 2009
Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition.
Philadelphia: Sanders, 2014
Toy E C. et.al. Case Files-Pharmacology Lange 3rd ed. New York: McGraw-Hill 2014.
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