1. Diuretics and Lipids

2. Diuretic Agents
Each diuretic agent acts upon a single anatomic segment of the nephron

3. Diuretic Agents
Because the segments have distinct transport functions, the action of each diuretic can be best understood in relation to its site of action in the nephron and the normal physiology of the segment

5. Notice the body increases the “filtration rate” by constricting the efferent arteriole

6. The purpose of the collection system is to reabsorb salts, nutrients and water from the filtrate.

7. The purpose of the collection system is to secrete toxins not already in the filtrate

10. Thiazide Diuretics
Hydrochlorothiazide

11. Thiazide diuretics inhibit NaCl reabsorption from distal convoluted tubule

12. Thiazide Diuretics Thiazides compete with secretion of uric acid
This causes uric acid to go up, increasing the risk of gouty arthritis

13. Thiazide Diuretics Hypertension Congestive Heart Failure
Nephrolithiasis due to hypercalciuria
Diapetes insipidus

14. Thiazide Toxicity HypoKalemia (low potassium K+)
HypoNatremia (low sodium Na+)
Hyperuricemia (uric acid leads to gout)

15. Thiazide Toxicity Allergic reaction (sulfonamide cross reactivity)
Photosensitivity

16. End in “zide”
Many,many drugs used to treat HTN include hydrochlorothiazide in the combination

17. Loop Diuretics
Furosemide (Lasix)

18. Loop Diuretics
Selectively inhibit NaCl reabsorption in thick ascending loop of Henle

19. Loop Diuretics
Most efficacious diuretics available-furosemide and ethacrynic acid
Rapid acting, relatively short duration

20. Lasix
The onset diuresis following oral administration is within 1 hour. The peak effect occurs within the first or second hour. The duration of diuretic effect is 6 to 8 hours.

21. Loop Diuretics Increase Ca++ and Mg++ excretion
Reduce left ventricular filling pressure in CHF and pulmonary congestion

22. Loop Diuretics Acute pulmonary edema
Acute renal failure – increase renal blood flow and enhance potassium excretion

23. Toxicity of Loop Diuretics
Hypokalemia
Hyperuricemia
Hypomagnesemia
Allergic reaction (furosemide is related to sulfonamide group)
Hypovolemia

24. K+ Sparing Diuretic Spirinolactone
Antagonizes aldosterone at late distal tubule and cortical collecting tubule
Used in states of aldosterone excess (CHF, cirrhosis, nephrotic syndrome)

25. K+ Sparing Diuretic Spironolactone
Toxicities include: severe hyperkalemia, gynecomastia and hyperchloremic metabolic acidosis

26. K+ Sparing Diuretic Spironolactone
Hyperkalemia is a major complication
- should not be use with ACE inhibitor

27. Osmotic Diuretics
Nonreabsorbable solute pulls water into urine and increases urine volume
Used to maintain urine volume and reduce intracranial and intraocular pressure IV

28. Toxicity of Osmotic Diuretics
Extracellular volume expansion which may complicate heart failure and produce pulmonary edema
Dehydration and hypernatremia

29. ADH Antagonists Only available agents are non-selective
- lithium salts and demeclocycline
- exact mechanism unknown

30. Carbonic Anhydrase Inhibitors
Enzyme in proximal tubule that allows reabsorption of sodium bicarbonate
Inhibitors reduce bicarb reabsorption and thus produce alkaline urine

31. Carbonic Anhydrase Inhibitors
Acetazolamide – used to treat glaucoma by reducing rate of aqueous humor formation
Also used to prevent acute “mountain sickness”

32. Toxicity carbonic anhydrase inhibitors
Hyperchloremic Metabolic Acidosis
Renal stones (calcium salts insoluble at alkaline pH)
Potassium wasting

33. Hyperlipidemia and Atherosclerosis

34. Atherosclerosis

35. Prevalence of CAD Coronary artery disease 23% of americans
42% of all deaths annually

36. Prevalence of CAD M.I. – 1.5 million (500,000 fatal)
Angina – 5.6 million (1,290 fatal)
If CAD was eliminated life expectancy would rise approximately 10 years

37. Classes of Lipoproteins
Chylomicrons – transport lipids from GI to liver

38. Classes of Lipoproteins
LDL – transport lipids from liver to body
- “bad cholesterol”

39. Classes of Lipoproteins
HDL – transfers lipids from body back to liver
- “good cholesterol”

40. Lipid Panel (lab test)
Total cholesterol
LDL
HDL
Triglyceride

41. Primary Hyperlipidemia
Familial Hypercholesteremia
Familial Hypertriglyceridemia
Familial Hyperlipidemia

42. Secondary Hyperlipidemia
Diabetes mellitus
Nephrotic syndrome
Uremia
Hypothyroidism
Obstructive liver disease
Alcoholism
Medication induced

43. Risk Factors Evidence of CAD HDL <40
Family history of premature CAD
Smoking
Hypertension
Diabetes mellitus

44. Goal is to lower LDLs If no CAD and less than 2 risk factors
- LDL less than 160

45. Goal is to lower LDLs If no CAD but 2 or more risk factors
- LDL less than 130

46. Goal is to lower LDLs
With CAD
- LDL less than 100

47. Therapeutic Lifestyle Changes
Diet
Increase physical exercise
Weight reductions
Alcohol reductions
Smoking cessation
Control hypertension
Control diabetes

48. Pharmacologic Agent
Nicotinic Acid, Niacin, Vit. B3
- Niaspan

49. Nicotinic Acid Should be avoided in patients with:
- active or chronic liver disease
- peptic ulcer disease
- diabetes
- gout

50. Nicotinic Acid Take with food Do not take with hot liquids
- taking ASA 325mg 30 minutes prior to dose may reduce flushing

51. Nicotinic Acid Side effects - flushes - pruritus - rash - nausea
- heartburn
- diarrhea

52. Nicotinic Acid Side Effects
Headache
Hypotension
Liver dysfunction
Glucose intolerance
Hyperuricemia
Exacerbation of peptic ulcer disease

53. Nicotinic Acid Drug interactions - statins (myopathy, rhabdomyolysis)
- fibrates (myopathy, rhabdomyolysis)

54. Nicotinic Acid Monitoring - FBS - Liver Function Tests - AST - ALT
Uric Acid

55. Bile Acid Sequestrants
Cholestyramine
Anion exchange resin
Lowers LDL cholesterol
May increase triglyceride

56. Bile Acid Sequestrants
Side effects
- bloating - abdominal pain
- constipation - flatulence
- nausea

57. Bile Acid Sequestrants
Drug Interactions
- binds to other medications, decreasing absorption (i.e., Warfarin, Coumadin)
Take 1 hour before or 4 hours after the bile acid sequestrant

58. Fibric Acids Gemfibrozil - Lopid® Fenofibrate - Tricor®
Biggest effect is lowering triglycerides by increasing lipolysis

59. Fibric Acids Side Effects - abdominal pain - nausea - diarrhea
- muscle aches

60. Fibric Acids Drug interactions
- HMG-CoA Inhibitors (statins) – increase risk of myopathy, rhabdomyolysis and acute renal failure
- Niacin (myopathy)
- Warfarin Coumadin (blood thinner)

61. Fibric Acids Monitoring - Liver Function Tests (LFT) – ALT, AST
- CBC periodically

62. HMG Co-A Reductase Inhibitors “Statins”
Lovastatin – Mevacor®
Simvastatin - Zocor®
Pravastatin - Pravachol®
Fluvastatin - Lescol®
Atorvastatin - Lipitor®
Risurvastatin – Crestor®

63. HMG Co-A Reductase Inhibitors
Inhibits the enzyme HMG Co-A reductase
- required for cholesterol synthesis

64. HMG Co-A Reductase Inhibitors
Inhibits the enzyme HMG-CoA reductase
Required for cholesterol synthesis
Decrease LDL and TG, some increase in LDL
Avoid in patients with:
- active for chronic liver disease
- persistent elevation in LFT’s
- pregnancy, lactation and women of child- bearing age

65. HMG Co-A Reductase Inhibitors
Side Effects
Gastrointestinal
Hepatotoxicity
Myopathy (muscle aches, weakness)
Insomnia
Headache
Rash

66. Monitoring
Liver Function Tests
AST
ALT