diuretics

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Author:
kodak168
ID:
240558
Filename:
diuretics
Updated:
2013-10-14 15:37:37
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Pharm
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Description:
drugs affecting hemodyamic status
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  1. Diuretics
    •Increase the output of urine

    –Treatment of hypertension



    –Mobilization of edematous fluids



    –Prevent renal failure
  2. Three Components
    of Urine Formation
    •Filtration

    •Reabsorption

    •Secretion
  3. types of diuretic and where they work along the renal tubule
  4. Adverse Effects of Diuretics
    •Hypovolemia

    • –Dehydration, orthostatic
    • hypotension , thirst



    •Acid-base imbalance

    • –All metabolic processes need
    • 7.35-7.45



    •Disturbance of electrolyte levels

    • –s/s of imbalances-movement, neuro,
    • cognitive
  5. High Ceiling (Loop)
    Furosemide/Lasix

    • •Ascending
    • loop of Henle

    • –Depends
    • on local prostaglandin availability

    • •Blocks
    • Na+ and Cl-
    • reabsorption

    • •Last
    • for: Oral (8 hr) IV (2 hr)

    • •Hyponatremia/lithium
    • toxicity, hypochloremia,
    • hypovolemia, hypotension, hypokalemia/dig toxicity, ototoxicity



    • •Ethacrynic
    • acid/Edacrin,
    • bumetanide/Bumex,
    • torsemide/Demadex
  6. Thiazide Diuretics
    Hydrochlothiazide/HCTZ/Hydrodiuril

    • •First
    • part of distal convoluted tubule

    • –Blocks
    • Na+ and Cl-
    • reabsorption

    • –Much
    • less H20 loss than loop-but lytes loss

    • •Do
    • not work if GFR <20cc/min

    • –Can’t
    • be used for renal failure

    • •Used
    • for hypertension and edema

    • •Paradoxical
    • affect in DI

    • •Hyponatremia,
    • hypochloremia,
    • hypovolemia, hypokalemia, retention of uric acid (gout)

    • 11
    • chemically similar drugs
  7. Potassium-Sparing Diuretics
    Spironolactone/Aldactone

    •Late distal tubule

    • •Limited urine production, but
    • significantly decreases K+ loss

    –Used with other diuretics

    • •Adosterone
    • Antagonist-spironolactone/Aldactone

    • –  NA+
    • excretion increased causing inc save
    • of K+

    •Non Aldosterone Antagonists

    • –-trimaterene/Dyrenium
    • & amiloride/Midamore

    • –Inc Na+
    • (H20) loss & Directly blocks K+ loss

    • –Given in combo with loop diuretics
    • to counter K+ loss
  8. Osmotic Diuretics
    Mannitol/Osmotrol

    • •Creates an osmotic force within the lumen
    • of the nephron

    • –Inhibits the passive reabsorption
    • of water

    • •Moves intracellular fluid into vascular
    • space

    •Physiologically inert

    •Not absorbed through gastric mucosa

    –Must be given IV

    •Given for edema-loss of tissue fluid

    –Decrease ICP
  9. Cholesterol Lowering Agents
    •Cholesterol

    • –component
    • of all cell membranes

    • –essential
    • for hormone and bile production

    • –produced
    • in the liver

    • –HMG-CoA
    • reductase

    • •provides
    • for cholesterol production

    • •Lipoproteins
    • carry cholesterol and triglycerides in the body

    • –LDL
    • carry cholesterol to the body tissues

    • –HDL
    • carry cholesterol back to the liver
  10. Atherosclerosis
    •LDL enters sub endothelial space

    •Attract inflammatory cells (macrophages)

    • •Macrophages engulf LDL becoming “foam
    • cells” that form fatty streaks (Plaques)

    •Plaques enlarge & damage the vessel

    • •Changes in vessel structure, smooth
    • muscle cells migrate, inflammatory process

    •Rupture of the plaque and vessel occlusion
  11. atherosclerosis in action
  12. Treatment of High Cholesterol
    •Therapeutic Lifestyle Changes Diet

    –200mg/day cholesterol intake

    –Sat fat <7% of total calories

    •Weight Control

    • –ADA-DM over age 40-treat if TC is
    • >135.

    •Exercise

    •Smoking Cessation

    •Drug Therapy

    • –Statins, bile acid sequestrants,
    • nicotinic acid
  13. HMG-CoA Reductase Inhibitors
    statins

    •Reduce LDL and increase HDL

    •Promote plaque stability

    –Used as ACS prevention

    • •LDL production is decreased AND there is
    • also an increase in hepatic LDL receptors

    • •Most cholesterol production is done at
    • night, so take drug in the evening.
  14. Statins
    •Atorvastatin/Lipitor

    •Simvastatin/Zocor- Never more than 80 mgs

    •Lovastatin/Mevacor





    •Risuvastatin/Crestor

    –Rhabdomyolysis
  15. Adverse Effects of Statins
    • •Headache,
    • rash, GI disturbances

    • –Mild
    • and transient

    •Hepatotoxicity-.5-2%

    • –Monitor
    • LFT (Mevacor
    • and Zocor)

    •Myositis-1-5%

    • –Myositis
    • progressing to myopathy to rhabdomyolysis

    • –Monitor
    • for muscle pain (CK levels)

    • •Grapefruit
    • juice, cyclosporine, antibiotics, and others increase blood levels (P450)
  16. Patho of Myositis
    • •Decreases in cholesterol content of
    • skeletal muscle membranes making them unstable and thus more prone to injury

    • •Depletion of coenzyme Q10 with subsequent
    • deleterious effects on mitochondrial function

    • •Reduced bioavailability of isoprenoids
    • which can lead to cell death in vitro
  17. Working with Side Effects (statins)
    •Try every-other-day statin dosing.


    •Check for thyroid imbalance.


    • –uncontrolled hypothyroidism
    • increased risk for muscle-related statin side effects.

    •Check vitamin D status.


    • –Anecdotal reports side effects
    • resolve with correction of vitamin D deficiency.
  18. Working with Side Effects
    (coenzymes)
    •Consider coenzyme Q10

    • •Several small trials
    • suggest that coQ10 (100-200 mg/day) can help prevent statin-related muscle side
    • effects.

    • •an antioxidant that
    • helps stabilize membrane

    • •a role in mitochondrial function: ATP
    • production

    •safe
  19. Nicotinic Acid
    Niacin

    • •Decreases
    • triglycerides & LDL production

    • –Stops
    • production of VLDL

    • –LDL
    • is a product of VLDL degradation

    •Increases HDL better than any drug

    • •Reduces
    • coronary risk and mortality

    • •Adverse
    • effects

    • –Skin
    • flushing and itching

    • –Gi
    • disturbances

    • –Hepatotoxic-with
    • high doses

    • –Hyperglycemia
    • and gouty arthritis
  20. Bile Acid Sequestrants
    Cholestyramine/Questran

    • •Binds
    • with bile acids in the gut to prevent reabsorption

    • •Decrease
    • in bile acids creates a demand for more production

    • •Bile
    • acids are made from cholesterol, so liver increases number of LDL receptors

    • •Constipation,
    • indigestion, nausea-(with food)

    • •Decrease
    • uptake of fat soluble vitamins, warfarin, statins, and other drugs

    • –Take
    • coumadin
    • 1 hour before
  21. New Bile Acid Sequestrant
    Colesevelam/WelChol

    • •Better tolerated, less constipation,
    • nausea

    •Does not affect fat soluble vitamins

    • •Does not reduce absorption of statins,
    • warfarin and other drugs

    •Very expensive
  22. Cholesterol Absorption Blocking
    Ezetimibe/Zetia

    • •Blocks cholesterol absorption in the
    • small intestine

    • •Affects dietary and cholesterol secreted
    • in bile

    • •Well-tolerated, use with caution in liver
    • failure

    •Post marketing reports

    • –Myopathy, rhabdomyolysis,
    • hepatitis, pancreatitis, thrombocytopenia
  23. Fibric Acid Derivatives
    (Fibrates)

    •Most effective for lowering triglycerides

    •Can raise HDL, no effect on LDL

    • •Accelerates the breakdown of
    • triglycerides

    •Rashes and GI disturbances

    •Gallstones, myopathy

    •Gemfibrozil/Lopid

    •Fenofibrate/Tricor
  24. CETPI
    cholesteryl ester transfer protein Inhibitor

    •Move cholesterol from HDL to LDL

    •Inhibit lipid transfer to increase HDL



    • •Dalcetrapib-phase
    • II in 2010-

    –Increased HDL do not decrease LDL

    • •Anacetrapib-phase
    • II interim results-encouraging continuing until 2012

    –Increased HDL, decrease LDL

    • •Evacetrapib-near
    • to marketing
  25. Others
    • •Plant
    • Stanol
    • & Sterol Esters

    • –derived
    • from plant material can reduce intestinal absorption of cholesterol

    • –Benecol
    • and Take Control margarines

    •Estrogen

    • –Reduces
    • LDL and raises HDL

    • –Does
    • not reduce M & M

    •Cholestin

    • –Dietary
    • supplement

    • –Rice
    • fermented in red yeast-contains lovastatin

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