diuretics

•Increase the output of urine

–Treatment of hypertension

–

–Mobilization of edematous fluids



–Prevent renal failure

•Filtration

•Reabsorption

•Secretion

•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

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

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

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

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

•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

•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

•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

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.

•Atorvastatin/Lipitor

•Simvastatin/Zocor- Never more than 80 mgs

•Lovastatin/Mevacor





•Risuvastatin/Crestor

–Rhabdomyolysis

• •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)

• •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

•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.

•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

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

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

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

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

(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

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

• •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