Diuretics (Ex2) Flashcards
What are diuretics?
- drugs that increase the rate of urine flow and urine volume
- also increase the rate of sodium excretion
What is the diuretic effect of Dopamine?
- increases urination
- activation of dopamine receptors dilates renal vascular beds
What is the diuretic effect of Epinephrine and Norepinephrine
- decreases urination
- stimulates cardiac contraction using beta-1 receptors, leading to vasoconstriction of renal arteries, and decreased GFR
What is the diuretic effect of Isoprotenol?
- an anti-diuretic
- beta-2 vasodilation, so not enough blood reaches the kidney
What are cardiovascular diuretics and what are they used for?
- not technically diuretics, but their effects on the heart leads to diuresis
- treatment of edema associated with congestive heart failure
What are some cardiovascular diuretic durgs?
- Digitalis (digoxin)
- Phosphodiesterase inhibitors: aminophylline, inamrinone, milrinone
- Caffeine: methylxanthine
What are the two physiological diuretics, and what are they used in?
Water: expanded blood volume, so inhibition of ADH in collecting duct
- used in compensated chronic interstitial nephritis of dogs
Sodium chloride: used in urolithiasis in sheep, calves, and cats
Name 4 osmotic diuretic drugs
- Mannitol
- Urea
- Glycerin
- Isosorbide
Where do osmotic diuretics act?
How effective are they? (1st, 2nd, etc.)
Primary site: loop of henle
Secondary site: proximal tubule
3rd most effective
Explain the mechanisms of action of osmotic diuretics
- interfere with transport mechanisms in thick aLOH, increasing urine excretion of Na, K, Ca, Mg, Cl, HCO3, and phosphate
- osmotic effect in tubule, and reduce medullary tonicity
- increase renal blood flow and renal medullary blood flow, which increases GFR
What are the therapeutic uses of osmotic diuretics?
- treatment of cerebral edema
- treatment of glaucoma
- treatment of acute renal failure
- mobilization of edema fluid
- used in patients with drug overdose
Mannitol
Type of drug, use, contraindications
- osmotic diuretic
- used to treat localized edema
- least likely to cause electrolyte imbalance
- can cause hypokalemia which can result in arrhythmias
- contraindicated in generalized edema
Explain the pharmacokinetics of the 4 osmotic diuretic drugs
- mannitol and urea administered IV, because they are poor penetrators of membranes
- mannitol is not metabolized, and is eliminated rapidly by the kidneys
- glycerin and isosorbide are administered orally
What are 3 loop diuretics?
Furosemide
Bumetanide
Ethacrynic acids
Where do loop diuretics act?
How effective are they?
Ascending loop of henle
Most effective diuretics because 25% of Na is absorbed here
Explain the mechanism of action of loop diuretics
- Inhibit Na-K-2Cl symporter in aLOH, also absorption of Mg and Ca
- creates a lumen negative transmembrane potential difference, facilitating K+ excretion and H+ secretion, resulting in hypokalemia and systemic alkalosis
- stimulates renin-angiotensin-aldosterone system
- increases total renal blood flow
- increases systemic venous capacitance (lowers blood pressure)
What are the therapeutic uses of loop diuretics?
- trtmt of acute pulmonary edema and congestion, generalized edema associated with CHF, renal failure, and liver cirrhosis
- with isotonic solution to treat hypercalcemia and to prevent volume depletion
- trtmt of increased intracranial pressure and udder edema
- trtmt of exercise induced pulmonary hemorrhage in horses (furosemide)
- used in drug overdoses
- with hypertonic saline for severe hyponatremia
- trtmt of edema of nephrotic syndrome
Adverse effects of loop diuretics
- ototoxicity
- hypokalemia, hypomagnesemia, hypovolemia
- hypotension
- cardiac arrhthymias
- hyperglycemia, hyperuricemia
- systemic alkalosis
- hypersensitivity to sulfonamides
Explain the pharmacokinetics of Furosemide
- administered orally and IV
- rapid onset, short duration
- partly metabolized by conjugation
- partly secreted unchanged in urine
- actively secreted in urine by the organic acid secretory mechanism
What are 2 thiazide diuretics?
- Hydrochlorothiazide
- Chlorothiazide
Where do thiazide diuretics act?
How effective are they?
- distal convoluted tubule
- 2nd most effective because 5% of Na is reabsorbed at the early distal tubule
Explain the mechanism of action of thiazide diuretics
- inhibit Na-Cl symporter in distal tubule
- inhibits K and Mg reabsorption
- increases reabsorption of Ca
What are the therapeutic uses of thiazide diuretics?
- trtmt of edema due to CHF, liver cirrhosis, nephrotic syndrome, and acute glomerular nephritis
- trtmt of hypertension
- trtmt of nephrogenic and central diabetes insipidus
- trtmt of calcium nephrolithasis and possibly osteoporosis
- trtmt of udder edema
Adverse effects of thiazide diuretics
- electrolyte imbalance (hyponatremia, hypokalemia, hypomagnesemia, hypercalcemia)
- hyperglycemia
- hypersensitivity to sulfonamides
- hyperlipidemia
