Thiazide Diuretics Flashcards
What is the mechanism of action of thiazide diuretics?
Inhibition of Na/Cl symporter is the distal convoluted tubule
Increase in reabsorption of Ca due to stimulation of Na/Ca counter transporter
What drugs are thiazide diuretics?
Chlorothiazide, Hydrochorothiazide, Trichlormethiazide, Chlorthalidone
What are thiazide diuretics referred to as?
rescue diuretics
In what routes are thiazide diuretics absorbed well in?
all routes
How quickly, and how long, do responses occur when thiazide diuretics are used?
the response occurs 2-3 hours and lasts 6-12 hours
What are thiazide diuretics used for?
antihypertensive agent, used as an adjunct, treatment of post parturient udder edema in cattle, Ca-oxalate uroliths, and nephrogenic diabetes insipidus in dogs
What are the adverse effects and contraindications of thiazides?
Adverse effects - fluid and electrolyte imbalance, hypokalemia and hyperuricemia
Contraindications - hyperglycemia and glucosuria if used in diabetic and prediabetic animals
What electrolyte imbalance is associated with prologed thiazide use?
hypercalcemia
How do thiazidees produce hyperglycemia and glucosuria in diabetic and prediabetic animals?
they inhibit the conversion of proinsulin to insulin
What are the types of potassium-sparing diuretics?
Na channel blockers and aldosterone antagonists
What drugs are the Na channel blockers?
triamterene and amiloride
What drugs are the aldosterone antagonists?
spironolactone and potassium canrenoate
How do Na channel blockers work?
They block Na channels and reduce the luminal potential and the driving force for K secretion. They also reduce the lumen negative potential which decreases H secretion in the intercalated cells
What is the net effect of Na channel blockers?
Increased Na, decreased K, decreased H
What is the mechanism of action of aldosterone antagonists?
they completely inhibit the binding of aldosterone to its receptors and thereby reduce the synthesis of Aldosterone-induced proteins (AIP). Therefore, the antagonists inhibit some functions of AIP
What AIP functions do aldosterone antagonists inhibit?
Synthesis of Na/K channels
Synthesis of Na/K ATPase
Mitochondrial ATP production
What is the net effect of aldosterone antagonists?
increased Na, decreased K, and decreased H
K sparing diuretics are used in combination with ____ ____ diuretics.
potassium losing
In what cases are potassium sparing diuretics used in combination with potassium losing diuretics?
Chronic use for treatment of CHF
Treatment of aldosteronism
Treatment of ascites
What type of drugs are carbonic anhydrase inhibitors?
sulfonamide derivitives
What do carbonic anhydrase inhibitors do?
they inhibit carbonic anhydrase enzyme and reduce the number of hydrogen ions available for Na/H exchange
What does carbonic anhydrase inhibitors result in?
Increase NaHCO3 (Na bicarbonate ) excretion Increased K excretion Increased Cl retention (causes hypercholermic acidosis)
What therapeutic uses are carbonic anhydrase inhibitors used for?
for glaucoma and metabolic alkalosis
How are carbonic anhydrase inhibitors effective in treating glaucoma?
inhibition of ciliary body carbonic anhydrase which causes decreases aqueous humor production
What drugs are the xanthines (methylxanthines)?
Aminophylline, Theophylline, caffeine, and theobromine
What is the mechanism of action of xanthines?
It increases renal blood flow and increases GFR which then decreases Na reabsorption in the proximal convoluted tubule
What are the therapeutic uses of xanthines?
they are rarely used soley for diuresis but increase urine output
What urinary acidifiers did we talk about in class?
ammonium chloride and methionine
What is ammonium chloride used for?
it is going to lower the pH of ECF and urine which eventually causes an increased Cl load in the kidney producing urinary loss of Na and Cl and mild diuresis
What are the therapeutic uses of urinary acidifiers?
They promote the excretion of ionizable drugs or poisons by urinary cailcfication
Urinary stone dissolution and prevention
What do ace inhibitors do?
they prevent ACE from converting angiotensin I into Angiotensin II
What do AT1 receptor blockers do?
They block angiotensin II from interacting with AT1 receptors in vasculature
What drugs are the ACE inhibitors?
Captopril, Enalapril, Lisinopril and others
What drugs are AT1 receptor blockers?
Losartan, Irbesartan, and Valsartan
What therapeutic uses do Ace inhibitors and AT1 receptor blockers?
Vasodilators in heart failure
Treatment of hypertension
Adjunctive treatment in chronic renal failure
At1 blockers reduce mortality associated with cardiac problems and may have anticancer and neuroprotective properties
What is the Renin-Angiotensin-Aldosterone System (RAAS) a key regulator of?
BP, fluid volume, and electrolytes
