This triple symporter is the most potent pump in the renal tubule and is located in the thick ascending limb. 

Loop diuretics like Furosemide and Ethacrynic Acid act here.

Acetazolamide and Dorzolamide are the carbonic anhydrase inhibitors. 

They act at the proximal tubule, where carbonic anhydrase is membrane-bound and normally catalyses H2CO3-> H2O + CO2 in the lumen and the reverse reaction in the cytoplasm.  By blocking CA, acetazolamide and dorzolamide inhibit NaHCO3 reabsorption in the proximal tubule.

ultimate effects= increased Na+ excretion, increased bicarb excretion, retention of H+ and NH4+

This means: alkaline urine, metabolic acidosis

Carbonic anhydrase inhibitors (acetazolamide and dorzolamide) may cause:

decreased CSF production
decreased Aqueous Humor production

Kidney Stones (nephrolithiasis) because of calcium phosphate salt precipitation in the alkaline urine

Metabolic Acidosis (because of H+ retention and HCO3- loss)

Hypokalemia

The carbonic anhydrase inhibitors are acetazolamide and dorzolamide.  As they cause alkaline urine and the retention of ammonia (NH4+), they should not be given to patients suffering liver cirrhosis because they already suffer impairment of ammonia excretion.

COPD patients should not be put on CA inhibitors because they will have difficulty compensating for metabolic acidosis.

People already in hypokalemic states should not be put on CA inhibitors.

CA inhibitors are useful for patients with open angle glaucoma (they decrease aqueous humor production)

Edema from heart failure

Alkalosis caused by loop diuretics or thiazides

Epilepsy

Thiazides result in metabolic alkalosis. The mechanisms are three:  Increased H+ excretion, Hypokalemia, and secondary hyperaldosteronism.

By blocking NaCl reuptake in the early distal tubule, thiazides increase NaCl delivery to the collecting duct.  This increases urine flow, maintaining a concentration gradient for K+ and H+ secretion by flushing them quickly from the tubules.  There is also a system in the collecting duct that takes up Na+. This favors the secretion of K+ and H+ in its place for electroneutrality (principal cells = K+, intercalated cells = H+).  Therefore, Thiazide diuretics promote the exretion of both K+ and H+ as a result of an increased Na+ gradient.  The loss of H+ results in alkalosis. (Remember: one HCO3- is absorbed for each H+ excreted). 

Additionally, the hypokalemia created causes K+ within the body's cells to leak out into the interstitium.  To maintain electroneutrality, H+ enters the cells in place of K+.  This also contributes to the alkalosis! 

Loss of Na+ leads to Aldosterone release, which further promotes hypokalemia and alkalosis.

Thiazide diuretics are the diuretics of choice for hypertension in patients that still have good renal function.  They are also used in the treatment of edema in situations of heart failure, cirrhosis, nephrotic syndrome, and ascites.

Nephrogenic diabetes insipidus is also treated with thiazide diuretics.  An initial reduction of sodium reabsorption in the distal tubule increases sodium excretion and causes extracellular fluid volume contraction. As a result, the glomerular filtration rate decreases and the proximal tubular sodium and water reabsorption increases. Consequently, less water and sodium are delivered to the collecting tubules and, as a result, less water is excreted.

The loop diuretics are:

Furosemide

Ethacrynic Acid

Ethacrynic acid is not a sulfonamide.

It can be given to patients with sulfa-drug allergies or G6PD deficiency

Loop diuretics inhibit the Na+/K+/2Cl- triple symporter in the thick ascending limb of the loop of Henle.

They increase diuresis, but also cause increased capacitance in the venous beds, both of which reduce preload to the heart.

The loop diuretics stimulate renin release, resulting in an increased GFR.

Remember, the loop diuretics act on the thick ascending limb of the loop of Henle.  The Macula Densa is located here.  Normal Macula Densa function is to sense the Na+ concentration of the tubular fluid.  It does this by monitoring the amount of Na+ absorbed by the triple symporter (Na+/K+/Cl-) located in this ascending limb.  Because loop diuretics block the symporter, the macula densa essentially senses no Na+, which mimics a low GFR.  Under these conditions, the macula densa signals the juxtaglomerular cells to release renin, eventually leading to aldosterone release, sodium reabsorption, increased blood volume, and a restoration (increase) of GFR. 

Triamterene is a potassium-sparing diuretic.  It blocks Na+ channels in the late DCT and collecting tubule

Like most K+ sparing diuretics, triamterene is contraindicated in chronic renal insufficiency because in this condition, the kidney cannot handle potassium well and there is already a hyperkalemic state.

Carbonic Anhydrase inhibitors cause acidosis by preventing bicarb reabsorption.  They cause hypokalemia by increasing the tubular flow, thereby maintaining a K+ excretion gradient and minimizing the ability to reabsorb it.

The carbonic anhydrase inhibitors are acetazolamide and dorzolamide.

Amiloride is a potassium-sparing diuretic.  Use it in cases of lithium-induced nephrogenic diabetes insipidus.

Recall, thiazides have some use here too.

like all K+ sparing diuretics, amiloride can also be used to treat or prevent hypokalemic states

Use sodium bicarbonate.  This can be combined with carbonic anhydrase inhibitors (acetazolamide) for better efficacy.  The CA inhibitor prevents the reuptake of bicarb in the kidney. 

These drugs are used to aid the excretion of organic acids.  (ex: aspirin)

lactate, acetate, and citrate can also be used for urine alkalinization.

thiazides

(recall: acutely, blood pressure is lowered by thiazides through diuresis.  Over long term, thiazides promote vasodilation by Ca++ leaving the vascular smooth muscle)

Loop diuretics can also dilate the veins and renal arteries.

Thiazides block the reabsorption of Na+ in the DCT.  This results in less sodium inside the tubule cell.  On the basal membrane of the cell, there is a Ca++/Na+ exchanger (Na+ in, Ca++ out).  The decreased intracellular Na+ favors this pump's function, so it brings Na+ in and pumps Ca++ into the interstitial fluid (blood).  This results in an increased Ca++ concentration in the blood, aka hypercalcemia.

so if there is a question about a woman with osteoporosis and hypertension that needs a diuretic, think thiazides because the increased calcium levels will be beneficial!

Remember: when sodium is low inside the cell, calcium is low inside the cell!  Similarly, high Na+ inside the cell prevents the Na+/Ca++ exchanger, keeping the calcium concentration high as well.  Calcium concentration inside the cell mirrors the sodium concentration!

The kidney is able to dilute the urine in the thick ascending limb of the loop of Henle and the early Distal Convoluted Tubule.  Here, the ions, but not water, can be reabsorbed.  Therefore, thiazides and loop diuretics, which act at these areas, decrease the diluting capacity of the kidney.  Thiazides block the reabsorption of Na+ and Cl-.  Loop diuretics block the triple symporter of the ascending limb.

It is important to note that thiazides block only the diluting capacity of the kidney.  On the other hand, loop diuretics, because of their effects on the counter-current mechanism, decrease the concentrating capacity in addition to the diluting capacity.

Give thiazides for hypertension.  They are the drugs of choice.

However, in cases of renal insufficiency or heart failure, loop diuretics become the diuretics of choice for hypertension.

Thiazides cause hypercalcemia.

Thiazides block the reabsorption of Na+ in the DCT.  This results in less sodium inside the tubule cell.  On the basal membrane of the cell, there is a Ca++/Na+ exchanger (Na+ in, Ca++ out).  The decreased intracellular Na+ favors this pump's function, so it brings Na+ in and pumps Ca++ into the interstitial fluid (blood).  This results in an increased Ca++ concentration in the blood, aka hypercalcemia.

Aldosterone promotes the reabsorption of sodium and the excretion of K+

Therefore, anything that decreases aldosterone effects (captopril, spironolactone, beta blockers) can cause hyperkalemia!

Beta-blockers suppress renin release (thereby reducing aldosterone)!  remember that an additional effect of B1 receptors is to promote renin release.

Furthermore, beta-blockers hinder K+ uptake into skeletal muscle (Babbini's notes say this, but I don't know the mechanism)

Both thiazides and loop diuretics cause hyponatremia and hypokalemia.  A distinguishing feature is that thiazides cause hypercalcemia and loop diuretics cause hypocalcemia.

looooooop diuretics cause hypoooooo-every ion, including hypo-H+ (alkalosis)

(They do cause hyperuricemia and hyperglycemia though)

Spironolactone can help prevent hypokalemia caused by other diuretics.

Side note: Spironolactone is also useful in stopping heart remodeling effects of aldosterone!