Diuretics

• ACIDazolamide causes acidosis.

• Loops Lose calcium

• It has been said that the initial phase of uricosuric therapy is the most worrisome period. Probenecid is a uricosuric drug, but that effect depends on having high (therapeutic) blood levels that are sufficient to inhibit active tubular reabsorption of urate. At subtherapeutic blood levels the main effect is inhibition of tubular secretion of urate, which reduces net urate excretion and raises serum urate levels (sometimes to the point of causing clinical gout). It is only once drug levels are therapeutic that the desired effects to inhibit tubular reabsorption of urate predominate. Thus, and intuitively, once a patient starts probenecid therapy drug levels must pass through that stage in which urate excretion will actually go down.

• Aspirin (given alone) has blood level–dependent effects on urate elimination by the kidneys. At “low doses” perhaps up to about 1 g/day, it selectively inhibits tubular secretion of urate and so can raise serum urate levels. At doses much higher than that (including doses sometimes prescribed for arthritis other than gout), the predominant effect (and the net, or overall, effect) is uricosuria due to blockade of tubular reabsorption of urate; this effect is greater than the drug’s inhibitory effect on tubular secretion of urate. Nonetheless, aspirin is not used as a uricosuric drug because the doses/serum levels needed to cause that are sufficiently high to cause significant side effects  that don’t arise with the traditional uricosurics such as probenecid.

• You might recall that diazoxide [mainly used as a parenteral drug for prompt lowering of blood pressure] can be used in its oral dosage form to raise blood glucose levels in some hypoglycemic states. It is, chemically, a thiazide, but is not used as a diuretic.