Nonsteroidal anti-inflammatory drugs excretion

Lithium toxicity can occur as a result of intentional overdose therefore, care must be taken when administering lithium to potentially suicidal patients with BPAD. Inadvertent lithium toxicity may also occur. For example, diuretics and nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin) slow the excretion of lithium and can lead to accidental toxicity. Consequently, the patient should be advised not to take such commonly available medications while treated with lithium. In addition, dehydration resulting from varied causes such as diarrhea, vomiting, and profuse sweating can lead to accidental lithium toxicity. One should advise the patient who takes lithium to be careful to remain well hydrated at all times and to contact his/her physician if any medical condition arises that may cause rapid fluid losses (e.g., stomach virus, high fevers). 

Nonsteroidal anti-inflammatory drugs (SSRIs given) [NE] Reduced renal lithium excretion (except sulindac and salicylates). 

Researchers at Rutgers University have developed biocompatible polymers that degrade into nonsteroidal anti-inflammatory drugs. For example, the reaction of two equivalents of benzyl salicylate and one equivalent of sebacoyl chloride forms a poly(anhydride ester) called PolyAspirin, which hydrolyzes to salicylic acid (an anti-inflammatory agent) and sebacic acid, which is excreted. This technology can perhaps be used for localized drug delivery at specific sites of injury. What is the structure of PolyAspirin ... 

Zafirovska KG, Bogdanovska SV, Marina N, GruevT, Lozance L Urinary excretion ofthree specific renal tubular enzymes in patients treated with nonsteroidal anti-inflammatory drugs (NSAID). Renal Failure 1993 15 51-54. 

B. Chronic intoxication may occur in patients on stable therapeutic doses. Lithium is excreted by the kidney, where it is handled like sodium any state that causes dehydration, sodium depletion, or excessive sodium reabsorption may lead to increased lithium reabsorption, accumulation, and possibly intoxication. Common states causing lithium retention include acute gastroenteritis, diuretic use, use of nonsteroidal anti-inflammatory drugs or angiotensinconverting enzyme (ACE) inhibitors, and lithium-induced nephrogenic diabetes insipidus. 

Drugs that are subject to enterohepatic cycling are, therefore, excreted slowly. Pertinent examples include digi-toxin and acidic nonsteroidal anti-inflammatory agents (p. 200). 

Interactions. Several types of drug interfere with lithium excretion by the renal tubules, causing the plasma concentration to rise. These include diuretics (thiazides more than loop type), ACE inhibitors and angiotensin-11 antagonists, and nonsteroidal anti-inflammatory analgesics. Theophylline and sodium-containing antacids reduce plasma lithium concentration. The effects can be important because lithium has such a low therapeutic ratio. Diltiazem, verapamil, carbamazepine and pheny-toin may cause neurotoxicity without affecting the plasma lithium. Concomitant use of thioridazine should be avoided as ventricular arrhythmias may result. 

The exact mechanism of the pentamidine-induced hyperkalemia has not yet been defined. Many different mechanisms can impair the renal handling of potassium and thus favor hyperkalemia in patients with AIDS. These include decreased renal function secondary to volume depletion, presence of under-lying renal disease, including tubular dysfunction with the possibility of hyporeninemic hypoaldos-teronism, hypoadrenalism, and the administration of drugs with potential for impairing renal potassium excretion (nonsteroidal anti-inflammatory agents, ACE inhibitors, potassium-sparing diuretics. 

In terms of drug disposition, OATl is the most important member of this transport family. Expressed mainly in the kidney tubule cell, OATl is a dicarboxylate exchange protein that is responsible for basolateral uptake of organic anions such as para-aminohippurate (PAH). OATl mediates the excretion of a diverse array of substrates, including environmental toxins. Substrates for this transporter include antibiotics, antiviral nucleoside analogs, and nonsteroidal anti-inflammatory medications. In fact, more than 100 medications and toxic compounds have been found to interact with OATl. 

Most of the renal tubular reabsorption ofU occurs in the proximal tubule. Nevertheless, Id retention can be increased by any diuretic that leads to depletion of Na, particularly the thiazides (see Chapter 28). Renal excretion can be increased by administration of osmotic diuretics, aceta-zolamide or aminophylline, and triamterene. Spironolactone does not increase the excretion of LiL Some nonsteroidal anti-inflammatory agents can facilitate renal proximal tubular resorption of Id and thereby increase concentrations in plasma to toxic levels. This interaction appears to be particularly prominent with indomethacin, but also may occur with ibuprofen, naproxen, and COX-2 inhibitors, and possibly less so with sulindac and aspirin. A potential drug interaction can occur with angiotensin-converting enzyme inhibitors, causing lithium retention (see Chapter 29). 

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