Diuretics, drug reaction

The expected outcomes for die patient depend on die reason for administration of die diuretic but may include an optimal response to drug dierapy, management of adverse drug reactions, correction of a fluid volume deficit, absence of injury, and an understanding of and compliance with the postdischarge drug regimen. 

Thiol elimination to create a C=C bond is also seen in the metabolism of spironolactone (11.101, Fig. 11.13) [131]. This diuretic drug undergoes a number of metabolic reactions in humans, one of which is ready hydrolysis at the thioester bond to yield deacetyl-spironolactone (see Chapt. 7). This reaction is in competition with other pathways such as lactone hydrolysis, S-oxygenation, and dethioacetylation. The latter reaction is the one of interest here, since the elimination of CH3CO-SH transforms the C(5)-C(6) bond into a C=C bond to produce the active metabolite canrenone (11.102, Fig. 

In face of the above discouraging results, recent innovative catalyst work has led to highly effective solutions for some otherwise very difficult and expensive problems. For example. Dolling and co-workers (Chapter 7) have shown that by careful choice of PTC catalyst and use of optimal reaction conditions one can obtain high chiral selectivity (greater than 90% enantiomeric excess) and have applied this chemistry to a commercial process for production of the diuretic drug candidate Indacrinone. 

Further investigation on the chemistry of the very potent diuretic drug ethacrinic acid W led to a compound that retained the high potency of the parent with reduced propensity for causing side effects, such as loss of body potassium and retention of uric acid. Friedel-Crafts acylation of dichioroanisole with phenyl acetyl chloride gives ketone 10. This is then reacted in a variant of the Mannich reaction which involves the aminal from dimethyl-... 

Hydrotalcite-derived materials also show good performances in analogous reactions, such as the Claisen-Schmidt condensation of substituted 2-hydroxyacetophe-nones with substituted benzaldehydes, the synthetic route to flavonoids and the condensation of 2,4-dimethoxyacetophenone with p-anisaldehyde to synthesize Vesidryl, a diuretic drug [270]. Another similar class of reactions in which HT-based materials give good results are Knoevenagel condensations [271]. An example is the synthesis of citronitrile, a perfumery compound with a citrus-like odor, which can be prepared by HT-catalyzed condensation of benzylacetone with ethyl cyanoacetate, followed by hydrolysis and decarboxylation (Figure 2.42b) [272]. 

The phototoxic diuretic drug furosemide 6, a 5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)-amino] benzoic acid, is photolabile under aerobic and anaerobic conditions. Previous studies have established that furosemide causes adverse photosensitizing effects in vivo and has a high in vitro photosensitizing capability. In this context, it is capable of initiating both energy transfer and free radical reactions. Irradiation of a methanol solution of 6 produces under an oxygen atmosphere photoproducts... 

The phototoxic diuretic drug acetazolamide 7 is photolabile under aerobic and anaerobic conditions in methanoUc solution as well as in buffered aqueous medium (pH = 7.2). The quantum yield under aerobic conditions was 0 = 0.24, and the reaction led to the formation of photoproducts 7a (yield 75%) and 7b (yield 25%) (Figure 63.4). The results indicate that Oj is directly involved in the photol) is of acetazolamide. The study of the influence of oxygen radicals on the decomposition of acetazolamide (irradiations in the presence of singlet oxygen quenchers) indicate that Oj may lead to degradation of 7 by oxygenation. 

Additional adverse reactions that may be seen when an antihypertensive drug is administered are listed in the Summary Drug Table Antihypertensive Drugs. For the adverse reactions that may be seen when a diuretic is used as an antihypertensive drug, see the Summary Drug Table Diuretics in Chapter 46. 

Discuss the uses, general drug actions, adverse reactions, contraindications, precautions, and interactions of the diuretics. 

Additional adverse reactions of these drugs are listed in tiie Summary Drug Table Diuretics. When a potassium-sparing diuretic and a thiazide diuretic are given together, tiie adverse reactions associated with both drugp may be seen. 

Administration of thiazides and related diuretics may be associated with numerous adverse reactions. However, many patients take these drug s without... 

ELECTROLYTE IMBALANCE The most common adverse reaction associated with the administration of a diuretic is the loss of fluid and electrolytes (see Display 46-1), especially during initial therapy with the drug. In some patients, the diuretic effect is moderate, whereas in others a large volume of fluid is lost. Regardless of the amount of fluid lost, there is always the possibility of excessive electrolyte loss, which is potentially serious. 

Oxcarbazepine Hyponatremia (serum sodium concentrations less than 125 mEq/L) has been reported and occurs more frequently during the first 3 months of therapy serum sodium concentrations should be monitored in patients receiving drugs that lower serum sodium concentrations (e.g., diuretics or drugs that cause inappropriate antidiuretic hormone secretion) or in patients with symptoms of hyponatremia (e.g., confusion, headache, lethargy, and malaise). Hypersensitivity reactions have occurred in approximately 25-30% of patients with a history of carbamazepine hypersensitivity and requires immediate discontinuation. 

Acute drug-related hypersensitivity reactions (allergic responses) may cause tubulointerstitial nephritis, which will damage the tubules and interstitium. These reactions are most commonly observed with administration of methicillin and other synthetic antibiotics as well as furosemide and the thiazide diuretics. The onset of symptoms occurs in about 15 days. Symptoms include fever, eosinophilia, hematuria (blood in the urine), and proteinuria (proteins in the urine). Signs and symptoms of acute renal failure develop in about 50% of the cases. Discontinued use of the drug usually results in complete recovery however, some patients, especially the elderly, may experience permanent renal damage. 

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