Kidney diazoxide

Diazoxide lowers blood pressure within 3 to 5 minutes after rapid intravenous injection, and its duration of action may be 4 to 12 hours. Interestingly, if diazoxide is either injected slowly or infused its hypotensive action is quite modest. This is believed to be due to a rapid and extensive binding of the drug to plasma proteins. Both the liver and kidney contribute to its metabolism and excretion. The plasma half-life is therefore prolonged in patients with chronic renal failure. 

AMP is related to certain mental diseases and may be involved in the action of tranquilizers and antidepressant drugs (60). Whether the ability of diuretic agents such as ethacrynic acid and chlorthalidone to inhibit the enzyme in kidney (68) is related to their diuretic action is also not known. It has been suggested that inhibition of diesterase by diazoxide (59) may explain the hyperglycemic activity of this agent. Several materials are known to activate the enzyme. Imidazole produces strong activation of the enzyme from mammalian tissues (36, 38, 42) but not from E. coli (41). It has been reported (61) that insulin activates the beef heart enzyme in vitro, but it is not known if this has relevance... 

Diazoxide is well absorbed orally. It is distributed to the plasma where it is highly bound (>90%) to the plasma proteins. It readily crosses both the placental and blood brain barriers. The volume of distribution is 180 ml kg The half-life of elimination for diazoxide is 15-30 h. Approximately 20-50% of diazoxide is eliminated unchanged by the kidney, with the remainder being metabolized by the liver to 3-carboxy and 3-hydroxymethyl derivatives. 

Three hours after receiving intravenous cisplatin 70 mg/m a patient experienced severe nausea and vomiting and his blood pressure rose from 150/90 to 248/140 mmHg. This was managed with furosemide 40 mg intravenously, hydralazine 10 mg intramuscularly, diazoxide 300 mg intravenously and propranolol 20 mg orally twice daily for 2 days. Nine days later the patient showed evidence of renal impairment (creatinine raised from about 88 micromol/L to 283 micromol/L), which resolved within 3 weeks. The patient was subsequently similarly treated on two occasions with cisplatin and again developed hypertension, but no treatment was given and there was no evidence of renal impairment. The reasons for the renal impairment are not known, but a study in rats indicate that kidney damage may possibly be related to the concentrations of cisplatin, and that furosemide can increase cisplatin levels in the kidney. However, another study in patients found that there was no difference in the toxicity or pharmacokinetics of cisplatin when furosemide was used to induce diuresis, compared with mannitol. Two other studies have also found that furosemide does not alter cisplatin pharmacokinetics. Another study showed that sodium chloride solution with or without furosemide was associated with less cisplatin nephrotoxicity than sodium chloride solution with mannitol. ... 

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