918 7. MERCURIALS 



(page 742). Thus mercurin (Mercuzan) is the un-ionized acid, the Na+ salt 

 is Novurit, the complex with thioacetate is mercaptomerin (Thiomerin), 

 and the complex with theophylline is Mercurophylline (Mercuzanthin), but 

 the fundamental active structure is the same in all cases. The complexers 

 alter the solubility, local actions on tissues, and rates of absorption, but 

 probably do not significantly affect the basic effects on the tubular trans- 

 port systems. 



Summary of the General Renal Actions of the Mercurials 



(A) The diuretic action is entirely renal. Since the classic transplantation 

 and unilateral injection studies of Govaerts in 1928 and Bartram in 1932 it 

 has been clear that any extrarenal actions of the mercurials are unimportant 

 for diuresis. Effects on tissues other than the kidneys may of course occur, 

 especially at high doses, but do not contribute significantly nor are they 

 necessary for diuresis. 



(B) The primary action is on tubular transport rather than glomerular fil- 

 tration. Clearance studies have demonstrated that glomerular filtration rates 

 are not altered much or at all during marked clinical diuresis. Analyses of 

 the changes in composition of the filtrate as it passes down the nephron 

 show that the increased flow of urine can be accounted for entirely by the 

 depression of certain tubular transport processes. Mercurials given intramus- 

 cularly or orally to human subjects do not affect renal blood flow or glom- 

 erular filtration (Brun et al., 1947), but injected intravenously in animals 

 they produce definite effects which may possibly modify the primary diu- 

 retic action. Vasoconstriction and a reduction in blood flow are usually ob- 

 served. Jackson (1926 b) reported that intravenous mersalyl causes a rise 

 in blood pressure and a profound constriction of the kidney (measured on- 

 cometrically), while Farah (1952) observed the renal blood flow to fall 50% 

 from mersalyl at 10 mg/kg intravenously and 70% from 4 mg/kg intraarte- 

 rially, these changes occurring before the onset of diuresis. Kessler et al. 

 (1957 b) invariably found a significant decrease in glomerular filtration rate 

 following various mercurial diuretics given intravenously, and such often 

 persists long after the maximal diuretic effect occurs. Occasionally a trans- 

 ient antidiuresis is noted after intravenous diuretics and this could be the 

 result of renal vasoconstriction and a reduced glomerular filtration rate 

 (Vargas and Cafruny, 1959; Cafruny and Palmer, 1961). It is interesting to 

 note that the nondiuretic p-MB likewise produces these vascular changes. 

 Thus the effects on glomerular filtration when observed experimentally 

 would be antidiuretic and might reduce the over-all diuretic response in- 

 stead of favoring it. 



(C) The diuretic action is mainly due to an inhibition of active iVa+ resorp- 

 tion in the proximal tubules. It is now generally agreed that the mercurials 



