Diuretic activity inhibition

Tyrosine hydroxylase 1 Thiazide diuretics, a group of drugs with moderate diuretic activity, includes hydrochlorothiazide, chlorthalidone, and xipamide. They decrease active reabsorption of sodium and accompanying chloride by binding to the chloride site of the electroneutral Na+/CF cotransport system in the distal convoluted tubule and inhibiting its action. 

Ureido derivatives of l-alkenyl-3-alkyl-6-aminouracils, such as (LXXI), are reported to have particular activity as appetite inhibitors. They also have anti-secretory, anti-iritic and mild diuretic activities [438]. The related 5-sulphon-amides, such as (LXXII), are said to inhibit the appetite without producing other pharmacological responses such as pressor-depressor, or diuretic effects [439]. 

These compounds competitively inhibit phosphodiesterase, resulting in an increase in cyclic AMP (see Box 14.3) and subsequent release of adrenaline. This leads to the major effects a stimulation of the central nervous system (CNS), a relaxation of bronchial smooth muscle, and induction of diuresis. These effects vary in the three compounds. Caffeine is the best CNS stimulant, and has weak diuretic action. Theobromine has little stimulant action, but has more diuretic activity and also muscle relaxant properties. Theophylline also has low stimulant action and is an effective diuretic, but it relaxes smooth muscle better than caffeine or theobromine. 

One of the side effects noted in the clinical use of the sulfonamide antibacterial agents was a diuretic effect caused by inhibition of the enzyme carbonic anhydrase. Attempts to capitalize on this side effect so as to obtain agents with greatly enhanced diuretic activity first met success when a heterocyclic ring was substituted for the benzene ring of the sulfonamide. Treatment of the hydrazine derivative, 151, with phosgene leads... 

A great advance in potency was achieved with the 1,2,4-benzothiadiazine 1,1-dioxide chlorothiazide (190), a cyclized aniline-2,4-disulfonamide which is a weaker inhibitor of carbonic anhydrase than acetazolamide, but a more powerful diuretic. The major contribution to diuretic activity in these compounds must come from some factor other than the inhibition of carbonic anhydrase since a ten-fold increase in activity was seen in the reduced compound hydrochlorothiazide (191 R1 = R2 = H, R3 = CI) which has only one-tenth of... 

Spironolactone competitively inhibits the physiologic effects of the adrenocortical hormone aldosterone on the distal tubules, thereby producing increased excretion of sodium chloride and water, and decreased excretion of potassium, ammonium, titratable acid, and phosphate. Spironolactone is a potassium-sparing diuretic that has diuretic activity only in the presence of aldosterone, and its effects are most pronounced in patients with aldosteronism. Spironolactone does not interfere with renal tubular transport mechanisms, and does not inhibit carbonic anhydrase. 

PUFAs suppress HMG-CoA reductase and ACE activities, inhibit platelet aggregation, enhance parasympathetic activity and, thus, enhance heart rate variabihty (and thus, have actions similar to that of fS-blockers), and possess diuretic properties either by themselves and/or by increasing the formation of PGAs and PGEs that have been shown to increase renal blood flow and augment diuresis. These actions of PUFAs are similar to that of the polypill that is a combination of aspirin, fS-blockers, statins, and ACE inhibitors, which is expected to reduce cardiovascular diseases by over 70-80% (92). This suggests that PUFAs could function as an endogenous polypill the evidence for this is detailed below. 

The hypoglycemic and lipolysis-inhibiting compounds, 5-dimethyl-pyrazole and 3>5-dimethylisoxazole, produce a significant diuresis in fasted rats at 100 and 50 mg./kg. i.p. This effect is greatly attenuated in water-loaded rats and is not observed in guinea pigs.5° The diuretic activity like the hypoglycemic activity of these compounds appears to be species-specific. 

T-type calcium channels (with the T standing for transient ) require only a weak depolarization for activation and carry a transient current at negative membrane potentials that inactivates rapidly during a prolonged pulse. In neurons, the T-type channel is responsible for neuronal oscillatory activity and is thought to play a role in the regulation of wakefulness and motor coordination. The pyrazine diuretic, amiloride, inhibits the T-type calcium channel. 

Hydrochlorothiazide/triamterene is a diuretic combination. Hydrochlorothiazide inhibits reabsorption of sodium and chloride in the ascending loop of Henle and early distal tubules. Triamterene interferes with sodium reabsorption at the distal tubule. The combination provides additive diuretic activity and antihypertensive effects and minimizes potassium depletion. They are indicated in the treatment of edema or hypertension in patients who have, or are at risk of developing, hypokalemia. 

The thiazide diuretics, also called sulfonamide or ben-zothiadiazide diuretics, vary in their actions. For instance, the potency of hydrochlorothiazide (Hydro-Diuril and Esidrix) is ten times greater than that of chlorothiazide (Diuril), but the drugs have equal efficacy. The duration of action of hydrochlorothiazide, which is 6 to 12 hours, equals that of chlorothiazide. On the other hand, chlorthalidone (Hygroton) has a duration of action lasting 48 hours. Some thiazide derivatives inhibit carbonic anhydrase, which is unrelated to their diuretic activity. Those that are active in this respect may, at sufficient doses, have the same effect on bicarbonate excretion as does acetazola-mide. They cause a moderate loss of sodium (5 to 10% of the filtered load), chloride, and water, and the clearance of free water is impaired. They may cause metabolic alkalosis (resorption of bicarbonate and loss of hydrogen ions), hyperuricemia (enhanced resorption of uric acid), or hyperglycemia (due to directly inhibited insulin release and to hypokalemia). 

Possesses diuretic activity on account of its action on the transport meehanism pertaining to the cells of the thick ascending limb of Henle s loop. However, the precise mechanism(s) by whieh muzolimine causes a diuretic action still remains to be established legitimately. Furthermore, it has been proposed that muzolimine, in fact, inhibits the K CH contransport system speeifieally upon the basolateral membrane of the thick ascending limb cells, whereby it affords an inhibition of the 1 Na /I K%2 d contransport system. ... 

A. Mannitol is an osmotically active solute diuretic. Mannitol inhibits water reabsorption at the loop of Henie and the proximal tubule. The increase in urine output is usually accompanied by an increase in solute excretion. In addition, mannitol transiently increases serum osmolality and decreases cerebrospinal fluid pressure by creating an osmotic gradient between brain tissue and the vascular compartment. Water moves across this gradient into the blood vessels, lowering the cerebrospinal fluid pressure and decreasing intracranial pressure. 

Toxicity On account of its structural similarity to l- arginine, C. is considered to be its antimetabolite and causes poisoning symptoms in mammals and plants C. inhibits biosynthesis, uptake, and transport of arginine. It can be bound to tRNA by arginyl-tRNA synthetase and be incorporated in place of arginine in proteins. This changes the tertiary and quaternary structure of the protein . C. exhibits diuretic activity . 

Substituent Relative Diuretic Activity Dog Man Lipid Partition Carbonic Anhydrase Inhibition Hydrolysis 2k hrs., 37° pH 4 pH 8 ... 

Leu2, Leu ]oxytocin, which has natriuretic activity and weak diuretic effects, is also an inhibitor of oxytocic activltyl in contrast to [Leu ]oxytocin which has considerable diuretic and natriuretic effects as well as anti-ADH activity (inhibiting the antidiuretic effect of vasopressin) other 4-substituted oxytocins have been reported to have anti-ADH... 

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