Sulphonamides diuretic

All these compounds grouped together under miscellaneous sulphonamide diuretics shall be treated individually as under ... 

How would you synthesize chlorthalidone, a sulphonamide diuretic, from 3-amino-4-chloro benzophenone-2-carboxylic acid ... 

There are a relatively large number of compounds that might be grouped together under the heading of sulphonamide diuretics. Within the group of compounds containing this functionality, we have a variety of different classes of diuretics based on their mechanism of action. These compounds are considered active as carbonic anhydrase inhibitors (acetazolamide), inhibitors of the reabsorption of Na+ Cl (thiazide and thiazide-like diuretics [benzthia-zide, hydrochlorothiazide]) and inhibitors of the Na K Cl symporter (fiirosemide). 

The development of sulphonamide diuretics arose from early observations concerning the use of sulfanilamide as an antibacterial agent. Sulfanilamide was shown to be the active metabolite of prontosil (Fig. 12.20) when used... 

The BNF lists a number of other compounds that can be classified as sulphonamide diuretics and these compounds are detailed in Figures 12.25 and 12.26. 

Fagerlund, C., Hartvig, E, and Lindstrom, B. (1979) Extractive alkylation of sulphonamide diuretics and their determination by electron-capture gas chromatography.of Chromatography, 168,107-116. 

The benzothiadiazides and the newer thiazide-like diuretics antagonise the absorption of Na-i- and Cl- in the DCT by inhibition of the Na+/CI- symport mechanism in the luminal membrane (Figure 12.4). They do not have any effect on the LoH. Some of the thiazides are thought to have a minor action on the PCT but this is minimal and is not due to inhibition of the Na-i-/CI- symporter. It may be due to carbonic anhydrase inhibition which is a feature of sulphonamide-derived drugs. 

PORFIMER I. ACE INHIBITORS -enalapril 2. ANALGESICS -celecoxib, ibuprofen, ketoprofen, naproxen 3. ANTIARRHYTHMICS — amiodarone 4. ANTIBIOTICS -ciprofloxacin, dapsone, sulphonamides, tetracyclines 5. ANTICANCER AND IMMUNOMODULATING DRUGS -fluorouracil (topical and oral) 6. ANTIDIABETIC DRUGS-glipizide 7. ANTIMALARIALS -hydroxychloroquine, quinine 8. ANTIPSYCHOTICS -chlorpromazine, fluphenazine 9. CALCIUM CHANNEL BLOCKERS - diltiazem 10. DIURETICS -bumetanide, furosemide, hydrochlorothiazide II. PARA-AMINOBENZOIC ACID (TOPICAL) 12. RETINOIDS-acitretin, isotretinoin 13. SALICYLATES (TOPICAL) t risk of photosensitivity reactions Attributed to additive effects Avoid exposure of skin and eyes to direct sunlight for 30 days after porfimer therapy... 

Systemically taken drugs that can induce photosensitivity are many. Of the drug groups given below, those most commonly reported are antimitotics dacarbazine, vinblastine antimicrobials demeclocycline, doxycycline, nalidixic acid, sulphonamides antipsychotics chlorpromazine, prochlorperazine cardiac arrhythmic amiodarone diuretics frusemide (furosemide), chlorothiazide, hydrochlorothiazide fibric acid derivatives, e.g. fenofibrate hypoglycaemic tolbutamide... 

Exanthematic/maculopapular reactions are the most frequent unlike a viral exanthem the eruption typically starts on the trunk the face is relatively spared. Continued use of the drug may lead to erythroderma. They commonly occur at about the ninth day of treatment (or day 2-3 in previously exposed patients), although onset may be delayed until after treatment is completed causes include antimicrobials, especially ampicillin, sulphonamides and derivatives (sulphonylureas, frusemide (furosemide) and thiazide diuretics). Morbilliform (measles-like) eruptions typically recur on rechallenge. 

Inhibitors to the enzyme carbonic anhydrase. This enzyme is widely distributed in the body and has a fundamental role in the control of acid-base balance. In the 1920s it was noticed that the SULPHONAMIDE sulfanilamide had a weak diuretic action. Acetazolamide is a subsequent thiadiazole-sulphonamide derivative with potent carbonic anhydrase inhibitor activity. Clinically, it is used for antiglaucoma TREATMENT, is a weak diuretic and can be used to treat mountain sickness. Dichlorphenamide and dorzolamide are sulphonamide derivatives also used for antiglaucoma treatment. Methazolamide is used as a diuretic. Now that seven or more isoenzymes of carbonic anhydrase have been cloned. Isolated and mapped, some new initiatives are aimed at developing agents with more selective actions. 

Removal or possible replaeement of the sulphonamide function at C-7 results into such compounds possessing either little or almost no diuretic activity. 

A most logical H-bonding mechanism which is believed to act competitively perhaps explains the action of some sulphonamide carbonic anhydrase inhibitors which predominantly exhibit both diuretic and antiglaucoma activities. It is, however, assumed that carbonic acid being the normal substrate which not only fits into a cavity but also complexes with the corresponding enzyme carbonic anhydrase (CA) as illustrated in Fig. 14.1(a). Consequently, this complex is strongly stabilized by four H-bonds. 

Selvaag, E., Anholt, H., Moan, J., and Thune, R, Inhibiting effects of antioxidants on drug-induced phototoxicity in ceU cultures. Investigation with sulphonamide-derived oral antidiabetics and diuretics,/. Photochem. Photobiol B Biol, 38, 88,1997. 

Some sulphonamides can be used as diuretics since they are able to block carbonic anhydrase enzyme. This will Increase the salt and the water retention in the urine. Side effects crystalluria, haemolytic anaemia and hypersensitivity are the most serious side effects. 

Figure 4.14 Sulphonamides used as hypoglycaemic and diuretic agents.

Some of the sulphonamides can be used as diuretics. The mechanism of their action relates to carbonic add excretion. Carbon dioxide generated from catabolic processes is carried to the lung and then removed by exhalation. However, part of the carbon dioxide is still dissolved in the blood. Hie dissolved carbon dioxide produces carbonic acid and its conjugated base (i.e. bicarbonate). This mixture of the weak acid and its conjugate base is one of the important buffer systems in the blood. The dissolved carbon dioxide is excreted in the urine. The processes of the conversion of carbon dioxide to carbonic acid and then... 

Figure 4.26 Mechanism of inhibition of carbonic anhydrase enzyme by diuretic sulphonamides.

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