| CAIs (site 1) in proximal convoluted tubuleCA is metallo
enz contain 1 Zn atm w catalyze reversible hydration
of Co2 ,the product H2Co3 w dissoc into H & HCO3 ,H is respos for reabs of K & Na by ion exchange also reabs of HCo3 conversion to H2co3 and dissoc to Co2 & H2O >net result is exc of Na ,K ,HCO3 |
| substituted meta -disulfamoyl benzene (Mefruside) |
|
*4-chloro -N'-[(tetrahydro-2-methyl-2-furanyl)methyl]- 1,3-benzene disulfonamide **** contain furan ring |
| Acetazolamide |
N-[5-(aminosulfonyl) -1,3,4- thiadiazol -2-yl] acetamide *used in ttt of long term therapy of glaucoma by reducing IOP *assar IR
*>syn |
| Salicylanilide (Xipamide) |
|
4-chloro-5-sulfamoyl -2',6' -salicyloxylidide ***contain xylene ring |
| Methazolamide |
*ylidine *more potent >more lipophilic
>greater potency >greater penetration into ocular fluids *used orally in ttt og glaucoma |
| Benzhydrazides (clopamide) |
|
3-(aminosulfamoyl)-4-chloro-N- (2,6-dimethyl-1-piperidinyl) benzamide |
| Ethoxzolamide |
resemble acetazolamide |
|
3-(aminosulfamoyl)-4-chloro-N-(2,3 -dihydro-2-ethyl -1H- indole- 1-yl) benzamide
*uses :ttt of ess hypertension ,edema due to CHF |
| Dichlorphenamide |
4,5-dichloro -1,3 -benzene disulfonamide
*similar to acetazolamide |
| tetrahydroquinazolinone (Quinethazone) |
|
7-chloro-2-ethyl-1,2,3,4-tetrahydro-4-oxo-6-quinazoline sulfonamide |
| thiazide
& thiazide like diuretics (site3) inhibit reabs of Na and Cl in distal
convoluted tubules (saluretic) loss of 5-8 % of sod *side effects :1-hypersensitivity due to So2NH2 2-hypokalemia due to + renal exc of K so K supplements used (Kcl ,K gluconate
,K citrate ,also food rich in K as banana ,or combination e K spairing
diuretics)>balance |
| phthalimide (Chlorthalidone) |
|
2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl) benzene sulfonamide*it
has 2 forms both are
active (equilibrium) *long duration 48-72 |
| chlorothiazide |
6-chloro -2H-1,2,4 -benzothiadiazine-7-sulfonamide -1,1-dioxide *duration 6-12 hrs |
High ceiling diuretics (site 2 diuretics) in loop of Henle A -amino benzoic a drv >SAR *uses of
ABA :ttt of edema e CHF ,cirrosis of liver *most import use of furosemide & bumetanide is ttt of pulmonary edema *side effects :So2NH2 2-can produce Ototoxicity so care e aminoglycosides |
| Flumethiazide |
6-(trifluoromethyl) |
(anthranilic a drv) ** Furosemide
(lasix) |
***2 amino benzoic a drv 4-chloro-N-furfuryl-5-sulfamoyl
anthranilic acid *stronger acid than benzothiadiazine *promote exc of
Na,K,Cl and HCo3 * >syn |
| Hydrochlorothiazide |
6-chloro-3,4-dihydro-2H- *duration up to 18 hrs due to saturation of d.b |
3-aminobenzoic a drv ** Bumetanide |
3-(n-butylamino)-4-phenoxy -5-sulfamoyl benzoic
acid *Cl replaced by phenoxy ,w is also electronegative *it is 50 times more potent than furosemide with shorter duratn |
| Hydroflumethiazide |
as hydrochlorothiazide (duration
18 hrs) |
B-phenoxyacetic a drv ** Ethacrynic acid |
[2,3-dichloro-4-(2-methylene-1- oxobutyl)
phenoxy] acetic acid *side effects :greater incidence of ototoxicity & more serious GI Hge than AMA drv SAR :1-a ,B unsat syst id ess 2-activating gp (Cl or CH3)
occupy either 3-position or 2- 3- positions so
removal of one cl atm ! act ,removal both abolish activity (2 cl >most
active) |
| polythiazide |
*6-chloro-3,4-dihydro-2-methyl
-3-[[(2,2,2-trifluoroethyl)thio]methyl]- 2H-1,2,4
-benzothiadiazine 1,1 -dioxide *duration 24-48 due to 1-satn 2-subst at osition 3 |
K spairing diuretics site 4
diuretics mainly inhibit reabs of 2-3% of Na , K secn is reduced or
diminished *used alone(prevent loss of K) or in combination e thiazide
diuretics (cause loss of K) |
|
|
A) pteridine (Triamterene) |
*2,4,7 -triamino -6-phenyl
pteridine *serious side
effects 1-hyperkalemia so
K level should be shacked and K supplements should be controlled 2-form renal stones -*prepn : triam alone or triam- + hydrochlorthiazide |
|
|
B)aminopyrazines = pyrazinoyl guanidines (Amiloride HCL) |
*6-chloro- 3,5-diamino -N' (aminoiminomethyl)
pyrazine -2- carboxamide *uses : ttt of mild edema assoc e CHF & cirrosis of hypertension *it is considered open chain analogue
of triamterene ,same action & same side effects
*products : alone or e hydrochlorthiazide (Moduretic) * > SAR |
|
|
C)antihor K spairing diuretics (spironolactone) |
aldosterone cause 1-reabs of NA & cl 2-+ K
exc >spironolactone antagonise aldosterone effect >good diuretic
activity (competitive antagonist)
** 7-(acetylthio)-17-hydroxy-3-oxopregn-4-ene-21-
carboxylic acid- g-lactone |
| thiazide
like diuretics subst of SO2 at pos 1 e another e negative gp para to
activating gp & opening bicyclic hetero syst in benzothiadiazine not affect diuretic activity |
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