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are drugs that increase the rate of urine formation primarily by inhibiting the reabsorption of ions (especially Na and CL) without affecting protein, vitamin, glucose, or amino acid reabsorption
these drugs interfere with reabsorption of sodium and other ions from the LUMINA of the NEPHRONS, the functional unit of kidney
diuretics interfere with reabsorption of sodium and other ions from the L_____ of the nephrons
structure of diuretic
diuretic determining factor in the amount of ion and accompanying water excreted as urine (S______ of D_____)
site of action
diuretic determining factor in the amount of ion and accompanying h20 excretion (S___ of A_____)
the amount of ion and h20 released are dependent on the salt intake of the patient and the amount of e_______ F______ present
These diuretics are low molecular weight and highly water soluble compounds that are freely filtered through Bowman's capsule into renal tubules and NOT reabsorbed
increase tonicity of tubular fluid, thereby causing the water to pass from the body into the tubule producing the diuretic effect
diuretics which act on both the PROXIMAL TUBULE and the LOOP of HENLE (latter primary site of action)
diuretics used in the treatment of cerebral edema and to decrease intraocular pressure in glaucoma
ubiquitous ZINC enzymes that catalyze a simple physiological rxn; interconversion between carbon dioxide and bicarbonate
Involved in many crucial physiological processes; plays a key role in Bicarbonate reabsorption and acid secretion
one of the two known classes of CAis (sulfonamide), which binds to the Zn(II) ion of the enzyme and inhibits activity
Monosubs. or Disubst. of sulfonamide portion results in a loss of diuretic activity, therefore the _____ __ function of SULFONAMIDE is important for diuretic activity
functional groups that (increase/decrease) acidity of sulfonamide NH group were found to improve activity
? INHIBIT ACTIVITY OF CA, REDUCING FORMATION OF CARBONIC ACID WITHIN THE PROXIMAL AND DISTAL TUBULAR CELLS TO LIMIT NUMBER OF H+ IONS AVAILABLE TO PROMOTE NA RE ABSORPTION
FOR DIURETIC RESPONSE TO BE OBSERVED MORE THAN 99% OF _____ _______ ACTIVITY MUST BE INHIBITIED
_____ ________ loses its effectiveness as a diuretic until normal acid base balance is restored
inhibition of _____ ______ decreases the rate of formation of aqueous humor and consequently reduces intraocular pressure, therefore inhibitors of this enzyme find use in the treatment of OPEN ANGLE GLAUCOMA
Open angle glaucoma
carbonic anhydrase decreases the rate of formation of aqueous humor, so it is used to treat ?
used primarily in reducing IOP in the treatment of glaucoma and absence seizures (i.g. acetazolamide)
MORE potent that acetazolamide, is a METHYL derivative of acetazolamide, METHYLATION DECREASES POLARITY and permits a GREATER PENETRATION into the ocular fluid where it acts as a CAi decreasing IOP
Ethoxzolamide and Dichlorphenamide are other __ _______ whose properties and uses resemble those of acetazolamide
synthesized in an effort to enhance potency of inhibitors of CA, unlike CA inhibitors which primarily increase bicarbonate excretion, were found to increase NACL excretion
expresses thiazide binding sites and is accepted as the PRIMARY site of action of thiazide diuretics, the proximal tubule may represent a secondary site of action
compete for the chloride binding site of the NA/Cl symporter and inhibit the reabsorption of sodium and chloride ions
little diuretic activity is seen with a hydrogen atom at position 6, whereas CHLORO or CF3 are highly active
___ substituted diuretics are more lipid soluble and have a longer duration of action than their chloro substitued analogs
replacement or removal of SULFONAMIDE group at position _ yields compounds with little or no diuretic activity (thiazides)
In regard to benzothiazides, saturation of the double bond to give 3,4 dihydro derivative produces a diuretic that is 10 times (more/less) active than UNsaturated derivatives
for thiazides haloalkyl, aralkyl, or thioether increases l____ S_____ of the molecule and yields compounds with a LONGER DURATION of ACTION
For Thiazides: ALKYL SUBSTITUTION AT THE 2-N POSITION (INCREASES/DECREASES) POLARITY AND (INCREASES/DECREASES) DURATION OF ACTION
benzothiazide derivatives in which the sulfone group at position 1 is replaced with a carbonyl group retains activity and increases duration of action
What ring is NOT an absolute requirement (analogs with open _ ring) for thiazide diuretic activity
the structural difference between the q________ diuretics and thiazides is the replacement of the 4-sulfone group with a 4-keto group
diuretic derivative which exhibit a LONG duration of action as a result of protein binding (18-24 hours)
also known as high ceiling, produce a PEAK diuresis much greater than observed with other diuretics
characterized by a quick onset and short duration of action. Diuretic effect appears in about 30 minutes and lasts for about 6 hrs
K (potassium) sparing
diuretics in which on their own cause HYPERKALEMIA leading to a fatal arrhythmia
diuretics gen. used in combo with OTHER diuretic drugs ie. loop that would otherwise LOWER potassium levels to dangerously low levels. Combo helps to maintain a normal reference range for potassium
Renal Epithelial Sodium Channel Inhibitors
Triamterine and amiloride are the ONLY two drugs of this class in clinical use (R__al E______lial S______ium Channel (i_______ors) (also works to maintain healthy K+ levels)
along with amiloride causes a SMALL increase in NACL excretion and usually are employed for their ANTIKAILURETIC actions to offset the effects of other diuretic that increase K+ excretion (T________erene)
a substance that antagonizes the effects of a______ could conceivably be a good diuretic drug. SPIRINOLACTONE is such an antagonist
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