Diuretic notes.ppt

Diuretics, sometimes called water pills, help rid your body of salt (sodium) and water. Most of these medicines help your kidneys release more sodium into your urine. The sodium helps remove water from your blood, decreasing the amount of fluid flowing through your veins and arteries.
Types of diuretics include:
Thiazide diuretics, such as hydrochlorothiazide (Microzide® or Oretic®) or chlorthalidone (Hygroton® or Thalitone®).

What they do: They make your kidneys pull salt and extra water into your pee.

Selected side effects:

Headache.
Loss of appetite.
Hair loss.
Loop diuretics, such as furosemide or bumetanide

What they do: They affect part of your kidneys (the loop of Henle) to get salt and excess water out of your body.

Selected side effects:

Dizziness.
Diarrhea.
Upset stomach.
Potassium-sparing diuretics, such as triamterene or amiloride

What they do: They help your kidneys clear salt and water out of your body, but don’t let you lose too much potassium in the process.

Selected side effects:

Gas.
Nausea.
Headache.
A mixture of two types in one pill, like triamterene and hydrochlorothiazide (Dyazide® or Maxzide®)

What they do: They make your kidneys move salt and extra water out while keeping you from losing too much potassium.

Selected side effects:

Headache.
Peeing often.
People usually take diuretics by swallowing diuretic pills, but your provider can give some diuretics through an IV in your arm during a hospital stay. Most people can take diuretics without getting serious problems from them.

How do diuretics work?
Diuretics make your kidneys take away your body’s extra salt and water by putting them into your urine (pee).'
1 Medical uses
2 Types
2.1 High-ceiling/loop diuretics
2.2 Thiazides
2.3 Carbonic anhydrase inhibitors
2.4 Potassium-sparing diuretics
2.5 Calcium-sparing diuretics
2.6 Osmotic diuretics
2.7 Low-ceiling diuretics
3 Mechanism of action
4 Adverse effects
5 Abuse in sports
6 See also
7 References

1. DIURETICS
MEDICINAL CHEMISTRY
BY
Miss. Waghhrutuja
ASSISTANT PROFESSOR
LOKMANYA TILAK INSTITUTE OF PHARMACETICAL SCIENCES, PUNE.

2. Diuretics
•DiureticsaredrugsthatpromotetheoutputofurineexcretedbytheKidneys.
•TheprimaryactionofmostdiureticsisthedirectinhibitionofNa+transportatone
ormoreofthefourmajoranatomicalsitesalongthenephron,whereNa+
reabsorptiontakesplace.
•Theincreasedexcretionofwaterandelectrolytesbythekidneysisdependenton
threedifferentprocessesviz.,glomerularfiltration,tubularreabsorption(activeand
passive)andtubularsecretion.
•DiureticsareveryeffectiveinthetreatmentofCardiacoedema,specificallytheone
relatedwithcongestiveheartfailure.
•Theyareemployedextensivelyinvarioustypesofdisorders,forexample,nephritic
syndrome,diabetesinsipidus,nutritionaloedema,cirrhosisoftheliver,
hypertension,oedemaofpregnancyandalsotolowerintraocularandcerebrospinal
fluidpressure.

3. Therapeutic Uses of Diuretics
•i) Congestive Heart Failure:
•The choice of the diuretic would depend on the severity of the disorder. In an
emergency like acute pulmonary oedema, intravenous Furosemide or Sodium
ethacrynate may be given. In less severe cases. Hydrochlorothiazide or
Chlorthalidone may be used. Potassium-sparing diuretics like Spironolactone or
Triamterene may be added to thiazide therapy.
•ii) Essential hypertension:
•The thiazides usually sever as primary antihypertensive agents. They may be used as
sole agents in patients with mild hypertension or combined with other
antihypertensives in more severe cases.
hyperaldosteronism

4. Therapeutic Uses of Diuretics
•iii) Hepatic cirrhosis:
•Potassium-sparing diuretics like Spironolactone may be employed. If
Spironolactone alone fails, then a thiazide diuretic can be added
cautiously. Furosemide or Ethacrymnic acid may have to be used if the
oedema is regractory, together with spironolactone to lessen potassium
loss. Serum potassium levels should be monitored periodically.
•iv) Nephroic syndrome:
•Doetary sodium restriction may be combined with a thioazide diuretic,
adding Spironolactone to control secondary

5. Classification Mechanism of Action Examples
Carbonic
anhydrase
inhibitors
Inhibits carbonic anhydrase (CA) enzyme in proximal convoluted
tubulesthus interferes with NaHCO3 re-absorption and causes
diuresis.
Acetazolamide &
methaolamide,
Dichlorphenamide
Loop diuretics
•Inhibit Na+ / K+ / 2 Cl-co-transporter in the luminal membrane
of the thick ascending loop of Henle (TAL)
•Inhibit Ca++ and Mg ++ re-absorption.
Furosemide,
bumetanide ,
ethacrynicAcid
Thiazide
diuretics
acts via inhibition of Na/Cl co-transporter on the luminal
membrane of distal convoluted
Chlorothiazide ,
Hydrochlorothiazide,
Hydroflumethazine,
cyclothiazide
Potassium
sparing
diuretics
Act in collecting tubules and ducts by inhibiting Na re-absorption
and K & H excretion
(blocking NA channels + antagonizing aldosterone)
Spironolactone,
triamterene , amiloride
Osmotic
diuretics
urine output by osmosis, drawing water out of cells and into the
blood stream.
Mannitol (sugar)

6. Diuretics -Learn with Visual Mnemonics!

7. ChemicalClassification
1.Loopdiuretics-
(i)Furosemide (ii)Bumetanide (iii)Torsemide
(iv)Ethacrynicacid

8. 2.Thiazidediuretics-
(i)Bendroflumethiazide(ii)Benzthiazide (iii)Chlorothiazide
(iv)Hydrochlorothiazide(v)Hydroflumethiazide

9. 3.Carbonicanhydraseinhibitors-
(i)Acetazolamide (ii)Methazolamide (iii)Ethoxzolamide
(iv)Dichlorphenamide .

10. 5.Aldosteroneantagonists(mineralocorticoidreceptorantagonists)-
(i)Spironolactone (ii)Eplerenone(iii)Canrenone
6.Potassium-sparingdiuretics-
(i)Amiloride (ii)Triamterene.

11. 7.Osmoticdiuretics-
(i)Mannitol (ii)Sorbitol

12. 1. CarbonicAnhydraseInhibitors

13. Mechanismofaction-
•Acetazolamideisasulfonamidederivativewithdiuretic,
antiglaucoma,andanticonvulsantproperties.
•Acetazolamideisanon-competitiveinhibitorofcarbonicanhydrase,
anenzymefoundincellsintheproximaltubeofthekidney.I
•nhibitionofthisenzymeinthekidneypreventsexcretionofhydrogen
ionsforactivetransportintherenaltubulelumen.
•Thisleadstoalkalineurineandanincreaseintheexcretionof
bicarbonate,sodium,potassium,andwater.
• Acetazolamidereducestheconcentrationofbicarbonate,
resultinginadecreasedsynthesisofaqueoushumorintheeye,
therebyloweringintraocularpressure.
•TheanticonvulsantactivityofAcetazolamidemaydependonadirect
inhibitionofcarbonicanhydraseintheCNS,whichdecreasescarbon
dioxidetensioninthepulmonaryalveoli,thusincreasingarterial
oxygentension.

14. SAR of Ca Inhibitiors
•Two groups of CAseinhibitors are
1.Heterocylicsulphonamides
2.Meta-disulphamoylbenzene derivatives 572 Drugs Acting on Urinary System
1. Heterocylicsulphonamides
•The C-2 sulphamoylgroup is important for activity.
•The free sulphamolylmoiety is necessary to bind with Zn++ in the enzyme; hence,
substitution of sulphamoylgroup gives inactive compound.
•The moiety to which the sulphamoylgroup is attached must be aromatic in
character.
•The heterocyclic sulphonamideswith higher partition coefficientand lowest Pka
value have greatest CAseinhibitory and diuretic activites. Example—acetazolamide,
methazolamide.
•N-alkylation with methyl group on ring N-of acetazolamideyields active compound
(methazolamide).

15. 2. m-Disulphamoyl benzene derivatives
•m-Disulphamoyl benzene do not have diuretic activity.
•Substituted m-sulphamoyl benzene exhibits diuretic activity.
•The unsubstituted sulphamoyl moiety is essential for the activity; any
substitution leads to affect the potency of the compound.
•The sulphamoyl moiety can be replaced with similar electrophilic groups
(e.g. carboxyl, carbamoyl) that may increase the potency of the
compound.
•Maximum diuretic activity is obtained when 4th is substituted by Cl, Br,
CF3, or NO2 group.
•Substitution of amino group at 6th position increases aleuronic activity,
but decreases CAse inhibitor activity.

16. SynthesisofAcetazolamide
Structure-
IUPACName-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide.Or
Acetamide,N-[5-(amino-sulphonyl)-1,3,4thiadiazol-2-yl].
Properties-
•Acetazolamideappearsaswhitetoyellowish-whitefinecrystallinepowder.Noodourortaste.
•It issparinglysolubleincoldwater,slightlysolubleinalcoholand acetone.
•ItisInsolubleinchloroform,diethylether,carbontetrachloride;
carbonatesolution.
•ItisStoredinbetween 15and30°C,ina well-closedcontainer.
readilysolublein1Nsodium
•Oral Absorption: nearly complete; Plasma Half-Life: 6-9 hours; and Route of Elimination: renal
excretion of intact drug.
•It is an orally effective diuretic, with a therapeutic effect that lasts approximately 8 to 12 hours.

17. Synthesis-

18. Uses-
•Anticonvulsants;CarbonicAnhydraseInhibitors;Diuretics.
•Itsdiureticactionislimitedbecauseofthesystemicacidosisit
produces.
•Acetazolamidehasalsobeenusedasadiureticinthetreatmentof
edemaduetocongestiveheartdiseaseanddrug-inducededema;
centrencephalicepilepsies;chronicsimple(open-angle)glaucoma.
Dose-
•The dose is 250 mg to 1 g per day in divided doses.