Thiazide diuretics are a class of diuretics comprising sulphonamide derivatives and inhibit sod-chlorine cotransport system.

1. PRESENTED BY:
DIBYENDU SAHA ROLL-18601917110
DEEPANJAN MITRA ROLL-18601917111
B.PHARM 5TH SEM SESSION-2017-2021
GURUNANAK INSTITUTE OF PHARMACEUTICAL SCIENCES AND
TECHNOLOGY
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2. SERIAL
NO.
CONTENTS SLIDE NO
1. INTRODUCTION 3
2. STRUCTURE ACTIVITY RELATIONSHIPS AND
DRUGS
4
3. MECHANISM OF ACTION 6
4. THERAPEUTIC USES 7
5. ADVERSE EFFECTS 8
6. CONCLUSION 9
7. REFERENCES 10
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3. • Diuretics are chemicals that increase the rate of urine formation leading to increased exceretion of
electrolytes and water from body not affecting protein, vitamins, glucose or amino acid
reabsorption
• Thiazide diuretics are drugs that comprise both sulfur containing molecule and a class of diurectic
molecule in it
• The chemical structure is based as of Benzothiadiazine
• Comprises a benzene ring and a thiadiazo ring.
• They are used to treat certain chronic diseases like hypertension, liver cirrhosis, etc.
• The thiazide receptor present is a NaCl transporter pulling Na+Cl- from lumen in distal convoluted
tubule
• Structure is:
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4. • GENERAL STRUCTURE: Fig.2. General structure of thiazide
and
Structure I= thiazide hydrothiazide
Structure II=hydrothiazide
• The 2nd position can tolerate the presence of small alkyl groups such as CH3.
• • Substituents with hydrophobic character in the 3rd position increases saluretic activity 1000 times.
• Substituents include –CH2Cl, –CHCl2, –CH2C6H5, –CH2S, –CH2 –S-CH2CF3. The increase in saluretic activity
correlating with the lipid solubility.
• • Saturation of double bond between the 3rd and 4th position of nucleus increases the diuretic activity
approximately 3-fold to 10-fold. Example— Hydrochlorthiazide.
• • Hydrogen atom at the 2nd position is more acidic due to the presence of neighbouring electron withdrawing the
sulphone group.
• A free sulphamoyl or potentially free sulphamoyl group at 7th postion is essential for activity.
• • Direct substitution of the 4th, 5th, or 8th position with an ethyl group usually results in diminished diuretic activity.
• • Substitution of the 6th position with an activating group is essential for diuretic activity. The substiutents include
Cl, Br, and CF3 groups. 4

5. fig.3.Chlorthiazide fig.4. Benzthiazide fig.5. Hydrochlorthiazide
fig.6.Trichlormethiazide fig.7. Methyclothiazide fig.8. Polythiazide
fig.9. Hydroflumethiazide fig.10. Bendroflumethiazide
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6. • blocks reabsorption of Na+Cl- in distal
convoluted tubule by inhibition of
luminal membrane bound Na+Cl-
cotransport system
• responsible for 5-8% urinary loss
• alters renal excretion rate of other
important ions except Na+ and Cl- ions
• enhances exchange of luminal fluid
Na+ for principal cell K+ which results in
increased urinary excretion of K+
Fig.11. Mechanism of action of thiazide
diuretics
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7. • treat ment of edema associated with congestive heart failure, renal
disorders(nephrotic syndrome), and hepatic disorders(liver cirrhosis).
• antihypertensive agent
• potent diuretic agent
• management of oedema associated with cardiac failure, premenstrual tension,
and hepatic cirrhosis.
• treat diabetes insipidus, type-II renal tubular acidosis, hypercalcIuria
• lowers blood pressure
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8. • hypokalemia- decreased blood K+ level
• dehydration and fall in bp causing acute saline depletion
• GIT Disturbances- nausea, vomitting, diarrhoea
• CNS Disturbances- headache, giddiness, weakness, paresthesiasis
• impotence
• allergic manisfestations
• hyperuricaemia- increased blood urate level
• hyperglycemia and dyslipidemia
• hypercalcemia- increased serum Ca2+ level
• magnesium depletion
• aggravated renal insufficiency by reducing glomerular filtration rate(g.f.r.) 8

9. • Thiazides and hydrothiazides therby, are one of the potent diuretics used as
treatment of hypertensive individuals by potentiating the antihypertensive agents.
• Hydrothiazides are being more potent than thiazides in diuretic action.
• Mostly these drugs are hydrophilic and thus can be taken with water and possess
duration of action upto 12-24 hours.
• They are continually in use today alongside primary antihypertensives to
potentiate their action(synergism) and enhance therapeutic effects.
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10. • Tripathi.K.D. Essentials of Medical Pharmacology eighth edition by jaypee brothers
medical publishers, Section:9 pg:628-632
• Block.H John, Jr,Beale.M John. Wilson and Gisvold's Textbook of ORGANIC
MEDICINAL and PHARMACEUTICAL CHEMISTRY eleventh edition by lippincott
williams & wilkins, CHAPTER: 18 pg: 605-610
• LEMKE.L THOMAS, WILLIAMS. A DAVID, ROCHE.F VICTORIA, WILLIAM
ZITO.S, FOYES'S Principles of Medicinal Chemistry seventh edition by Wolters
Kluwer, PART:III Section: 2 Chapter: 22 pg:729, 736-738
• Alagarsamy.V, TEXTBOOK OF MEDICINAL CHEMISTRY VOLUME I, by
ELSEVIER, SECTION: VI Chapter: 2 pg: 560-568
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