advances in thiazide diuretics
Prepared by/
Mayar Nashat
Abeer Mohamed
Reham Mahmoud
Esraa Ahmed
Ereny Romany
Introduction
Thiazides are a class of sulfur-containing organic molecules and diuretics. They
were discovered in the 1950s, with the first approved drug, chlorothiazide,
introduced in 1958. Thiazides are among the least expensive antihypertensive
medications available in most countries. (1)
Mechanism of action
MOA of thiazide diuretics is inhibiting the apical sodium/chloride transporter in
epithelial cells of the distal convoluted tubules to reduce ECF and cardiac output.
(2)
SAR
PHYSICAL PROPERTIES
Thiazide diuretics, such as hydrochlorothiazide, have the following physical
properties :
- State: Solid
- Appearance: White powder
- Melting Point: 266-268°C
- Solubility: 722 mg/L (at 25°C), with a predicted water solubility of 2.24 g/L
- LogP: -0.07 (experimental), -0.16 (predicted by ALOGPS), and -0.58 (predicted
by ChemAxon)
- pKa: 9.09 (strongest acidic) and -2.7 (strongest basic)
- Molecular Formula: C7H8ClN3O4S2
- Average Molecular Mass: 297.739 g/mol
- Monoisotopic Mass: 296.964 g/mol (4)
PREPARATION
Each tablet for oral administration contains 25 mg or 50 mg hydrochlorothiazide,
USP. In addition, each tablet contains the following inactive ingredients: corn
starch, dibasic calcium phosphate dihydrate, FD&C Yellow No. 6 Aluminum Lake,
lactose monohydrate and magnesium stearate (5)
PHARMACOKINETICS
(ADME) of Thiazide Diuretics:
• Absorption:
Thiazide diuretics are generally well absorbed orally.
•Distribution:
They are widely distributed throughout the body and exhibit a high affinity for
albumin binding, which can reduce the concentration of the free, active drug.
•Metabolism:
Thiazides undergo variable degrees of hepatic metabolism.
•Excretion:
The effects of thiazides on the kidney depend on their excretion into the renal
tubule. Their efficacy decreases with increasing renal impairment. The onset of the
diuretic effect typically occurs within one hour, and the effect can last for about 12
hours. The antihypertensive effect is more gradual and long-lasting, often
persisting for 24 hours with once-daily dosing. (6)
ASSAY
Chromatographic Techniques:
• High-Performance Liquid Chromatography (HPLC): This is a widely used
technique for the separation and quantification of thiazide diuretics. HPLC
methods offer good sensitivity and selectivity can be used for both pharmactical
preparation and biological matrices.
• Ultra-Performance Liquid Chromatography (UPLC):
UPLC offers higher speed, resolution, and sensitivity compared to traditional
HPLC. It has been applied for the analysis of hydrochlorothiazide and other
thiazides in urine and pharmaceutical formulations.
• High-Performance Thin Layer Chromatography (HPTLC):
HPTLC is another chromatographic technique used for the quantitative analysis of
thiazides, often with UV detection.
•LiquidChromatography-MassSpectrometry (LC-MS):
Coupling liquid chromatography with mass spectrometry provides enhanced
selectivity and sensitivity, particularly useful
for analyzing thiazides.
Spectroscopic Techniques:
•Ultraviolet (UV) Spectrophotometry:
Thiazides absorb UV light, and this property can be used for their quantification.
This method is relatively simple and cost-effective but may lack specificity in
complex mixtures.
•Spectrofluorimetry:
Some thiazides or their derivatives exhibit fluorescence, which can be measured
for quantitative analysis. This technique can offer higher sensitivity than UV
spectrophotometry.(7)
IR OF THIAZIDE
MASS SPECTRUM
NMR
CONCLUSION
Over the years, thiazide diuretics have remained a cornerstone in the management
of hypertension, owing to their proven efficacy in lowering blood pressure and
reducing cardiovascular risks. Recent advancements have highlighted the benefits
of combining thiazide diuretics with potassium-sparing agents to enhance
therapeutic outcomes and minimize adverse effects. Moreover, the emergence of
aldosterone synthase inhibitors offers promising avenues for antihypertensive
therapy. These developments underscore the evolving landscape of hypertension
treatment, emphasizing the need for personalized and combination therapies to
optimize patient care.(8)
REFERENCES
