Product Information
Registration Status: ActiveGLIOTENZIDE 20 TABLET is approved to be sold in Singapore with effective from 2005-01-14. It is marketed by ZYFAS MEDICAL CO, with the registration number of SIN12641P.
This product contains Enalapril 20mg, and Hydrochlorothiazide 12.5mg in the form of TABLET. It is approved for ORAL use.
This product is manufactured by LABORATORIOS BAGO SA in ARGENTINA.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Enalapril is a prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly metabolized in the liver to enalaprilat following oral administration. Enalaprilat is a potent, competitive inhibitor of ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Enalapril may be used to treat essential or renovascular hypertension and symptomatic congestive heart failure.
Indication
For the treatment of essential or renovascular hypertension and symptomatic congestive heart failure. It may be used alone or in combination with thiazide diuretics.
Mechanism of Action
There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Enalaprilat, the principle active metabolite of enalapril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Enalapril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. Enalaprilat's affinity for ACE is approximately 200,000 times greater than that of ATI and 300-1000 times greater than that enalapril.
Pharmacokinetics
- Absorption
- 55-75%, absorption is unaffected by food; enalaprilat (clinically administered IV) is poorly absorbed, 3-12%, due to its high polarity.
- Distribution
- Metabolism
- ~ 60% of absorbed dose is extensively hydrolyzed to enalaprilat, primarily by liver esterases
- Elimination
Toxicity
Overdosage may result in marked hypotension and stupor. Most common adverse effects include hypotension, headache, dizziness and fatigue.
Active Ingredient/Synonyms
(S)-1-(N-(1-(Ethoxycarbonyl)-3-phenylpropyl)-L-alanyl)-L-proline | (S)-1-{(S)-2-[1-((S)-ethoxycarbonyl)-3-phenyl-propylamino]-propionyl}-pyrrolidine-2-carboxylic acid | 1-(N-((S)-1-Carboxy-3-phenylpropyl)-L-alanyl)-L-proline 1'-ethyl ester | Analapril | Enalapril | Enalaprila | Enalaprilum | Enalapril |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Description
A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. [PubChem]
Indication
For the treatment of high blood pressure and management of edema.
Mechanism of Action
Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.
Pharmacokinetics
- Absorption
- 50-60%
- Distribution
- Metabolism
- Hydrochlorothiazide is not metabolized.
- Elimination
Toxicity
The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.
Active Ingredient/Synonyms
HCTZ | Hydrochlorothiazide |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.