Chlorpropamide

Chlorpropamide
Systematic (IUPAC) name
4-chloro-N-(propylcarbamoyl)benzenesulfonamide
Clinical data
Trade names Diabinese
AHFS/Drugs.com monograph
MedlinePlus a682479
Licence data US FDA:link
  • AU: C
  • US: C (Risk not ruled out)
Oral
Pharmacokinetic data
Bioavailability >90%
Protein binding 90%
Metabolism <1%
Half-life 36 hours
Excretion Renal (glomerular filtration → reabsorption → tubular secretion)
Identifiers
94-20-2 Yes
A10BB02
PubChem CID 2727
DrugBank DB00672 Yes
ChemSpider 2626 Yes
UNII WTM2C3IL2X Yes
KEGG D00271 Yes
ChEBI CHEBI:3650 Yes
ChEMBL CHEMBL498 Yes
Chemical data
Formula C10H13ClN2O3S
276.74 g/mol
Physical data
Melting point 126 to 130 °C (259 to 266 °F)
 Yes (what is this?)  (verify)

Chlorpropamide is a drug in the sulfonylurea class used to treat type 2 diabetes mellitus. It is a long-acting 1st generation sulfonylurea. It has more side effects than other sulfonylureas and its use is no longer recommended.

Mechanism of action

Like other sulfonylureas, chlorpropamide acts to increase the secretion of insulin, so it is only effective in patients who have some pancreatic beta cell function. It can cause relatively long episodes of hypoglycemia; this is one reason why shorter-acting sulfonylureas such as gliclazide or tolbutamide are used instead. The risk of hypoglycemia makes this drug a poor choice for the elderly and patients with mild to moderate hepatic and renal impairment. Chlorpropamide is also used in partial central diabetes insipidus.[1]

Pharmacokinetics

Maximal plasma concentrations are reached 3 to 5 hours after quick and nearly complete (>90%) resorption from the gut. Plasma half life is 36 hours; the drug is effective for about 24 hours, longer than other sulfonylureas. A stable plasma level is only reached after three days of continuous application. 90% of the drug are bound to plasma proteins; at least two albumin binding sites exist. More than 99% of chlorpropamide are excreted unchanged via the kidneys. It is first filtrated in the glomeruli, then reabsorbed, and finally secreted into the tubular lumen.[1]

Cautions and contraindications

Chlorpropamide and other sulfonylureas encourage weight gain, so they are generally not favored for use in very obese patients. Metformin (Glucophage) is considered a better drug for these patients. Sulfonylureas should be used with caution or generally avoided in patients with hepatic and renal impairment, patients with porphyria, patients who are breastfeeding, patients with ketoacidosis, and elderly patients.[1][2]

Other side effects

The most common side effects are skin related, such as rashes, photoallergy and (in rare cases) Stevens-Johnson syndrome.[1] Less common side effects of chlorpropamide include gastrointestinal symptoms such as nausea, vomiting, and diarrhea.[2] It may cause facial flushing after the ingestion of alcohol.[3] In very high doses it can increase secretion of antidiuretic hormone (ADH), which can lead to hyponatremia.[1] It also markedly raises the serum level of alkaline phosphatase.

Chemical properties

Chlorpropamide is a white crystalline powder with no characteristic taste or smell. It exhibits polymorphism. Its acid dissociation constant pKa is 5.0 at 20 °C.[1]

Solubility

Solvent Solubility[1]
Water, pH 6 1:450
Water, pH 7.3 insoluble
Acetone 1:5
Dichlormethane 1:9
Ethanol 1:12
Diethylether 1:200

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Dinnendahl, V.; Fricke, U., eds. (2010). Arzneistoff-Profile (in German) 4 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
  2. ↑ 2.0 2.1 Drugs.com: Chlorpropamide
  3. ↑ Fitzgerald, M.G. (1962). "Alcohol sensitivity in diabetics receiving chlorpropamide". Diabetes 11: 40–46.