Chlorpropamide

Chlorpropamide is a drug in the sulfonylurea class used to treat diabetes mellitus type 2. It is a long-acting first-generation sulfonylurea.

Not to be confused with Chlorpromazine.
Chlorpropamide
Clinical data
Trade namesDiabinese
AHFS/Drugs.comMonograph
MedlinePlusa682479
License data
Pregnancy
category
  • AU: C
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability>90%
Protein binding90%
Metabolism<1%
Elimination half-life36 hours
ExcretionRenal (glomerular filtration → reabsorption → tubular secretion)
Identifiers
IUPAC name
  • 4-chloro-N-(propylcarbamoyl)benzenesulfonamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.002.104
Chemical and physical data
FormulaC10H13ClN2O3S
Molar mass276.74 g·mol−1
3D model (JSmol)
Melting point126 to 130 °C (259 to 266 °F)
SMILES
  • O=S(=O)(c1ccc(Cl)cc1)NC(=O)NCCC
InChI
  • InChI=1S/C10H13ClN2O3S/c1-2-7-12-10(14)13-17(15,16)9-5-3-8(11)4-6-9/h3-6H,2,7H2,1H3,(H2,12,13,14) Y
  • Key:RKWGIWYCVPQPMF-UHFFFAOYSA-N Y
  (verify)

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
Further information: Sulfonylurea § Side-effects and cautions

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] Chlorpropamide, while effective in the treatment of diabetics in patients of Chinese descent, should never be used in people of Mongolian descent.

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
SolventSolubility[1]
Water, pH 61:450
Water, pH 7.3insoluble
Acetone1:5
Dichlormethane1:9
Ethanol1:12
Diethylether1:200

See also

References
  1. Dinnendahl V, Fricke U, eds. (2010). Arzneistoff-Profile (in German). Vol. 4 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
  2. "Chlorpropamide". Drugs.com.
  3. Fitzgerald MG, Gaddie R, Malins JM, O'Sullivan DG (1962). "Alcohol sensitivity in diabetics receiving chlorpropromide". Diabetes. 11: 40–3. PMID 13893349.
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