Chlorpropamide

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

Chlorpropamide
Clinical data
Trade namesDiabinese
AHFS/Drugs.comMonograph
MedlinePlusa682479
License data
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    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
    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 g·mol−1
    3D model (JSmol)
    Melting point126 to 130 °C (259 to 266 °F)
      (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

    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). 4 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
    2. Drugs.com: Chlorpropamide
    3. Fitzgerald, M.G. (1962). "Alcohol sensitivity in diabetics receiving chlorpropamide". Diabetes. 11: 40–46.
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