Chlorpropamide

Not to be confused with Chlorpromazine.
Chlorpropamide
Names
Pronunciationklor proe' pa mide[1]
Trade namesDiabinese, Glucamide, others
IUPAC name
  • 4-chloro-N-(propylcarbamoyl)benzenesulfonamide
Clinical data
Drug class1st generation sulfonylurea[2][1]
Main usesType 2 diabetes[2]
Side effectsHeadache, dizziness, numbness, abdominal discomfort, weight gain, nausea[1][2]
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    use    		By mouth
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa682479
    Legal
    License data
    Legal status
    Pharmacokinetics
    Bioavailability>90%
    Protein binding90%
    Metabolism<1%
    Elimination half-life36 hours
    ExcretionKidney (glomerular filtration → reabsorption → tubular secretion)
    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) checkY
    • Key:RKWGIWYCVPQPMF-UHFFFAOYSA-N checkY

    Chlorpropamide, sold under the brand name Diabinese among others, is a medication used to treat type 2 diabetes.[2] It is used together with diet and exercise.[2] It is a second line treatment.[2] It is taken by mouth.[2]

    Common side effects include headache, dizziness, numbness, abdominal discomfort, weight gain, and nausea.[1][2] Other side effects may include low blood sugar and liver problems.[1][2] Safety in pregnancy is unclear.[2] It is a first generation sulfonylurea and works by increasing the release of insulin.[2][1][3]

    Chlorpropamide was approved for medical use in the United States in 1958.[2] Commercial sale has been discontinued in the United States.[4]

    Medical uses

    Dosage

    The recommended dose initially being 100 to 250 mg daily with increases every 5 to 7 days to a maximum of 750 mg daily.[1]

    Side effects

    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.[5][6] Chlorpropamide, while effective in the treatment of diabetics in patients of Chinese descent, should never be used in people of Mongolian descent.

    The most common side effects are skin related, such as rashes, photoallergy and (in rare cases) Stevens–Johnson syndrome.[5] Less common side effects of chlorpropamide include gastrointestinal symptoms such as nausea, vomiting, and diarrhea.[6] It may cause facial flushing after the ingestion of alcohol.[7] In very high doses it can increase secretion of antidiuretic hormone (ADH), which can lead to hyponatremia.[5] It also markedly raises the serum level of alkaline phosphatase.

    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.[5]

    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.[5]

    Chemistry

    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.[5]

    Solubility

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

    See also

    References

    1. 1 2 3 4 5 6 7 "Sulfonylureas, First Generation". Archived from the original on 11 January 2022. Retrieved 4 January 2022.
    2. 1 2 3 4 5 6 7 8 9 10 11 12 "Chlorpropamide Monograph for Professionals". Drugs.com. Archived from the original on 4 March 2021. Retrieved 4 January 2022.
    3. ↑ BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 749. ISBN 978-0857114105.
    4. ↑ "Drugs@FDA: FDA-Approved Drugs". www.accessdata.fda.gov. Archived from the original on 3 March 2016. Retrieved 4 January 2022.
    5. 1 2 3 4 5 6 7 Dinnendahl V, Fricke U, eds. (2010). Arzneistoff-Profile (in Deutsch). Vol. 4 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
    6. 1 2 "Chlorpropamide". Drugs.com. Archived from the original on 2021-03-04. Retrieved 2020-12-02.
    7. ↑ Fitzgerald MG, Gaddie R, Malins JM, O'Sullivan DG (1962). "Alcohol sensitivity in diabetics receiving chlorpropromide". Diabetes. 11: 40–3. PMID 13893349.
    Identifiers:
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