Chlorpropamide

Chlorpropamide
Clinical data
Trade names	Diabinese
AHFS/Drugs.com	Monograph
MedlinePlus	a682479
License data	US FDA: Chlorpropamide;
Pregnancy; category	AU: C; ;
Routes of; administration	Oral
ATC code	A10BB02 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	>90%
Protein binding	90%
Metabolism	<1%
Elimination half-life	36 hours
Excretion	Renal (glomerular filtration → reabsorption → tubular secretion)
Identifiers
	IUPAC name 4-chloro-N-(propylcarbamoyl)benzenesulfonamide;
CAS Number	94-20-2 ;
PubChem CID	2727;
IUPHAR/BPS	6801;
DrugBank	DB00672 ;
ChemSpider	2626 ;
UNII	WTM2C3IL2X;
KEGG	D00271 ;
ChEBI	CHEBI:3650 ;
ChEMBL	ChEMBL498 ;
CompTox Dashboard (EPA)	DTXSID9020322 ;
ECHA InfoCard	100.002.104
Chemical and physical data
Formula	C10H13ClN2O3S
Molar mass	276.74 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	126 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) ; Key:RKWGIWYCVPQPMF-UHFFFAOYSA-N ;
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Chlorpropamide is an antidiabetic drug, belonging to the sulfonylurea class of organic compounds. It is used to treat diabetes mellitus type 2. It is a long-acting first-generation sulfonylurea.

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.^{[citation needed]}

Chemical properties

Chlorpropamide is a white crystalline powder with no characteristic taste or smell. It exhibits polymorphism. Its acid dissociation constant pK_a 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

References

^ ^a ^b ^c ^d ^e ^f ^g 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.
^ ^a ^b "Chlorpropamide". Drugs.com. Archived from the original on 2021-03-04. Retrieved 2018-01-23.
^ Fitzgerald MG, Gaddie R, Malins JM, O'Sullivan DG (1962). "Alcohol sensitivity in diabetics receiving chlorpropromide". Diabetes. 11: 40–3. PMID 13893349.