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
Pregnancy category	AU: C US: C (Risk not ruled out)
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	>90%
Protein binding	90%
Metabolism	<1%
Biological half-life	36 hours
Excretion	Renal (glomerular filtration → reabsorption → tubular secretion)
Identifiers
CAS Number	94-20-2^Y
ATC code	A10BB02
PubChem	CID 2727
IUPHAR/BPS	6801
DrugBank	DB00672^Y
ChemSpider	2626^Y
UNII	WTM2C3IL2X^Y
KEGG	D00271^Y
ChEBI	CHEBI:3650^Y
ChEMBL	CHEMBL498^Y
Chemical data
Formula	C₁₀H₁₃ClN₂O₃S
Molar mass	276.74 g/mol
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
Physical data
Melting point	126 to 130 °C (259 to 266 °F)
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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

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 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

1 2 3 4 5 6 7 Dinnendahl, V.; Fricke, U., eds. (2010). Arzneistoff-Profile (in German) 4 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
1 2 Drugs.com: Chlorpropamide
↑ Fitzgerald, M.G. (1962). "Alcohol sensitivity in diabetics receiving chlorpropamide". Diabetes 11: 40–46.

Oral anti-diabetic drugs, insulins and insulin analogs, and other drugs used in diabetes (A10)

Insulin

Sensitizers

Biguanides	Metformin^# Buformin<sp>‡ Phenformin^‡

TZDs/"glitazones" (PPAR)	Ciglitazone^§ Darglitazone^§ Englitazone^§ Lobeglitazone Netoglitazone^§ Pioglitazone Rivoglitazone^† Rosiglitazone Troglitazone^‡

Dual PPAR agonists	Aleglitazar^† Muraglitazar^§ Saroglitazar Tesaglitazar^§

Secretagogues

K+ ATP

Sulfonylureas	1st generation: Acetohexamide Carbutamide Chlorpropamide Metahexamide Tolbutamide Tolazamide 2nd generation: Glibenclamide (Glyburide)^# Glibornuride Glipizide Gliquidone Glisoxepide Glyclopyramide Glimepiride Gliclazide

Meglitinides/"glinides"	Nateglinide Repaglinide Mitiglinide

GLP-1 agonists

DPP-4 inhibitors

GPR40 Free fatty acid receptor 1

Fasiglifam^†

Analogs/other insulins

fast-acting (Insulin lispro
Insulin aspart
Insulin glulisine)
short-acting (Regular insulin)
long-acting (Insulin glargine
Insulin detemir
NPH insulin)
ultra-long-acting (Insulin degludec^†)
inhalable Exubera^‡
Afrezza

Other

Aldose reductase inhibitors	Epalrestat Fidarestat^§ Ranirestat^† Tolrestat^‡ Zenarestat^§

Alpha-glucosidase inhibitors	Acarbose Miglitol Voglibose

Amylin analog	Pramlintide

Sodium glucose transporter (SGLT2) inhibitors	Canagliflozin Dapagliflozin Empagliflozin Remogliflozin^§ Sergliflozin^§ Tofogliflozin^†

Other	Benfluorex^‡ Bromocriptine

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

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