Tolbutamide Health Dictionary

Lindl.

Family Rosaceae.

Habitat: Native to China; now cultivated mainly in Saharanpur, Dehradun, Muzaffarnagar, Meerut, Kanpur, Bareilly districts of Uttar Pradesh, Amritsar, Gurdaspur and Hoshiarpur districts of Punjab.

English: Loquat, Japanese Medlar.

Ayurvedic: Lottaaka (non-classical).

Unani: Lokaat.

Siddha: Ilakotta, Nokkotta (Tamil).

Action: Leaves—used in China and India for the treatment of diabetes mellitus and skin diseases. Fruit— sedative, antiemetic. Flower— expectorant.

The plant contains lipopolysaccha- rides (LPS), which exhibit antirheu- matic activity. LPS is also found useful for treating diabetes mellitus and lowering high cholesterol level. The ethanolic extract of the leaves showed anti-inflammatory activity on carra- geenan-induced oedema in rats and significant hypoglycaemic effect in normal rabbits like the standard drug tolbutamide. The sesquiterpene gly- coside and polyhydroxylated triterpe- noids showed a marked inhibition of glycosuria in genetically diabetic mice; also reduced blood glucose level in nor- moglycaemic rats. The hypoglycaemic effect is mediated through the release of insulin from pancreatic beta cells.

The leaves gave ionone-derived gly- cosides and triterpenes. Maslinic and ursolic acids have also been isolated. Maslinic acid possesses significant anti-inflammatory activity. It also exhibits inhibitory effect on histamine- induced contraction in isolated ileum of guinea pig.

Hot aqueous extract of the leaves showed hepatoprotective activity experimentally.

The leaves yield an essential oil containing nerolidol (61-74%).

The presence of an antifungal compound, eriobofuran, is also reported.

The methanolic extract of the plant exhibits antioxidant and radical scavenging activity.... eriobotrya japonica

Linn.

Family: Moraceae.

Habitat: Sub-Himalayan tract and Peninsular India. Planted along roadsides, and in gardens.

English: Banyan tree.

Ayurvedic: Vata, Nyagrodha, Bahupaada, Dhruv.

Unani: Bargad, Darakht-e-Reesh.

Siddha/Tamil: Aalamaram.

Action: Infusion of bark—used in diabetes, dysentery, and in seminal weakness, leucorrhoea, menorrhagia, nervous disorders, erysipelas, burning sensation. Milky juice and seeds—applied topically to sores, ulcers, cracked soles of the feet, rheumatic inflammations. Buds—a decoction in milk is given in haemorrhages. Aerial roots— antiemetic, topically applied to pimples. Leaves—a paste is applied externally to abscesses and wounds for promoting suppuration.

Along with other therapeutic applications, The Ayurvedic Pharmacopoeia of India recommends the aerial root in lipid disorders.

Phytosterolin, isolated from the roots, given orally to fasting rabbits at a dose of 25 mg/kg, produced maximum fall in blood sugar level equivalent to 81% of the tolbutamide standard after 4 h. The root bark showed antidiabetic activity in pituitary diabetes and alloxan-induced diabetes.

The alcoholic extract of the stem bark also exhibited antidiabetic activity on alloxan-induced diabetes in albino rats, and brought down the level of serum cholesterol and blood urea. This activity is attributed to a glucoside, bengalenoside and the flavonoid glycosides, leucocyanidin and leucopelargonidin. Bengalenoside is half as potent as tolbutamide. The leucopelargonidin glycoside is practically nontoxic and may be useful in controlling diabetes with hyperlipi- demia. The leucocyanidin, when combined with a low dose of insulin, not only equalled in response the effects brought about by a double dose of insulin, but also excelled in amelioration of serum cholesterol and triglycerides.

(Additional references: Indian J Physiol Pharmacol, 1975, 19(4), 218220; J Ethnopharmacol, 1989, 26(1), 155; Indian J Physiol Pharmacol, 1994, 38(3), 220-222.)... ficus benghalensis

Linn.

Synonym: O. tenuiflorum Linn.

Family: Labiatae; Lamiaceae.

Habitat: Throughout India; grown in houses, gardens and temples.

English: Holy Basil, Sacred Basil.

Ayurvedic: Tulasi, Surasaa, Surasa, Bhuutaghni, Suravalli, Sulabhaa, Manjarikaa, Bahumanjari, Deva- dundubhi, Apet-raakshasi, Shuu- laghni, Graamya, Sulabhaa.

Unani: Tulasi.

Siddha/Tamil: Tulasi, Nalla-Tulasi.

Action: Leaf—carminative, stomachic, antispasmodic, antiasthmatic, antirheumatic, expectorant, stimulant, hepatoprotective, antiperiodic, antipyretic and diaphoretic. Seed— used in genitourinary diseases. Root—antimalarial. Plant—adap- togenic, antistress. Essential oil— antibacterial, antifungal.

The Ayurvedic Pharmacopoeia of India recommends the use of the leaf and seed in rhinitis and influenza; the seed in psychological disorders, including fear-psychosis and obsessions.

Major components of the essential oil are eugenol, carvacrol, nerol and eugenolmethylether. Leaves have been reported to contain ursolic acid, api- genin, luteolin, apigenin-7-O-glucu- ronide, luteolin-7-O-glucuronide, orientin and molludistin.

Ursolic acid, isolated from leaves, exhibited significant protection of mast cell membrane by preventing granulation and decreased histamine release. The ethanolic extract (50%) of fresh leaves, volatile oil from fresh leaves and fixed oil from seeds showed antiasth- matic activity and significantly protected guinea-pigs against histamine and dyspnoea. They also showed anti- inflammatory activity against carrage- enan-, serotonin-, histamine- and PGE-2-induced inflammation and inhibited hind paw oedema in rats.

The ethanol extract (90%) of the leaves showed hepatoprotective effect against paracetamol-induced liver damage.

The plant extract exhibited antiul- cerogenic property against experimental ulcers.

Oral administration of alcoholic extract of leaves lowers blood sugar level in normal, glucose-fed hyperglycaemic and streptozotocin-induced diabetic rats. The activity of the extract was 91.55 and 70.43% of that of tolbutamide in normal and diabetic rats respectively.

Administration of the juice of the plant affected a significant reduction in the size of urinary brushite crystals.

A study of methanol extract and aqueous suspension of the leaves showed immunostimulation of humoral immunologic response in albino rats indicating the adaptogenic action of the plant.

Dosage: Seed—1-2 g powder (API, Vol. IV); plant—50-10 ml infusion (CCRAS.).... ocimum sanctum

These oral agents reduce the excessive amounts of GLUCOSE in the blood (HYPERGLYCAEMIA) in people with type 2 (INSULIN-resistant) diabetes (see DIABETES MELLITUS). Although the various drugs act di?erently, most depend on a supply of endogenous (secreted by the PANCREAS) insulin. Thus they are of no value in treating patients with type 1 diabetes (insulin-dependent diabetes mellitus (IDDM), in which the pancreas produces little or no insulin and the patient’s condition is stabilised using insulin injections). The traditional oral hypoglycaemic drugs have been the sulphonylureas and biguanides; new agents are now available – for example, thiazolidine-diones (insulin-enhancing agents) and alpha-glucosidase inhibitors, which delay the digestion of CARBOHYDRATE and the absorption of glucose. Hypoglycaemic agents should not be prescribed until diabetic patients have been shown not to respond adequately to at least three months’ restriction of energy and carbohydrate intake.

Sulphonylureas The main group of hypoglycaemic agents, these act on the beta cells to stimulate insulin release; consequently they are e?ective only when there is some residual pancreatic beta-cell activity (see INSULIN). They also act on peripheral tissues to increase sensitivity, although this is less important. All sulphonylureas may lead to HYPOGLYCAEMIA four hours or more after food, but this is relatively uncommon, and usually an indication of overdose.

There are several di?erent sulphonylureas; apart from some di?erences in their duration or action (and hence in their suitability for individual patients) there is little di?erence in their e?ectiveness. Only chlorpropamide has appreciably more side-effects – mainly because of its prolonged duration of action and consequent risk of hypoglycaemia. There is also the common and unpleasant chlorpropamide/ alcohol-?ush phenomenon when the patient takes alcohol. Selection of an individual sulphonylurea depends on the patient’s age and renal function, and often just on personal preference. Elderly patients are particularly prone to the risks of hypoglycaemia when long-acting drugs are used. In these patients chlorpropamide, and preferably glibenclamide, should be avoided and replaced by others such as gliclazide or tolbutamide.

These drugs may cause weight gain and are indicated only if poor control persists despite adequate attempts at dieting. They should not be used during breast feeding, and caution is necessary in the elderly and in those with renal or hepatic insu?ciency. They should also be avoided in porphyria (see PORPHYRIAS). During surgery and intercurrent illness (such as myocardial infarction, COMA, infection and trauma), insulin therapy should be temporarily substituted. Insulin is generally used during pregnancy and should be used in the presence of ketoacidosis.

Side-effects Chie?y gastrointestinal disturbances and headache; these are generally mild and infrequent. After drinking alcohol, chlorpropamide may cause facial ?ushing. It also may enhance the action of antidiuretic hormone (see VASOPRESSIN), very rarely causing HYPONATRAEMIA.

Sensitivity reactions are very rare, usually occurring in the ?rst six to eight weeks of therapy. They include transient rashes which rarely progress to erythema multiforme (see under ERYTHEMA) and exfoliate DERMATITIS, fever and jaundice; chlorpropamide may also occasionally result in photosensitivity. Rare blood disorders include THROMBOCYTOPENIA, AGRANULOCYTOSIS and aplastic ANAEMIA.

Biguanides Metformin, the only available member of this group, acts by reducing GLUCONEOGENESIS and by increasing peripheral utilisation of glucose. It can act only if there is some residual insulin activity, hence it is only of value in the treatment of non-insulin dependent (type 2) diabetics. It may be used alone or with a sulphonylurea, and is indicated when strict dieting and sulphonylurea treatment have failed to control the diabetes. It is particularly valuable in overweight patients, in whom it may be used ?rst. Metformin has several advantages: hypoglycaemia is not usually a problem; weight gain is uncommon; and plasma insulin levels are lowered. Gastrointestinal side-effects are initially common and persistent in some patients, especially when high doses are being taken. Lactic acidosis is a rarely seen hazard occurring in patients with renal impairment, in whom metformin should not be used.

Other antidiabetics Acarbose is an inhibitor of intestinal alpha glucosidases (enzymes that process GLUCOSIDES), delaying the digestion of starch and sucrose, and hence the increase in blood glucose concentrations after a meal containing carbohydrate. It has been introduced for the treatment of type 2 patients inadequately controlled by diet or diet with oral hypoglycaemics.

Guar gum, if taken in adequate doses, acts by delaying carbohydrate absorption, and therefore reducing the postprandial blood glucose levels. It is also used to relieve symptoms of the DUMPING SYNDROME.... hypoglycaemic agents

n. one of a group of *oral hypoglycaemic drugs, derived from a *sulphonamide, that are used in the treatment of type 2 diabetes mellitus; they act by stimulating the islet cells in the pancreas to produce more insulin. The group includes *glibenclamide, *gliclazide, and *tolbutamide. Side-effects, such as nausea, vomiting, and diarrhoea, are usually mild.... sulphonylurea

Sulphonylureas are sulphonamide derivatives which lower the blood sugar when they are given by mouth by enhancing the production of INSULIN. They are e?ective in treating DIABETES MELLITUS only when some residual pancreatic beta-cell function is present. All may lead to HYPOGLYCAEMIA if given in overdose and this is particularly common when long-acting sulphonylureas are given to elderly patients. There is no evidence for any di?erence in the e?ectiveness of the various sulphonylureas. TOLBUTAMIDE was the ?rst of the sulphonlyurea drugs; it has a short duration of action and is usually given twice daily. CHLORPROPAMIDE has a more prolonged action and only needs to be given once daily, but its prolonged action causes more side-effects – including sensitivity reactions. Other oral hypoglycaemic agents of this family include glibenclamide, which has a duration of action intermediate between tolbutamide and chlorpropamide and also produces side-effects (in about 30 per cent of outpatients, according to a recent study). Other sulphonlyureas include acetohexamide, glibornuride, gliclazide, glipizide, gliquidone and tolazamide. Glymidine is a related compound with a similar action to the sulphonylureas. It is particularly useful in patients who are hypersensitive to sulphonylureas.

Sulphonylureas are best avoided in patients who are overweight, as they tend to stimulate the appetite and aggravate obesity. They should be used with caution in patients with hepatic or renal disease. Side-effects are infrequent and usually not severe, the most common being epigastric discomfort with occasional nausea, vomiting and anorexia. In about 10 per cent of patients, chlorpropamide and tolbutamide may cause facial ?ushing after drinking alcohol. Some patients are hypersensitive to oral hypoglycaemic agents and develop rashes which may progress to ERYTHEMA multi-forme and exfoliative DERMATITIS. These reactions usually appear in the ?rst 6–8 weeks of treatment.... sulphonylureas

(L.) Pers.

Synonym: T. hamiltonii Drumm.

Family: Papilionaceae; Fabaceae.

Habitat: All over India; also grown as green manure and as cover crop.

English: Purple Tephrosia, Wild Indigo.

Ayurvedic: Sharapunkhaa, Vishikha-punkhaa, Sarphokaa.

Unani: Sarponkhaa, Sarphukaa.

Siddha/Tamil: Kattu-kolingi, Kolingi, Paavali, Mollukkay, Kollukkayvelai.

Action: The drug is considered specific for the treatment of inflammation of spleen and liver (is known as Plihaa-shatru, Plihaari in Indian medicine).

Dried herb—diuretic, deobstruent, laxative. Given for the treatment of cough, bronchitis, bilious febrile attacks, insufficiency of the liver, jaundice (not effective in infantile cirrhosis), kidney disorders and for the treatment of bleeding piles, boils, pimples. Also used as a gargle. Root—decoction used in dyspepsia, diarrhoea, cough, bronchitis, adenoids, asthma and rheumatism. Juice is applied to skin eruptions. A liniment prepared from the root is employed in elephantiasis. Oil from seeds—specific against eruptions of the skin, eczema, scabies, leprosy. Seed extract—hypoglycaemic.

Powdered aerial parts prevented elevation of SGOP, SGPT and bilirubin levels.

Hepatoprotective effect of aerial parts was evaluated against (+)-galac- tosamine-induced and carbon tetra- chloride-induced hepatotoxicity in rats.

The leaves contain rutin and rote- noids (0.65-0.80% on dry basis). Rote- noid content is highest in the seed (1.60-1.80%).

The leaves also contain a triterpe- noid, lupeol, and beta-sitosterol.

Seeds contain a diketone-pongamol; a dimethylchromene flavanone iso- lonchocarpin; furanoflavones karan- jin and kanjone; a flavanone purpurin; and sitosterol. A flavonoid, lanceolarin B, is also present in seeds.

The plant extract led to marked lowering of blood glucose level in normal and alloxan-induced diabetic rabbits. In diabetic rabbits the extract exerted 60-70% hypoglycaemic effect as compared to tolbutamide.

Shveta Sharapunkhaa (stems: covered with white hair; flowers: pale pink or pale violet) is equated with T. villosa Pers.

The roots gave a prenylated fla- vanone 7-methylglabranin; pods contain rotenoids—villosin, villon, vil- losol, villosinol, villinol and villosone.

The fresh root is credited with hy- poglycaemic properties, but leaves did not show any such effect. The juice of the leaf is given in dropsy. Ayurve- dic classical texts describe it as a special drug for treating sterility in women.

Boiled leaves of T. uniflora subspecies petrosa (Kant-punkhaa) are used for the treatment of syphilis. The medicinal properties of the plant are more or less similar to those of T. purpurea, but to a milder degree.

T. spinosa Pers. (South India, ascending to 400 m in hills) is also known as Kant-punkhaa (Mulukolingi in Tamil Nadu).

The root is applied to inflammations and swellings of joints; a decoction is given in rheumatism.

Chalcones, spinochalones A and B and flemistrictin A have been isolated from the root. Spinochalone C and spinoflavonones A and B, and fulvin- ervin A have been isolated from the plant.

Dosage: Plant, root, seed—3-5 g powder. (CCRAS.)... tephrosia purpurea