Hypoglycemic agents, oral

A number of different routes are available for the preparation of tolbutamide (32-3), the hrst oral hypoglycemic agent to be used clinically. The shortest route involves the simple addition of para-toluenesulfonamide (32-1) to butyl isocyanate (32-2) [31]. An alternate route is required for the preparation of a dmg that includes a tertiary urea nitrogen. The same starting material (32-1) is converted to its carbamate (32-4) with ethyl chloroformate in the presence of a base. Heating that intermediate with hexamethyleneimine leads to the displacement of the ethoxy group and the formation of tolazemide (32-5) [32]. 

The very low potency of hrst-generation sulfonylureas required the daily intake of doses measured in grams. The incorporation of complex side chains on the 

Lipodystrophy can also result from insulin therapy and is characterized by atrophy of subcutaneous fat. Insulin edema is manifested by a generalized retention of fluid. Insulin resistance arises when there is an excess insulin requirement that exceeds 200 units per day. 

The mechanisms that underlie the hypoglycemic actions of sulfonylureas are as follows  

Improved insulin secretion Reduced glucagon secretion Extrapancreatic 

Increased receptor binding Improved postbinding action Indirect 

Decreased plasma concentrations of free fatty acids Reduced hepatic insulin extraction 

The cholinesterase inhibitors are divided into two categories organophosphorous compounds, such as parathion, malathion, and tetraethyl pyrophosphate (TEPP), and the carbamates, such as naphthyl-A-methyl carbamate (carbaryl and Sevin). 

Orlistat is a lipase inhibitor that acts as a reversible lipase inhibitor for obesity management by inhibiting absorption 

A major portion of the pancreas essentially eomprises of glandular tissue whieh speeially eontains acinar cells that predominantly gives rise to the secretion of certain digestive enzymes. Besides, there also exist some isolated gronps of pancreatic cells commonly known as the islets of Langerhans which usually made up of four cell types, each of which generates a distinct polypeptide hormone, namley  

Interestingly, the P-cells made up 60-80% of the islets of Langerhans most predominantly and distinctly. 

Diabetes — a general term for diseases marked by excessive urination and is usually refers to 

However, the clinical diabetes mellitus invariably occurs in two forms, associated with different causes and methods of therapy. 

Type 2 Diabetes The noninsulin-dependent diabetes mellitus (NIDDM), i.e., type 2 diabetes, is most abundantly linked with obesity in its adult patients largely. In such a situation, the insulin levels could be either elevated or normal and therefore, in short, it is nothing but a disease of abnormal insulin resistance . However, it has been duly observed that the impact of the disease is relatively 

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Table 2. Sulfonylureas Used as Oral Hypoglycemic Agents...

Treatment of piperidine with nitrous acid affords the N-nitroso derivative (190) reduction gives the corresponding hydrazine (191). Condensation of this intermediate with the carbamate (192) obtained from p-toluenesulfonamide leads to the oral hypoglycemic agent tolazemide (193). In a similar vein, reaction of the hydrazine obtained by the same sequence from azepine (194) with the carbamate, 188, gives azepinamide (195). ... 

Perhaps surprisingly, the p-methyl benzenesulfonylurea analogue called tosi fen (45), which is structurally rather close to the oral hypoglycemic agents, is an anti anginal agent... 

Amenorrhea, other menstrual irregularities, development of cushingoid state, suppression of growth in children, secondary adrenocortical and pituitary unresponsive (particularly in times of stress), decreased carbohydrate tolerance, manifestation of latent diabetes mellitus, increased requirements for insulin or oral hypoglycemic agents (in diabetics)... 

Lifestyle modifications are always in order in patients who have developed or those who are at increased risk of developing NODAT.74 Insulin therapy and oral hypoglycemic agents are used often (Table 52-8) in patients in whom lifestyle modifications alone have not controlled blood glucose levels. See Chapter 40 for appropriate treatment regimens for diabetes. 

A 60-year-old diabetic male on an oral hypoglycemic agent develops abnormal liver function tests. Which of the following agents can cause this finding ... 

A 60-year-old male alcoholic treated for type 11 diabetes mellitus develops lactic acidosis. Which of the following oral hypoglycemic agents might cause this adverse effect ... 

The frequency of hypoglycemia is greater in patients with type 2 diabetes who have not been previously treated with oral hypoglycemic agents or whose HbA- c is less... 

Oral hypoglycemic agents Concurrent use of oral hypoglycemic agents is not recommended there are no data to support such use. 

Transfer from other antidiabetic therapy When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to metformin, generally no transition period is necessary. When transferring patients from chlorpropamide, exercise care during the first 2 weeks because of the prolonged retention of... 

Biood giucose abnormaiities Disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent or with insulin. 

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