Thiazolidinedione drugs

A nuclear receptor that is a key transcription factor in adipocytes. It plays a critical role in the control of adipocyte differentiation and is involved in the regulation of the expression of specific adipokines, including leptin and adiponectin. It has anti-inflammatory actions and is the target of the thiazolidinedione drugs. The preintegration complex is a complex of retroviral DNA and proteins that translocates from the cytosol into the nucleus prior to integration. Gene Therapy... 

Synthetic ligands Thiazolidinediones and some non-steroidal antiinflammatory drugs... 

Thiazolidinediones (synonyms glitazones, insulin sensitizers rosiglitazone, pioglitazone) are a novel class of oral antidiabetic drugs that activate the transcription factor peroxisome proliferator-activated receptor (PPARy). Thiazolidinediones ameliorate insulin resistance in obese animal models and in individuals... 

THIAZOLIDINEDIONES. The thiazolidinediones, piogli-tazone and rosiglitazone, are given with or without meals. If the dose is missed at the usual meal, the drug is taken at the next meal. If the dose is missed on one day, do not double the dose the following day. If the drug is taken, do not delay the meal. Delay of a meal for as little as y2 hour can cause hypoglycemia. 

Thiazolidinediones may produce fluid retention and edema however, the mechanism by which this occurs is not completely understood. It is known that blood volume increases approximately 10% with these agents, resulting in approximately 6% of patients developing edema. Thus, these drugs are contraindicated in situations in which an increased fluid volume is detrimental, such as heart failure. Fluid retention appears to be dose-related and increases when combined with insulin therapy. 

Isocyanates can be formed by oxidative dehydrogenation (see Oxidative Dehydrogenation section and Figure 4.71 in Chapter 4). Isocyanates can also be formed from the oxidation of sulfonylureas (e.g., tolbutamide) (29) and thiazolidinediones (e.g., trogli-tazone) (30), as shown in Figure 8.19. Both of these classes of drugs are used to treat... 

In summary, results from several studies in to the effects of impaired insulin action can now be linked to CVD. Because of the numbers of people exhibiting sings of insulin resistance, there has been a lot of research effort has gone in to finding suitable therapeutic interventions. One group of drugs in particular, the thiazolidinediones (also known as glitazones) has attracted attention because they both increase insulin sensitivity and help to normalize plasma lipid concentrations. 

The members of this class are derivatives of the parent compound thiazolidinedione, and include rosiglitazone, pioglitazone and troglitazone which was withdrawn from the market due to an increased incidence of drug-induced hepatitis. 

Sitagliptin is a selective dipeptidylpeptidase 4 (DPP-4) inhibitor which increases the active form of GLP-1 (glucagon-like-peptide-1) and GIP (glucose-dependent insulinotropic peptide). This enzyme-inhibiting drug is to be used either alone or in combination with metformin or a thiazolidinedione for control of type 2 diabetes mellitus. Adverse effects were as common with sitagliptin (whether used alone or with metformin or pioglitazone) as they were with placebo, except for nausea and common cold-like symptoms. 

II.f.2.1. Oral hypoglycaemic agents. There are now five groups of orally active drugs available to lower blood glucose in clinical practice (Table 2). These are sulphonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, and the incretin derivatives. 

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