Classify the oral hypoglycaemic drugs; include their mechanism of action, and their
most significant side effects.
A good answer would have best been served by a tabular structure and some understanding of the information required. One system of classification of oral hypoglycaemic drugs is by their mechanism of action, or drug group e.g. Biguanides, Sulfonylureas, Thiazolidinediones, Alpha-glucosidase inhibitors, Meglitinides and Dipeptidyl peptidase (DPP) -IV inhibitors.
| Class mechanism of action | Adverse effects |
|
Biguanides: By disabling the mitochondrial respiratory chain, decrease the ATP supply to hepatocytes, activating AMPK (a fuel-sensing enzyme which regulates the balance of anabolic and catabolic activity). The result is an activation of fatty acid oxidation and a deactivation of glycogenolysis and gluconeogenesis. Systemic glucose delivery from the liver is therefore decreased. |
- lactic acidosis - diarrhoea - abdominal discomfort - anorexia - taste disturbance |
|
Sulfonylureas: By binding to the ATP-sensitive K channel, these drugs act like ATP (i.e. same as a rise in blood glucose), closing the channel and stopping the efflux of potassium from the cell, which promotes depolarisation. The depolarisation then leads to insulin release |
- undesirable severe hypoglycaemia - hypokalemia - secondary failure of therapy (as beta-cells burn out) - erythema multiforme - exfoliative dermatitis - photosensitivity |
|
α-glucosidase inhibitors: By acting as a pseudocarbohydrate, they substitute themselves as a substrate for α-glucosidase enzymes such as sucrase, maltase, dextranase and glucoamylase, which results in decreased intestinal absorption of complex carbohydrates |
- malabsorption of carbohydrates - diarrhoea - flatulence - abdominal bloating |
|
Meglitinides: By binding to the ATP-sensitive K channel, meglitinides act like ATP (i.e. same as a rise in blood glucose), closing the channel and stopping the efflux of potassium from the cell, which promotes depolarisation. The depolarisation then leads to insulin release |
- undesirable severe hypoglycaemia (but less likely than with sulfonylureas) - respiratory tract infections - headache |
|
Thiazolidinediones: PPARγ receptor activation leads to the increased synthesis and activity of cellular proteins involved in glucose uptake and processing, which results in an increased effect from any insulin binding in insulin-sensitive tissues (espeically adipocytes). The result is an increase in insulin sensitivity |
- weight gain - increased risk of bone fractures - fluid retention and oedema - cardiac ischaemia (rosiglitazone only) |
|
DPP-4 inhibitors: By decreasing the degradation of GLP-1, DPP-4 inhibitors produce an increase in insulin secretion. GLP-1 binds to its G-protein-coupled receptors on pancreatic β-cells, where it increases intracellular cAMP, and therefore the availability of intracellular calcium that drives insulin exocytosis |
- headache - nasopharyngitis |
|
GLP-1 receptor agonists: By directly activating GLP-1, receptors, these drugs produce an increase in insulin secretion. This occurs because of an increase in intracellular cAMP, and therefore the availability of intracellular calcium that drives insulin exocytosis |
- pancreatitis - weight loss |
|
SGLT-2 inhibitors: Inhibit the reabsorprtion of glucose in the proximal tubule, increasing glucose loss via the urine. In this fashion 30-50% (50-90g) of the total daily filtered glucose is lost, resulting in reduced hyperglycaemia and total body calorie loss |
- euglycaemic ketoacidosis - polyuria - volume depletion - UTIs |
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