Sulfonylureas Side Effects
Side Effects of Oral Antidiabetic Agents
Sulfonylureas are associated with weight gain and hypoglycemia.(35) Sulphonylureas should be avoided where possible in severe hepatic impairment and in acute porphyria . They should not be used during pregnancy or breast-feeding .Sulphonylureas are contra-indicated in the presence of ketoacidosis.(36)
Biguanides is associated with a low frequency of lactic acidosis. Biguanides major side effects are seen in the gastrointestinal tract, with nausea, cramps, and diarrhea. These side effects occur in 30% of patients but are usually transient and can be ameliorated or avoided by prescribing Biguanides to be taken after meals and starting with a low dose that is built up slowly. Only 3% of patients have to …show more content…
discontinue Biguanides because of gastrointestinal problems, and many in this group, in my experience, are also lactose intolerant. Vitamin B12 deficiency occurs after 1 year in approximately 7% of patients using Biguanides and can be prevented with oral calcium supplements.(37) Many side effects of Biguanides can be ameliorated if it is taken in the slow-release form.
Biguanide is contraindicated in ketoacidosis, use of iodine-containing X-ray contrast
Media and use of general anaesthesia, pregnancy and breast-feeding.
(38)
The major side effect of a-glucosidase inhibitors is flatulence. This occurs when undigested carbohydrate enters the large bowel, where it is digested by colonic bacteria resulting in gas formation. At high doses or in the presence of renal decompensation, hepatic necrosis may occur due to high serum a-glucosidase levels. In addition, because of suppressed a-glucosidase activity, sucrose is unlikely to correct hypoglycemia in those patients who take insulin or sulfonylureas in addition to taking an a-glucosidase inhibitor; in these patients, glucose tablets should be given to correct hypoglycemia.(39)
Therapy with acarbose has been linked to elevations in serum transaminase levels and the use of this agent is contraindicated in patients with liver cirrhosis. Likewise, concentrations of the alpha-glucosidase inhibitors have been shown to increase proportionally to the degree of renal dysfunction and their use in patients with a serum creatinine level more than 2.0 mg per dL is not recommended. Other contraindications include patients with inflammatory bowel disease or a history of bowel obstruction.
(40)
The thiazolidinediones pioglitazone and rosiglitazone, unlike their predecessor, troglitazone, have not been associated with significant hepatic problems, though because of the history of hepatic problems with trogliazone, we are still required to monitor liver function tests on a regular basis. At this time, the major problems with the thiazolidinediones are those of fluid retention, weight gain, and a normochromic, normocytic, dilutional anemia. The dilutional anemia may even be beneficial, since the oxygen carrying capacity of the blood is maintained, and with the increased plasma volume there is a decrease in blood viscosity and improved blood flow. The weight gain that occurs with the thiazolidinediones is in excess of that which would be associated with better glycemic control; it is mostly due to formation of new adipocytes in the subcutaneous fat, where it is not associated with an increase in insulin resistance. The weight gain that occurs with the thiazolidinediones may also be associated with fluid retention, however. Fluid retention is most likely to occur with higher doses of thiazolidinediones and in the more obese patient, but especially occurs when thiazolidinediones are used in combination with insulin. The mechanisms proposed for the fluid retention are excess production of the cytokine vascular endothelial growth factor (VEGF), which causes increased permeability in the microcirculation, closure of calcium channels, and excess stimulation of the peroxisome proliferator-activated receptor (PPAR) gamma receptors.(41) The usual edema associated with thiazolidinediones does not respond to loop diuretics, thiazide diuretics, or spironolactone, and only responds to reduction or discontinuance of the drug. In this respect, it resembles the edema seen with the dihydropyridine calcium channel blockers. Should the edema respond to diuretics, then it is most likely due to an underlying condition associated with high aldosterone levels (congestive heart failure, hepatic dysfunction, or renal dysfunction) being worsened by the addition of a thiazolidinedione.(42)
Thiazolidinedione contraindicated in hepatic impairment, history of heart failure, pregnancy and breast-feeding (43)
Sulfonylureas are associated with weight gain and hypoglycemia.(35) Sulphonylureas should be avoided where possible in severe hepatic impairment and in acute porphyria . They should not be used during pregnancy or breast-feeding .Sulphonylureas are contra-indicated in the presence of ketoacidosis.(36)
Biguanides is associated with a low frequency of lactic acidosis. Biguanides major side effects are seen in the gastrointestinal tract, with nausea, cramps, and diarrhea. These side effects occur in 30% of patients but are usually transient and can be ameliorated or avoided by prescribing Biguanides to be taken after meals and starting with a low dose that is built up slowly. Only 3% of patients have to …show more content…
discontinue Biguanides because of gastrointestinal problems, and many in this group, in my experience, are also lactose intolerant. Vitamin B12 deficiency occurs after 1 year in approximately 7% of patients using Biguanides and can be prevented with oral calcium supplements.(37) Many side effects of Biguanides can be ameliorated if it is taken in the slow-release form.
Biguanide is contraindicated in ketoacidosis, use of iodine-containing X-ray contrast
Media and use of general anaesthesia, pregnancy and breast-feeding.
(38)
The major side effect of a-glucosidase inhibitors is flatulence. This occurs when undigested carbohydrate enters the large bowel, where it is digested by colonic bacteria resulting in gas formation. At high doses or in the presence of renal decompensation, hepatic necrosis may occur due to high serum a-glucosidase levels. In addition, because of suppressed a-glucosidase activity, sucrose is unlikely to correct hypoglycemia in those patients who take insulin or sulfonylureas in addition to taking an a-glucosidase inhibitor; in these patients, glucose tablets should be given to correct hypoglycemia.(39)
Therapy with acarbose has been linked to elevations in serum transaminase levels and the use of this agent is contraindicated in patients with liver cirrhosis. Likewise, concentrations of the alpha-glucosidase inhibitors have been shown to increase proportionally to the degree of renal dysfunction and their use in patients with a serum creatinine level more than 2.0 mg per dL is not recommended. Other contraindications include patients with inflammatory bowel disease or a history of bowel obstruction.
(40)
The thiazolidinediones pioglitazone and rosiglitazone, unlike their predecessor, troglitazone, have not been associated with significant hepatic problems, though because of the history of hepatic problems with trogliazone, we are still required to monitor liver function tests on a regular basis. At this time, the major problems with the thiazolidinediones are those of fluid retention, weight gain, and a normochromic, normocytic, dilutional anemia. The dilutional anemia may even be beneficial, since the oxygen carrying capacity of the blood is maintained, and with the increased plasma volume there is a decrease in blood viscosity and improved blood flow. The weight gain that occurs with the thiazolidinediones is in excess of that which would be associated with better glycemic control; it is mostly due to formation of new adipocytes in the subcutaneous fat, where it is not associated with an increase in insulin resistance. The weight gain that occurs with the thiazolidinediones may also be associated with fluid retention, however. Fluid retention is most likely to occur with higher doses of thiazolidinediones and in the more obese patient, but especially occurs when thiazolidinediones are used in combination with insulin. The mechanisms proposed for the fluid retention are excess production of the cytokine vascular endothelial growth factor (VEGF), which causes increased permeability in the microcirculation, closure of calcium channels, and excess stimulation of the peroxisome proliferator-activated receptor (PPAR) gamma receptors.(41) The usual edema associated with thiazolidinediones does not respond to loop diuretics, thiazide diuretics, or spironolactone, and only responds to reduction or discontinuance of the drug. In this respect, it resembles the edema seen with the dihydropyridine calcium channel blockers. Should the edema respond to diuretics, then it is most likely due to an underlying condition associated with high aldosterone levels (congestive heart failure, hepatic dysfunction, or renal dysfunction) being worsened by the addition of a thiazolidinedione.(42)
Thiazolidinedione contraindicated in hepatic impairment, history of heart failure, pregnancy and breast-feeding (43)