The glucose metabolism of normal people is in a relatively dynamic and stable state through the regulation of nerves and hormones. However, certain congenital enzyme defects, nervous system disorders and endocrine disorders can cause glucose metabolism disorders and make blood sugar fluctuate. When the blood sugar cannot be controlled by diet control and proper exercise, it needs to be regulated by drugs. However, some common clinical drugs also have influence on glucose-lowering drugs, and as a primary care physician, we must understand this. He Yan, Department of Neurology, Shandong Qianfo Mountain Hospital
Antihypertensive drugs
Angiotensin converting enzyme inhibitors (ACEI) Hypertensive patients often have impaired insulin utilization, and ACEI is effective in improving insulin utilization. For example, enalapril is more effective than captopril in lowering blood glucose. Cilazapril can increase insulin secretion when blood glucose is elevated, but it is not effective in improving insulin utilization. Some scholars compared the effects of captopril, enalapril, quinapril, ramipril, lenopril and placebo on insulin utilization, and all five ACEIs were effective in improving insulin utilization, among which the effect of lenopril was the most obvious. Another trial showed that perindopril caused a significant increase in insulin sensitivity when lowering blood pressure, and it has been suggested that the improvement of insulin sensitivity by ACEI is not dependent on the decrease in angiotensin II, which may be related to the increase in endogenous kinins.
Angiotensin II receptor antagonists
Most angiotensin II receptor antagonists do not have any effect on insulin sensitivity, but some have reported that candesartan has an effect on improving insulin sensitivity. This may be related to alterations in the activity of the renin-angiotensin system, which leads to alterations in the activity of other neurofactors. Calcium antagonists This class of drugs improves insulin sensitivity. A double-blind controlled study with amlodipine has been performed and showed that amlodipine increases insulin-mediated glucose uptake by a possible mechanism: restoration of insulin-mediated vasodilatation by decreasing cellular calcium ion levels, which in turn increases blood perfusion to muscle tissue and improves glucose utilization.
Epinephrine-mimetics
Most adrenomimetic drugs can cause hyperglycemia, such as epinephrine, which is an alpha and beta agonist that promotes glycogen and lipolysis and increases blood glucose, and is prohibited in diabetic patients. When applied in high doses, norepinephrine can promote glycogenolysis and interfere with insulin secretion, resulting in hyperglycemia. Isoprenaline is a β1 and β2 receptor agonist, which can promote glycogenolysis and free fatty acid release, and its effect on raising blood glucose is slightly weaker than epinephrine. Other drugs such as m-hydroxylamine and phenylephrine can also cause hyperglycemia. β2 receptor excitation can be physiologically manifested as smooth muscle relaxation, increased glycogenolysis in skeletal muscle and insulin release. β2 receptor agonists are often used clinically in patients with asthma, but for diabetic patients, these drugs should be used with caution because of their glucose-raising effect.
Beta-blockers
Although these drugs can inhibit glycogenolysis, they do not directly affect the blood glucose and insulin levels of normal people at rest, nor do they affect the hypoglycemic effect of insulin, but slow down the recovery of blood glucose after hypoglycemia caused by insulin. However, when hyperglycemia occurs, these drugs can inhibit insulin secretion and prolong the duration of hyperglycemia, thus forcing the dose of insulin to be increased. Application of non-selective β-blockers, such as propranolol, can prevent adrenaline from raising blood glucose and interfere with the body’s function of regulating blood glucose, delaying the recovery of blood glucose to normal levels. When it is combined with hypoglycemic drugs, it can enhance the hypoglycemic effect, and also can mask some hypoglycemic symptoms (such as tachycardia), resulting in prolonging the duration of hypoglycemia. Therefore, caution should be exercised when applying this drug to patients with diabetes mellitus fasting or patients under anesthesia. This is less likely to occur with small doses of selective beta-blockers such as atenolol and metoprolol.
Hormonal drugs
Glucocorticoids such as prednisone, cortisone, dexamethasone, etc. These drugs can increase the synthesis of hepatic glycogen and reduce the utilization and breakdown of glycogen by tissues, which can increase blood glucose. Androgens can significantly affect the stability of the internal environment of glucose and insulin, causing reduced glucose tolerance and hyperinsulinemia, and weakening the hypoglycemic effect of insulin, thus also weakening the hypoglycemic effect of oral sulfonylurea hypoglycemic agents (SU), so the two should not be used together. Oral contraceptives can reduce the utilization of glucose by peripheral tissues and increase blood glucose; while high dose application of progestin can also increase blood glucose. For example, ethinyl estradiol can reduce glucose tolerance and induce diabetes in people with latent diabetes. This may be because estrogen can enhance the vitality of growth hormone and cause the increase of urine sugar and blood sugar. Growth hormone, on the other hand, has an antagonistic effect on insulin, which can affect glucose metabolism and make glucose tolerance diminish, and can even cause diabetes. Growth inhibitors can inhibit the secretion of glucagon and insulin, and long-term application can cause hyperglycemia. Thyroxine can increase blood glucose concentration, and corticotropin can promote the secretion of glucocorticoids.
Anti-infective drugs
Sulfonamides can compete with insulin for plasma proteins, thus increasing the free insulin in the blood. At the same time, when sulfonamides are combined with sulfonylurea hypoglycemic agents, especially methanesulfonylurea, the free portion of sulfonylurea hypoglycemic agents can increase in concentration. In addition, it can also reduce the renal excretion of sulfonylureas and prolong their effects.
Chloramphenicol Chloramphenicol can inhibit hepatic enzymes and reduce the hepatic metabolism of sulfonylurea hypoglycemic agents, thus enhancing their hypoglycemic effect, such as the combination with methylsulfonylurea and other hypoglycemic agents can cause hypoglycemia.
Penicillin penicillin can weaken the binding power of sulfonylurea hypoglycemic drugs to plasma proteins, thus enhancing their hypoglycemic effect.
Quinolone application of this class of drugs can lead to hypoglycemia, especially for elderly patients and those with renal dysfunction. For example, high-dose application of levofloxacin in diabetic patients can lead to hypoglycemia; application of sparfloxacin, as well as other new quinolones, can occasionally result in hypoglycemic symptoms. Application of ciprofloxacin can also occasionally lead to hyperglycemia.
Tetracyclines Tetracycline and hygromycin can inhibit hepatic enzymes, which enhances the effect of hypoglycemic drugs. However, tetracyclines can be stored for a long time or subject to changes in light, heat and humidity and decompose to produce toxic substances, and such toxic substances can cause kidney damage and retinitis pigmentosa in patients.
The addition of flavopiridol in cases where metformin alone is not effective in controlling blood glucose can lead to better control of blood glucose. This may be related to the effect of flavopiridol on anti-glycemic hormones and on promoting regeneration and functional recovery of pancreatic β-cells, but the exact relevance of this remains to be verified in controlled trials with large samples.
Anti-tuberculosis drugs
Anti-tuberculosis drugs such as isoniazid and rifampin can promote the liver to secrete more drug enzymes to accelerate the metabolism and excretion of methanesulfonylurea, thus shortening the half-life of methanesulfonylurea, affecting the hypoglycemic effect, reducing the efficacy of hypoglycemic drugs and raising blood glucose. In addition, other anti-tuberculosis drugs such as pyrazinamide and ethambutol can also make it difficult to control blood sugar.
Imidazole antifungal drugs
Imidazole antifungal drugs such as fluconazole and miconazole, combined with sulfonylurea hypoglycemic drugs, can inhibit the metabolism of sulfonylurea hypoglycemic drugs, thus prolonging the half-life of sulfonylurea hypoglycemic drugs, but hypoglycemia may also occur.
Diuretics and other drugs
Thiazide diuretics can inhibit the release of insulin and the utilization of glucose by peripheral tissues, causing blood glucose to rise. In addition, tachykinuria, butanuric acid, acetazolamide and aminopterin can also cause blood glucose to rise, so they should be used with caution in diabetic patients. However, sodium diuretic, anti-aldosterone preparations, and mipyridamole have almost no effect on blood glucose. Diazoxide can raise blood glucose, it can inhibit the release of insulin and reduce the utilization of glucose, and at the same time promote the release of endogenous catecholamines to increase blood glucose. Indapamide has a weak diuretic effect and calcium antagonism, which can make glucose tolerance worse in diabetic patients, so it should be used with caution. Prazosin can improve insulin sensitivity and lower blood glucose.
Non-steroidal anti-inflammatory and analgesic drugs
Glucagon and salicylates can weaken the binding power of sulfonylurea hypoglycemic drugs to plasma proteins, thus increasing the free sulfonylurea hypoglycemic drugs in the blood, and the hypoglycemic effect of sulfonylurea hypoglycemic drugs can be enhanced by taking such drugs in large doses.
In addition, salicylates can reduce the renal excretion of sulfonylurea hypoglycemic agents, resulting in enhanced action of sulfonylurea hypoglycemic agents and increased secretion of insulin, which can also increase the absorption of glucose by surrounding tissues. In addition, Protaxon reduces the hepatic metabolism and renal excretion of sulfonylurea hypoglycemic agents. Aspirin, when used in children with diabetes, is more likely to cause hypoglycemia, so it should be used with caution in children with diabetes. Other drugs such as paracetamol can also cause hypoglycemia.
Other
Enzyme inducers such as carbamazepine, phenobarbital, phenytoin sodium and ashwagandha can activate hepatic microsomal enzymes and increase the metabolism of sulfonylurea hypoglycemic agents in the liver and weaken the hypoglycemic effect. Monoamine oxidase inhibitors, such as isoniazid and dysentery, can inhibit hepatic enzymes and enhance the hypoglycemic effect by affecting the metabolism of hypoglycemic drugs. Niacin can cause a decrease in glucose tolerance and inhibit the utilization of glucose through end tissues. Anti-psychotic drugs such as chlorpromazine and fenugreek have the effect of raising blood sugar. When anticoagulants such as bicoumarin and sulfonylurea hypoglycemic drugs are combined, the plasma concentration of each increases initially, but decreases later, so the dosage of both needs to be adjusted.