Antifungal Drugs
December 10, 2017Thyroid and antithyroid drugs
December 13, 2017Diabetes mellitus occurs because of a lack of insulin or resistance to its action. It is diagnosed by measuring fasting or random blood-glucose concentration (and occasionally by glucose tolerance test). Although there are many subtypes, the two principal classes of diabetes are type 1 diabetes and type 2 diabetes. Type 1 diabetes, also referred to as insulin-dependent diabetes mellitus (IDDM), occurs as a result of a deficiency of insulin following autoimmune destruction of pancreatic beta cells. Patients with type 1 diabetes require administration of insulin. Type 2 diabetes, also referred to as non-insulin-dependent diabetes (NIDDM), is due either to reduced secretion of insulin or to peripheral resistance to the action of insulin. Although patients may be controlled on diet alone, many also require oral antidiabetic drugs or insulin (or both) to maintain satisfactory control.
Insulins
The aim of treatment is to achieve the best possible control of blood-glucose concentration without making the patient obsessional and to avoid disabling hypoglycaemia; close co-operation is needed between the patient and the medical team because good control reduces the risk of complications. Mixtures of insulin preparations may be required and appropriate combinations have to be determined for the individual patient. Insulin preparations can be divided into 3 types:
- those of short duration which have a relatively rapid onset of action, namely soluble insulin, insulin lispro and insulin aspart.
- those with an intermediate action, e.g. isophane insulin and insulin zinc suspension.
- those whose action is slower in onset and lasts for long periods, e.g. insulin zinc suspension.
During pregnancy and breast-feeding, insulin requirements may alter and doses should be assessed frequently by an experienced diabetes physician. The dose of insulin generally needs to be increased in the second and third trimesters of pregnancy. Hypoglycaemia is a potential problem with insulin therapy. All patients must be carefully instructed on how to avoid it.
Short-acting insulins
Soluble insulin is a short-acting form of insulin. For maintenance regimens it is usual to inject it 15 to 30 minutes before meals. Soluble insulin is the most appropriate form of insulin for use in diabetic emergencies e.g. diabetic ketoacidosis and at the time of surgery. It can be given intravenously and intramuscularly, as well as subcutaneously. Insulin aspart and insulin lispro can be administered intravenously and can be used as alternatives to soluble insulin for diabetic emergencies and at the time of surgery.
INSULIN (Insulin Injection; Neutral Insulin; Soluble Insulin):
Indications: diabetes mellitus; diabetic ketoacidosis.
Contraindications: Hypoglycemic Disorder.
Dose and Administration: By subcutaneous, intramuscular or intravenous injection or intravenous infusion, according to requirements.
INSULIN ASPART (Recombinant human insulin analogue):
Indications: Diabetes Mellitus, Hyperglycemia, Type 1 Diabetes Mellitus.
Contraindications: Hypoglycemic Disorder.
Dose and Administration: By subcutaneous injection, immediately before meals or when necessary shortly after meals, according to requirements.
INSULIN GLULISINE (Recombinant human insulin analogue):
Indications: Diabetes Mellitus, Type 1 Diabetes Mellitus.
Contraindications: Hypoglycemic Disorder.
Dose and Administration: By subcutaneous injection, immediately before meals or when necessary shortly after meals, according to requirements. child and adolescent under 17 years not recommended.
INSULIN LISPRO (Recombinant human insulin analogue):
Indications: Diabetes Mellitus, Hyperglycemia, Type 1 Diabetes Mellitus.
Contraindications: Hypoglycemic Disorder.
Dose and Administration: By subcutaneous injection, immediately before meals or when necessary shortly after meals, according to requirements.
Intermediate- and long-acting insulins
When given by subcutaneous injection, intermediate- and long-acting insulins have an onset of action of approximately 1–2 hours, a maximal effect at 4–12 hours, and a duration of 16–35 hours. Some are given twice daily in conjunction with short-acting (soluble) insulin, and others are given once daily, particularly in elderly patients. Soluble insulin can be mixed with intermediate and long-acting insulins (except insulin detemir and insulin glargine) in the syringe, essentially retaining the properties of the two components.
INSULIN DETEMIR (Recomb. human insulin analogue —long acting):
Indications: Diabetes Mellitus, Type 1 Diabetes Mellitus.
Contraindications: Hypoglycemic Disorder.
Dose and Administration: By subcutaneous injection, adult and child over 6 years, according to requirements.
INSULIN GLARGIN (Recomb. human insulin analogue —long acting):
Indications: Diabetes Mellitus, Hyperglycemia, Type 1 Diabetes Mellitus.
Contraindications: Hypoglycemic Disorder.
Dose and Administration: By subcutaneous injection, adult and child over 6 years, according to requirements. It is not recommended for routine use in patients with type 2 diabetes unless they suffer from recurrent episodes of hypoglycemia or require assistance with their insulin injections.
ISOPHANE INSULIN (Isophane Insulin Injection; Isophane Protamine Insulin Injection; Isophane Insulin (NPH)—intermediate acting):
Indications: Diabetes Mellitus, Hyperglycemia, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus.
Contraindications: Hypoglycemic Disorder.
Dose and Administration: By subcutaneous injection, according to requirements.
BIPHASIC INSULIN ASPART (Intermediate-acting insulin):
Indications: Diabetes Mellitus, Hyperglycemia, Type 1 Diabetes Mellitus, Type 2
Diabetes Mellitus.
Contraindications: Hypoglycemic Disorder.
Dose and Administration: By subcutaneous injection, up to 10 minutes before
or soon after a meal, according to requirements
BIPHASIC ISOPHANE INSULIN (Biphasic Isophane Insulin Injection— intermediate acting):
Indications: Diabetes Mellitus, Hyperglycemia, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus.
Contraindications: Hypoglycemic Disorder.
Dose and Administration: By subcutaneous injection, according to requirements.
Antidiabetic drugs
Oral antidiabetic drugs are used for the treatment of type 2 (non-insulindependent) diabetes mellitus. They should be prescribed only if the patient fails to respond adequately to at least 3 months’ restriction of energy and carbohydrate intake and an increase in physical activity. They should be used to augment the effect of diet and exercise, and not to replace them. For patients not adequately controlled by diet and oral hypoglycaemic drugs, insulin may be added to the treatment regimen or substituted for oral therapy. When insulin is added to oral therapy, it is generally given at bedtime as isophane insulin, and when insulin replaces an oral regimen it is generally given as twice-daily injections of a biphasic insulin (or isophane insulin mixed with soluble insulin). Weight gain and hypoglycaemia may be complications of insulin therapy but weight gain may be reduced if the insulin is given in combination with metformin.
Sulphonylureas
The sulphonylureas act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present; during long-term administration they also have an extrapancreatic action. All may cause hypoglycaemia but this is uncommon and usually indicates excessive dosage. Sulphonylurea-induced hypoglycaemia may persist for many hours and must always be treated in hospital. Sulphonylureas are considered for patients who are not overweight, or in whom metformin is contra-indicated or not tolerated.
GLIBENCLAMIDE:
Indications: type 2 diabetes mellitus.
Contraindications: Ketoacidosis, Severe Renal Disease, Debilitation, Hepatic Porphyria, High Fever >101 Degree, Hypoglycemic Disorder, Severe Hepatic Disease, Severe Infection, Surgical Procedure, Trauma.
Dose and Administration: Initially 5 mg daily with or immediately after breakfast, dose adjusted according to response; max. 15 mg daily.
GLICLAZIDE:
Indications: type 2 diabetes mellitus.
Contraindications: severe hepatic impairment and in severe renal impairment and in porphyria. They should not be used while breast-feeding, and insulin therapy should be substituted during pregnancy. Sulphonylureas are contraindicated in the presence of ketoacidosis.
Dose and Administration: Initially, 40–80 mg daily, adjusted according to response; up to 160 mg as a single dose, with breakfast; higher doses divided; max. 320 mg daily. For the modified release Dose Initially 30 mg daily with breakfast, adjusted according to response every 4 weeks (after 2 weeks if no decrease in blood glucose); max. 120 mg daily.
GLIMEPIRIDE:
Indications: type 2 diabetes mellitus.
Contraindications: severe hepatic impairment and in severe renal impairment and in porphyria. They should not be used while breast-feeding, and insulin therapy should be substituted during pregnancy. Sulphonylureas are contraindicated in the presence of ketoacidosis.
Dose and Administration: Initially 1 mg daily, adjusted according to response in 1-mg steps at 1–2 week intervals; usual max. 4 mg daily (exceptionally, up to 6 mg daily may be used); taken shortly before or with first main meal.
GLIPIZIDE:
Indications: type 2 diabetes mellitus.
Contraindications: severe hepatic impairment and in severe renal impairment and in porphyria. They should not be used while breast-feeding, and insulin therapy should be substituted during pregnancy. Sulphonylureas are contraindicated in the presence of ketoacidosis.
Dose and Administration: Initially 2.5–5 mg daily shortly before breakfast or lunch, adjusted according to response; max. 20 mg daily; up to 15 mg may be given as a single dose; higher doses divided.
Biguanides
Metformin, the only available biguanide, It exerts its effect mainly by decreasing gluconeogenesis and by increasing peripheral utilisation of glucose; since it acts only in the presence of endogenous insulin it is effective only if there are some residual functioning pancreatic islet cells. Metformin is the drug of first choice in overweight patients in whom strict dieting has failed to control diabetes, if appropriate it may also be considered as an option in patients who are not overweight. It is also used when diabetes is inadequately controlled with sulphonylurea treatment.
METFORMIN HYDROCHLORIDE:
Indications: diabetes mellitus and polycystic ovary syndrome.
Contraindications: renal impairment, ketoacidosis, withdraw if tissue hypoxia likely (e.g. sepsis, respiratory failure, recent myocardial infarction, hepatic impairment), use of iodine-containing X-ray contrast media (do not restart metformin until renal function returns to normal) and use of general anaesthesia (suspend metformin on the morning of surgery and restart when renal function returns to normal), pregnancy and breast-feeding.
Dose and Administration: Diabetes mellitus, adult and child over 10 years initially 500 mg with breakfast for at least 1 week then 500 mg with breakfast and evening meal for at least 1 week then 500 mg with breakfast, lunch and evening meal; usual max. 2 g daily in divided doses.
METFORMIN HYDROCHLORIDE- GLIBENCLAMIDE:
Indications: diabetes mellitus type 2 in adults and as replacment for previous treatment with metformin and glibenclamide in patients whose glycaemia is stable and well controlled.
Contraindications: renal impairment, ketoacidosis, withdraw if tissue hypoxia likely (e.g. sepsis, respiratory failure, recent myocardial infarction, hepatic impairment), use of iodine-containing X-ray contrast media (do not restart metformin until renal function returns to normal) and use of general anaesthesia (suspend metformin on the morning of surgery and restart when renal function returns to normal), pregnancy and breast-feeding.
Dose and Administration: the starting dose should not exceed the daily dose of glibenclamide and metformin already being taken. The daily dose may be titrated every two weeks to the minimum effective dose.
Other antidiabetics
ACARBOSE:
Indications: diabetes mellitus inadequately controlled by diet or by diet with oral antidiabetic drugs.
Contraindications: inflammatory bowel disease, predisposition to partial intestinal obstruction; hernia, previous abdominal surgery; hepatic impairment; renal impairment; pregnancy; breast-feeding.
Dose and Administration: Initially 50 mg daily increased to 50 mg 3 times daily, then increased if necessary after 6–8 weeks to 100 mg 3 times daily; max. 200 mg 3 times daily; child and adolescent under 18 years not recommended.
REPAGLINIDE:
Indications: type 2 diabetes mellitus (as monotherapy or in combination with metformin when metformin alone inadequate).
Contraindications: ketoacidosis; severe hepatic impairment; pregnancy and breast-feeding.
Dose and Administration: Initially 500 micrograms within 30 minutes before main meals (1 mg if transferring from another oral hypoglycaemic), adjusted according to response at intervals of 1–2 weeks; up to 4 mg may be given as a single dose, max. 16 mg daily; child and adolescent under 18 years and elderly over 75 years, not recommended.
PIOGLITAZONE:
Indications: type 2 diabetes mellitus (alone or combined with metformin or a
sulphonylurea, or with both).
Contraindications: hepatic impairment, history of heart failure, pregnancy,
breast-feeding.
Dose and Administration: Initially 15–30 mg once daily increased to 45 mg
once daily according to response.
ROSIGLITAZONE:
Indications: type 2 diabetes mellitus (alone or combined with metformin or a sulphonylurea, or with both).
Contraindications: hepatic impairment, history of heart failure, pregnancy, breast-feeding.
Dose and Administration: Initially 4 mg daily; may be increased after 8 weeks to 8 mg daily (in 1–2 divided doses) according to response; child and adolescent under 18 years not recommended.
ROSIGLITAZONE-METFORMIN:
Indications: type 2 diabetes mellitus.
Contraindications: hepatic impairment, history of heart failure, pregnancy, breast-feeding, Acutely Decompensated Chronic Heart Failure, Alcohol Intoxication, Alcoholism, Bacterial Septicemia, Cardiogenic Shock, Dehydration, Disease of Liver, Drug-Induced Hepatitis, Hypoxia, Ketoacidosis, Lactic Acidosis, Metabolic Acidosis, Myocardial Infarction, Radiography with IV Iodinated Contrast Agent, Renal Disease, Respiratory Depression, Severe Chronic Heart Failure, Shock, Surgical Procedure, Trauma.
Dose and Administration: Type 2 diabetes mellitus not controlled by metformin alone, initially one-tablet 2mg/500 mg twice daily increased after 8 weeks according to response, max. 8 mg rosiglitazone and 2 g metformin hydrochloride daily; child and adolescent under 18 years not recommended
ROSIGLITAZONE-GLIPIZIDE:
Indications: type 2 diabetes mellitus.
Contraindications: Acutely Decompensated Chronic Heart Failure, Drug-Induced Hepatitis, Lactating Mother, Severe Chronic Heart Failure, Angina, Body Fluid Retention, Chronic Heart Failure, Coronary Artery Disease, Disease of Liver, Edema, Hepatic Porphyria, Hypoglycemic Disorder, Myocardial Infarction, Myocardial Ischemia, Osteopenia, Osteoporosis, Pulmonary Edema, Type 1 Diabetes Mellitus.
Dose and Administration: therapy should be individualized for each patient and should be given once daily with the first meal of the day.
DPP-4 INHIBITORS
SITAGLIPTIN:
Indications: type 2 diabetes mellitus (in combination with metformin or a
thiazolidinedione, when metformin or thiazolidinedione is inadequate).
Contraindications: ketoacidosis; pregnancy and breast-feeding.
Dose and Administration: adult over 18 years, 100 mg once daily.
VILDAGLIPTIN:
Indications: type 2 diabetes mellitus (in combination with metformin or a thiazolidinedione, when metformin or thiazolidinedione is inadequate).
Contraindications: Hypersensitivity to the active substance or to any of the excipients.
Dose and Administration: When used in dual combination with metformin or a thiazolidinedione, the recommended daily dose of vildagliptin is 100mg, administered as one dose of 50 mg in the morning and one dose of 50 mg in the evening. Doses higher than 100mg are not recommended.
Treatment of hypoglycaemia
Hypoglycaemia which causes unconsciousness is an emergency. Glucagon, a polypeptide hormone produced by the alpha cells of the islets of Langerhans, increases plasma-glucose concentration by mobilising glycogen stored in the liver. In hypoglycaemia, if sugar cannot be given by mouth, glucagon can be given by injection. Carbohydrates should be given as soon as possible to restore liver glycogen; glucagon is not appropriate for chronic hypoglycaemia.
GLUCAGON:
Indications: Hypoglycemic Disorder.
Contraindications: Diabetes Mellitus, Glucagonoma, Insulinoma, and Pheochromocytoma.
Dose and Administration: Insulin-induced hypoglycaemia, by subcutaneous, intramuscular, or intravenous injection, adult and child over 8 years (or body-weight over 25 kg), 1 mg; child under 8 years (or body-weight under 25 kg), 500 micrograms; if no response within 10 minutes intravenous glucose must be given.
