Treatment Of Dm PDF

# TREATMENT OF DM ## Diabetes Mellitus * Diabetes is a disease characterized by chronic hyperglycemia due to an absolute or relative lack of insulin (reduced sensitivity to its action [insulin resistance]). * It is diagnosed by: * Fasting blood sugar (FBS) ≥ 126 (normal < 120 mg/dl). * 2-h...

# TREATMENT OF DM ## Diabetes Mellitus * Diabetes is a disease characterized by chronic hyperglycemia due to an absolute or relative lack of insulin (reduced sensitivity to its action [insulin resistance]). * It is diagnosed by: * Fasting blood sugar (FBS) ≥ 126 (normal < 120 mg/dl). * 2-hours blood sugar after oral 75 g glucose ≥ 200 (normal < 140 mg/dl). * Glycated hemoglobin (A1C) * A1C ≥ 6.5% (upper limit in nondiabetic = 6.1%). * Target for therapy according to the American Diabetes Association: <7% * N.B.: the degree in reduction of A1C gives an idea about the efficacy of therapy. ## Types of Diabetes * Type 1 DM * Type 2 DM * Other specific types: e.g. Genetic defects of beta-cell function, diseases of the exocrine pancreas, endocrinopathies or drug or chemical induced. * Gestational diabetes mellitus ## Type 1 DM vs Type 2 DM | | Type 1 DM | Type 2 DM | |--------------------|-------------------------------------|-------------------------------------| | **Pathogenesis** | Absolute insulin deficiency due to massive β cell destruction. | Resistance to both endogenous and exogenous insulin commonly accompanied by insufficient insulin release. | | | May be immune mediated or idiopathic. | | | | Insulin must be given to control hyperglycemia (insulin dependent). | It may be adequately treated without exogenous insulin. | | | Ketoacidosis is liable to occur. | Ketoacidosis is rare. | ## Drugs Inducing Diabetes 1. Glucocorticoids 2. Oral contraceptives 3. Thiazide diuretics (↓ Insulin release). 4. Beta blockers (glucose intolerance) ## Drug therapy of diabetes ### Insulin Therapy **Preparations of Human Insulin (biosynthetic “recombinant DNA”)** | Type | Description | Advantages | |---------------|---------------------------------------------------------------------------------|------------------------------------| | Ultra-rapid | Ultra-rapid onset, very short duration. → given SC 15 minutes before meals. | * Rapid absorption & rapid onset → better postprandial glycemic control. | | | | * Very short duration of action → less risk of hypoglycemia. | | Short-Acting | Rapid onset, short duration → given SC 30-45 min before meals. | * Used IV/ IM in emergencies: ketoacidosis.... | | Intermediate-Acting | Intermediate onset and duration given SC 2-4 times /d in type 1 | * Can be mixed with regular insulin''’. | | | may be given once/d in type 2 | * Premixed fixed concentrations are available. | | | Variable absorption > 50% | * Useful in all forms of diabetes except ketoacidosis. | | Long-Acting | Slow onset - long acting (broad conc. plateau) → SC once or twice /day | * Maximum effect maintained for 24 h →↑ compliance. | **Inhaled insulin: Afrezza (rapid acting human insulin inhalation powder)** * Covers prandial insulin requirements. * Type 1 diabetics on afrezza as prandial insulin must also use SC, long-acting insulin. **Disadvantages:** * Fine dose adjustments are not possible. * Not recommended in smokers & contraindicated in cases of chronic lung disease. ## Indications of Insulin Therapy [Compare with CI of sulfonylureas] 1. Type 1 DM. 2. Type 2 DM: insulin is added if diet regulation & exercise plus metformin or other oral antidiabetics fail to control hyperglycemia. 3. DM with pregnancy & lactation: To avoid risk of sulfonylurea-induced hypoglycemia in fetus & newborn. 4. DM with stress & emergency: regular insulin is used in diabetic ketoacidosis, surgery, infection, myocardial infarction or severe psychic stress (oral hypoglycemics fail to control hyperglycemia as stress →↑ insulin requirements). 5. DM with severe liver or renal disease: To avoid risk of hypoglycemia by sulfonylurea. 6. Treatment of hyperkalemia: Insulin enhances k influx into cells. *N.B.: Insulin use in pregnancy, lactation, stress, emergency or hyperkalemia is temporary.* ## Adverse Reactions of Insulin | Type | Description | |---------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Hypoglycemia | Most frequent and most serious. See below. | | ↑ Body Weight | | | Immune Reactions | Due to anti-insulin antibodies: A. Insulin resistance: Insulin requirements >120 units/d. B. Allergy: Urticaria (rare). | | Lipodystrophy | Lipohypertrophy: Due to repeated injection at same site change site regularly. Lipoatrophy13 Extremely rare. | *N.B.: Hypokalemia may occur when high doses of insulin are used (e.g. in treatment of* ## I. Insulin Secretagogues ### A. Sulfonylureas **Mechanism of Action** * ↑ Insulin secretion by binding with specific receptors on β cell membrane ATP-sensitive K channels (K AIP) blocks channels → depolarization influx → insulin release from granules (Main action). * ↓ Glucagon on chronic use. **Indication:** * Type 2 DM: If initial therapy with metformin + diet control + exercise metformin is contraindicated. **Sulfonylurea Preparations** | Generation | Description | |------------|---------------------------------------------------------------------------------| | 1st | Less frequently used due to adverse effects & drug interactions. | | 2nd | 150 times more potent than 1st generation. (↑ receptor affinity). | | | Fewer adverse effects & interactions. | **Members:** * Glipizide (short acting) * Gliclazide¹" (intermediate acting) * Glibenclamide (long acting more hypoglycemic risk). * Glimepride¹³: long acting (24 h) given once/day. *Acts on a different receptor at K ATP channel.* ## Contraindications of Sulfonylureas 1. Past history of allergy to sulfa compounds. 2. Type 1 DM as they require functioning ẞ cells. 3. DM with pregnancy & lactation: they cross placenta & are excreted in milk with stress, e.g. infection, surgery, trauma or myocardial infarction (ineffective and ketoacidosis is liable to occur as stress increases insulin requirements). 4. DM with liver or renal disease→↑ risk of hypoglycemia as their action is prolonged since they are metabolized in liver & are excreted in urine. ## Adverse Reactions 1. Hypoglycemia: more with drugs with long t, as glibenclamide particularly if elimination is impaired e.g. in elderly, renal or liver disease. 2. Hypersensitivity: drug allergy as skin rash. 3. Heavy weight (weight gain). ## II. Insulin Sensitizers ### A. Biguanides #### (Metformin) **Mechanism of Action (not fully understood)** 1. Hepatic glucose production by inhibiting gluconeogenesis (Main effect). 2. Direct stimulation of glycolysis in skeletal muscles & adipose tissue → rapid removal of glucose from blood with slight ↑ in blood lactate. 3. Intestinal glucose absorption with mild anorectic action. **Advantages of metformin** * No increase in body weight → ↑ Insulin resistance. * No hypoglycemia (i.e. euglycemic acts in hyperglycemia only). * No drug interactions (no plasma proteins binding or hepatic metabolism). **Indications of Metformin** * Initial therapy of type 2 diabetes together with diet regulation & exercise. **Side Effects** 1. GIT: Metallic taste, anorexia, dyspepsia & diarrhea (common, minimized by starting with small dose and gradually increasing it). 2. Lactic acidosis (dangerous but infrequent): Metformin is CI in renal failure, heart failure & severe hypoxia (as HF, MI, pneumonia and alcoholics) due to ↑ risk of lactic acidosis (anaerobic metabolism) in these patients.