Insulin Therapy: Pharmacology and Therapeutics

• Insulin is used to treat diabetes, and can have several side effects
• The Clinical Pharmacology and Therapeutics Module covers the pharmacology of insulin
• Key topics include the classification, mechanisms, pharmacokinetics/dynamics, side effects, insulin therapy selection, and diabetic ketoacidosis

Learning Objectives:

• Primary antidiabetic drug classes should be categorized
• Explain the mechanisms by which different antidiabetic drug classes lower blood glucose levels and their effects
• Discuss the pharmacokinetic and pharmacodynamic properties of key antidiabetic medications
• Common side effects, contraindications, and potential drug interactions should be listed for each class of antidiabetic drugs
• Select the appropriate insulin therapy based on onset, peak, and action duration
• Provide a definition of diabetic ketoacidosis along with treatment goals

Insulin Overview:

• Insulin is a small protein containing 51 amino acids
• Two chains (A and B) are linked by disulfide bonds
• Pancreatic B cells in the islets of Langerhans secrete insulin

Normal Insulin Secretion:

• Insulin is released at a steady rate, with additional releases in response to increased blood glucose
• Insulin is secreted in a steady rate during fasting to regulate glucose
• Increased blood glucose stimulates an additional insulin response
• The duration of action of endogenous insulin is 4-5 minutes

Insulin Action:

• Insulin stimulates cells to take up glucose from the blood (muscle and adipose tissue)
• It also increases the storage of glucose, amino acids, and fatty acids
• Insulin increases glycogen formation and storage in the liver
• Insulin inhibits liver glycogen breakdown

Diabetes Mellitus:

• Diabetes mellitus is characterized by elevated blood glucose
• High blood sugar is associated with absent or inadequate pancreatic insulin secretion, and/or impaired insulin action

Types of Diabetes:

• Type 1 Diabetes (IDDM): autoimmune destruction
• Type 2 Diabetes (NIDDM)
• Secondary: caused by drugs, pancreatectomy, or genetics
• Gestational diabetes

Treatment of Diabetes Mellitus:

• Drugs used to control diabetes mellitus fall into two groups
• Insulin: key for type 1 diabetes
• Antidiabetic agents: synthetic preparations that stimulate insulin release, sensitivity, or alter metabolic response to hyperglycemia
• Type II diabetics use a staged approach
• Stage 1 - diet control and weight management
• Stage 2 - oral antidiabetic medications
• Stage 3 - addition of insulin if oral agent therapy fails

Insulin Delivery Systems:

• Insulin Syringes: 100 unit (1.0ml)
• Insulin Pens
• Insulin Pumps
• Insulin Inhalers

Types of Insulin Preparations:

• Rapid-Acting: very fast onset and short duration
• Short-Acting: rapid onset of action
• Intermediate-Acting
• Long-Acting: slow onset of action
• Recombinant DNA technology produces insulin
• Insulin can be chemically identical to human insulin or a modification of human insulin to improve pharmacokinetics

Rapid-Acting Insulin:

• Lispro, Aspart, Glulisine and inhaled insulin are versions
• Closely mimics normal endogenous prandial insulin secretion
• Allows the body to undergo more normal insulin replacement
• It can be taken immediately before a meal without sacrificing glucose control
• Action duration is rarely >4-5 hours, which decreases the risk of late postmeal hypoglycemia

Short-Acting Insulin:

• Regular insulin is a form
• Particularly useful for IV therapy in the management of diabetic ketoacidosis
• It is used when insulin requirements are changing rapidly, like after surgery or during acute infections

Intermediate-Acting and Long-Acting Insulins:

• NPH (neutral protamine hagedorn, or isophane) insulin, is an intermediate-acting
• Insulin Glargine and Insulin Detemir are examples of long-acting insulin

Premixed Insulin Combinations:

• NPH mixed with both rapid and short-acting insulin analogs:
• 70:30 (70% NPH, 30% Regular)
• 50:50 (50% NPH and 50% insulin Lyspro)
• 70:30 mixtures (70% NPH, 30% insulin aspart)

Clinical Uses of Insulin:

• Patients with type 1 diabetes mellitus require long-term insulin
• An intermediate-acting preparation or a long-acting analog is often combined with soluble or rapid-acting forms
• Used IV in emergency treatment of hyperglycemic emergencies
• About 1/3 of patients with type 2 diabetes mellitus ultimately benefit
• Prescribred Short-term for patients with type 2 diabetes mellitus with impaired glucose tolerance during events like operations, infections, and myocardial infarction
• Used for gestational diabetes not controlled by diet alone

Insulin Regimens:

• Basal Only Regimens
• Basal-Bolus Regimen: An intermediate or long-lasting version is used to provide a basal level
  • It extends overnight and is supplemented with fast or short-acting forms injected with meals
• Premixed to be given twice a day, with morning and evening meals:
  • No mixing, a single injection, administered once or twice daily
• The typical does is between 0.5-0.8 IU/Kg/day

Insulin Therapy Side Effects:

• Hypoglycemia: Early symptoms include weakness, hunger, pallor, sweating, palpitation, irritability, tremor and headache
  • If not treated it may lead to convulsion and coma
• Lipodystrophy at injection sites
• Weight gain
• Allergic reaction
• Generalized Urticaria