Pharmacology I: Diabetes Mellitus (DM) PDF

Pharmacology I Diabetes mellitus (DM) Dr. Sana’ AL Aqqad Ph.D. in Clinical Pharmacy & Therapeutics [email protected]  ▪ DM: is a group of metabolic disorders characterized by chronically: ✓ elevated blood glucose (BG)...

Pharmacology I Diabetes mellitus (DM) Dr. Sana’ AL Aqqad Ph.D. in Clinical Pharmacy & Therapeutics [email protected]  ▪ DM: is a group of metabolic disorders characterized by chronically: ✓ elevated blood glucose (BG) ✓abnormal carbohydrate, fat, & protein metabolism. ▪ It is a common disease that affects the ability of the body to produce and/or utilize insulin ▪ DM has categories, including: Introduction 1. Type 1 2. Type 2 ▪ Without effective treatment, DM can lead to acute complications such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS). ▪ Chronic hyperglycemia can cause microvascular, macrovascular, and neuropathic complications.  Pathophysiology 1. Type 1 DM 2. Type 2 DM ▪ (5%–10% of cases) →the pancreas ▪ (90%–95% of cases) does not make insulin ▪ Age ≥45 years ▪ usually results from autoimmune ▪ Insulin resistance: manifested by: destruction of pancreatic β-cells → a. excessive hepatic glucose production leading to absolute deficiency of insulin. b. ↓ skeletal muscle uptake of glucose ▪ In children and adolescents but can c. ↑ lipolysis and F.A production. occur at any age. ✓ With times →impaired insulin ▪ Amylin (a hormone co-secreted from secretion: β-cell mass and function pancreatic β-cells with insulin) is also are both reduced, and β-cell failure deficient in type 1 DM due to β-cell is progressive. destruction. ✓ ↓ incretin effects: Normally, the gut ▪ Amylin suppresses inappropriate incretin hormones (GLP-1) & (GIP) glucagon secretion, slows gastric are released & stimulate insulin emptying, and causes central satiety. secretion &suppress glucagon release in response to a meal  ✓Patients often have symptoms in the days or weeks preceding the diagnosis. ✓The most common initial symptoms are ✓polyuria ✓Polydipsia ✓ polyphagia Clinical ✓ weight loss Presentation ✓ fatigue Type 1 ✓lethargy. ✓Individuals are often thin and are prone to develop DKA in the absence of an adequate insulin supply; many patients initially present with DKA. ✓ Symptom onset can be triggered by infection, trauma, or psychological stress.  Most patients are asymptomatic or have only mild fatigue at the time of diagnosis. Many patients are incidentally found to have type 2 DM after: routine lab. testing (plasma glucose or A1C) or development of complications (eg, myocardial infarction, stroke). Clinical ✓Hemoglobin A1c also called HbA1c, is an Presentation important blood test that provides an average over the past 2 to 3 months of blood sugar (glucose) Type II control. Because mild hyperglycemia may exist for years prior to the diagnosis, microvascular and macrovascular complications are often present at the time of diagnosis. Most patients are overweight or obese with an elevated waist: hip ratio.  DIAGNOSIS ▪ Prediabetes is a condition of abnormal BG that is not sufficiently high to meet the thresholds that define DM but often progresses to the diagnosis. Goals of Treatment ▪ No cure ▪ The primary goal is to prevent or delay progression of long-term microvascular and macrovascular complications. ▪ Additional goals are to alleviate symptoms of hyperglycemia, minimize hypoglycemia and other adverse effects, minimize treatment burden, and maintain quality of life (QoL). ▪ General glycemic targets for most nonpregnant adults with DM are listed in Table 19-1.  Treatments: ❑Insulin Endogenous insulin acts to move glucose out of the blood into the cells, resulting in ↓ serum glucose levels. There are 2 groups of exogenous insulin used for hyperglycemia: 1. Human Insulin: include isophane (NPH) insulin & regular insulin 2. Insulin Analogues: include insulin aspart, lispro, glulisine, detemir, and glargine. The main advantage of insulin over other antihyperglycemic agents is that ✓it can achieve a wide range of glucose targets ✓the dose can be individualized based on glycemic levels. Disadvantages include : ✓the risk of hypoglycemia ✓ need for injections ✓ weight gain ✓ treatment burden. ▪ Most insulin products are administered (SC) for chronic diabetes management ✓Except for inhaled human insulin, which is a dry powder of regular insulin that is inhaled and absorbed through pulmonary tissue.  The most commonly used insulin concentration is 100 units/mL (U-100). More concentrated insulins (U-200, U-300, U-500) may be considered for patients requiring larger doses. ✓U-500 regular insulin is reserved for patients with extreme insulin resistance and is usually given two or three times a day. The pharmacokinetics of insulin products is characterized by their onset, peak, and duration of action: ✓Onset – How quickly insulin lowers your blood sugar. ✓Peak Time – When insulin is at maximum strength. ✓Duration – How long insulin works to lower your blood sugar. ▪ All basal insulins can achieve similar A1C reductions if dosed and titrated properly, but the longer-acting products have a lower risk of hypoglycemia (particularly nocturnal hypoglycemia) and may result in less glucose variability. However, they are more expensive.  Insulin Type Onset Peak Time Duration Method Rapid acting 15 minutes 1 hour 2 to 4 hours Usually taken right before a (Humulin R) meal. Often used with longer-acting insulin. Rapid-acting 10 to 15 minutes 30 minutes 3 hours Usually taken right before a inhaled meal. Often used with injectable long-acting insulin. Regular/short 30 minutes 2 to 3 hours 3 to 6 hours Usually taken 30 to 60 acting minutes before a meal. Intermediate 2 to 4 hours 4 to 12 hours 12 to 18 Covers insulin needs for acting hours half a day or overnight. (NPH) (Humulin N) Often used with rapid- or short-acting insulin. Long acting 2 hours Does not peak Up to 24 Covers insulin needs for hours about a full day. Often used, when needed, with rapid- or short-acting insulin. Ultra-long acting 6 hours Does not peak 36 hours or Provides steady insulin for longer long periods. Premixed 5 to 60 minutes Peaks vary 10 to 16 Combines intermediate- and (Mixtard) hours short-acting insulin. Usually taken 10 to 30 minutes before breakfast and dinner.  Basal insulin ▪ Basal insulin (background insulin) refers to longer-acting insulins that → regulate BG levels in between meals by suppressing hepatic glucose production and maintaining near-normal glycemic levels in the fasting state. ▪ People take it between mealtimes & before bedtime to control blood sugar outside of eating. ▪ Options include the following insulins: 1. Neutral protamine Hagedorn (NPH) insulin is the least ideal product because it has a distinct peak and a duration of action much less than 24 hours and usually requires twice-daily dosing (intermediate action) 2. Detemir (Levemir®) also has a peak and often lasts