Diabetes Oral Agants Flashcards
Criteria for Diagnosing Diabetes
-Symptoms
Increased thirst, hunger, and urination
-Plasma glucose ≥200 mg/dL
-Fasting glucose level ≥126 mg/dL
-Two-hour oral glucose tolerance ≥200 mg/dL
-Hemoglobin A1C ≥6.5%
-Convenient but not as accurate
-Can’t diagnose gestational diabetes
-Not for patients with conditions that affect turnover rate of red blood cells (iron deficiencies, etc.)
-Helpful for finding prediabetes (between 5.7 and 6.4%)
Diabetes SE
- More than just glucose issue
- Chronic disorder characterized by abnormalities in glucose, fat, and protein metabolism
- Over time, most patients will develop microvascular (RETINOPATHY), macrovascular (PAD + NEUROPATHY), and neurologic complications
- Depression
- Three times more common in diabetes patients
- Type 1 and type 2
- More common in women
- Not clear if complications causes depression or vice versa
- Sometimes patients lack clear goals; feel discouraged, overwhelmed
- Patients sent home to take care of themselves, causing anxiety
- Constant concern about food and eating
- Uncomfortable interactions with family (“diabetes police”)
Type 1 Diabetes
- 10% of diabetes patients have type 1.
- Autoimmune destruction of beta cells, +GAD (glutamic acid decarboxylase) antibodies, Ketone production
- Injected insulin necessary, Multiple injections give better control
- Onset often sudden, Increased thirst (polydipsea), increased hunger (polyphagia), increased urination (polyurea), weight loss
- LADA (latent autoimmune diabetes in adults) can mimic type 2 diabetes
Type 2 Diabetes
- 90% of diabetes patients have type 2.
- Resistance to endogenous and exogenous insulin
- 75% of patients are obese at diagnosis
- Impaired first- and second-phase insulin secretion, Insulin levels can start high and then drop off to normal and low levels, Increased hepatic glucose production
- Ketosis is unlikely
- Onset often insidious with no or mild “polys.” 50% of patients are diagnosed at their first cardiac event, and diagnoses are increasing in children.
Insulin Resistance
- Normally, insulin binds to specific receptors on cell surface, which activates glucose transport.
- Insulin resistance = post binding defects
- Occurs in hepatic and muscle tissue
- Decreased glucose transport
- Decreased glycogen synthesis
Hyperglycemia: The Omnious Octet
- Decreased Incretin Effect in Gut
- Decreased Glucose Uptake in Muscles
- Decreased Insulin Secretion in Pancreas
- Increased Lipolysis in Fat Tissue
- Increased Glucose Reabsorption in Kidneys
- Increased Hepatic Glucose Production (HGP) in Liver
- Increased Glucagon Secretion in Islet-Alpha Cells
-Neurotransmitter Dysfunction
Labs and Goals
-Lab assessment
Glucose, glycohemoglobin
Lipids
Renal and liver functions
-Establish goals
SBGM/glycohemoglobin
Weight, meal plan, activity plan
Pharmacologic treatmentInitial Diabetes Treatment:
Mild/ No Symptoms
Negative Ketones
A1C
- Management activity
- Consider Metformin
-in 6-8 wks if Target not met, add Oral Agent
Initial Diabetes Treatment: FPG >150 Random >250 Not Mild/ or Severe A1C >7%
- Start Metformin
- Choose alternative drug if Metformin is Contraindicated
- Continue Management Activity
Initial Diabetes Treatment: Marked Hyperglycemia Weight Loss Severe Symptoms > 2+ Ketones DKA Hyperosmolar Severe Illness Surgery
- Start Insulin
- Management Activity
Choose Right Treatment
-Treat the person and the physiologic defect.
-Is the person obese or less obese?
Obese people are usually insulin resistant.
-Biguinides: decrease hepatic glucose production, lower fasting glucose
-GLP-1 receptor agonists: stimulate insulin production, slow gastric emptying, decrease hepatic glucose production, decrease appetite
-Thiazolidinediones: improve glucose transport
Less obese people may be more insulin deficient
-Insulin secretagogues: Stimulate beta cell insulin production
-Are there other signs of insulin resistance, e.g., hypertension, hyperlipidemia?
-Is the patient’s diabetes new or long term?
New cases indicate lack of first-phase insulin secretion.
Lack of first phase = high postmeal
-Long-term cases see decreased first- and second-phase insulin.
High BG all day
-Decide between monotherapy or combination therapy.
Insulin secretagogues: Stimulate beta cell insulin production
- Alpha-glucosidase inhibitors: slow carb breakdown/absorption
- Meglitinide or d-phenylalanines: increase insulin secretion
- DPP-4 inhibitors: inhibit breakdown of incretins
- GLP-1 receptor agonists
- Bile acid sequestrant: action unclear
- Centrally acting agents: affect neurotransmitters
Insulin Sensitizers
-Biguanides
Metformin (Glucophage)
Metformin extended release
-Thiazolidinediones
Rosiglitazone (Avandia)
Pioglitazone (Actos)Biguanides
- Used as first-line therapy unless contraindicated, and in the obese (insulin resistant) with normal liver and renal functions.
- For overweight, new diagnosis, normal renal and liverfunction
- Decrease hepatic glucose production
- Inhibit gluconeogenesis (PRIMARY ACTION)
- Stimulate glucose uptake in skeletal muscle and adipocytes
- Cell receptors
- Glucose transport GLUT 4
- Associated with 1- to 2-kg weight loss
- Usually do not cause hypoglycemia
Risk of Lactic Acidosis
- To prevent lactate buildup do not use in patients with renal dysfunction.
- Males: creatinine ≥1.5 mg/dL
- Females: creatinine ≥1.4 mg/dL
- Abnormal creatinine clearance: ≥80 years old
- Also avoid use in people with liver dysfunction, alcohol abuse/binge drinking, CV collapse (acute MI or acute CHF), and anyone undergoing major surgical procedure.
- Stop metformin day of contrast study, then recheck creatinine in 48 hours. If levels are okay, metformin can be restarted.
- Trend of glucose in a day
Metformins
-Initially, take with food to minimize gas and diarrhea.
-Glucophage
Starting dose: 500 mg qd/bid; 850 mg qd
Maximum dose: 2,550 mg/day
Take with meals bid–qid
-Riomet (oral solution)
-Glucophage XR (extended release)
Take with evening meal
-Fortamet and Glumetza (extended release)
Take with evening meal
Thiazolidinediones (TZDs)
-TZDs increase risk for new or worsening macular edema and may increase risk of bone fracture.
-Good for Renal Pts
-TZDs decrease hepatic glucose production, do not cause hypoglycemia, and are associated with weight gain. Pioglitazone may improve lipid profile.
-Rosiglitazone (Avandia)
No significant drug interactions
Starting dose: 4 mg qd or 2 mg bid
Adjust dose after 8–12 weeks
Maximum dose: 8 mg qd in single or divided doses
Pioglitazone (Actos)
Drug interactions: OCs not studied; may interact with ketoconazole
Thiazolidinediones: Who and How
- Typically used in obese patients without liver disease or severe heart disease.
- LFTs should be at baseline, then check periodically.
- TZDs can cause or worsen CHF. Risk increases with addition of insulin.
- Do not use rosiglitazone with insulin*
- Contraindicated in Class III or IV heart failure.
- TZDs improve glucose transport into cells by binding to peroxisome proliferator-activated receptors (PPARs), and affect multiple genes. Protein production affects insulin sensitivity, perhaps inflammation (increases apidonectin).
Metformin vs. TZD
- Metformin can affect GI.
- Metformin is less expensive*
- Metformin is associated with weight loss; TZDs are associated with weight gain.*
- Metformin can’t be used with renal disease; TZDs can*
- Metformin doesn’t cause edema; TZDs can.
Secretagogues
- Meglitinides: repaglinide (Prandin)
- Amino acid derivatives: nateglinide (Starlix)
- Sulfonylureas: long and short acting CANNOT TAKE W/ SULFA/BACTRIM ALLERGY
-Intended for the “less obese” patient with type 2 diabetes of longer duration, and decreased insulin production
-How they work:
Stimulate release of insulin from beta cells PRIMARY ACTION
Bind to cell receptor, inhibit potassium efflux, depolarize beta cell
Decrease hepatic glucose production
Potential for hypoglycemia
-Avoid/use with caution in patients with liver and renal disease to prevent prolonged hypoglycemia.
Meglitinides: Repaglinide (Prandin)
- Chemically unrelated to sulfonylureas, making it an important tool for patients with sulfa allergies
- They stimulate the release of insulin from beta cells. -The binding that occurs differs from sulfonylureas, and the action is shorter. There is risk for hypoglycemia.
- Can be taken 0–30 minutes BEFORE MEALTIME, 2–4 TIMES/Day. If a meal is skipped or added, dose should be skipped or added as well.
- Dose range: 0.5–4 mg; MAX DOSE 16 MG/DAY
- Not for use with NPH insulin due to increased risk for myocardial ischemia.
- Contraindicated with gemfibrozil; risk of protracted hypoglycemia.
Repaglinide or Nateglinide vs. Sulfonylureas
-Short-acting secretagogues diminish risk of protracted hypoglycemia
More mealtime flexibility with short-acting secretagogues
-Potency
Sulfonylureas more potent
Repaglinide/Nateglinide won’t lower A1C as much
-Sulfa allergies
Avoid sulfonylureas altogether
-Cost (example of cost difference by some pharmacy programs)
Max dose of Prandia per month = $199
Max dose of second generation sulfonylureas per month = $11–$62
