Diabetes Mellitus Flashcards
Pancreatic Hormones
α - cells = Glucagon
β - cells = Insulin, Amylin
δ - cells = Somatostatin
Produced in Islets of Langerhams
Insulin Hormones
Storage Hormone
Promotes glucose uptake, Glucose usage
Results to Glycogenesis?
Type 3 receptor (enzyme-linked) - tyrosine kinase
Glucagon
Increase hepatic glucose input
Results to Glycogenolysis
Type 1 DM
Absolute deficiency on insulin due to β-cells destruction
Insulin-Dependent DM
Type II DM
Inadequate secretion of insulin for β-cells
Insulin resistance (decrease sensitivity of insulin receptors)
Goals of Therapy for DM
- Control hyperglycemia
- Inc. insulin secretion
- Enhance insulin action
- Delay carbohydrate absorption
- Enhance excretion of glucose
Secretagogues
A. Insulin
B. Sulfonylurea Drugs (OHAs)
C. Meglitinides
Insulin
Rapid-Acting
* Insulin Lispro
* Insulin Aspart
* Insulin Glulisine
Short-Acting
* Regular Insulin (Humulin-R®)
* Semi-Lente
Intermediate-Acting
* Neutral Potamine Hagedorn (Isophane Insulin)
* Lente (30% semilente, 70% ultralente)
Long-Acting
* Insulin Glargine
* Insulin Detemir
* Insulin Levemir
* Insulin Degludec
* Ultralente
Rapid-Acting Insulin
SQ
5 min before meals
Rapid onset of action in 5-15 minutes
Short-Acting Insulin
SQ/IV; 20 min before meals
USES:To prevent Postprandial Hyperglycemia
Intermediate-acting insulin:
AM - 2/3 of the dose
PM - 1/3 of the dose
Long-acting insulin
SQ, OD
Insulin Glargine (peak-less insulin) - has a character release pattern that shows no peak & a plateau serum insulin level that is maintained for about 24 hours
Sulfonylureas (OHAs)
First Generation:
* Chlorpropamide - longest t1/2
* Tolbutamide - most cardiotoxic
* Acetahexamide
* Tolazamide - safest for elderly
Less Potent, More side effects
SE: Disulfiram-like reaction
2nd generation
* Glibenclamide (Euglucon®)
* Glipizide (Minidiab®)
* Gliclazide (Diamicron®)
* Glimepiride (Solosa®)
More potent
Once daily dosing
MOA of Sulfonylureas
Block potassium channels (ATP-sensitive channels), resulting to β-cell depolarization and insulin release
A/E: Weight Gain, Hypoglycemia
Meglitinides
Repaglitide (Prandin®, Novonorm®)
Nateglitide (Starlix®)
Controls postprandial glycemia (taken before meals)
Meglitinides
* Repaglinide
* Nateglinide
MOA of Meglitinides
Inhibiting ATP-Sensitive Potassium Channels
Insulin Sensitizers
Biguanides
* Metformin
Thiazolidinedione - must not be given to patient w/ CHF (ClassIII-IV)
* Rosiglitazone (Avandia®) - risk of cardiovascular mortality
* Pioglitazone (Actos®) - bladder cancer
* Troglitazone
1st line initial treatment of type 2 DM esp. among obese patients
Metformin
Only biguanide type of oral antidiabetic
MOA of Metformin
Liver: Reduce Hepatic Gluconeogenesis
Adipose Tissue & Muscle: Increase Glucose Uptake/usage
A/Es of Metformin
Weight loss
Diarrhea
Lactic acidosis (Rare)
Advantage: Less hypoglycemia
CI: Chronic Alcoholics, Renal Failure, Hepatitis
MOA of Thiazolidinediones
Regulates gene expression by binding to PPAR- γ
Activate PPAR ( Peroxisome Proliferator-acting receptor ) , Gamma → Increases transcription of insulin-responsive genes
Adjunct only, not first line
Adverse effects of Thiazolidinediones
-glitazone
Edema (Contraindicated to CHF)
Weight Gain
Hepatotoxicity
Alpha-glucosidase Inhibitors
Acarbose (Glucobay®, Gluconase®)
Voglibose (Basen®)
Miglitol (Glyset®)
MOA of α-glucosidase Inhibitors
Inhibit intestinal α-glucosidases responsible for the breakdown of complex polysaccharides & sucrose into asbsorbable monosaccharides
May be given to Type 1 DM patients as a combination therapy with Insulin
S/E of α-glucosidase Inhibitors
Diarrhea
Flatulence
Abdominal Bloating
Glucose Reabsorption Inhibitors
Canagliflozin
Dapaglifozin
Empaglifozin
MOA of Glucose Reabsorption Inh
-gliflozin
Blocks Sodium Glucose Cotransporter 2 Inhibitor (SGLT2) → reabsorption of glucose from the kidney is decreased, renal excretion of glucose is increased, and blood glucose levels are lowered
Adverse Effects of Glucose Reabsorption Inhibitors
UTI
Dehydration
Genital yeast infection
Incretin Hormone
t50 = 2 mins
Degraded by peptidyl dipeptidase 4 (DPP 4)
Actions of Incretin
Increase Insulin Secretions, glucose uptake
Decrease glucagon secretions, Gastric emptying
GLP-1 analogue (Glucagon-like peptide-1)
Exenatide (Byetta®)
Liraglutide
A/E: Weight loss, Nausea, Risk of pancreatitis in px with high VLDL
DPP-4 inhibitor (Dipeptide peptidase IV)
Sitagliptin (Januvia®)
Alogliptin
A/E: Less weight loss, suited for older patients
DPP-4 inhibitor (Dipeptide peptidase IV)
Co-secreted with insulin by pacreatic β-cells in response to elevated blood glucose levels
Dec. gastric emptying, suppression of glucagon secretion, dec. appetite
Amylin mimetic
Pramlintide acetate
Synthetic analog of human amylin
Pramlintide acetate
Slows the rate at which food is delivered from stomach to intestine
A/E: Anorexia, Wt. loss, Inc risk of hypoglycemia
Dopamine Agonist
Bromocriptine
Treatment of hyperprolactinemia and Parkinson’s Disease
Dopamine Agonist
Bromocriptine (Cycloset)
Taken within 2 hrs after wakiing in the morning
Taken w/ food
