Treatment of Diabetes Flashcards
autoimmune disease, symptoms of hyperglycemia due to inappropriate insulin secretion, destruction of beta cells, insulin dependent
type 1 diabetes
non insulin dependent diabetes, associated with obesity and metabolic syndrome, beta cells desensitized to a glucose challenge, peripheral tissues resistant to insulin actions
type 2 diabetes
insulin is a 51 amino acid peptide with two dipeptide chains linked by a _______ bond, active form is insulin + _________
disulfide, C peptide
- insulin secretion stimulated by increase _______ ratio (glucose, fatty acids, parasympathetic activity, GLP-1)
- insulin acts through stimulation of _______ receptor
ATP/ADP
tyrosine kinase
- mainstay treatment for type 1 diabetes, final drug of choice for type 2 diabetes
- classification based on duration of action (rapid, short, intermediate, long acting)
exogenous insulin
lispro, aspart, and glulisine are _______ acting insulins
rapid (peak 30 min)
novolin and humulin are ________ acting insulins
short (peak at 3 hours)
NPH humulin N, novolin N are _______ acting insulins
intermediate
detemir and glargine are ______ acting insulins
long
- IV infusion of regular insulin at a low rate
- admin glucose along with regular insuling to prevent hypoglycemia
- add fluids and electrolytes
diabetic ketoacidosis
- MOA: activate residual beta cells to release insulin by binding to and activating SUR!
- replace Mg/ADP that activate the K/ATP channel, closed channel –> cell depolarizes, insulin release via calcium influx
- oral, bound to plasma albumin, metabolized by liver
- adverse: hypoglycemia, weight gain
sulfonylureas
tolbutamide, tolazamide, chlorporpramide
first generation sulfonylureas
glyburide, glipizide, gilmepiride
second generation sulfonylureas
- control hyperglycemia in type 2 DM who can’t achieve control with diet change alone
- contraindications: type 1 DM, pregnancy, lactation, hepatic or renal insufficiency (for older preparations)
sulfonylureas
- bind to SUR1 but at a different site to activate K/ATP channel
- cleared by liver
- adverse: hypoglycemia
- glinide suffix
meglitinides
repaglinidine, nateglinide
meglitinides
- insulin sensitizers, euglycemia effect
- maintain normal blood glucose without producing hypoglycemia
- MOA: increase peripheral insulin sensitivity, reduces hepatic gluconeogenesis, activates AMP activated protein kinase, inhibits mTOR-C1
bigaunides (metformin)
- inhibits gluconeogenesis in the liver, does not promote weight gain or hypoglycemia,can reduce plasma TGs
- 1st line therapy for diabetes type 2, PCOS, NAFLD
- oral, not bound to plasma protein, excreted by kidney
metformin
- lactic acidosis by blocking gluconeogenesis may impair hepatic metabolism of lactic acid
- more common in patients with renal insufficiency
- acute: GI, reduced B12 absorption
metformin toxicity
- PPAR agonists
- promote transport of serum lipids to adipose tissues
- liver and muscle promote insulin sensitivity
- decrease hepatic gluconeogenesis, enhance uptake of glucose by skeletal muscle cells
- adverse: weight gain, hepatic toxicity, CHF
thiazolidinediones (TZDs)
rosiglitazone, pioglitazone
thiazolidinediones
- competitive and reversible inhibitors of pancreatic amylase and intestinal alpha-glucosidase enzymes
- increased time required to absorb complex carbs, reduce postprandial glucose peak
- no risk of hypoglycemia
- adverse: flatulence, bloating, diarrhea
alpha glucosidase inhibitors (acarbaose, miglitol)
- secretion: enteroendocrine cells in ileum, encoded by proglucagon gene and derived from natural proglucagon protein
- release stimulated by nutrients entering gut
- increase insulin secretion, decrease glucagon secretion
- delay gastric emptying, decrease appetite
incretins: GLP-1 and GIP
-exenatide, liraglutide, albiglutide, duraglutide
GLP-1 analogs (incretins)
- the enzyme degrades endogenous incretins
- the drug increases the level of endogenous incretins
- not used in combo with GLP-1 analogs
DDP-4 inhibitors
- glucose freely filtered by renal glomeruli, reabsorbed in proximal tubules by sodium glucose transporters
- inhibition causes glycosuria and lowers glucose levels
- efficacy reduced in chronic kidney disease
- adverse: genital infxns, UTIs, hypotension due to osmotic diuresis
SGLT2 inhibitors
canagliflozin, dapagliflozin, empagliflozin
-promote weight loss, neutral with regard to hypoglycemia
SGLT2 inhibitors
- mimics high dose effects of amylin
- in pancreas increases insulin secretion and decrease glucagon secretion
- delays gastric emptying, decreases appetite
- preprandial use as an adjunct to insulin
- renal metabolism and excretion
- adverse: hypoglycemia, GI symptoms
pramlintide (amylin analog)
- bile acid sequestrant, cholesterol lowering drug
- interrupts enterohepatic circulation, can exacerbate hypertriglyceridemia
covesevalam
- dopamine agonist
- lowers glucose levels
- nausea, fatigue, dizziness, vomiting, headache
bromocriptine
