Treatment of Diabetes

Question 1

autoimmune disease, symptoms of hyperglycemia due to inappropriate insulin secretion, destruction of beta cells, insulin dependent

Answer 1

type 1 diabetes

Question 2

non insulin dependent diabetes, associated with obesity and metabolic syndrome, beta cells desensitized to a glucose challenge, peripheral tissues resistant to insulin actions

Answer 2

type 2 diabetes

Question 3

insulin is a 51 amino acid peptide with two dipeptide chains linked by a _______ bond, active form is insulin + _________

Answer 3

disulfide, C peptide

Question 4

• insulin secretion stimulated by increase _______ ratio (glucose, fatty acids, parasympathetic activity, GLP-1)
• insulin acts through stimulation of _______ receptor

Answer 4

ATP/ADP

tyrosine kinase

Question 5

• 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)

Answer 5

exogenous insulin

Question 6

lispro, aspart, and glulisine are _______ acting insulins

Answer 6

rapid (peak 30 min)

Question 7

novolin and humulin are ________ acting insulins

Answer 7

short (peak at 3 hours)

Question 8

NPH humulin N, novolin N are _______ acting insulins

Answer 8

intermediate

Question 9

detemir and glargine are ______ acting insulins

Answer 9

long

Question 10

• IV infusion of regular insulin at a low rate
• admin glucose along with regular insuling to prevent hypoglycemia
• add fluids and electrolytes

Answer 10

diabetic ketoacidosis

Question 11

• 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

Answer 11

sulfonylureas

Question 12

tolbutamide, tolazamide, chlorporpramide

Answer 12

first generation sulfonylureas

Question 13

glyburide, glipizide, gilmepiride

Answer 13

second generation sulfonylureas

Question 14

• 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)

Answer 14

sulfonylureas

Question 15

• bind to SUR1 but at a different site to activate K/ATP channel
• cleared by liver
• adverse: hypoglycemia
• glinide suffix

Answer 15

meglitinides

Question 16

repaglinidine, nateglinide

Answer 16

meglitinides

Question 17

• 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

Answer 17

bigaunides (metformin)

Question 18

• 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

Answer 18

metformin

Question 19

• lactic acidosis by blocking gluconeogenesis may impair hepatic metabolism of lactic acid
• more common in patients with renal insufficiency
• acute: GI, reduced B12 absorption

Answer 19

metformin toxicity

Question 20

• 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

Answer 20

thiazolidinediones (TZDs)

Question 21

rosiglitazone, pioglitazone

Answer 21

thiazolidinediones

Question 22

• 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

Answer 22

alpha glucosidase inhibitors (acarbaose, miglitol)

Question 23

• 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

Answer 23

incretins: GLP-1 and GIP

Question 24

-exenatide, liraglutide, albiglutide, duraglutide

Answer 24

GLP-1 analogs (incretins)

Question 25

• the enzyme degrades endogenous incretins
• the drug increases the level of endogenous incretins
• not used in combo with GLP-1 analogs

Answer 25

DDP-4 inhibitors

Question 26

• 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

Answer 26

SGLT2 inhibitors

Question 27

canagliflozin, dapagliflozin, empagliflozin

-promote weight loss, neutral with regard to hypoglycemia

Answer 27

SGLT2 inhibitors

Question 28

• 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

Answer 28

pramlintide (amylin analog)

Question 29

• bile acid sequestrant, cholesterol lowering drug

- interrupts enterohepatic circulation, can exacerbate hypertriglyceridemia

Answer 29

covesevalam

Question 30

• dopamine agonist
• lowers glucose levels
• nausea, fatigue, dizziness, vomiting, headache

Answer 30

bromocriptine