Insulin and Diabeetus

Question 1

Type 1 diabetes

Answer 1

insulin-dependent, loss of beta cells. 5-10% of diabetics

Question 2

Type 2 diabetes

Answer 2

insulin-independent, decreased response to insulin, 85-90% of diabetics

Question 3

Type 3 diabetes

Answer 3

caused by gene mutations

Question 4

Type 4 diabetes

Answer 4

gestational diabetes (4% of all pregnancies)

Question 5

Central goal of DM therapy

Answer 5

correct hyperglycemia and maintain BGL near normal range. preventing, delaying, or reducing complications, minimizing side effects of therapy, and improving quality of life

Question 6

non-pharmological approaches to treatment

Answer 6

diet and exercise: large reduction in type 2 incidence

Question 7

what stimulates insulin release?

Answer 7

glucose, which stimulates depolarization of beta cells through closing K+ channels, causing the opening of Ca2+ channels

Question 8

what does insulin do?

Answer 8

stimulates the production of triglycerides in adipose tissue, stimulates the production of glycogen in liver cells, and stimulates the production of protein in muscles

Question 9

types of insulin

Answer 9

rapid acting, short acting, intermediate acting, and long acting

Question 10

rapid-acting

Answer 10

peak in 30 min-2 hrs, can be injected or inhaled

Question 11

inhaled insulin (Exubera)

Answer 11

used in combination with other insulin in Types 1 and 2 or alone in Type 2. contraindicated in smokers, not recommended for asthma or COPD patients. side effects are cough, shortness of breath, hypoglycemia

Question 12

oral hypoglycemic agents

Answer 12

Sulfonylureas and meglitinides; act to increase the levels of insulin

Question 13

sulfonylurea mechanism of action

Answer 13

block K+ channels, causing beta cell depolarization

Question 14

prototypical sulfonylureas

Answer 14

tolbutamide (1st gen,~8hr duration) and glyburide (2nd gen, ~12-24 hr duration)

Question 15

sulfonylurea contraindications

Answer 15

sulfa drug alerrgy, pregnancy, major stress (surgery, trauma, infection)

Question 16

sulfonylurea side effects

Answer 16

hypoglycemia, weight gain, rash, elevated liver enzymes, allergic reaction

Question 17

Meglitinides mechanism

Answer 17

inhibition of K+ channel at a different site from sulfonylureas

Question 18

prototypical meglitinides

Answer 18

repaglinide, nateglinide

Question 19

meglitinide pharmacokinetics

Answer 19

rapid onset and short duration, intended to be taken after meal

Question 20

meglitinide side effects

Answer 20

diarrhea, allergic reactions, headache. less chance of hypoglycemia than sulfonylureas

Question 21

antihyperglycemic agents

Answer 21

biguanides, alpha-glucosidase inhibitors, thiazolidinediones. act without changing insulin levels

Question 22

biguanide mechanism of action

Answer 22

inhibit production of glucose in liver, increase sensitivity to insulin, decrease GI glucose absorption. comparable to sulfonylureas in efficacy

Question 23

prototypical biguanide

Answer 23

metformin

Question 24

metformin side effects

Answer 24

metallic taste, nausea/diarrhea, reduced absorption of B12 and folic acid

Question 25

metformin pharmacokinetics

Answer 25

little binding to plasma proteins, no active metabolites

Question 26

advantages of metformin

Answer 26

no hypoglycemia or increased weight

Question 27

a-glucosidase inhibitor prototype

Answer 27

acarbose

Question 28

acarbose mechanism

Answer 28

competitive inhibition of intestinal alpha-glucosidase, reduction in starch digestion and glucose absorption

Question 29

acarbose side effects

Answer 29

bloating and flatulence. can cause hypoglycemia in combo with insulin, treatable with glucose

Question 30

acarbose contraindications

Answer 30

intestinal diseases exacerbated by gas (ulceration, inflammatory bowel disease)

Question 31

thiazolidinediones prototypes

Answer 31

risigilitazone, pioglitazone

Question 32

thiazolidinedione mechanism of action

Answer 32

agonist for PPAR-gamma, increases insulin sensitivity in muscle, liver, and adipose tissue, and increases insulin’s action on glucose and lipid metabolism. reduces A1c by 1.0-1.5%

Question 33

pharmacokinetics of thiazolidinediones

Answer 33

take 3-6 weeks to reach maximum effect

Question 34

thiazolidinediones side effects

Answer 34

weight gain, fluid retention, some liver toxicity

Question 35

thiazolidinedione contraindications

Answer 35

heart failure; rosigilitazone can cause MI (43% increase in MIs in one study) and CHF

Question 36

new drugs

Answer 36

sitagliptin, exenatide, pramlintide

Question 37

sitagliptin mechanism

Answer 37

inhibition of DPP4, an enzyme that leads to increased insulin production and decreased glucagon production

Question 38

sitagliptin pharmacokinetics

Answer 38

rapid absorption (PO), little metabolism (79% excreted whole in urine), hl of 11.8-14.4 hr. used as sole therapy or in combo with metformin or thiazolidinediones

Question 39

sitagliptin side effects

Answer 39

none, no hypoglycemia or weight gain

Question 40

exenatide mechanism

Answer 40

enhances glucose dependent insulin release, suppresses elevated glucagon secretion, slows gastric emptying
decreases HbA1c by .4-.8% and 2 hr PPG bt 63-71 mg/dl

Question 41

exenatide pharmacokinetics

Answer 41

subQ, used in combo with sulfonylureas and/or metformin

Question 42

exenatide side effects

Answer 42

indigestion, diarrhea, weight loss (1-3 kg)

Question 43

pramlintide mechanism

Answer 43

synthetic analog of amylin, a hormone co-secreted with insulin that slows gastric emptying, suppresses glucagon secretion after meals, and modulates appetite
decrease H1c by .5%, 1.5 kg weight loss

Question 44

pramlintide pharmacowhatever

Answer 44

SubQ before meal