Oral Medications in Diabetes

Question 1

T/F all glucose lowering agents are only used for t2d

Answer 1

T

Question 2

T/F all glucose lowering agents are contraindicated in pregnancy

Answer 2

F –> all except sulfonylurea and metformin

Question 3

T/F all glucose lowering agents can be used in any combination

Answer 3

F –> any combination except sulfonylurea and meglitinides should not be mixed

Question 4

T2D first drug of choice

Answer 4

metformin

Question 5

Metformin/diguanide action and mechanism

Answer 5

activation of ampk –>

1. increase muscle glucose tranport
2. reduces hepatic glucose production
3. sensitizes insulin (via reduced ACC and SREBP expression and consequent reduced hepatic FA production)

–>improves pre meal glucose and modestly affects post-prandial glucose

Question 6

Thiazolidinendiones (TZD)/PPARgamma agonists MOA/Action

Answer 6

binds nuclear ppar gamma receptor –> increases GLUT4 transporter–> decreases peripheral insulin resistance in skeletal muscle, adipose, liver –> lowers premeal/post meal glucose

Question 7

Insulin secretagogues

Answer 7

Induce beta cell secretion of insulin (short and long acting) –> suflonylureas and meglitinides

Question 8

alpha glucosidase inhibitors MOA/action

Answer 8

competitively inhibit enzymes in brush border to breakdown carbohydrates –> delay carbohydrate absorption in gut –> reduce post prandial glucose only

Question 9

GLP1 agonist

Answer 9

slows gut motility, induces satiety, increased insulin/lower glucagon

Question 10

Incretin enhancers (DPP-4 inhibitors)

Answer 10

increase duration of action of GLP1 via 80% inhibition of DPP4 –> mostly on post-meal glucose

Question 11

Advantageous characteristics of a good drug for t2d

Answer 11

weight loss/neutral, no hypoglycemia, oral, frequency of delivery

Question 12

Disadvantageous characteristics of a good drug for t2d

Answer 12

weight gain (reversal of osmotic diuresis, reversal of relative starvation/normalization, fluid retention), hypoglycemia, frequency of delivery, injectable

Question 13

T/F metformin is weight neutral and can induce weight loss

Answer 13

T

Question 14

T/F metformin is metabolized at the liver

Answer 14

F –> renally excreted unexchanged and can accumulate if pt has renal insufficiency

Question 15

Adverse effects of metformin

Answer 15

anorexia, nausea, diarrhea, lactic acidosis

Question 16

T/F metformin does not cause hypoglycemia

Answer 16

T

Question 17

Contraindications of metformin

Answer 17

prone to metabolic acidosis, hypoxic states, renal failure, t1d, cardiac ischemia

Question 18

T/F metformin requires presence of insulin for its action

Answer 18

T

Question 19

Sulfonylurea action and MOA

Answer 19

binds to sulfonyl receptor in beta cell –> depolarization of ATP K channels –> pancreatic insulin secretion for 12-24 hours –> mostly premeal glucose effect

Question 20

T/F Sulfonylurea does not get metabolised

Answer 20

F –> hepatic and excreted in kidney

Question 21

Contraindications of sulfonylurea

Answer 21

T1d, DKA, sulfa allergy

Question 22

Adverse effects of sulfonylurea

Answer 22

hypoglycemia, weight gain, hunger

Question 23

K+ channel in the beta cell

Answer 23

induces calcium current which causes insulin release –> sulfonylurea and meglitinide binding sites

Question 24

Meglitinide action/MOA

Answer 24

stimualtes K+ channel on beta cells –> pancreatic insulin for 3-4 hours

Question 25

T/F Meglitinide is fast onset

Answer 25

T

Question 26

Adverse effects of meglitinide

Answer 26

low glucose after meal, weight gain

Question 27

Contraindications of meglitinide

Answer 27

T1d, liver failure, DKA, sulfa allergy

Question 28

T/F meglitinide is metabolized in the kidney

Answer 28

F --> in liver by p450 --> excreted mostly in GI tract

Question 29

Adverse effects of TZD

Answer 29

weight gain, hepatocellular injury

Question 30

Contraindications of TZD

Answer 30

active liver disease, heart failure, renal insufficiency

Question 31

T/F TZD has slow onset of action

Answer 31

T

Question 32

T/F TZD can induce low blood glucose

Answer 32

F --> no insulin secretory effect

Question 33

Adverse effects of alpha glucosidase inhibitors

Answer 33

flatulence, abdominal bloating

Question 34

T/F alpha glucosidase inhibitors are metabolized in the liver

Answer 34

F--> renally excreted unchanged

Question 35

T/F alpha glucosidase inhibitors can cause low glucose

Answer 35

F

Question 36

Metabolism of GLP agonists

Answer 36

rapidly degraded by DPP4 in blood

Question 37

SGLT2

Answer 37

major transporter of glucose in kidney, low affinity/high capacity- -> 90 % of renal glucose reabsorption in proximal tubule

Question 38

SGLT2 inhibitors

Answer 38

inhibit reabsorption of glucose --> excretion by kidney