Block 1 Lecture 3 -- Diabetes III Flashcards Preview

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Flashcards in Block 1 Lecture 3 -- Diabetes III Deck (52):
1

What meglitinide analogs are available on the market?

1) repaglinide (Prandin)
2) nateglinide (Starlix)

2

describe absorption of meglitinide analogs.

30 minute onset; peak effect in 1 hour

3

how should meglitinide analogs be administered?

take 5 min before a meal multiple times a day

4

what is the half-life of meglitinide analogs?

1 hour

5

What is the MoA of meglitinide analogs?

Same as sulfonylureas except quicker and weaker affinity for sulfonylurea receptor
-- much more highly selective for beta KATP, not CV
-- partially restore initial insulin release

6

When are meglitinide analogs most effective?

for isolated postprandial hyperglycemia
-- less effective for fasting hyperglycemia
-- combined with metformin (not sulfonylureas)

7

What is an advantage of meglitinide analogs over other secretagogues?

fewer episodes of hypoglycemia

8

What are the first generation sulfonylureas?

1) tolbutamide (Oranase)
2) tolazamide (Tolinase)
3) chlorpropamide (Diabinese)

9

Why are 1st gen sulfonylureas no longer used?

long t1/2 = hypoglycemia, interactions

10

What are the 2nd gen sulfonylureas?

1) glyburide (Micronase, Diabeta)
2) micronized glyburide tablets (Glynase PresTab)
3) Glipizide (Glucotrol, XL)
4) Glimepiride (Amaryl)

11

Describe elimination of sulfonylureas

major hepatic, partial renal

12

What are contraindications for sulfonylureas?

1) T1DM
2) pregnancy
3) severe hepatic/renal dysfunction

13

What things interact with sulfonylureas?

1) excessive EtOH
-- enhance action
2) sulfonamides, clofibrate, ASA
-- protein displacement
3) nonselective beta-blockers
-- mask hypoglycemia
4) diuretics, beta blockers
-- hyperglycemic agents

14

How does EtOH interact with sulfonylureas?

enhanced action

15

How do sulfonamides, clofibrate interact with sulfonylureas?

displace protein bound (99%) sulfonylureas

16

How do nonselective beta-blockers interact with sulfonylureas?

mask hypoglycemia Sxs

17

How do diuretics, beta-blockers interact with sulfonylureas?

hyperglycemic agents

18

What factors of other drugs should trigger an interaction warning?

1) metabolism
2) excretion
3) protein displacement

19

What is the MoA of sulfonylureas?

bind sulfonylurea receptor (SUR) on beta cells's ATP-sensitivie K+ channel to inhibit outward flow of K+ and cause depolarization
-- does not increase biosynthesis

20

What occurs over time with prolonged admin of sulfonylureas?

1) decreased hepatic gluconeogenesis
2) increased insulin sensitivity via receptor expression/signaling

21

What happens with administration greater than 1 year?

1) downregulation of SURs on beta-cells
-- fasting [insulin] declines to pre-tx levels
2) FPG levels are maintained, though, due to decreased gluconeogenesis

22

What happens with long-term administration of sulfonylureas?

progressive beta-cell failure --> hyperglycemia after 1 year
-- not due to drug metabolism
-- other drugs may reduce failure

23

Describe comparative efficacy of sulfonylureas

less long-term efficacy vs. metformin/glitazones

24

What are ADRs of sulfonylureas?

1) hypoglycemia
2) weight gain

25

What effect do sulfonylureas have on first-phase insulin secretion?

none...they do not correct this

26

treatment for IGT/pre-diabetes?

diet

27

general tx for 0-5 years of T2DM?

diet + metformin

28

general tx for 5-15 years of T2DM?

combo therapy

29

general tx for 15+ years of T2DM?

insulin inj.

30

Agents in the biguanide class:

1) metformin (Glucophage)
-- of historical note: phenformin

31

What ADRs of metformin?

1) n/v/d, cramps in 20% of pts

2) BLACK BOX: lactic acidosis

32

How to deal with GI ADRs of metformin

titrate of weeks
will decrease with time

33

Why does metformin cause lactic acidosis?

inhibition of gluconeogenesis interferes with hepatic lactate metabolism

34

MoA of metformin:

increases activity of AMP-dependent PK (AMPK)
-- increases AMP: inhibits gluconeogenic enzymes, decreases cholesterol synthesis, increases FA oxidation, increases glucose uptake

35

Why is phenformin no longer on market?

caused more severe lactic acidosis

36

When is lactic acidosis most likely to occur?

1) renal failure (decreased clearance of lactate and metformin)
2) alcoholism (NAD depletion so LDH can't work)
3) tissue anoxia (cardiopulmonary dysfunction)

37

When should metformin's dose be adjusted?

when CrCl less than 50

38

What does IV iodinated contrast media cause?

decreased renal fx

39

Effects of metformin:

1) decreased gluconeogenesis
2) increased skeletal muscle glucose uptake
3) decreased intestinal glucose absorption

40

What are metformin's advantages over sulfonylureas?

1) no increase in insulin (less hypoglycemia)
2) effective for 2-5 yrs
3) positive TG, cholesterol changes
4) no weight gain
5) delays progression

41

How is metformin excreted?

unchanged renally
-- secreted via OCT2
-- adjust if concomitant cationic drug

42

What is OCT2?

Organic cation transporter 2

43

What is protein-binding quality of metformin?

none in plasma

44

Dosing of glyburide:

24hr duration = QD or BID

45

Duration of micronized glyburide:

12 hrs

46

Duration and t1/2 + dosing of glimepiride:

t1/2 = 10 hr
duration = 24 hr (QD dosing)

47

t1/2 and duration of glipizide

3 hr; duration = 12 hr

48

How is glipizide supplied?

conventional and XL

49

compare F among 2nd gen sulfonylureas:

1) glyburide: poor/variable
2) micronized glyburide: quick/consistent
3) glipizide: rapid/consistent
4) glimepiride: quick/consistent

50

How does glimepiride compare to glyburide?

equivalent clinically...
glimepiride = lower insulin/C-peptide
glimepiride = increased glucose uptake

51

What sulfonylureas should be used with caution in renal impairment (hypoglycemia)?

glyburide and glimepiride

52

Which sulfonylureas should be adjusted in hepatic impairment?

all