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Pharmacology Test #3 > Diabetes Day 3: Oral Agents and Non-Insulin Injectables > Flashcards

Diabetes Day 3: Oral Agents and Non-Insulin Injectables Flashcards

1
Q

What are the oral agents that are used to treat type II diabetes?

A

Biguanides

Sulfonylureas

Meglitinides

TZDs

Alpha glucosidase inhibitors

Incretin Mimetics

Sodium glucose co-transporters

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2
Q

What are the 3 incretin mime tics?

A

DPP-IV inhibitors

GLP-1 agonists

Amylin mimetics

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3
Q

Which drug class is the first line treatment for type II diabetes?

A

Biguanides (Metformin)

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4
Q

What is the mode of action of biguanides (metformin)?

A

Inhibits hepatic glucose production

Increases insulin sensitivity to peripheral tissues

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5
Q

What is the A1C Reduction of metformin?

A

1.5 - 2%

**most effective @ reducing A1C levels

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6
Q

What are the side effects of metformin?

A

GI (diarrhea) … take w/ meals

Lactic acidosis (rare –> breakdown of muscles –> kidney damage)

Vitamin B12 deficiency

Weight loss (or at least no weight gain)

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7
Q

What are the absolute contra-indications of Biguanides (metformin)?

A

Creatinine ≥ 1.4 (women)

Creatinin ≥ 1.5 (men)

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8
Q

Does metformin cause hypoglycemia on its own?

A

No

**won’t cause the release of insulin

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9
Q

Which patients do you want to take precaution with when prescribing biguanides (metformin)?

A

> 80 yo

Liver dz

Alcohol intake of > 2 drinks/day

Acute CHF, infection, surgery

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10
Q

What are the 2nd generation sulfonylureas?

A

Glimepiride

Glipizide

Glyburide

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11
Q

What is the mode of action of sulfonylureas?

A

Increases insulin production from beta cells in the pancreas

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12
Q

What is the sulfonylureas place in therapy?

A

As monotherapy if pt can’t take metformin

Adjunct to basal insulin/other oral agents (like metformin)

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13
Q

How long can a patient be on sulfonylureas?

A

3 - 5 years –> will eventually become less effective b/c of loss of beta cell function

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14
Q

Can sulfonylureas cause hypoglycemia by itself?

A

Yes

**Causes release of insulin

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15
Q

How much of an A1C reduction will you see with sulfonylureas?

A

1 - 2 %

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16
Q

What are the side effects of sulfonylureas?

A

Hypoglycemia

Weight gain**

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17
Q

What precautions do you need to use with sulfonylureas?

A

Sulfa allergies

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18
Q

What are the meglitinides?

A

Nateglinide

Repaglinide

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19
Q

What is the mode of action of the meglitinides?

A

Increase insulin production from the beta cells in the panaceas

**binds to different receptors than sulfonylureas

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20
Q

What is the place in therapy of the meglitinides?

A

Similar to sulfonylureas

Monotherapy

Adjunct w/ other oral agents

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21
Q

How long can patients take meglitinides?

A

3 - 5 yrs –> will eventually become less effective b/c of loss of beta cell function

**Similar to sulfonylureas

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22
Q

What is the A1C reduction w/ meglitinides?

A

0.5 - 2%

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23
Q

What are the side effects of meglitinides?

A

Hypoglycemia/weight gain but less than w/ sulfonylureas

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24
Q

What should you do if you’re taking meglitinides and you skip/miss a meal?

A

Skip the dose

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25
Q

What are the TZDs?

A

Rosiglitizone

Pioglitizone

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26
Q

What is the mode of action of TZDs?

A

Potent peroxisome proliferator-activated receptor-gamma (PPAR) agonist

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27
Q

What do PPAR agonists do?

A

Increase insulin-dependent glucose disposal

Decreases hepatic glucose output by decreasing insulin resistance in periphery and in liver

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28
Q

What is the place in therapy of TZDs?

A

Monotherapy

Adjunct to oral agents or insulin

**going out of favor

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29
Q

How much A1C reduction do you see w/ TZDs?

A

0.5 - 1%

30
Q

What are the side effects of TZDs?

A

Weight gain

Edema

Increase ovulation in women

Hepatic dysfunction

Rostiglitizone = increases risk of MI; (-) lipid effects (no longer sold in US)

Pioglitizone = (+) effects on lipids BUT increased risk of bladder cancer

31
Q

What are the contra-indications of TZD use?

A

Stage 3/4 heart failure (b/c of edema)

Pts w/ active liver dz or ALT > 2.5x normal

32
Q

What are the precautions with TZD use?

A

Monitor LFTs in all pts @ baseline

Monitor every 2 months for first year

Monitor periodically after first year

Discontinue if ALT > 3x upper limit of normal

33
Q

What are the alpha glucosidase inhibitors?

A

Miglitol

Acarbose

34
Q

What is the mode of action of alpha glucosidase inhibitors?

A

Inhibit enzyme that hydrolyzes complex starches/sugars into readily absorbable molecules

Delay absorption of glucose

35
Q

What is the place in therapy of alpha glucosidase inhibitors?

A

Monotherapy

Conjunction w/ other oral agents

**i have written down that it is only used as adjunct agent

36
Q

How much of a reduction of A1c will you see with alpha glucosidase inhibitors?

A

0.5 - 1%

37
Q

What are the side effects of alpha glucosidase inhibitors?

A

GI!!

Flatulence/diarrhea

Hypoglycemia

38
Q

How should you treat a pt who has hypoglycemia who is taking alpha glucosidase inhibitors?

A

Simple sugars (glucose tablet)

39
Q

What are the contra-indications for alpha glucosidase inhibitors?

A

GI disorders

Conditions that would risk bowl perforation

40
Q

What are the DDP-IV inhibitors?

A

Sitagliptin

Saxagliptin

Linagliptin

Alogliptin

41
Q

What is the mode of action of DPP-IV inhibitors?

A

Block DPP-IV –> activates GLP-1 –> increase the release of insulin and decrease glucagon –> decrease blood sugar levels

42
Q

What is the place in therapy of DPP-IV inhibitors?

A

Adjunct to other oral agents

Type 2 Diabetes only

43
Q

How much of a reduction in A1C will you see with DPP-IV inhibitors?

A

0.4 - 0.85%

44
Q

What are the side effects of DPP-IV inhibitors?

A

Headache

URI

Weight loss/weight neutral

45
Q

What are the precautions w/ the use of DPP-IV inhibitors?

A

Pancreatitis (has been reported)

46
Q

What are the GLP-1 Analogs?

A

Exenatide

XR (long release?) Exenatide

Liraglutide

47
Q

What is the mode of action of GLP-1 analogs?

A

Stimulate Insulin Release

Inhibit Glucagon Release

48
Q

What is the place in therapy of GLP-1 Analogs?

A

Adjunctive therapy in pts w/ type II diabetes who are already taking metformin, sulfonylurea, TZD or a combo of the above but haven’t achieved adequate glycemic control

49
Q

How much of a reduction in A1C will you see with GLP-1 Analogs?

A

1 - 1.5%

50
Q

How is GLP-1 analog taken?

A

Injectable

51
Q

What are the side effects of GLP-1 analog?

A

GI upset

Some hypoglycemia (if combined w/ sulfonylurea)

Some weight reduction (pts eat less)

52
Q

What is the black box warning on Liraglutide?

A

Thyroid Carcinoma (seen in rats)

53
Q

What precautions need to be taken when using GLP-1 analogs?

A

Take antibiotics/birth control pill at least 1 hr before injecting

54
Q

How is GLP-1 analog stored?

A

Refrigerator

Away from light

Discard after 30 days

55
Q

What is the name of the amylin analog?

A

Pramlintide

56
Q

What is the mode of action of amylin analog (pramlintide)

A

Works centrally in (-) feed back loop

Tells brain we have enough glucagon and need more insulin

57
Q

What is the place in therapy of amylin analog (pramlintide)?

A

Adjunct therapy in type 1 OR type 2

58
Q

What is the A1C reduction seen with amylin analog (pramlintide)?

A

0.3 - 0.6%

59
Q

How is amylin analog (pramlintide) administered?

A

Injection

60
Q

What do you need to do with pre-prandial insulin if you’re taking amylin analog (pramlintide)?

A

Reduce by 50%

61
Q

What are the side effects of amylin analog (pramlintide)?

A

GI = nausea, vomitting, anorexia

Headache

Some weight loss/weight neutral

Risk of hypoglycemia when administered w/ insulin

62
Q

Which drugs should you avoid when taking amylin analog (pramlintide)?

A

Other agents that also slows gastric emptying –> constipation

63
Q

What are the precautions when taking amylin analog (pramlintide)?

A

Take other meds either 1 hour before or 2 hours after injection

64
Q

Which patients should not be prescribed amylin analog (pramlintide)?

A

Poor compliance w/ current insulin regimen

Poor compliance w/ monitoring blood glucose

A1C > 9%

Recurrent severe hypoglycemia in past 6 mo

Hypoglycemia unawareness

Confirmed gastroparesis dx

use of drugs that stimulate gastricc motility

pediatric pts

65
Q

What do the SGLT-2 receptors do that are inhibited by sodium glucose co-transporter inhibitors (SGLT-2)?

A

Glucose reabsorption

66
Q

Why would SGLT-2 inhibitors be an effective treatment in pts w/ diabetes?

A

DM pts have more SGLT-2 receptors

67
Q

What is the result of SGLT-2 inhibitors?

A

Leads to 200-300 k/cal per day lost –> weight loss

68
Q

What is the SGLT-2 inhibitor that is FDA approved?

A

Canagliflozin

69
Q

How much of an A1C reduction will you see with SGLT-2 inhibitor (canagliflozin)?

A

~ 1%

70
Q

What are the beneficial effects of SGLT-2 inhibitors?

A

Reduction in fasting plasma glucose

Weight loss = 4 - 7 lbs

Modestly lower BP

71
Q

What are the adverse effects of SGLT-2 inhibitors?

A

Slight increase in LDL (bad cholesterol)

Polyuria

Thirst

Nasophargengitis

UTIs

Genital infections

72
Q

What is the general algorithm for treatment of type II diabetes?

A

Initial drug monotherapy –> metformin

                        ↓

2 drug combo –> Metformin + (sulfonylurea OR TZD OR DPP-4 inhibitor OR GLP-1 agonist OR basalar insulin)

                        ↓

3 drug combo –> Metformin + 2 other drugs

                        ↓

Complex insulin strategies

Pharmacology Test #3 (6 decks)

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