Diabetes Drugs Flashcards Preview

Pharm > Diabetes Drugs > Flashcards

Flashcards in Diabetes Drugs Deck (120):
1

What are the treatment goals for:
Fasting plasma glucose
2hr Peak postprandial glucose
HbA1C

Fasting plasma glucose: 90-130
2hr Peak postprandial glucose:

2

What is the only current treatment for type I diabetes?

Insulin

3

Insulin stimulates glucose uptake in liver, muscle, and adipose tissue via upregulation of ___ transporter

GLUT4 glucose transporter

4

Rapid acting Insulin

Insulin aspart
Insulin lispro
Insulin glulisine

5

Rapid acting insulin: (Insulin aspart, Insulin lispro, Insulin glulisine)
Onset
Peak
Duration

Onset: 5-15 mins
Peak : 45-75 mins
Duration: 2-4 hours

6

Rapid acting insulin: (Insulin aspart, Insulin lispro, Insulin glulisine) Usage

For meals or acute hyperglycemia
Can be inject immediately before meals

7

Regular insulin
Onset
Peak
Duration

Onset: 30-60 mins
Peak: 2-4 hours
Duration: 6-8 hours

8

Regular insulin Usage

For meals or acute hyperglycemia, needs to be injected 30-45 mins prior to meal

9

Intermediate acting insulin

NPH insulin (Isophane)

10

Intermediate acting insulin Formulation

Conjugated with protamine peptide- delays absorption until proteolytically cleaved by tissue proteases

11

Intermediate acting insulin
Onset
Peak
Duration

Onset: 1.5-2 hours
Peak: 6-10 hours
Duration: 16-24 hours

12

Intermediate acting insulin Usage

Provides basal insulin and overnight coverage

13

Long acting insulin

Insulin glargine
Insulin detmir

14

Long acting insulin formulation:
Insulin glargine
Insulin detmir

Insulin glargine: amino acid substituted insulin
Insulin detmir : insulin with fatty acid side chain that associates w/ tissue bound albumin

SLOWS ABSORPTION

15

Long acting insulin formulation:
Insulin glargine
Insulin detmir
Onset
Peak
Duration

Onset: 2 hours
Peak: no peak
Duration:
Insulin glargine: 20-24 hours
Insulin detmir: 6-24 hours

16

Long acting insulin formulation:
Insulin glargine
Insulin detmir
Usage

Provides basal insulin and overnight coverage

17

Insulin administration

Give SQ
Syringe, pen, pump

18

Sites of insulin administration

upper arms, thighs, buttocks, abdomen

19

Sites of insulin admin should be rotated to avoid

lipodystrophy

20

Conventional insulin therapy

2 daily injections of pre-mixed intermediated insulin (NPH) + regular insulin

21

Risk of conventional insulin therapy

Hypoglycemia in afternoon or overnight (insulin> carb consumption)
Risk of hyperglycemia in the morning=Dawn phenomenon (cortisol raises glucose levels)

22

Intensive insulin therapy

One/twice daily basal insulin (NPH or glargine)- lowers fasting glucose
Pre meal rapid acting insulin- postprandial glucose

23

Dose of pre-meal bolus determined by

Blood glucose level
Size and composition of meal (amount of carbs)
Degree of anticipated physical activity

24

Drawbacks of intensive therapy

patient commitment and effort
higher cost
increased risk of adverse effects

25

Major adverse effect of insulin therapy

Hypoglycemia

26

Hypoglycemia

blood glucose

27

Treatment of mild-moderate hypoglycemia

Oral dose of simple carbohydrate

28

Treatment of severe hypoglycemia

IV glucose or glucagon

29

Non-drug therapies for type II DM

Diet and exercise
decrease refined sugar
decrease fat

30

Bariatric surgery in treatment of type II DM

Roux-en-Y gastric bypass surgery can restore normoglycemia in obese

31

Insulin sensitizers

Biguanides (Metformin)

Thiazolidinediones (Pioglitazone, Rosiglitazone)

32

Insulin Secretagogue

Sulfonylureas (Chlorpropamide, Tolbutamide, Glimepiride, Glyburide, Glipizide)

Meglitinides (Repaglinide, Nateglinide)

33

Incretin Mimics and Modulators

GLP-1 homologs (Exenatide, Liraglutide)

DPP-IV inhibitors (Sitigliptin, Saxagliptin)

34

Inhibitors of carbohydrate digestion

a-glucosidase inhibitors (acarbose, miglitol)

35

SGLT2 inhibitors

Canagliflozin
Dapagliflozin

36

Bile acid-binding resin

Colesevelam

37

Amylin Homolog

Pramlintide

38

What is the recommended initial drug of choice in the treatment of ALL types of DM 2 patients (unable to control with diet/exercise alone)?

Metformin

39

Metformin Actions

Anti-hyperglycemia drug
Lowers fasting plasma glucose
Decreases hepatic gluconeogenesis
Increases insulin sensitivity/glucose uptake

40

What does Metformin require for its effects?

presence of insulin

41

How much does Metformin lower HbA1c?

1-5.2%

42

Advantages of metformin

NO hypoglycemia
NO weight gain
Improves lipid prodile
Decreases MI, DM death, mortality

43

Metformin MOA

Inhibits complex I of mitochondrial oxidative phosphorylation
Block ATP, Increase in AMP
Antagonizes Glucagon by inhibiting AC activity (x hep gluc)
Indues AMP-dependent kinase (Inc insulin sens)

44

Metformin adverse effects

Well tolerated
GI effects
Bad taste
Inhibits absorption of Vit B12 (megaloblastic anemia, neuropathy)

LACTIC ACIDOSIS

45

Rare but serious adverse effect of metformin?

Lactic acidosis
(Pts w/ renal/liver insuff, CHF, MI, hypoxia)

46

Symptoms of lactic acidosis

Deep and rapid breathing, vomiting, abdominal pain and severe weakening of muscles in the legs and arms
Increased lactic acid in the blood

47

Metformin contraindications

Pregnant/lactating
Impaired renal/liver function
Elderly >80
Iodinated contrast agent (contrast induced renal failure)
Alcohol abuse
CHF
MI
Shock/septicemia
Acute illness
Hypoxia

48

Thiazolidinediones
"glitazones"

Pioglitazone
Rosiglitazone

49

Thiazolidinediones
"glitazones" description

Insulin sensitizers
Increase sensitivity of adipose, muscle, and liver to insulin

50

Thiazolidinediones
"glitazones" MOA

Agonists of peroxisome proliferator activated recepor-Y TF (PPAR-y)
Increases insulin sensitivity
Decreased plasma glucose levels

51

Thiazolidinediones
"glitazones" Indications

Monotherapy or combo w/ metformin, sulfonylureas or insulin for DM T2
Decreases fasting blood glucose, moderate effects on postprandial glucose

52

How much do Thiazolidinediones
"glitazones" decrease HbA1C?

0.5-1.4%

53

How long does it take Thiazolidinediones
"glitazones" to have a max effect?

6-14 weeks

54

Thiazolidinediones
"glitazones" adverse effects

Weight gain (subQ)
Fluid retention > edema
Risk of heart failure
Bone fracture risk
Bladder cancer risk
Hepatotoxicity

55

Thiazolidinediones
"glitazones" Contraindications

Liver disease
Heart failure (BLACK BOX)
Pregnancy

56

Thiazolidinediones
"glitazones" BLACK BOX WARNING

Increased risk of heart failure (fluid retention)

57

Sulfonylureas vs. Meglitinides onset and half life

Sulfonylureas: slow onset, long half life > fasting glucose
Meglitinides: Rapid onset, short half life > postprandial glucose

58

Sulfonylureas

First generation (rarely used)
Chlorpropamide
Tolbutamide

Second generation
Glimepiride
Glyburide
Glipizide

59

Sulfonylureas Description

Oral drugs that lower blood glucose levels by stimulating beta cells to secrete insulin

60

Sulfonylureas MOA

Directly bind to the regulatory subunit of the K channel (Sur1)
Mimic the effects of ATP, block channel
> K induced membrane depol
release of insulin

61

Sulfonylureas Uses

Long duration of glucose lowering effect (16-24 h)
Stimulate insulin production in absence of glucose
REDUCE FASTING PLASMA GLUCOSE

62

How much do Sulfonylureas reduce HbA1c?

1.5-2%

63

Activity of Sulfonylureas is dependent on

Functional beta cells
Most effective in pts w/ DM

64

Sulfonylureas adverse effects

Hypoglycemia (renal/hepatic impairment, eldly)
Weight gain (subQ)

65

Sulfonylureas metabolism

Met in liver
Excreted in kidney

Glyburide and Glimepiride increase conc in R/H insuff

Glipizide is safer for patients with renal insufficiency

66

Which Sulfonylurea is safer in pts with renal insufficiency and elderly?

Glipizide

67

Sulfonylureas Contraindications

Elderly (give Glipizide)
Impaired R/H function (give Glipizide or Repaglinide for R)
Type 1 diabetes
Pregnant (teratogenic)
Sulfa allergies

68

Sulfonylureas Drug Interactions

Highly protein bound
Displacement > high risk of hypoglycemia

69

Meglitinides (Insulin Secretagogues)

Repaglinide
Nateglinide

70

Meglitinides Description

Short acting glucose-lowering oral drugs
Stimulate pancreatic beta cells to secrete insulin

71

Meglitinides MOA

Trigger insulin secretion similarly to sulfonylureas but bind a different region of the SUR1 K/ATP channel

72

Important difference between Meglitinides and Sulfonylureas

Rapid, shorter duration
Glucose dependent
**Decreased risk of hypoglycemia

73

How much do Meglitinides reduce HbA1c?

1-1.5%

74

Meglitinides Indications

Post prandial glucose elevations
Often used in combo w/ drugs that affect fasting plasma glucose (metformin, thiazolidinediones)

75

What is the difference between Nateglinide and Repaglinide?

Nateglinide affects POSTPRANDIAL glucose, and is rapidly reversed

Repaglinide affects postprandial and fasting glucose and effect is more prolonged

76

Meglitinides metabolism

Repaglinide:
100% met in liver
90% fecal elimin
*good alternative to sulfonyl in renal insufficiency

Nateglinide:
80% met in liver
80% elim in urine
*Does not require dosage adjustment in renal insufficiency

77

Meglitinides adverse effects

Hypoglycemia (less than sulfonyl)
Weight gain

78

Meglitinides Contraindications

Liver disease
Pregnancy

79

GLP-1 homologs

Exenatide
Liraglutide

80

DPP-IV inhibitors

Sitagliptin
Saxagliptin

81

GLP-1 homolog description

Analogs of GLP-1
GLP-1 is made in L cells of SI, mediates the incretin effect on plasma insulin

82

GLP-1 MOA

Binds GLP-1 receptor on beta cells and potentiates glucose-induced insulin secretion
Suppresses hepatic glucose production (inhibits production of glucagon)
Promotes beta cells survival
Slows gastric emptying
Increases satiety

83

GLP-1 homolog indications

Alterative to starting insulin in DM T2
Reduces both Fasting and postprandial glucose

84

GLP-1 homolog duration of action

Exenatide: 6-8 hours
Liraglutide: 11-15 hours

85

How much do GLP-1 homologs reduce HbA1c?

0.5-0.7%

86

GLP-1 homolog advantages

Little risk of hypoglycemia (glucose dependent)
Promotes weight loss

87

GLP-1 homolog adverse effects

Frequent; nausea vomiting diarrhea

88

DPP-IV inhibitors

Sitagliptin
Saxagliptin

89

DPP-IV inhibitors

Decrease fasting and postprandial glucose

90

How much do DPP-IV inhibitors reduce HbA1c?

0.48-0.61%

91

DPP-IV inhibitors MOA

Inhibitors of DPP-IV, promotes actions of GLP-1

92

DPP-IV inhibitors adverse effects

metabolism of other hormones?

93

Alpha-glucosidase inhibitors

Acarbose
Miglitol

94

Alpha-glucosidase inhibitors Description

Reduce postprandial glucose
Inhibit digestion of polysaccharides in small intestine

95

Alpha-glucosidase inhibitors MOA

Inhibit alpha-glucosidase (enzyme in brush border of SI - hydrolysis of dietary carbs)

96

Alpha-glucosidase inhibitors Indications

Control of postprandial glucose (needs to be taken with meal)
Not considered first line anti-diabetic drug
Less potent than sulfmet
NO hypoglycemia

97

How much do Alpha-glucosidase inhibitors lower HbA1c?

0.5-0.8%

98

Alpha-glucosidase inhibitors Adverse effects

GI (abd pain, flatulence)

99

Alpha-glucosidase inhibitors Contraindications

Chronic intestinal disease
Inflammatory bowel disease
Colonic ulceration/ intestinal obstruction

100

SGLT2 Inhibitors

Canagliflozin
Dapagliflozin

101

SGLT2 Inhibitors Description

Drugs that reduce hyperglycemia by promoting glucose excretion in the urine

102

SGLT2 Inhibitors MOA

Inhibit sodium-glucose linked transporter 2 protein (SGLT2)
prevents glucose reabsorption in proximal renal tubules

103

SGLT2 Inhibitors Indications

Mono/ combo
Low risk of hypoglycemia when used mono
Decreases body weight
decreases BP

104

How much do SGLT2 Inhibitors decrease HbA1c?

0.5-0.9%

105

SGLT2 Inhibitors Adverse Effects

UTI
Thirst/Dehydration
Hypotension
Increased LDL cholesterol
Hyperkalemia

106

SGLT2 Inhibitors Contraindications

Renal impairment

107

Bromocriptine description

Sympatholytic dopamine D2 receptor agonist
Normalize decreased AM dopamine levels in DMT2

Take within 2 hours of waking

108

How much does Bromocriptine lower HbA1c?

0.5%

109

Colesevelam Description

Bile acid binding resin
LDL-lowering drug
Used as adjunct
Indirectly increases GLP-1

110

Colesevelam MOA

Bind bile acids in SI
Form insoluble complexes
Excreted in feces
Prevents bile acid reabsorption
Bile acid bind to TGR5 in colon >stimulation GLP-1 secretion

111

Colesevelam Indications

+ metformin, sulf, insulin
NOT 1st line
Helpful in pts w/ high LDL

112

How much does Colesevelam lower HbA1c?

0.5%

113

Which medication should be considered as initial therapy for patients presenting with HbA1c >1%

Insulin

114

Who requires more insulin - DM Type 1 or 2?

Due to insulin resistance, type-2 diabetics require considerably more Insulin compared to the doses used in the treatment of type-1 diabetes

115

Amylin homolog

Pramlintide

116

Amylin homolog Description

Synthetic analog of amylin (co-secreted with insulin, helps with postprandial glucose control)
Amylin is absent in diabetics
Used w/ insulin in DM T1&2

117

Pramlintide actions

Decreases hepatic gluconeogeneiss
Decreases postprandial glucagon
Slows gastric emptying
Increases satiety

118

Amylin homolog (pramlintide) indications

Adjunct + insulin
Post prandial glucose control
Effects are ADDITIVE to sinulin (reduce insulin by 50%)
Weight loss

119

How much does amylin homolog lower HbA1c?

0.5-0.7%

120

Amylin homolog adverse effects

Nasuea, vomiting, anorexia, headache
Increases risk of severe hypoglycemia (w/ insulin)