Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endocrine System > Pharmacology of Drugs Used for the Treatment of Diabetes Mellitus > Flashcards

Pharmacology of Drugs Used for the Treatment of Diabetes Mellitus Flashcards

1
Q

What are the drug treatment strategies for reducing hyperglycemia? (5)

A
  1. Increasing insulin levels
  2. Improving sensitivity to insulin
  3. Delaying the delivery and absorption of carbohydrates (glucose) from the GIT
  4. Increasing urinary glucose excretion
  5. Combination of the above
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the classifications of anti-diabetic drugs? (7)

A
  1. Insulin Secretagogues: agents that stimulate the secretion of insulin
  2. Insulin sensitizers: agents that sensitive tissues to insulin
  3. α-Glucosidase Inhibitors
  4. Amylin Analog
  5. Incretin-based therapies
  6. SGLT2 Inhibitors (Sodium Glucose Co-Transporters 2)
  7. Miscellaneous Agents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the different types of Insulin Secretagogues?

A

Sulfonylureas: first and second generations
Non-sulfonylureas: meglitinides and D-phenylalanine derivative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the different types of Insulin sensitisers?

A

Biguanides
Thiazolidinediones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the different types of incretin-based therapies?

A
  1. GLP-1 agonists
  2. Dipeptidyl - Peptidase 4 Inhibitors
  3. Dual GIP and GLP1 receptor agonists
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the different types of miscellaneous agents?

A

Bile acid Sequestrants
Dopamine agonists

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which agents for type 2 diabetes are not taken orally? How are they taken?

A

Most GLP-1 agonists and Amylin analog (Pramlintide) –> Taken via injection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Which anti-diabetes drugs can be used for both diabetes types?

A

Insulin and Amylin analog

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are examples of Sulfonylureas?

A

First generation: Tolbutamide, Chlorpropamide, Tolazamide

Second Generation: Glyburide, Glipizide, Gliclazide, Glimepiride

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the MOA of Sulfonylureas?

A
  1. Insulin release from beta cells (a major mechanism) –> Binds to sulfonylurea receptor 1 (SUR1) present on K(ATP) channels in the bet cell membrane and blocks ATP-dependent K+ channels –> Inhibition of K+ efflux, which causes depolarization, the opening of voltage Ca2+ channels which means Ca2+ influx and thus the release of insulin
  2. Inhibit Glucagon secretion –> due to enhanced release of somatostatin, which inhibits glucagon secretion from alpha cells
  3. Decrease hepatic glucose production
    4Increased peripheral insulin sensitivity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the difference between first and second generations of Sulfonylureas?

A

Second generation is less protein binding, higher potency and longer half-life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the PK of Sulfonylureas?

A

They are well absorbed orally, but their duration of action and half-lives vary

Metabolized by the liver, excreted in the urine

Crosses placenta and secreted in breast milk –> contraindicated in pregnancy and breast feeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the relative potency and half-life of Tolbutamide?

A

Relative potency: 1
Half-life: 6 to 12 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the relative potency and half-life of Glibenclamide?

A

Relative potency: 150
Half-life: 18 to 24 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the relative potency and half-life of Glipizide?

A

Relative potency: 100
Half-life: 16 to 24 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the PK of 1st generation of Sulfonyluraes?

A

1st generation: high protein binding –> drug interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the PK of the 2nd generation of Sulfonyluraes?

A

Minimal protein binding -=> less interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the adverse effects of Sulfonyluares?

A

Hypoglycemia
Weight gain
Cholestatic jaundice, bone marrow damage & allergic reactions,
Should be administered with caution in patients with renal or hepatic insufficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the incidence of hypoglycemia highest/lowest?

A

Highest incidence –> Chlorpropamide & Glyburide
Lowest incidence –> Tolbutamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Which drug is the safest for elderly diabetes?

A

Tolbutamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What do Sulfonylureas act synergistically with?

A

Metformin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What do Sulfonylureas have clinically shown to decrease?

A

Decrease macro and microvascular complications of diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are examples of Non-sulfonylureas?

A

Meglitinides –> Repaglinide (PRANDIN)
D-Phenylalanine Derivatives –> Nateglinide (STARLIX)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are non-sulfonylureas?

A

A newer class of agents that lack sulfonylurea moiety but stimulate insulin secretion
Exhibit fast onset and short-duration action (2-hour duration of action)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the MOA of Non-sulfonylureas?

A

Bind and inhibit ATP-sensitive K+ channels to increase Ca2+ influx and insulin secretion. Similar to sulfonylureas except that they require the presence of glucose to stimulate insulin secretion (e.g. glucose-dependent)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the clinical uses of Non-sulfonylureas?

A

For administration just before meals to reduce the post-prandial rise in glucose levels in type 2 diabetic patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the advantages/disadvantages of Non-sulfonylureas?

A

Advantages: less hypoglycemia & weight gain (least with Nateglinide) than conventional sulfonylureas

Disadvantages: hypoglycemia; not been shown to reduce macro and micro-vascular complications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is an example of Insulin Sensitizers?

A

Biguanides: Metformin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is the MOA of Metformin? (5)

A

Primary mechanism: 1. Decreased hepatic glucose production (gluconeogenesis) through activation of the enzyme AMP-activated protein kinase
2. Increased glucose uptake & utilization in skeletal muscle
3. Increased insulin action in muscle & fat (reduction in insulin resistance)

Minor mechanisms:
1. Showing of glucose absorption from GIT
2. Increased conversion of glucose to lactate in enterocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the advantages of Metformin?

A
  1. Euglycemic agent –> does not cause hypoglycemia, as it does not cause release of insulin from beta cells, even in large doses
  2. Reduces LDL and VLDL
  3. Does NOT cause weight gain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are the PK of Metformin?

A
  1. Not bound to plasma proteins & half-life is about 3 hours
  2. Excreted unchanged in urine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are the clinical uses of Metformin?

A

First-line therapy as a single agent for patients with type 2 diabetes

It can also be given in combination with other anti-diabetic drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What drug does Metformin act synergistically with?

A

Acts synergistically with Suphonylureas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What are the adverse effects of Metformin?

A

GI: anorexia, nausea, vomiting, abdominal discomfort and diarrhea
Lactic acidosis: rare but potentially fatal toxic effect
Vitamin B12 deficiency: may occur with long-term use

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What causes Vitamin B12 deficiency with Metformin?

A

Due to its interference with the intestinal absorption of vitamin B12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Which drug was withdrawn from the market due to incidence of severe lactic acidosis?

A

Phenformin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

How to prevent Vitamin B12 deficiency with Metformin?

A

Periodic screening should be considered, especially in patients with peripheral neuropathy or macrocytic anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What are the contraindications of Metformin?

A

Patients with renal or hepatic disease, alcoholism –> increased risk of lactic acidosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What are TZDs?

A

Agonists of peroxisome proliferator-activated receptor gamma family of nuclear receptirs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Where are proliferator-activated receptor - gamma found?

A

Fat, muscle, and liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is the function of proliferator-activated receptor - gamma?

A

Modulate the expression of genes involved in lipid & glucose metabolism, insulin signaling, and adipocyte differentiation
Agonsim increases insulin sensitivity by increasing glucose utilization and decreasing glucose production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is the MOA of TZDs?

A

Stimulate PPAR-gamma receptors to bind to DNA & promote transcription of insulin-responsive genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What are the principal effects of TZDs?

A
  1. Increase insulin sensitivity in peripheral tissues (reduce insulin resistance)
  2. Increase glucose uptake by increasing GLUT-4 expression in muscle and fat
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What are the clinical advantages of TZDs?

A

Combination of TZDs with metformin does not case hypoglycemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What are Pioglitazone?

A

Tzd with both PPAR-alpha and gamma agonist activity, not reported to cause hepatotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What is the purpose of Pioglitazone?

A

Lowers plasma triglyceride levels and increases HDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What kind of tests need to be performed prior to administratin of Pioglitazone?

A

Liver fuction tests

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What are the adverse effect of Pioglitazone?

A

Weight gain and fluid retention –> edema
Hear failure
Increased risk of bone fracture in women

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What are the contraindications for Pioglitazone?

A

Heart failure, pregnancy& breast fedding, children
Not recommended in patients with active liver disease or pretretment elevation of ALT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What ae examples of α-Glucosidase inhibitors?

A

Acarbose
Miglitol
Voglibose (available only in Japan, Korea and India)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is the MOA of α-Glucosidase inhibitors?

A

Competitive inhibitors of intestinal α-Glucosidases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Where are α-Glucosidases found?

A

In brush border cells of the small intestine convert to starch, oligosaccharides & disaccharides into monosaccharides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What is the function of α-Glucosidase inhibitors?

A

Inhibitors slow hydrolysis of carbohydrates into glucose and thus inhibit GI absorption of glucose

Relatively minor glucose lowering effect

54
Q

What are the adverse effects of α-Glucosidase inhibitors?

A

GI: Flatulence, diarrhea, and abdominal pain

55
Q

What are the contraindications for α-Glucosidase inhibitors?

A

Patients with inflammatory bowel disease (IBD)

56
Q

What is amylin?

A

37 amino acid peptide co-secreted with insulin by pancreatic beta cells

57
Q

What are the physiological effects of Amylin?

A

Reduces glucagon secretion –> modulates postprandial glucose levels

Slows gastric emptying

Decreases apetite

58
Q

What are type 1 diabetics like?

A

Lack of amylin (similar to insulin)

59
Q

What are type 2 diabetics like?

A

Relatively deficient in amylin

60
Q

What are the limitations of Amylin?

A

Forms aggregates and insoluble fibrils upon infusion
Not feasible for therapeutic use

61
Q

What is an example of amylin analogs?

A

Pramlintide

62
Q

What is Pramlintide?

A

A synthetic analog of amylin (with three proline substitutions, which reduce their tendency to aggregate into insoluble fibrils)

63
Q

What are the pharmacologic effects of Pramlintide?

A

Suppress glucagon release; delay gastric emptying and reduce food intake

64
Q

What is the clinical use of Pramlintide?

A

For pre-prandial use in type 1 and 2 DM patients
Administered SC in addition to insulin in those who are unable to achieve their target postprandial blood sugar levels

65
Q

What are the adverse effects of Pramlintide?

A

Nausea, vomiting and anorexia
Hypoglycemia (when combined with insulin; therefore, mealtime insulin doses should be reduced by 50% or more to avoid the risk of hypoglycemia))

66
Q

What are incretin and incretin-based therapies?

A

Peptide hormones released in response to food intake from enterocytes in small intestine that augment glucose-dependent insulin secretion

67
Q

What is the difference between sulfonylureas and incretins & incretin-based therapies?

A

Do not increase insulin secretion by themselves; they require glucose to augment insulin secretion (like non-sulfonylureas)

68
Q

What are the two major types of incretin?

A

Glucagon-like peptide 1 (GLP-1)
Glucose-dependent insulinotropic polypeptide or Gastric Inhibitory Peptide (GIP)

69
Q

When are both types of incretin decreased?

A

In type 2 DM

70
Q

What are the clinically available incretin based therapies?

A

Synthetic GLP-1 agonists
Inhibitors of GLP-1 degradation (DPP4 inhibitors)
Dual acting GLP-1 and GIP agonists

71
Q

Where is GLP-1 secreted from?

A

L cells of jejunum and ileum

72
Q

What are the physiological actions of GLP-1?

A

Increase glucose-dependent insulin secretions
Decrease glucagon secretion
Decrease gastric emptying
Decrease appetite

–> They are all unique properties to reduce postprandial hyperglycemia & also to induce weight loss

73
Q

What are the PK of GLP-1?

A

Very short half-life
GLP-1rapidly inactivated within 1 to 5 minutes

74
Q

What is GLP-1 deactivated by?

A

Dipeptidyl peptidase IV enzyme

75
Q

What is GLP-1 inactivated into?

A

GLP-1 and Dipeptide

76
Q

What are the uses of GLP-1 action therapeutically?

A
  1. Use long-acting DPP4-resistant analogs
  2. Block DPP-4, the enzyme that degrades GLP-1
  3. Dual-acting GLP-1 and GIP agonists
77
Q

What are the different types of GLP-1 targeted therapy?

A

Injectables
Oral agents

78
Q

What are the examples of GLP-1 targeted therapy that are injectable ?

A

GLP-1 analogs (Incretin mimetics)
1. Exenatide
2. Albiglutide
3. Liraglutide
4. Dulaglutide

79
Q

What are examples of GLP-1 targeted therapy that are oral agents?

A

DDP-4 Inhibitors (Incretin enhancers)
1. Sitagliptin
2. Linagliptin
3. Saxagliptin
4. Alogliptin

80
Q

What is the examples of dual acting GLP-1 and GIP agonist?

A

Tirzepatide

81
Q

What is the FIRST orally active GLP-1 agonist?

A

Semaglutide

82
Q

What is the MOA of Incretin (GLP-1) based therapies?

A
  1. DDP-4 inhibitors block Dpp-4 and decrease glucose
  2. DDP-4 enzyme inactivates GLP-1
  3. Increatin, GLP-1
  4. Either stimulates insulin release or inhibits glucagon release
  5. Lowering of blood glucose levels

Acts as a GLP-1 agonist and case potentiation of glucose-mediated insulin secretion, suppression

83
Q

What are examples of GLP-1 analogs?

A

Exenatide
Liraglutide
Albiglutide
Dulaglutide

84
Q

What is exenatide?

A

A synthetic form of the peptide exendin-4 (similar to GLP-1) found in Gila monster venom

85
Q

What is the difference between GLP-1 and Exenatide?

A

Unlike GLP-1, it is not degraded by the enzyme DPP-4

86
Q

What is the half-life of Exenatide like?

A

About three hours

87
Q

How is Exenatide excreted?

A

Glomerular filtration

88
Q

What are the clinical uses of Exenatide?

A

Injected SC (twice daily) for type 2 DM patients not achieving target glycemic levels with other agents

A once a week release is now available

89
Q

What is Liraglutide?

A

Long-acting synthetic GLP-1 analog –> more stable than Exenatide

90
Q

What is Albiglutide?

A

Recombinant modified human GLP-1 dimer fused to albumin

91
Q

What is Dulaglutide?

A

Consists of two GLP-1 analog molecules covalently linked to an Fc fragment of human Ig

92
Q

What is a characteristic of all GLP-1 analogs administered?

A

All offer the advantage of once-weekly dosing (SC)

93
Q

What are the adverse effects of GLP-1 analogs?

A

Nausea, vomiting and diarrhea (the most common)
Hypoglycemia (when combined with sulfonylureas and insulin)
Weight loss
Necrotizing and hemorrhagic pancreatitis

94
Q

What is Semaglutide co-formulated with?

A

An absorption enhancer, salcaprozate sodium (SNAC)

95
Q

How is Orally active semaglutide administered?

A

Orally; given once daily (3mg, 7mh or 14mg)

Taken at least 30 minutes before the first food, beverage or other oral medications of the day.

Food should be eaten 30 to 60 minutes after taking oral semaglutide

96
Q

Why should food be eaten about an hour after oral semaglutide administration?

A

Oral semaglutide has low bioavailability and requires optimal conditions for absorption

97
Q

What is the safety profile of Semaglutide like?

A

Similar to other injectable GLP-1 agonists

98
Q

What is Tirzepatide?

A

Markets, as Mounjaro, it is a first-in-class dual GIP and GLP-1 agonist

99
Q

What is the purpose of Tirzepatide?

A

HAs remarkable glycemic and weight-reducing efficacy compared to GLP-1 agonists alone in diabetic or obese patients

100
Q

How is Tirzeparide administered?

A

Half-life –> 5 days, once weekly administration by SC injection

101
Q

What are the safety profile and adverse effects of Tirzepatide like?

A

SImilar to other GLP-1 agonists

102
Q

What are examples of DPP-4 inhibitors?

A

Sitagliptin
Saxagliptin
Linagliptin
Alogliptin
Vildagliptin

103
Q

What is the MOA of DPP-4 inhibitors?

A

Specific inhibitors of DPP-4, which is the enzyme that degrades GLP-1 and other incretins –> Increase in circulating levels of GLP-1 and GIP –> Decrease postprandial hyperglycemia by increasing glucose-mediated insulin secretion & decreasing glucagon levels

104
Q

Do DPP-4 inhibitors affect gastric emptying and appetite?

A

Unlike GLP-1 and amylin analogs, they do not affect gastric emptying and appetite

105
Q

What is the clinical use of DPP-4 inhibitors?

A

As adjunctive therapy for type 2 diabetics who have failed to achieve glycemic goals

106
Q

What are the advantages of DPP-4 inhibitors?

A

Taken orally, once a day, unlike most GLP-1 agonists that must be infected

107
Q

What are the adverse effects of DPP-4 inhibitors?

A

Upper respiratory tract infections, nasopharyngitis, headache, hypoglycemia (when combined with sulfonylureas), pancreatitis, and allergic recations

108
Q

What are examples of SGLT-2 Inhibitors?

A

Canagliflozin
Dapagliflozin
Empagliflozin

109
Q

What is the SGLT2?

A

A co-transporter responsible for 90% of glucose reabsorption in the kidney

110
Q

What is the MOA of SGLT2 inhibitors?

A

Block the reabsorption of glucose via SGLT2 in the proximal tubules of the kidney –> INcresaed glucose excretion –> Decrease in blood glucose levels

111
Q

What are the clinical uses of SGLT2 inhibitors?

A

To be used with diet and exercise, to improve glycemic control in adults with type 2 diabetes

–> Cna help prevent the development of heart disease and reduce the progression of renal impairment or ESRD

112
Q

When can SLGT2 inhibitors not be used?

A

In patients with type1 diabetes, diabetic ketoacidosis, severe renal impairment or ESRD

113
Q

What are the adverse effects of SLGT2 inhibitors?

A

Dehydration
Genital yeast infections
UTI
Hypoglycemia (when combined with sulfonylureas or insulin)

114
Q

Why is dehydration an adverse effect of SLGT2 inhibitors?

A

Due to osmotic diuresis and frequent urination

115
Q

What are examples of bile acid sequestrants (miscellaneous agents)?

A

Colesevelam

116
Q

What are examples of dopamine agonists (miscellaneous agents)?

A

Bromocriptine

117
Q

What are miscellaneous agents approved as?

A

Adjunctive therapy for type 2 diabetic patients

118
Q

What is the efficacy of miscellaneous agents in lowering glucose levels?

A

Very modest efficacy

119
Q

What is the MOA of miscellaneous agents?

A

Exact MOA is still unknown

120
Q

What are the adverse effects of bile acid sequestrants?

A

Constipation,
Indigestion,
Flatulence
Interfere with the absorption of several drugs

121
Q

What is the MOA of Dopamine D2 receptor agonists?

A

Improves insulin sensitivity by altering hypothalamic circadian activity

Enhanced suppression of hepatic glucose production

122
Q

What are the adverse effects of Dopamine D2 receptor agonists?

A

Nausea, vomiting, headache, dizziness, orthostatic hypotension, and hypoglycemia

123
Q

What is the contraindication for Dopamine D2 receptor agonists?

A

Not recommended in patients with physchotic disorders

124
Q

What is the diabetic treatment for cardiorenal protection in high risk patients?

A

GLP-1 agonists or SLGT 2 inhibitors

125
Q

What is the diabetic treatment for weight control in obese patients?

A

Dual GLP-1/GIP agonsist or GLP-1 agonists

126
Q

What are the drugs given for severe HYPOglycemia?

A

Glucagon and Diazoxide

127
Q

When is glucagon given?

A

For severe hypoglycemia, parenterally

128
Q

What is the action of glucagon?

A

Opposite actions to insulin –> increases hepatic glucose production

129
Q

What is the purpose of Diazoxide?

A

Binds to K+ channels in beta cells to prevent the closing of these channels and inhibit insulin secretion

130
Q

What drug does Diazoxide have opposite effect from?

A

Sulfonylureas as it binds to a unique site

131
Q

When is Diazoxide given?

A

Chronic or recurring hypoglycemia
Treatment of inoperable inulinomas

132
Q
A

Endocrine System (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions