Anti-Diabetes

Question 1

Classification of Diabetes Mellitus

Answer 1

Type I-Insulin dependent (deficiency)

Type II-Insulin independent (resistance)

Question 2

What diabetes can cause

Answer 2

major cause of heart disease and stroke; 7th leading cause of death in United States.

Question 3

Macrovascular complications of diabetes

Answer 3

Coronary artery disease, cerebral vascular problem, peripheral vascular disease

Question 4

Microvascular complications of diabetes

Answer 4

Nephropathy, retinopathy and neuropathy

Question 5

Diagnostic Criteria for Diabetes

Answer 5

• Fasting plasma glucose (FPG)
• HbA1c level (also considering FPG results)
• Glucose level 2 hrs after a 75 g glucose load (less used)

Question 6

Type I Diabetes

Answer 6

 Insulin dependent
 Juvenile onset
10%
 Inflammation of islets or antibodies to islet
 Prone to ketoacidosis
 HLA association
 No obesity
 Vascular complications*

Question 7

Type II Diabetes

Answer 7

 NOT Insulin dependent  Maturity onset
90%
 Inability of insulin action  Not prone
 No association with HLA
 Obesity is a common risk factor  Vascular complications*

Question 8

Model of insulin action on glucose transport in myocytes & adipocytes

Answer 8

Insulin binds to the α subunits of the insulin receptor and stimulates the tyrosine kinase activity of the β subunits. Glucose transport proteins are then activated and translocated from the cytoplasm to the cell membrane which stimulates glucose entry into the cell.

Question 9

Long-acting therapy

Answer 9

`Glargine

Question 10

Short-acting

Answer 10

Aspart/Lispro

Regular

Question 11

Insulin management schedules:

Answer 11

2 or 3 meals (+/-PM) considerations; single or mixed insulin preps

Question 12

Insulin Delivery Devices:

Answer 12

Syringes; Refillable/Prefilled Pens; Insulin Pumps

Question 13

Complications of Insulin

Answer 13

Hypoglycemia: relieved by glucose (food intake; i.v. injection, etc.), ketoacidosis, insulin allergy, or lipodystrophy at injection site.

Question 14

Pathophysiology of T2D

Answer 14

know how glucagon and insulin work

Question 15

Sulfonylureas(SFUs):

Answer 15

Glyburide

Question 16

Glyburide mode of action

Answer 16

Induce insulin release from pancreas (closing ATP-K+ channels)
Reduce serum glucagon levels
Potentiates action of insulin on its target tissues

Question 17

Adverse drug reactions of glyburide

Answer 17

Severe hypoglycemia; weight gain, nausea, vomiting, hypersensitivity reactions

Question 18

Indication for glyburide

Answer 18

T2D patients failed to achieve glycemic control with diet & life-style modifications; may be used in patients with kidney disease

Question 19

Biguanides:

Answer 19

Metformin, generally 1st choice therapy

Question 20

Metformin Mode of Action

Answer 20

↓ hepatic glucose production (HGP) (activates AMP-kinase)
↑ insulin action on peripheral muscle and fat tissues
Non-insulin-dependent effects, thus no hypoglycemia & no weight gain; No effect on release of growth hormone, glucagon.

Question 21

Contraindications of Metformin

Answer 21

Contraindicated in patients with renal impairment, hepatic diseases, heart problems, acidosis, blood infection, etc.

Question 22

Thiazolidinediones(TZDs)

Answer 22

Rosiglitazone and Pioglitazone

Question 23

Mode of Action of rosiglitazone and pioglitazone

Answer 23

Agonists for nuclear peroxisome proliferator-activated receptor-γ (PPAR γ) & activate insulin responsive genes that regulate carbohydrate and lipid metabolism
Promote glucose uptake to muscles/fat & decrease HGP
Require insulin presence for action

Question 24

Adverse drug reactions of rosiglitazone and pioglitazone

Answer 24

1st year liver function monitoring
Edema (fluid retention), weight gain
Rosiglitazone (FDA restricted access): risk of heart attack/MI;
Pioglitazone: common usage in the US

Question 25

Indications and other considerations for rosiglitazone and pioglitazone

Answer 25

Good for overweight/obese patients;

Slow onset: 4-6 wks to affect blood glucose (may even take 3-4mos)

Question 26

α-GlucosidaseInhibitors

Answer 26

Acarbose

Question 27

Mode of action of acarbose

Answer 27

Delays carbohydrate digestion and slows glucose absorption in the gut
No effect on insulin release

Question 28

Adverse drug reaction of acarbose

Answer 28

Dose related malabsorption, flatulence, nausea and diarrhea (No weight gain)

Question 29

Newer Anti-Diabetics

Answer 29

Two main gut incretins:
GIP and GLP-1 (diminished in T2D post-meal)
Exenatide- IV
DPP-4 inhibitors (oral): sitagliptin
Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).

Question 30

Incretins

Answer 30

are a group of GI hormones that increase insulin release from the beta cells of the islets of Langerhans after eating. Incretin levels become elevated even before blood glucose levels. They also slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. They also inhibit glucagon release from the alpha cells of the Islets.

Question 31

Glucagon-LikePeptide1(GLP-1)Agonists

Answer 31

Exenatide

Question 32

Mode of action of exenatide

Answer 32

Induces insulin release (glucose-dependent)
Reduces post-meal glucagon, and hence HGP Slows stomach emptying
Promotes satiety and inhibits appetite
Preserves beta cell mass

Question 33

Exenatide dosing regimens:

Answer 33

injected twice daily 1hr pre-meal; or ER (Extended Release) for once weekly

Question 34

Adverse drug reactions to exenatide

Answer 34

Nausea, vomiting, headache. Avoid in patients with severe kidney & GI problems

Question 35

InhibitorsofDipeptidePeptidase-4(DPP-4)

Answer 35

Sitagliptin

Question 36

Mode of action of sitagliptin

Answer 36

Inhibits degradation of incretins thus increasing GLP-1

Can be administered orally (once daily)

Question 37

Adverse reactions of sitagliptin

Answer 37

Headache, risk of infections

Caution in kidney problems and potential contraindications