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Endocrine > T2 Diabetes Drugs > Flashcards

T2 Diabetes Drugs Flashcards

1
Q

Diagnostic Criteria for T2DM?

A
  1. Casual Glucose >11.1
  2. Fasting Glucose >7.0
  3. 2h Post Challenge Glucose >11.1
  4. HbA1c
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2
Q

Fasting Glucose for Pre-DM? What should they do next?

A

Fasting Glucose 6.1-6.9.

Undergo 75g oral glucose tolerance test to determine if impaired glucose tolerance of DM

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3
Q

7 Principles of T2DM Management? and examples of classes of drugs for each principle?

A
  1. Increase Insulin Sensitivity (Biguanides, Thiazolidinediones)
  2. Stimulate Insulin Release (sulfonyureas, meglitinides, GLP1-agonists)
  3. Inhibit Glucagon Release (GLP1-agonist, biguanides)
  4. Reduce Glucose Release from Liver (Biguanides)
  5. Slow down intestinal carbohydrate digestion (alpha-glucosidase inhibitors)
  6. Increase incretin levels (DPP4 inhibitors, Bile Acid Sequestrants)
  7. Block glucose reabsorption at Kidneys (SGLT2 Inhibitors)
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4
Q

Mechanism of Action of Metformin?

A
  1. Increases density of insulin receptors at tissues
  2. Decrease Hepatic Glucose Production
  3. Decreases Intestinal Glucose Absorption, improves muscular glucose absorption
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5
Q

PK of Metformin
a) Route of Administration
b) Distribution
c) Metabolism
d) Half Life
e) Duration of Action
f) Excretion

A

a) Oral
b) Rapid, little bound to serum proteins
c) NA
d) 1.5-3h
e) 8-12h
f) Urine

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6
Q

Side Effects of Metformin?

A
  1. GI Issues - Diarrhea, Vomitting, Indigestion
  2. Risk of Vit B12 Malabsorption
  3. Risk in Renal Issues & Lactic Acidosis (Hepatic Disease + CVS problems) patients
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7
Q

How to reduce GI side effects of metformin?

A

Take with meals or after meals

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8
Q

What is a concomitant benefit of Metformin?

A

Help with weight loss and improving lipid levels

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9
Q

What are examples of thiazolidinediones?

A
  1. Pioglitazone
  2. Rosiglitazone
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10
Q

Mechanism of action of thiazolidinediones?

A

Activation of PPAR-gamma which regulate glucose metab, adipogenesis and improve insulin sensitivity at adipose, liver and skeletal muscles,

Stimulation of these receptors increase production of GLUT1 and GLUT4, enhancing tissue sensitivity to insulin

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11
Q

PK of Thiazolidinediones
a) Route of Administration
b) Distribution
c) Metabolism
d) Half Life
e) Duration of Action
f) Excretion

A

a) oral
b) Bind extensively to serum proteins
c) hepatic
d) 3-7h for parentl 16-24h for metabolites
e) 24h
f) fecal

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12
Q

Side Effects of thiazolidinediones?

A
  1. Weight Gain
  2. Peripheral Edema
  3. Increased risk of heart failure
  4. Bone Fractures
  5. CYP450 inducer, reducing serum concentration of oral contraceptives
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13
Q

Examples of first generation (1) and second generation (4) sulfonyureas? Advantage of Second Generation?

Which have lower risk of hypoglycemia?

A

First Gen: Tolbutamide

Second Gen: Glipizide, Glicazide, Glibenclamide, Glimepiride

More potent than 1st Gen

Glipizide & Glicazide

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14
Q

Mechanism of Action of Sulfonyureas?

A

Targets pancreatic beta cells’ ATP-dependent potassium channels. Binds to SU receptor proteins, subunits of the potassium channel, and inhibits K+ efflux, causing depolarisation, and hence entry of calcium and so exocytosis of insulin granules from the cell

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15
Q

Route of Administration for Sulfonyureas?

A

All Oral

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16
Q

Sulfonyurea with longest onset of action? How long is it? What is the roughly the Onset of Action of the rest?

A

Glicazide. 4-6h. 0.5-1.5h

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17
Q

Metabolism of Sulfonyureas?

A

Hepatic for all

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18
Q

Which sulfonyurea has the longest duration of action? What is the duration? What is the roughly the rest?

A

Gibenclamide. Intermediate to Long (12-24h to >24h). Rest are about intermediate, glipizide is short to intermediate (<12h to 12-24h)

19
Q

Excretion of sulfonyureas?

A

Renal for all; gibenclamide and glimepiride have partial fecal

20
Q

How to improve absorption of sulfonyureas?

A

Take 0.5h before food

21
Q

What are the side effects of sulfonyureas?

A
  1. Weight Gain
  2. Hypoglycemia
  3. Sulfa allergy
22
Q

Mechanism of Action of Meglitinides?

A

Bind to SUR1 receptor on beta cell, close ATP-dependent channel, depolarisation, calcium entry, exocytosis of insulin

23
Q

Two examples of meglitinides?

A

Repaglitinide
Nateglitinide

24
Q

Metabolism of Meglitinides?

A

Hepatic

25
Q

Half life of meglitinides?

A

1-1.5h

26
Q

Duration of Action of Meglitinides? What is the significance of this?

A

Repa = short
Nate = 4h

Rapid onset, short duration = useful for administration just before meals to control post-prandial levels - NOT useful in controlling basal levels

27
Q

Excretion of Meglitinides?

A

Repa = 90% fecal, 8% renal
Nate = 83% renal, 10% fecal

28
Q

Side Effects of Meglitinides?

A

Hepatic Impairment Caution

29
Q

Advantage of Sulfonyureas and Meglitinides? Condition of use?

A

Glucose-dependent, so lower risk of hypoglycemia; functioning beta cells

30
Q

Mechanism of Action of alpha-glucosidase inhibitors?

A

Reversibly inhibit membrane bound alpha-glucosidase (amylase, maltase, sucrase, isomaltase), slowing down rise of glucose after a meal

30
Q

PK of Acarbose
a) Route of Administration
c) Metabolism
d) Half Life
e) Duration of Action
f) Excretion

A

a) oral
c) intestinal bacteria & digestive enzymes
d) 2h
e) 2-4h
f) fecal

30
Q

Side Effects of Acarbose?

A

Gaseous distention due to glucose in colon = flatulence

NO in GI diseases, renal, hepatic diseases

31
Q

Disadvantage of Acarbose?

A

Lower Efficiacy (only works when eating)
Poorer tolerance

32
Q

Examples of Incretins and their normal actions? What are they inhibited by?

A

GIP & GLP-1
GIP: Expansion of beta cell mass + insulin secretion
GLP-1: Delayed gastric emptying, satiety = less eating = less glucose; expansion of beta cell mass + insulin secretion

Inhibited by DPP4

33
Q

Types of Incretin Based Therapies?

A
  1. DPP4 Inhibitors (Sitagliptin, Vildagliptin, Linagliptin)
  2. GLP-1 Agonists (Exenatide, Liraglutide)
34
Q

What class of drug is administered by SubCu injection?

A

GLP-1 Agonists.

35
Q

Side Effects of DPP4 Inhibitors?

A
  1. GI
  2. Flu like symptoms
  3. skin rash
  4. caution in pancreatitis
36
Q

Side Effects of GLP-1 Agonists?

A
  1. GI Effects
  2. Caution in Pancreatitis
37
Q

Advantages of GLP-1 Agonists?

A
  1. Low risk of hypoglycemia - insulin secretion stops as euglycemia approaches
  2. Weight Loss
  3. Good for CVS
38
Q

Access-related limitation of incretin based therapy?

A

Expensive

39
Q

Examples of SGLT2 inhibitors?

A
  1. Empaglifozin
  2. Canaglifozin
  3. Dapaglifozin
40
Q

Additional benefit of SGLT2 inhibitors??

A

CVS effects

41
Q

Side Effects of SGLT2 inhibitors?

A
  1. UTI
  2. Lower Limb Amputation
  3. DKA
  4. Increased urination
42
Q

Factors to consider when planning treatment regimen?

A
  1. Risk of Hypoglycemia
  2. Co-morbidities
  3. Degree of hyperglycemia
  4. Weight
  5. Access to Treatment
  6. Patient Preferences

Endocrine (6 decks)

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