T2DM pt 2 Flashcards

1
Q

Sitagliptin dosing

A

25, 50, or 100 mg po daily

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2
Q

Saxagliptin dosing

A

2.5 or 5 mg po daily

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3
Q

linagliptin dosing

A

5 mg po daily

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4
Q

alogliptin dosing

A

25 mg po daily

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5
Q

DPP-4 inhibitors advantages

A

administered orally
reduce hyperglycemia and HgbA1c
low risk of hypoglycemia
considered weight neutral (no significant weight loss, usually co-administered with weight loss drug)
available in combination with metformin

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6
Q

Januvia and Nesina are excreted in the?

A

urine, kidney

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7
Q

Tradjenta is excreted in the?

A

feces, liver

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8
Q

Onglyza is excreted in the?

A

urine, kidney

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9
Q

Januvia, Nesina, and Tradjenta metabolism

A

not extensively metabolize

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10
Q

Onglyza metabolism

A

CYP3A4/5 substrate, major metabolite is active

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11
Q

DPP-4 inhibitor side effects

A

N/V, constipation, headache, severe skin reactions, pancreatitis, joint pain, HF

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12
Q

DPP-4 on immune cells

A

off target effects that cause reduced white blood cell counts (infections) and a potential increased risk of cancers

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13
Q

Pramlintide

A

amylin analog
37 aa peptide, normally co-secreted with insulin

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14
Q

Pramlintide mechanism

A

slows gastric emptying, decreases food intake, and inhibits glucagon secretion, blunts postprandial rise in BG
Useful in both Type 1 and Type 2 diabetes

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15
Q

Pramlintide dosing

A

used in conjunction with insulin
injected SC

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16
Q

a-glucosidase inhibitor drugs

A

acarbose (Precise)
miglitol (Miglitol)

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17
Q

a-glucosidases

A

enzyme located in the intestinal brush border that is used to break down carbs into simple sugars (glucose)

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18
Q

a-glucosidase inhibitor mechanism

A

decrease the absorption of carbohydrate from the intestine via inhibition of gut a-glucosidases

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19
Q

a-glucosidase inhibitor place in therapy

A

taken orally with meals to reduce postprandial glucose surge

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20
Q

a-glucosidase inhibitor absorption

A

acarbose is only minimally absorbed
miglitol is completely absorbed

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21
Q

a-glucosidase inhibitor adverse effects

A

GI - diarrhea, nausea, flatulence
risk of liver damage at acarbose doses > 100 mg tid

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22
Q

SGLT2 inhibitor drugs

A

Canagliflozin (Invokana)
Dapagliflozin (Farxiga)
Empagliflozin (Jardiance)
Ertugliflozin (Steglatro)
Bexagliflozin (Benzavvy)

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23
Q

SGLT2 glucose transporter

A

located on the PCT, responsible for 90% of glucose reabsorption

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24
Q

SGLT2 inhibitor Mechanism

A

block the SGLT2 glucose transporter, increases urinary excretion of glucose

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25
Q

SGLT2 advantages

A

decreases A1c as monotherapy with metformin or sufonylureas
significant weight loss observed with monotherapy

26
Q

SGLT2 disadvantages

A

increased risk of genital/UT infections
increased urine flow/volume depletion/hypotension
increased risk of diabetic ketoacidosis (DKA)
increased risk of lower limb amputation
contraindicated in patients with renal impairment (eGFR>30ml/min/1.73m^2)

27
Q

SLGT2 inhibitor place in therapy

A

indicated for type 2 diabetics as an adjunct to diet and exercise
not used in type 1 diabetics (increased risk of DKA)

28
Q

Biguanides

A

Metformin (Glucophage)

29
Q

Thiazolidinediones

A

Pioglitazone (Actos)
Rosiglitazone (Avandia)

30
Q

Insulin resistance

A

decreased responsiveness to insulin

31
Q

insulin resistance characterized by

A

OGTT with prolonged elevation of plasma glucose with normal or elevated insulin levels

32
Q

causes of insulin resistance

A

polymorphisms in insulin signaling pathway proteins (rare)
obesity - especially accumulation of fat in the abdominal cavity
inactivity

33
Q

insulin resistance in skeletal muscle

A

impaired glucose uptake

34
Q

insulin resistance in adipose tissue

A

impaired glucose uptake
impaired inhibition of lipolysis
mobilization of FAs to other tissues

35
Q

insulin resistance in liver

A

impaired inhibition of glucose output (via gluconeogenesis or glycogenolysis)

36
Q

link between obesity and insulin resistance

A

free fatty acid (FFA) levels are increased in obese people
acute raising FFA levels cause insulin resistance (IR)
acute lowering of plasma FFA levels reduces chronic IR

37
Q

increase FFA and insulin resistance

A

Serine is phosphorylated instead of Tyrosine on IR and IRS proteins which inhibits signaling. This is promoted by FA uptake, lipid byproducts, and inflammatory mediators

38
Q

Metformin

A

classified as an anti hyperglycemic agent
decreases blood glucose concentrations in NIDDM without the concentration falling below normal

39
Q

biguanides advantages

A

rarely cause hypoglycemia
rarely cause weight gain

40
Q

Metformin Mechanism

A

activator of AMP-activated kinase (AMPK) increases the efficiency or sensitivity to insulin in liver (decreased gluconeogenesis, fat, and muscle cells (increased glycolysis, glucose uptake)

41
Q

metformin dosage

A

500-850 mg BID/TID before meals (to eliminate diarrhea)
can be used in combination with sulfonylureas

42
Q

metformin mechanism in the liver

A
  1. inhibits mitochondrial respiration via complex 1 inhibitiion
  2. increase in AMP:ATP ratio and ADP:ATP ratio which decreases the energy availability of the cell
  3. glucagon receptor is inhibited leading to decreased cAMP signal
  4. decreased cAMP signal effects many downstream signals leading to decreased lipid and cholesterol synthesis
  5. Increased AMP inhibits FBPase, an enzyme required in gluconeogenesis
  6. Decreased gluconeogenesis decreases glucose production
43
Q

Metformin contraindications

A

patients with disorders which increase the tendency towards lactic acidosis (occurs in patients with a hard time getting oxygen to the heart and lung tissues)

44
Q

Metformin mechanism in the skeletal muscle

A
  1. During exercise the skeletal muscle burns up ATP and causes a build up of AMP
  2. Build up of AMP during exercise activates AMPK
  3. AMPK phosphorylates TBC1D1/4 which promotes GTPase activity of Rab
  4. Rab dissociates from GLUT4, allowing translocation
45
Q

Metformin AEs

A

decreased vitamin B-12
GI discomfort (N/V/D)

46
Q

metformin effects on lipid profile

A

decreased serum triglycerides
decreased serum LDL
reduced risk of adverse CV events

47
Q

Canagliflozin dosing

A

100 or 300 mg daily

48
Q

dapagliflozin dosing

A

5 or 10 mg daily

49
Q

ertuglifloxin dosing

A

5 or 10 mg daily

50
Q

bexagliflozin dosing

A

20 mg daily

51
Q

empagliflozin dosing

A

10 or 25 mg daily

52
Q

Thiazolidinediones effect

A

decrease insulin resistance or improve target cell response to insulin

53
Q

Thiazolidinediones Mechanism

A

activates of peroxisome proliferator-activated receptor gamma (PPARy), a transcription factor

54
Q

TzDs effect in the liver

A

enhances glucose uptake
reduced hepatic glucose production

55
Q

TzDs effect in adipocytes

A

main target
- enhances adipocyte differentiation
- enhances FFA uptake into SC fat
- reduces serum FFA
- shifts lipids into fat cells from non-fat cells

56
Q

TzDs effect in skeletal muscle

A

enhances glucose uptake

57
Q

Rosiglitazone dosing

A

4-8 mg once daily

58
Q

Pioglitazone dosing

A

15-30 mg once daily

59
Q

TzDs contraindications

A

NYHA Class III/IV heart failure

60
Q

TzDs advantages

A

do not cause hypoglycemia

61
Q

TZDs disadvantages

A

Pioglitazone is associated with an increased risk of bladder cancer
both can cause some hepatoxicity (check liver function)