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PR3152 Endocrine sys > Diabetes Mellitus > Flashcards

Diabetes Mellitus Flashcards

1
Q

Describe the implications of renal impairment on SGLT2i dosing.

A

If purely for glycemic control:
Do not initiate dapa or empa if eGFR <45 mL/min
Discontinue if eGFR <45 mL/min

If for cardiorenal benefit:
Do not initiate dapa if <25 mL/min
Do not initiate empa if <20 mL/min
Discontinue if dialysis is initiated

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2
Q

What is the recommended dosing regimen for liraglutide?

A

Ini: 0.6 mg once daily
Titration: Increase to 1.2 mg one daily after 1 week
Max: 1.8 mg once daily

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3
Q

Describe the MOA of SGLT2i.

A

Inhib SGLT on PCT of renal tubules, inhib Na and glucose reabsorption
Increase threshold of renal tubule for glucose, increase clearance of glucose in urine

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4
Q

What are the DDI associated with sulfonylureas?

A

BB - mask the symptoms of hypotension
Disulfiram like rxn w alc - facial flushing, skip dose if drinking a lot
CYP2C9 inhib (e.g. amiodarone, fluoxetine) - may increase glipizide and glimepiride

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5
Q

What are the special considerations for SGLT2i?

A

Beneficial in CKD

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6
Q

Describe the ADME of DPP4i.

A

A (sitagliptin):
- Good PO F ~87%

D (sitagliptin):
- t1/2: 10-12h

M (sitagliptin):
- Low liver meta

E (sitagliptin):
- 80% xcre unchanged in urine, rest in faeces

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7
Q

Name the biguanides.

A

Metformin

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8
Q

What is the recommended dosing regimen for tolbutamide?

A

Strength: 500
Ini: 1-2g once daily or 500 mg - 1g BD (more GI tolerable)
Max: 3g once daily

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9
Q

What are the CV effects of GLP-1?

A

All SC/IM hv ASCVD benefits
All neut for HF

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10
Q

What are the CV effects of biguanides?

A

Reduced CV events

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11
Q

What are the side effects of alpha glucosidase inhibitors?

A

GI: flatulence, abdo pain, diarrhoea
Elevated LFT

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12
Q

What are the CV effects of thiazolidinediones?

A

Decreased stroke but increased HF

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13
Q

Name the DPP-4 inhibitors.

A

Sitagliptin
Linagliptin
Vidagliptin

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14
Q

Describe the MOA of sulfonylureas.

A

Primary: Binds to and inhibits the sulfonylurea protein subunit on ATP dependent K+ channels of pancreatic beta cells.
Inhib K+ efflux
Triggers Ca dep exocytosis of insulin granules from pancreatic beta cells

Secondary: Decreases hepatic glucose pdtn (gluconeogenesis), increase glucose uptake by muscles and adipose tissue

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15
Q

What are the side effects of thiazolidinediones?

A

Hepatotoxicity
Fluid retention - caution/CI in H
Bone fracture - women higher risk
Wt gain - dose related
Risk of bladder cancer
Mild hypoglycemia w insulin

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16
Q

What is the recommended dosing regimen for gliclazide?

A

Gliclazide immediate release
Strength: 80 mg
Ini: 80 mg once daily (doses >120 mg shld be taken BD)
Max: 320 mg daily (160 mg BD)

Gliclazided modified release
Strength: 60 mg
Ini: 30-120 mg once daily

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17
Q

What is the glucose lowering effect of alpha glucosidase inhibitor?

A

Decrease A1c by 0.5-0.8%
FPG: None
PPG: Moderate

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18
Q

What are the special considerations of sulfonylureas?

A

Relies on fning pancreatic beta cells
Not reco in pregnancy
CI in BB, sulfonamide allergy

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19
Q

What are the DDI associated with thiazolidinediones?

A

CYP3A4 and CYP2C8 inducers or inhibitors

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20
Q

What are the DDI associated with GLP-1 agonists?

A

-

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21
Q

What are the DDI associated with alpha glucosidase inhibitors?

A

Intestinal adsorbents and digestive enzyme preparations

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22
Q

What are the side effects of GLP-1 agonists?

A

Thyroid T cell cancer
Headache
NV (must counsel!!)
Acute pancreatitis
Acute cholecystitis
Injection site rxns

Liraglutide: +diarrhoea, constipation

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23
Q

What is the glucose lowering effect of DPP4-i?

A

Decrease A1c by 0.5-0.8%
FPG: Low
PPG: Moderate

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24
Q

Describe the MOA of meglitinides.

A

Binds to a different site on the sulfonylurea protein rece of the ATP dep K+ channel on pancreatic beta cells.
Stim insulin secre

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25
Q

What is the glucose lowering effect of thiazolidinediones?

A

Decrease A1c by 0.5-1.4%
FPG: Moderate
PPG: Moderate

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26
Q

What is the glucose lowering effect of sulfonylureas and meglitinides?

A

Decrease A1c by 1.5%
FPG: Low
PPG: Marked

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27
Q

What is the recommended dosing regimen for semaglutide SC/IM?

A

Ini: 0.25 mg once weekly
Titration: Increase to 0.5 mg once weekly after 4 weeks
Max: 1 mg once weekly

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28
Q

What is the glucose lowering effect of metformin?

A

Decrease A1c by 1.5-2%
FPG: Marked
PPG: Low

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29
Q

What are the special considerations for DPP4i?

A

Dose adjustment in renal impairment
CI in liver impairment
CI in Hx of acute pancreatitis

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30
Q

What is the recommended dosing regimen for linagliptin?

A

Ini: 5 mg once daily

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31
Q

Name the thiazolidinedione.

A

Pioglitazone

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32
Q

Describe the MOA of biguanides.

A

Primary: Inhibit hepatic glucose pdtn (gluconeogenesis)

Secondary: Increase uptake of glucose uptake by peripheral, muscle

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33
Q

What is the recommended dosing regimen for pioglitazone?

A

Strengths: 15, 30
Ini: 15 mg once daily
Titrate: Increase by 15 mg Q4-12 weeks
Max: 45 mg once daily

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34
Q

Name the alpha glucosidase inhibitor.

A

Acarbose

35
Q

What is the recommended dosing regimen for vidagliptin?

A

Ini: 50 mg BD (if w metformin or TZD) or 50 mg once daily (if w SU)

36
Q

What are the special considerations of biguanides?

A

Safe in pregnancy and children >=10y
CI in renal insufficiency (accum, longer t1/2)
Beneficial in ASCVD
CI in hypoxic states e.g. HF, sepsis respi failure, liver impairment, alcoholism, >=80y

37
Q

Name the GLP-1 agonists.

A

Liraglutide, Dulaglutide, Semaglutide

38
Q

Describe the ADME of SGLT2i.

A

A (empagliflozin):
- Good PO F, 60-80%
- Cmax: 1-2h

D (empagliflozin):
- t1/2: 12h
- Highly plasma protein bound ~90%

M (empagliflozin):
- Minimal meta by liver (glucuronidation)

E (empagliflozin):
- 40% unchanged in faeces
- 27% unchanged in urine

39
Q

What are the special considerations of thiazolidinediones?

A

Avoid in pregnancy (limited data)
CI in hepatic failure, active liver disease
Beneficial for NFALD, NASH
CI in symptomatic or Hx of HF
CI in Hx of bladder cancer
Neut in diabetic kidney disease progression

40
Q

Describe the MOA of alpha glucosidase inhib.

A

Competitively inhib alpha glucosidase enzyme which breaks down complex carbohydrates at the intestinal brush border
Delayed glucose absorption, decrease in PPG.

41
Q

Describe the implication of renal impairment on GLP-1 agonist dosing.

A

No renal dose adjustment is required for the 4 agents learnt in PR3152

42
Q

Describe the ADME of alpha glucosidase inhib.

A

D: Onset rapid w each meal
Elim: 50% via faeces as unabsorbed drug

43
Q

Describe the implications of renal impairment on DPP4i dosing.

A

Linagliptin does not require dosage adjustment with renal impairment.

Sitagliptin
If CrCL >=30-44 mL/min/1.73m^2: 50 mg once daily
If CrCL < 30 mL/min/1.73m^2: 25 mg once daily

Vidagliptin
If CrCL >= 50mL/min: 50 mg BD
If CrCL <50 mL/min: 50 mg once daily

44
Q

Describe the ADME of sulfonylureas.

A

A:
- Good PO F
- Glipizide - F>95% (delayed w food intake), onset of action: 0.5h, duration of action: 12-24h

D (Glipizide):
- ~99% plasma protein binding
- t1/2: 2-4

M (Glipizide):
- Hepatic 90%

E:
- Tolbutamide, glipizide and glimepiride are predom hepatic elim while the rest are renal dominany
- Glibenclamide: 50-50
- Glipizide: <10% xcre unchanged in urine & faeces

45
Q

What is the recommended dosing regimen for Dapagliflozin?

A

Strengths: 5, 10 mg
Ini: 5 mg once daily w or without food
Max: 10 mg once daily

46
Q

Which anti-diabetics are associated with weight changes?

A

Wt gain: Sulfonylureas, meglitinides

Wt loss: SGLT2i, GLP-1

47
Q

What is the recommended dosing regimen for semaglutide PO?

A

Ini: 3 mg once daily 30 min before first meal of day
Titration: Increase to 7 mg once daily after 30d
Max: 14 mg once daily

48
Q

Describe the MOA of GLP-1 agonists.

A

GLP-1 are agonists. Bind to glucagon rece –> stim activation of adenylyl cyclase
Increased cAMP –> increased activation of PKA
Increased insulin release
Increase glucose uptake
Decrease alpha cell mediated glucagon release –> decreased hepatic glucose pdtn (gluconeogenesis)
Decreased glycogenolysis
Increased glycogenesis

49
Q

Name the sulfonylureas.

A

1st gen: Tolbutamide
2nd gen: Glipizide, gliclazide, glibenclamide
3rd gen: Glimepiride

50
Q

Name the meglitinides.

A

Nateglinide
Repaglinide

51
Q

What are the DDI associated with SGLT2i?

A

-

52
Q

What are the classes of anti-diabetic medication?

A

Biguanides
Thiazolidinediones
Sulfonylureas
Meglitinides
Dipeptidyl peptidase-4 inhib (DPP-4 inhib)
SGLT2i
Alpha glucosidase inhib
Glucagon-like peptide-1 (GLP-1) agonist
Insulin

53
Q

What are the side effects of biguanides?

A

GI - NV, diarrhoea, dyspepsia, flatulence, abdo pain, metallic taste, LOA
(Transient, take w food to reduce side effects)

B12 deficiency - increases the risk of malabsorption

Lactic acidosis - decreases clearance/increases production of lactate in body

54
Q

What is the recommended dosing regimen for glimepiride?

A

Strengths: 1, 2, 4
Ini: 1-4 mg once daily
Max: 8 mg once daily

55
Q

What are the DDI associated with biguanides?

A

Alc - increased risk of lactic acidosis
Iodinated contrast medium - may cause worsening renal fn, withhold 48h after, restart when renal fn stable
Cationic transporters (e.g. cimetidine, dolutegravir) - may increase metformin by reducing renal elim

56
Q

What are the special considerations for GLP-1 agonists?

A

CI in Acute pancreatitis or Hx of pancreatitis
CI in thyroid T cell cancers
CI in pregnancy
Does not cause hypoglycemia
Minimal CKD effects on decreasing microalbuminuria

Semaglutide (PO):
- Take on empty stomach for better F, 30min before any food or other meds.
- No more than 120mL of water
- SNAC req alkaline env

57
Q

What is the recommended dosing regimen for dulaglutide?

A

Ini: 0.75 mg once weekly
Titration: Increase by 1.5 mg once weekly after 4 weeks
Max: 3.0 mg or 4.5 mg once weekly

58
Q

What are the CV effects of alpha glucosidase inhibitors?

A

Neutral

59
Q

Describe the MOA of DPP-4i.

A

Inhib DPP-4 enzyme responsible for the breakdown of GLP-1
More GLP-1 in circulation
Increase gastric emptying time, feel fuller, eat less
Stim insulin release
Increase glucose uptake
Decrease alpha cell mediated glucagon release –> decrease hepatic glucagon pdtn (gluconeogenesis)
Decrease glycogenolysis
Increase glycogenesis

60
Q

What is the glucose lowering effect of SGLT2i?

A

Decrease A1c by 0.8-1.0%
FPG: Moderate
PPG: Low

61
Q

What are the side effects of DPP4-i?

A

Severe joint pains
Headache
Acute pancreatitis
Hypersensitivity
Dermatologic rxns: bullous pemphigold, skin rash, pruritus

62
Q

What is the recommended dosing regimen for metformin?

A

Metformin immediate release
Strengths: 250, 500, 850, 1000 mg
Ini: 500-850 mg once daily
Titration: Increase by 500-850 mg Q1-2 weeks in divided doses
Max: 2500-2550 mg (850 mg TDS)

Metformin extended release
Strengths: 500, 750, 1000 mg
Ini: 500 mg once daily
Titration: Increase by 500 mg weekly
Max: 2000 mg once daily or 1000 mg BD if once daily dosing doesnt achieve adequate blood glucose lowering. If >2000 mg needed, opt for immediate release

63
Q

What are the principles of diabetes management?

A
  1. Screening
  2. Diagnosis
  3. Diabetes management
  4. Management of hypoglycemia
  5. Management of ASCVD (HTN, dyslipidemia, CKD, DKD)
  6. Screening for complications
  7. Adjunctive antiplatelet therapy
  8. Preventative immunisation
64
Q

What are the CV effects of SGLT2i?

A

Empagliflozin and canagliflozin decreases ASCVD risk
All beneficial for HF

65
Q

What is the recommended dosing regimen for glibenclamide?

A

Strength: 1.25, 2.5, 5
Ini: 2.5 mg once daily to BD
Max dose: 10 mg BD

66
Q

Describe the ADME of GLP-1 agonists (e.g. Liraglutide)?

A

A:
- Given SC once daily
- F ~55%

D:
- C16 FA binds to plasma protein
- t1/2: 13h

M: non-organ specific peptidases ~ other polypeptides

E: Little or none xcre unchanged

67
Q

What are the CV effects of DPP4i?

A

Neutral

68
Q

What are the side effects of sulfonylureas and meglitinides?

A

Hypoglycemia - glipizide < others
Wt gain (2-5kg)

Meglitinides: Elevated LFTs (rare)

69
Q

What is the recommended dosing regimen for glipizide?

A

Strengths: 5, 10
Ini: 2.5-5 mg once daily (UptoDate)
Titration: Increase by 2.50-5 mg Q1-4 weeks
Labelled max: 40 mg once daily
Effective max: 20 mg once daily

70
Q

What is the glucose lowering effect of GLP-1 agonist?

A

Decrease A1c by 1-2%
FPG: Moderate
PPG: Marked

71
Q

What is the recommended dosing for alpha glucosidase inhibitors (acarbose)?

A

Strengths: 25, 50, 100
Ini: 25 mg BD-TDS (w each meal)
Titration: Increase by 25 mg/day Q2-4 weeks
Max: 150 mg daily (<=60kg) or 300 mg daily (>60kg)

72
Q

Name the SGLT2i.

A

Dapagliflozin
Empagliflozin
Canagliflozin

73
Q

What is the recommended dosing regimen for empagliflozin?

A

Strengths: 10, 25 mg
Ini: 10 mg every morning w or without food

74
Q

What is the recommended dosing regimen for canagliflozin?

A

Strengths: 100, 300 mg
Ini: 100 mg every morning before first meal of day
Max: 300 mg once daily (if eGFR>60 mL/min)

75
Q

Describe the ADME of thiazolidinediones.

A

D:
- Max effect up to a month

M:
- Hepatic

76
Q

What is the recommended dosing regimen for sitagliptin?

A

Ini: 100 mg once daily

77
Q

Describe the MOA of thiazolidinediones.

A

Peroxisome proliferator activated rece-gamma (PPAR-gamma) agonist

Stimulates uptake of glucose by muscles and adipose tissues

78
Q

Describe the ADME of biguanides.

A

A:
- Good PO F, 40-60%
- Duration of action: 8-12h

D:
- Rapidly distr
- Limited plasma protein binding
- t1/2: 3h
- Onset within days, max effect up to 2 weeks

M:
- No meta!!

E:
- 90% excre renally unchanged

79
Q

What are the side effects of SGLT2i?

A

Hypotension
Genital mycotic infection, UTI
Increased of diabetic ketoacidosis, esp euglycemic ketoacidosis
Fournier’s gangrene

Canagliflozin: increased risk of lower limb amputation, hyperkalemia, fractures

80
Q

What are the special considerations for alpha glucosidase inhibitors?

A

CI in GI diseases (obstruction, IBD)
CI in liver cirrhosis
Useful in carb rick diet
Mainly used to control PPG

81
Q

Which anti-diabetics are neutral for weight change?

A

Metformin, thiazolidindiones, DPP4-i, alpha glucosidase inhibitors

82
Q

What are the DDI associated with DPP4-i?

A

Sitagliptin: digoxin
Linagliptin: CYP3A4 inducers (reduce lina [ ])

83
Q

What are the CV effects of sulfonylureas and meglitinides?

A

Neutral

PR3152 Endocrine sys (11 decks)

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