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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
What is the glucose lowering effect of thiazolidinediones?
Decrease A1c by 0.5-1.4% FPG: Moderate PPG: Moderate
26
What is the glucose lowering effect of sulfonylureas and meglitinides?
Decrease A1c by 1.5% FPG: Low PPG: Marked
27
What is the recommended dosing regimen for semaglutide SC/IM?
Ini: 0.25 mg once weekly Titration: Increase to 0.5 mg once weekly after 4 weeks Max: 1 mg once weekly
28
What is the glucose lowering effect of metformin?
Decrease A1c by 1.5-2% FPG: Marked PPG: Low
29
What are the special considerations for DPP4i?
Dose adjustment in renal impairment CI in liver impairment CI in Hx of acute pancreatitis
30
What is the recommended dosing regimen for linagliptin?
Ini: 5 mg once daily
31
Name the thiazolidinedione.
Pioglitazone
32
Describe the MOA of biguanides.
Primary: Inhibit hepatic glucose pdtn (gluconeogenesis) Secondary: Increase uptake of glucose uptake by peripheral, muscle
33
What is the recommended dosing regimen for pioglitazone?
Strengths: 15, 30 Ini: 15 mg once daily Titrate: Increase by 15 mg Q4-12 weeks Max: 45 mg once daily
34
Name the alpha glucosidase inhibitor.
Acarbose
35
What is the recommended dosing regimen for vidagliptin?
Ini: 50 mg BD (if w metformin or TZD) or 50 mg once daily (if w SU)
36
What are the special considerations of biguanides?
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
Name the GLP-1 agonists.
Liraglutide, Dulaglutide, Semaglutide
38
Describe the ADME of SGLT2i.
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
What are the special considerations of thiazolidinediones?
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
Describe the MOA of alpha glucosidase inhib.
Competitively inhib alpha glucosidase enzyme which breaks down complex carbohydrates at the intestinal brush border Delayed glucose absorption, decrease in PPG.
41
Describe the implication of renal impairment on GLP-1 agonist dosing.
No renal dose adjustment is required for the 4 agents learnt in PR3152
42
Describe the ADME of alpha glucosidase inhib.
D: Onset rapid w each meal Elim: 50% via faeces as unabsorbed drug
43
Describe the implications of renal impairment on DPP4i dosing.
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
Describe the ADME of sulfonylureas.
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
What is the recommended dosing regimen for Dapagliflozin?
Strengths: 5, 10 mg Ini: 5 mg once daily w or without food Max: 10 mg once daily
46
Which anti-diabetics are associated with weight changes?
Wt gain: Sulfonylureas, meglitinides Wt loss: SGLT2i, GLP-1
47
What is the recommended dosing regimen for semaglutide PO?
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
Describe the MOA of GLP-1 agonists.
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
Name the sulfonylureas.
1st gen: Tolbutamide 2nd gen: Glipizide, gliclazide, glibenclamide 3rd gen: Glimepiride
50
Name the meglitinides.
Nateglinide Repaglinide
51
What are the DDI associated with SGLT2i?
-
52
What are the classes of anti-diabetic medication?
Biguanides Thiazolidinediones Sulfonylureas Meglitinides Dipeptidyl peptidase-4 inhib (DPP-4 inhib) SGLT2i Alpha glucosidase inhib Glucagon-like peptide-1 (GLP-1) agonist Insulin
53
What are the side effects of biguanides?
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
What is the recommended dosing regimen for glimepiride?
Strengths: 1, 2, 4 Ini: 1-4 mg once daily Max: 8 mg once daily
55
What are the DDI associated with biguanides?
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
What are the special considerations for GLP-1 agonists?
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
What is the recommended dosing regimen for dulaglutide?
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
What are the CV effects of alpha glucosidase inhibitors?
Neutral
59
Describe the MOA of DPP-4i.
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
What is the glucose lowering effect of SGLT2i?
Decrease A1c by 0.8-1.0% FPG: Moderate PPG: Low
61
What are the side effects of DPP4-i?
Severe joint pains Headache Acute pancreatitis Hypersensitivity Dermatologic rxns: bullous pemphigold, skin rash, pruritus
62
What is the recommended dosing regimen for metformin?
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
What are the principles of diabetes management?
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
What are the CV effects of SGLT2i?
Empagliflozin and canagliflozin decreases ASCVD risk All beneficial for HF
65
What is the recommended dosing regimen for glibenclamide?
Strength: 1.25, 2.5, 5 Ini: 2.5 mg once daily to BD Max dose: 10 mg BD
66
Describe the ADME of GLP-1 agonists (e.g. Liraglutide)?
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
What are the CV effects of DPP4i?
Neutral
68
What are the side effects of sulfonylureas and meglitinides?
Hypoglycemia - glipizide < others Wt gain (2-5kg) Meglitinides: Elevated LFTs (rare)
69
What is the recommended dosing regimen for glipizide?
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
What is the glucose lowering effect of GLP-1 agonist?
Decrease A1c by 1-2% FPG: Moderate PPG: Marked
71
What is the recommended dosing for alpha glucosidase inhibitors (acarbose)?
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
Name the SGLT2i.
Dapagliflozin Empagliflozin Canagliflozin
73
What is the recommended dosing regimen for empagliflozin?
Strengths: 10, 25 mg Ini: 10 mg every morning w or without food
74
What is the recommended dosing regimen for canagliflozin?
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
Describe the ADME of thiazolidinediones.
D: - Max effect up to a month M: - Hepatic
76
What is the recommended dosing regimen for sitagliptin?
Ini: 100 mg once daily
77
Describe the MOA of thiazolidinediones.
Peroxisome proliferator activated rece-gamma (PPAR-gamma) agonist Stimulates uptake of glucose by muscles and adipose tissues
78
Describe the ADME of biguanides.
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
What are the side effects of SGLT2i?
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
What are the special considerations for alpha glucosidase inhibitors?
CI in GI diseases (obstruction, IBD) CI in liver cirrhosis Useful in carb rick diet Mainly used to control PPG
81
Which anti-diabetics are neutral for weight change?
Metformin, thiazolidindiones, DPP4-i, alpha glucosidase inhibitors
82
What are the DDI associated with DPP4-i?
Sitagliptin: digoxin Linagliptin: CYP3A4 inducers (reduce lina [ ])
83
What are the CV effects of sulfonylureas and meglitinides?
Neutral

PR3152 Endocrine sys (11 decks)

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