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Endocrine System > Management of Type II Diabetes > Flashcards

Management of Type II Diabetes Flashcards

1
Q

Why is metformin normally first choice?

A

Improves outcomes, well tolerated and cheap

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2
Q

What solution does metformin do?

A

Improves insulin action

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3
Q

Where does metformin work?

A

On the liver and muscles

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4
Q

What is the mechanism of action of metformin?

A

Biguanide
Improves insulin sensitivity - affects glucose production and decreases FA synthesis
Improves receptor function and inhibits gluconeogenic pathways

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5
Q

What is the half life of metformin?

A

6 hrs

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6
Q

What are the advantages of metformin?

A

Improves cardiovascular outcomes and mortality in obese
Efficacious
Normally well tolerated
Not associated with weight gain
HbA1c reduction
Also can be used in pregnancy
Cheap

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7
Q

What are the disadvantages of metformin?

A

GI side effects - diarrhoea and bloating
Risk of lactic acidosis by inhibiting lactic acid uptake by liver
Risk vitamin B12 malabsorption

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8
Q

What are some types of Sulphonylureas?

A

Glimepiride, Gliclazide and Glipizide
The Gli…ides

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9
Q

When are Sulphonylureas used?

A

If osmotic symptoms or HbA1c increasing rapidly titration based on home glucose monitoring

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10
Q

What is the solution of Sulphonylureas?

A

Increases insulin release - works on defected Beta cell function but lowers across all body

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11
Q

What is the mechanism of action of Sulphonylureas?

A

Binds to sulfonylurea receptor on functioning pancreatic beta cells
Binding closes the linked ATP sensitive potassium channels
Decreased influx - depolarisation of beta cell
Voltage gated Ca channels open - translocation and exocytosis of secretory granules of insulin

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12
Q

Describe glimepiride

A

1-6mg given daily
Metabolised by liver
60% renal excretion in 24 hrs
Actions lasts 12-24hrs

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13
Q

Describe gliclazide

A

40-320mg twice daily
Metabolised by liver
Less than 5% excretion in 24hrs
Action lasts 10-15hrs

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14
Q

Describe Glipizide

A

2.520mg twice daily
Metabolised by liver
90% excretion in 3 days
Action lasts 6-12 hrs

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15
Q

What are some drug interactions with Sulphonylureas?

A

Displace sulfonylureas from plasma proteins
Reduce hepatic sulfonylurea metabolism
Decrease urinary excretion of sulfonylureas or their metabolism
Intrinsic hypoglycaemic activity

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16
Q

What are the advantages of Sulphonylureas?

A

Rapid improvement in control
Rapid improvement if symptomatic
Rapid titration
Cheap
Generally well tolerated

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17
Q

What are the disadvantages of sulphonylureas?

A

Risk of hypoglycaemia
Weight gain
Caution in renal and hepatic disease
CI in pregnancy and breast feeding
Side effects - hypersensitivity and photosensitivity reaction, and blood disorders

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18
Q

What thiazolidinedione (glitazone) is used?

A

Pioglitazone

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19
Q

What is the solution of Pioglitazone?

A

Improves insulin action by acting on liver, adipose tissue and muscle

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20
Q

What is the mechanism of action of pioglitazone?

A

Selectively stimulates the nuclear receptor peroxisome proliferator activated receptor gamma and to lesser extent PPAR alpha
Modulates transcription of insulin sensitive genes

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21
Q

What is the action of Pioglitazone?

A

Reduces insulin resistance in liver and peripheral tissues, increases expense of insulin dependant glucose, decreases withdrawal of glucose from liver, and reduces quantity of glucose, insulin and glycated haemoglobin

22
Q

What are the advantages of Pioglitazone?

A

Good if people are insulin resistance is significant
HbA1c reduced by 0.6-1.3%
Cheap
Cardiovascular safety

23
Q

What are the disadvantages of Pioglitazone?

A

Increase risk of bladder cancer
Fluid retention - CCF
Weight gain
Fractures in females

24
Q

When is insulin used in T2D?

A

Progressive relative insulin deficiency
Use may become inevitable

25
Q

Describe supplementary insulin therapy

A

Easy introduction to insulin
Low risk of hypoglycaemia
Possible weight gain

26
Q

When is isophane insulin given?

A

Humulin I or H insulatard
Once daily injection
Usually at bedtime

27
Q

What are some gliflozins (SGLT2 inhibitors)?

A

Canagliflozin, Dapagliflozin and Empagliflozin

28
Q

What is the solution of gliflozins?

A

Increase excretion of glucose in urine as majority of glucose is reabsorbed by SGLT2 in proximal tubule - selectively inhibit receptors

29
Q

What are the SGLT2 inhibitor effects?

A

Gets rid of glucose - lowers HbA1c
Gets rid of water - hypotension and dehydration
Gets rid of calories - lose weight with same intake
Gets rid of sodium - lowers systolic blood pressure
Greater risk of urogenital infection

30
Q

Describe SGLT2 inhibitors and CV safety

A

Reduces CV outcomes and mortality

31
Q

Describe renal outcomes with canagliflozin

A

Reduction in renal outcomes like end stage kidney disease and mortality

32
Q

Describe dapagliflozin and heart failure

A

Reduces HF and its outcomes/ mortality

33
Q

Describe Canagliflozin

A

100mg once daily
Do not start if eGFR under 30
On GJF

34
Q

Describe Empagliflozin

A

10mg once daily
Without CV disease then don’t start if eGFR is under 60 and if under 40 with CV disease then stop
On GJF

35
Q

Describe dapagliflozin

A

10mg once daily
Do not start if eGFR is under 15
On GJF

36
Q

When is SGLT2 inhibitors used?

A

2nd line is those with high CV risks
1st line in those whose CV risk is high but metformin not tolerated
Check if increased risk of DKA

37
Q

What are the advantages of SGLT2 inhibitors?

A

Weight loss
No risk of hypoglycaemia
Good effects on glycaemic control
Beneficial effect for CV and renal outcomes
2nd or 3rd line agent
Can add to insulin regimens

38
Q

What are the disadvantages of SGLT2 inhibitors?

A

Expensive
Side effects - UTI, fungal infections and osmotic agents
Risk of digital amputation
Risk of DKA
Cl in pregnancy and breast feeding
Don’t use in renal impairment

39
Q

What are incretin mimetics?

A

GLP1 - gliptins
DPPIV - tides
There is diminished incretin effect if have T2D

40
Q

What are types of DPPIV inhibitors?

A

Gliptins
Saxagliptin, sitagliptin and vildagliptin

41
Q

What is the solution of incretin mimetics?

A

Increase insulin release

42
Q

What is the mode of action of gliptins?

A

DPP4 inhibitors that delay the breakdown of incretins and thereby increase active incretin levels
Increase of incretins - increase insulin and decreases glucagon so decreases glucose

43
Q

What are the advantages of DPPIV inhibitors?

A

Usually well tolerated
Can be used as 2nd or 3rd line agents
Can be used in renal impairment
No risk of hypoglycaemia
Weight neutral

44
Q

What are the disadvantages of DPPIV inhibitors?

A

Relatively small effects on glycaemic control
CI in pregnancy and breastfeeding
Nausea

45
Q

What are some GLP-1 analogues?

A

Tides
Exenatide, Liraglutide and Lixisenatide

46
Q

What is the mode of action for GLP1 analogues?

A

Injectable analogues of GLP1 - resistant to enzyme degradation and greatly prolonged biological half life
Release incretin gut hormones so increase insulin and decrease glucagon

47
Q

What are the guidelines for GLP1 analogues?

A

BMI<35
Stop after 6/12 unless HbA1c -1% and weight -3%
3rd line agent
Can be in combination with oral agents and/ or basal insulin

48
Q

What are the advantages of GLP-1 analogues?

A

Weight loss
No risk of hypoglycaemia
3rd line agent
Can be used with basal insulin
Some have benefit for CV disease

49
Q

What are the disadvantages of GLP-1 analogues?

A

Injection
Expensive
Cl in pregnancy and breastfeeding
Nausea and vomiting

50
Q

What medication is given first line not at high CV risk?

A

Metformin

51
Q

What medication is given if chronic heart failure or established atherosclerotic CVD?

A

Metformin
As soon as metformin is tolerable then SGLT2 inhibitor and if metformin contraindicated then SGLT2 inhibitor alone
Same for high risk CVD

52
Q

What is considered if metformin is contraindicated?

A

DPP4 inhibitors - gliptins
Pioglitazone
Sulfonylurea
SGLT2 inhibitor for some people

Endocrine System (23 decks)

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