Diabetes Mellitus Flashcards

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1
Q

Stepwise pharmacological management of diabetes mellitus

A
  • first line: metformin
  • add SGLT-2 inhibitor once settled on metformin if existing CVD or heart failure
  • second line: add sulfonylurea, pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor
  • third line: triple therapy (*metformin + 2 second line drugs) | insulin therapy
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2
Q

Outline insulin release

A
  • secreted by B cells in pancreas
  • in response to increase [glucose] + incretins
  • parasympathetic response M3
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3
Q

What is insulin release inhibited by?

A
  • Decreased [glucose]
  • Cortisol
  • (Sympathetic response a2)
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4
Q

What is the role of insulin?

A
  • Decrease hepatic glucose output via inhibition of gluconeogenesis + glycogenolysis > increasing glycogen stores
  • Promote uptake of glucose into muscle + adipose tissue
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5
Q

What is the half life of insulin?

A

5 minutes in plasma

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6
Q

What are the diagnosis factors of type 1 diabetes mellitus?

A
  • Polyuria
  • Polydipsia
  • Weight loss
  • HbA1c >48mmol/mol
  • hyperglycaemia
  • plasma or urine ketones
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7
Q

What does HbA1c measure?

A
  • Percentage of RBCs with ‘sugar coating’
  • Reflects average blood sugar over last 10-12 weeks
  • in mmol/mol
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8
Q

Why is insulin secreted in blood even during fasting

A

Prevents down regulation of receptors

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9
Q

Why is insulin routinely administer s.c and not p.o?

A

It is a protein - to avoid digestion in gut

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10
Q

What is human insulin made from?

A

Recombinant DNA
Enzymatic modification of porcine

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11
Q

What ways are insulin preparations made for slow absorption?

A
  • protamine / zinc complex with natural insulin
  • soluble insulin form hexamers
  • insulin analogues
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12
Q

Reason for rotating site of insulin administration

A

To limit lipodystrophy

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13
Q

Affect of insulin analogies on pharmacokinetics + pharmacodynamics

A
  • changes PK
  • doesnt change PD
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14
Q

List the insulin types from fastest acting to slowest

A
  • insulin aspart
  • soluble insulin
  • NPH
  • insulin glargine
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15
Q

What are adverse effects of insulin?

A

Hypoglycaemia
Lipodystrophy

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16
Q

How should insulin be prescribed?

A

By brand name

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17
Q

Contraindications of insulin

A

Renal impairment
Hypoglycaemia risk

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18
Q

What are the important drug drug interactions of insulin

A
  • Dose needs to be increased with systemic steroids
  • other hypoglycaemic agents
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19
Q

Outline the speed of action of basal bolus dosing

A
  • bolus: rapid acting e.g. aspart
  • basal: long acting e.g. glargine
  • tries to mimic ‘normal’ insulin profile in non diabetic person
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20
Q

What are the different types of insulin?
Examples

A
  • rapid acting insulins - novorapid
  • short acting insulins - actrapid
  • intermediate acting insulins - hummulin I
  • long acting insulins - levemir + lantus
  • combination insulins - humalog 25, humalog 50, novomix 30
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21
Q

How long does it take for rapid acting insulins to work + how long do they last?
Example

A
  • start working after 10 mins
  • last 4 hours
  • novorapid
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22
Q

How long does it take for short acting insulins to work + how long do they last?
Example

A
  • start working after 30 mins
  • last for 8 hours
  • actrapid
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23
Q

How long does it take for intermediate acting insulins to work + how long do they last?
Example

A
  • start working after 1 hour
  • last for 16 hours
  • humulin I
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24
Q

How long does it take for long acting insulins to work + how long do they last?
Example

A
  • start working in 1 hour
  • last for 24+ hours
  • levemir, lantus
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25
Q

What are combination insulins?
Examples

A

Contains rapid acting + intermediate acting insulins
humalog 25
humalog 50
novomix 30

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26
Q

What is diabulimia?

A

When a type 1 diabetic stops or reduces their insulin to control their weight

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27
Q

Differentiate between [glucose] and HbA1c?

A
  • [glucose]: immediate measure of glucose levels at that moment in time
  • HbA1c: % of RBCs with sugar coating - average blood sugar over last 10-12 weeks
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28
Q

Do you need to increase or decrease insulin in a patient with renal impairment?

A

decrease
Due to reduced renal clearance of insulin > hypoglycaemic risk

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29
Q

What is the first line drug treatment of diabetes mellitus?

A

Metformin

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30
Q

Example of biguanides

A

Metformin

31
Q

What is the mechanism of action of metformin?

A
  • decrease hepatic glucose production by inhibition gluconeogensis
  • some gluconeogenic activity remain to reduce hypoglycaemic risk
  • suppresses appetite > limits weight gain
32
Q

What class of drug is metformin?

A

Biguanides

33
Q

What are adverse drug effects of metformin?

A

GI upset - nausea, vomiting, diarrhoea

34
Q

What are important drug drug interactions of metformin?

A
  • drugs that can impair renal function e.g. ACEi, diuretics, NSAIDs
  • loop + thiazide like diuretics > increase glucose
35
Q

Example of sulfonylureas

A

Gliclazide

36
Q

What is the mechanism of action for sulfonylureas?

A
  • simulate B cell pancreatic insulin secretion
  • block ATP dependent K+ channels
  • work at low [glucose]
  • need residual pancreatic function to work
37
Q

What are adverse effects of sulfonylureas?

A
  • GI upset - N+V, diarrhoea
  • hypoglycaemia
  • weight gain
38
Q

What are contraindications of sulfonylureas?

A

Hepatic + renal disease
Risk of hypoglycaemia

39
Q

What are important drug drug interactions of sulfonylureas?

A
  • Other hypoglycaemic agents
  • Loop + thiazide diuretics - increase glucose so an reduce SU action
40
Q

Examples of glitazones

A

Pioglitazone
Rosiglitazone

41
Q

What is the mechanism of action of glitazones?

A
  • Insulin sensitisation in muscle + adipose
  • decrease hepatic glucose output by activating PPAR-y > gene transcription
42
Q

What are adverse effects of glitazones?

A
  • GI upset
  • fluid retention
  • bladder cancer
  • weight gain
43
Q

What are the contradictions of glitazones?

A

Heart failure due to fluid retention

44
Q

What are the important drug drug interactions with glitazones?

A

Other hypoglycaemic agents

45
Q

Uses of SGLT-2 inhibitors

A
  • type II DM as add on
  • HFrEF
46
Q

Examples of SGLT2 inhibitors

A

Dapagliflozin
Empagliflozin

47
Q

What is the mechanism of action of SGLT-2 inhibitors (gliflozins)?

A
  • competitive reversible inhibition of SGLT2 in PCT
  • decrease glucose absorption from tubular filtrate
  • increase glucose excretion
48
Q

What are adverse effects of SGLT2 inhibitors (gliflozins)

A
  • UTI
  • Genital infection
  • thirst + polyuria
  • pancreatitis
49
Q

What are contradincations of SGLT2 inhibitors (gliflozins)?

A

Hypovolaemia

50
Q

What are important drug drug interactions of SGLT2 inhibitors (gliflozins)

A

Antihypertenives
Other hypoglycaemic agents

51
Q

Physiological effect of GLP1

A
  • increased insulin secretion + biosynthesis
  • decreases glucagon secretion
  • decreases gastric emptying in stomach
  • increases satiety > reducing food intake
  • indirectly increases glucose uptake in muscle
  • indirectly decreases glucose production in liver
52
Q

What is GLP-1?

A

Glucagon like peptide-1

53
Q

Examples of dipeptidyl peptidase 4 inhibitors (gliptins)?

A

Sitagliptin
Saxagliptin

54
Q

What is the mechanism of action of dipeptidyl peptidase 4 inhibitors (gliptins)?

A

Prevent incretin degradation > increase plasma incretin conc. > insulin release

55
Q

Why do gliptins have a low hypoglycaemia risk?

A

Do not stimulate insulin secretion at normal plasma glucose

56
Q

What are adverse effects dipeptidyl peptidase 4 inhibitors (gliptins)?

A
  • GI upset
  • small pancreatitis risk
57
Q

What are contraindications of dipeptidyl peptidase 4 inhibitors (gliptins)?

A

Pregnancy
History of pancreatitis

58
Q

What are important drug drug interactions of dipeptidyl peptidase 4 inhibitors (gliptins)?

A
  • Other hypoglycaemic agents
  • loop + thiazide like diuretics > increase glucose
59
Q

Examples of GLP1 receptor agonists (incretin mimetics)?

A

Exanatide
Liraglutide
Semaglutide

60
Q

What is the suffix of GLP1 receptor agonists (incretin mimetics)?

A

-tide

61
Q

What is the mechanism of action of GLP1 receptor agonist (incretin mimetics)?

A
  • increase glucose dependent synthesis of insulin secretion from B cells
  • activate GLP1 receptor
62
Q

Adverse side effects of GLP1 receptors agonists (incretin mimetics)

A
  • GI upset
  • decreased appetite with weight loss
63
Q

What are contraindications of GLP1 receptor agonists (incretin mimetics)?

A

Renal impairment

64
Q

What are important drug drug interactions of GLP1 receptor agonists (incretin mimetics)?

A

Other hypoglycaemic agents

65
Q

Blood glucose levels for:
- normal
- prediabetes
- diabetes

A
  • normal: 5.6mmol/L
  • prediabetes: 5.6-6.9mmol/L
  • diabetes: >7mmol/L
66
Q

What is lipodystrophy?

A

Syndrome which causes a person to lose fat from an area of the body whilst gaining it in others

67
Q

List drug classes used in DM treatment

A
  • biguanide
  • Sulfonylurea
  • SGLT-2 inhibitors
  • incretin mimetics/GLP1 agonists
  • gliptins/dipeptidul peptidase inhibitors
  • Glitazones
68
Q

What are key things to inform a patient of during insulin prescribing (safe insulin prescribing)?

A
  • keep unopened pens in fridges + opened at room temp
  • expel 1 until of insulin before administration to remove air bubbles
  • rotate administration site
  • bin after 1 month of opening
  • teach injection techniques
  • encourage regular blood glucose checks + education on what valves mean
  • ensure correct type of insulin is used
  • education on hypoglycaemia - symptoms, managment + driving
69
Q

Symptoms of hypoglycaemia

A
  • sweaty
  • shaky
  • confused
  • increased appetite
  • dizzy
70
Q

What should someone do if they are hypoglycaemic?

A

Drink a sugary drink e.g. apple/orange juice then eat a simple carb
Do not drive

71
Q

What antidiabetic drugs have a hypoglycaemic risk?

A

Insulin
Gliclazide

72
Q

What adjustment should be made to insulin dosage when taking systemic steroids + why?

A

Insulin should be increased
Steroids increase blood glucose levels

73
Q

At what eGFR should metformin be stopped?

A

Below 30ml/min