Diabetes Mellitus Flashcards
(73 cards)
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
2
Q
Outline insulin release
A
- secreted by B cells in pancreas
- in response to increase [glucose] + incretins
- parasympathetic response M3
3
Q
What is insulin release inhibited by?
A
- Decreased [glucose]
- Cortisol
- (Sympathetic response a2)
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
5
Q
What is the half life of insulin?
A
5 minutes in plasma
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
7
Q
What does HbA1c measure?
A
- Percentage of RBCs with ‘sugar coating’
- Reflects average blood sugar over3 months
- in mmol/mol
8
Q
Why is insulin secreted in blood even during fasting
A
Prevents down regulation of receptors
9
Q
Why is insulin routinely administer s.c and not p.o?
A
It is a protein - to avoid digestion in gut
10
Q
What is human insulin made from?
A
Recombinant DNA
Enzymatic modification of porcine
11
Q
What ways are insulin preparations made for slow absorption?
A
- protamine / zinc complex with natural insulin
- soluble insulin form hexamers
- insulin analogues
12
Q
Reason for rotating site of insulin administration
A
To limit lipodystrophy
13
Q
Affect of insulin analogies on pharmacokinetics + pharmacodynamics
A
- changes PK
- doesnt change PD
14
Q
List the insulin types from fastest acting to slowest
A
- insulin aspart
- soluble insulin
- NPH
- insulin glargine
15
Q
What are adverse effects of insulin?
A
Hypoglycaemia
Lipodystrophy
16
Q
How should insulin be prescribed?
A
By brand name
17
Q
Contraindications of insulin
A
Renal impairment
Hypoglycaemia risk
18
Q
What are the important drug drug interactions of insulin
A
- Dose needs to be increased with systemic steroids
- other hypoglycaemic agents
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
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
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
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
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
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
25
What are combination insulins?
Examples
Contains rapid acting + intermediate acting insulins
*humalog 25*
*humalog 50*
*novomix 30*
26
What is diabulimia?
When a type 1 diabetic stops or reduces their insulin to control their weight
27
Differentiate between [glucose] and HbA1c?
- **[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
28
Do you need to increase or decrease insulin in a patient with renal impairment?
**decrease**
Due to reduced renal clearance of insulin > hypoglycaemic risk
29
What is the first line drug treatment of diabetes mellitus?
Metformin
30
Example of biguanides
Metformin
31
What is the mechanism of action of metformin?
- **decrease hepatic glucose production by inhibition gluconeogensis**
- some gluconeogenic activity remain to reduce hypoglycaemic risk
- suppresses appetite > limits weight gain
32
What class of drug is metformin?
Biguanides
33
What are adverse drug effects of metformin?
GI upset - nausea, vomiting, diarrhoea
Lactic acidosis
34
What are important drug drug interactions of metformin?
- drugs that can impair renal function *e.g. ACEi, diuretics, NSAIDs*
- loop + thiazide like diuretics > increase glucose
35
Example of sulfonylureas
Gliclazide
36
What is the mechanism of action for sulfonylureas?
- **simulate B cell pancreatic insulin secretion**
- block ATP dependent K+ channels
- work at low [glucose]
- need residual pancreatic function to work
37
What are adverse effects of sulfonylureas?
- GI upset - N+V, diarrhoea
- hypoglycaemia
- weight gain + increased appetite
- SIADH
38
What are contraindications of sulfonylureas?
Hepatic + renal disease
Risk of hypoglycaemia
39
What are important drug drug interactions of sulfonylureas?
- Other hypoglycaemic agents
- Loop + thiazide diuretics - increase glucose so an reduce SU action
40
Examples of glitazones
Pioglitazone
Rosiglitazone
41
What is the mechanism of action of glitazones?
- Insulin sensitisation in muscle + adipose
- decrease hepatic glucose output by activating PPAR-y > gene transcription
- g**LIT**azone in the p**PAR(*t*)-y**
42
What are adverse effects of glitazones?
- weight gain
- GI upset
- fluid retention
- fractures
- bladder cancer
43
What are the contradictions of glitazones?
Heart failure due to fluid retention
44
What are the important drug drug interactions with glitazones?
Other hypoglycaemic agents
45
Uses of SGLT-2 inhibitors
- type II DM as add on
- HFrEF
46
Examples of SGLT2 inhibitors
Dapagliflozin
Empagliflozin
47
What is the mechanism of action of SGLT-2 inhibitors (gliflozins)?
- **competitive reversible inhibition of SGLT2 in PCT**
- decrease glucose absorption from tubular filtrate
- increase glucose excretion
48
What are adverse effects of SGLT2 inhibitors (gliflozins)
- UTI
- Genital infection
- thirst + polyuria
- pancreatitis
49
What are contradincations of SGLT2 inhibitors (gliflozins)?
Hypovolaemia
DKA
50
What are important drug drug interactions of SGLT2 inhibitors (gliflozins)
Antihypertenives
Other hypoglycaemic agents
51
Physiological effect of GLP1
- 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
What is GLP-1?
Glucagon like peptide-1
53
Examples of dipeptidyl peptidase 4 inhibitors (gliptins)?
Sitagliptin
Saxagliptin
54
What is the mechanism of action of dipeptidyl peptidase 4 inhibitors (gliptins)?
Prevent incretin degradation > increase plasma incretin conc. > insulin release
55
Why do gliptins have a low hypoglycaemia risk?
Do not stimulate insulin secretion at normal plasma glucose
56
What are adverse effects dipeptidyl peptidase 4 inhibitors (gliptins)?
- GI upset
- small pancreatitis risk
57
What are contraindications of dipeptidyl peptidase 4 inhibitors (gliptins)?
Pregnancy
History of pancreatitis
58
What are important drug drug interactions of dipeptidyl peptidase 4 inhibitors (gliptins)?
- Other hypoglycaemic agents
- loop + thiazide like diuretics > increase glucose
59
Examples of GLP1 receptor agonists (incretin mimetics)?
Exanatide
Liraglutide
Semaglutide
60
What is the suffix of GLP1 receptor agonists (incretin mimetics)?
-tide
61
What is the mechanism of action of GLP1 receptor agonist (incretin mimetics)?
- increase glucose dependent synthesis of insulin secretion from B cells
- activate GLP1 receptor
62
Adverse side effects of GLP1 receptors agonists (incretin mimetics)
- GI upset
- decreased appetite with weight loss
63
What are contraindications of GLP1 receptor agonists (incretin mimetics)?
Renal impairment
64
What are important drug drug interactions of GLP1 receptor agonists (incretin mimetics)?
Other hypoglycaemic agents
65
Blood glucose levels for:
- normal
- prediabetes
- diabetes
- **normal**: 5.6mmol/L
- **prediabetes**: 5.6-6.9mmol/L
- **diabetes**: >7mmol/L
66
What is lipodystrophy?
Syndrome which causes a person to lose fat from an area of the body whilst gaining it in others
67
List drug classes used in DM treatment
- biguanide
- Sulfonylurea
- SGLT-2 inhibitors
- incretin mimetics/GLP1 agonists
- gliptins/dipeptidul peptidase inhibitors
- Glitazones
68
What are key things to inform a patient of during insulin prescribing (safe insulin prescribing)?
- 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
Symptoms of hypoglycaemia
- sweaty
- shaky
- confused
- increased appetite
- dizzy
70
What should someone do if they are hypoglycaemic?
Drink a sugary drink *e.g. apple/orange juice* then eat a simple carb
Do not drive
71
What antidiabetic drugs have a hypoglycaemic risk?
Insulin
Gliclazide
72
What adjustment should be made to insulin dosage when taking systemic steroids + why?
Insulin should be increased
Steroids increase blood glucose levels
73
At what eGFR should metformin be stopped?
Below 30ml/min
