Diabetes Mellitus Flashcards
Stepwise pharmacological management of diabetes mellitus
- 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
Outline insulin release
- secreted by B cells in pancreas
- in response to increase [glucose] + incretins
- parasympathetic response M3
What is insulin release inhibited by?
- Decreased [glucose]
- Cortisol
- (Sympathetic response a2)
What is the role of insulin?
- Decrease hepatic glucose output via inhibition of gluconeogenesis + glycogenolysis > increasing glycogen stores
- Promote uptake of glucose into muscle + adipose tissue
What is the half life of insulin?
5 minutes in plasma
What are the diagnosis factors of type 1 diabetes mellitus?
- Polyuria
- Polydipsia
- Weight loss
- HbA1c >48mmol/mol
- hyperglycaemia
- plasma or urine ketones
What does HbA1c measure?
- Percentage of RBCs with ‘sugar coating’
- Reflects average blood sugar over3 months
- in mmol/mol
Why is insulin secreted in blood even during fasting
Prevents down regulation of receptors
Why is insulin routinely administer s.c and not p.o?
It is a protein - to avoid digestion in gut
What is human insulin made from?
Recombinant DNA
Enzymatic modification of porcine
What ways are insulin preparations made for slow absorption?
- protamine / zinc complex with natural insulin
- soluble insulin form hexamers
- insulin analogues
Reason for rotating site of insulin administration
To limit lipodystrophy
Affect of insulin analogies on pharmacokinetics + pharmacodynamics
- changes PK
- doesnt change PD
List the insulin types from fastest acting to slowest
- insulin aspart
- soluble insulin
- NPH
- insulin glargine
What are adverse effects of insulin?
Hypoglycaemia
Lipodystrophy
How should insulin be prescribed?
By brand name
Contraindications of insulin
Renal impairment
Hypoglycaemia risk
What are the important drug drug interactions of insulin
- Dose needs to be increased with systemic steroids
- other hypoglycaemic agents
Outline the speed of action of basal bolus dosing
- bolus: rapid acting e.g. aspart
- basal: long acting e.g. glargine
- tries to mimic ‘normal’ insulin profile in non diabetic person
What are the different types of insulin?
Examples
- 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
How long does it take for rapid acting insulins to work + how long do they last?
Example
- start working after 10 mins
- last 4 hours
- novorapid
How long does it take for short acting insulins to work + how long do they last?
Example
- start working after 30 mins
- last for 8 hours
- actrapid
How long does it take for intermediate acting insulins to work + how long do they last?
Example
- start working after 1 hour
- last for 16 hours
- humulin I
How long does it take for long acting insulins to work + how long do they last?
Example
- start working in 1 hour
- last for 24+ hours
- levemir, lantus
What are combination insulins?
Examples
Contains rapid acting + intermediate acting insulins
humalog 25
humalog 50
novomix 30
What is diabulimia?
When a type 1 diabetic stops or reduces their insulin to control their weight
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
Do you need to increase or decrease insulin in a patient with renal impairment?
decrease
Due to reduced renal clearance of insulin > hypoglycaemic risk
What is the first line drug treatment of diabetes mellitus?
Metformin
Example of biguanides
Metformin
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
What class of drug is metformin?
Biguanides
What are adverse drug effects of metformin?
GI upset - nausea, vomiting, diarrhoea
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
Example of sulfonylureas
Gliclazide
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
What are adverse effects of sulfonylureas?
- GI upset - N+V, diarrhoea
- hypoglycaemia
- weight gain
What are contraindications of sulfonylureas?
Hepatic + renal disease
Risk of hypoglycaemia
What are important drug drug interactions of sulfonylureas?
- Other hypoglycaemic agents
- Loop + thiazide diuretics - increase glucose so an reduce SU action
Examples of glitazones
Pioglitazone
Rosiglitazone
What is the mechanism of action of glitazones?
- Insulin sensitisation in muscle + adipose
- decrease hepatic glucose output by activating PPAR-y > gene transcription
- gLITazone in the pPAR(t)-y
What are adverse effects of glitazones?
- GI upset
- fluid retention
- bladder cancer
- weight gain
What are the contradictions of glitazones?
Heart failure due to fluid retention
What are the important drug drug interactions with glitazones?
Other hypoglycaemic agents
Uses of SGLT-2 inhibitors
- type II DM as add on
- HFrEF
Examples of SGLT2 inhibitors
Dapagliflozin
Empagliflozin
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
What are adverse effects of SGLT2 inhibitors (gliflozins)
- UTI
- Genital infection
- thirst + polyuria
- pancreatitis
What are contradincations of SGLT2 inhibitors (gliflozins)?
Hypovolaemia
DKA
What are important drug drug interactions of SGLT2 inhibitors (gliflozins)
Antihypertenives
Other hypoglycaemic agents
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
What is GLP-1?
Glucagon like peptide-1
Examples of dipeptidyl peptidase 4 inhibitors (gliptins)?
Sitagliptin
Saxagliptin
What is the mechanism of action of dipeptidyl peptidase 4 inhibitors (gliptins)?
Prevent incretin degradation > increase plasma incretin conc. > insulin release
Why do gliptins have a low hypoglycaemia risk?
Do not stimulate insulin secretion at normal plasma glucose
What are adverse effects dipeptidyl peptidase 4 inhibitors (gliptins)?
- GI upset
- small pancreatitis risk
What are contraindications of dipeptidyl peptidase 4 inhibitors (gliptins)?
Pregnancy
History of pancreatitis
What are important drug drug interactions of dipeptidyl peptidase 4 inhibitors (gliptins)?
- Other hypoglycaemic agents
- loop + thiazide like diuretics > increase glucose
Examples of GLP1 receptor agonists (incretin mimetics)?
Exanatide
Liraglutide
Semaglutide
What is the suffix of GLP1 receptor agonists (incretin mimetics)?
-tide
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
Adverse side effects of GLP1 receptors agonists (incretin mimetics)
- GI upset
- decreased appetite with weight loss
What are contraindications of GLP1 receptor agonists (incretin mimetics)?
Renal impairment
What are important drug drug interactions of GLP1 receptor agonists (incretin mimetics)?
Other hypoglycaemic agents
Blood glucose levels for:
- normal
- prediabetes
- diabetes
- normal: 5.6mmol/L
- prediabetes: 5.6-6.9mmol/L
- diabetes: >7mmol/L
What is lipodystrophy?
Syndrome which causes a person to lose fat from an area of the body whilst gaining it in others
List drug classes used in DM treatment
- biguanide
- Sulfonylurea
- SGLT-2 inhibitors
- incretin mimetics/GLP1 agonists
- gliptins/dipeptidul peptidase inhibitors
- Glitazones
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
Symptoms of hypoglycaemia
- sweaty
- shaky
- confused
- increased appetite
- dizzy
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
What antidiabetic drugs have a hypoglycaemic risk?
Insulin
Gliclazide
What adjustment should be made to insulin dosage when taking systemic steroids + why?
Insulin should be increased
Steroids increase blood glucose levels
At what eGFR should metformin be stopped?
Below 30ml/min
