Thiazolidinediones (glitazones) Flashcards
Give 2 examples of glitazones
- Pioglitazone
- Rosiglitazone
What is the mechanism of action of glitazones?
Result in binding of a PPARy-complex to DNA, which causes transcription of genes whose products are involved in insulin signalling. Tissues also become more sensitive to insulin by recruiting glucose transports to cell surfaces. This reduces peripheral insulin resistance, leading to a reduction of blood glucose concentration
Are glitazones effective without insulin?
No
What is the result of glitazones only being effective in the presence of insulin?
They can only be used in patients who have endogenous insulin production or who inject insulin
What is the route of delivery of glitazones?
PO
What are the indications for glitazones?
Used in type 2 diabetes mellitus in the following ways;
- Single therapy
- Dual therapy
- Triple therapy
How are glitazones used in single therapy?
In overweight diabetic patients who cannot take metformin (contraindicated or not tolerated)
How are glitazones used in dual therapy?
With metformin or a sulphonylurea, when blood glucose control is not achieved with one drug and metformin and sulphonylurea
How are glitazones used in triple therapy?
With metformin and sulphonylurea, when blood glucose control is inadequate (an alternative to starting insulin)
When should you avoid prescribing glitazones?
- History of heart failure
- Previous or active bladder cancer and uninvestigated macroscopic haematuria
- Pregnancy and breastfeeding
- Hepatic impairment
- Patients receiving dialysis
Why should you avoid prescribing glitazones in patients with a history of heart failure?
There are concerns about increased incidence of heart failure in patients who take pioglitazones combined with insulin, particularly in those with cardiovascular risk factors - such patients require monitoring for signs of heart failure
Why should you avoid prescribing glitazones in previous or active bladder cancer, and uninvestigated macroscopic haematuria?
There is a small increased risk of bladder cancer in patients who take a pioglitazone
Why should glitazones be used with caution in the elderly?
Increased risk of fractures
What should be done before starting pioglitazone?
Assess patient for risk factors of bladder cancer and investigate any unexplained haematuria
What monitoring is required with glitazones?
- Monitor closely for signs of heart failure, especially in patients with a history of cardiovascular disease
- Check LFTs at baseline then every 2-6 months
What should you do if a patient on glitazones develops jaundice?
Discontinue
What might glitazones interact with?
- Insulin
- Beta blockers
- Other anti-diabetic drugs and alcohol
What might happen if glitazones are given with insulin?
Increased risk of heart failure - use with caution
What might happen if glitazones are given with beta blockers?
May mask signs of hypoglycaemia, e.g. tremor
What might happen if glitazones are given with other anti-diabetic drugs or alcohol?
Increased risk of hypoglycaemia
What are the common side effects of glitazones?
- Anaemia
- GI disturbance
- Weight gain
- Fluid retention
- Dizziness
- Headache
- Vertigo
- Visual disturbance
- Impotence
- Hypoaesthesia
What are the less common side effects of glitazones?
- Fatigue
- Alteration of blood lipids
- Hypoglycaemia
- Bladder cancer
- Liver dysfunction and liver toxicity
- Increased risk of bone fractures, especially in women
What patient counselling is required with glitazones?
- Risks of treatment
- Alcohol
- Signs of liver toxicity
- Driving advice
What should a patient on glitazones be told about the risks of treatment?
Inform patient about side-effects and risks of treatment, including heart failure, bone fractures, and bladder cancer
What should a patient on glitazones be told about alcohol?
It is not recommended to drink whilst on pioglitazone as this increases the risk of hypoglycaemia
What should a patient on glitazones be told about signs of liver toxicity?
The patient should be told to seek urgent medical help if they develop nausea, vomiting, abdominal pain, fatigue, and dark urine. If they become jaundiced, they must stop taking the medication immediately and contact their doctor
