Diabetes treatment Flashcards
What is first line oral therapy for type 2 DM and what class of drug is it?
Metformin - Biguanide
What is the main method of action of Metformin?
Inhibition of gluconeogenesis by the liver (by stimulating AMP-activated protein kinase)
What are the main benefits to Metformin being used in T2DM?
- Reduces HbA1c by 15-20mmol/mol (lowering insulin resistance)
- weight loss ss
prevention of micro- & macrovascular complications - may be combined with other agents
- No risk of hypoglycaemia
What is the maximum dose of metformin?
1g bd
When should the dose of metformin be lowered and when should it be stopped?
Lowered (halved) - eGFR 30-45ml/min
Stopped eGFR <30ml/min
Give some SE of metformin.
GI upset - anorexia, nausea, D&V, taste disturbance
Interference with Vit B12 and folic acid absorption
Lactic acidosis
Liver failure
Rash
Are there any contraindications to metformin?
Renal failure Hepatic disease Cardiac failure Alcoholism Chroni lung disease Mitochondrial myopathy Any serious current illness
In what liver pathology may Metformin be useful in?
NAFLD
Give 3 examples of Sulphonlyureas.
Glicazide
Glibenclamide
Glimepiride
In diabetes when are SUs used?
In patients who are not overweight but have intolerance or contraindications to meformin
Are SUs used in type 1 DM?
No - need functioning beta-cells for these to work
Briefly describe the method of action of SUs.
- displace ADPMg from SUR1 subunit closing the KATP channel
- tonic, hyperpolarizing effect of potassium occurs and the cell membrane is depolarized
- Voltage gated Ca channels open
- Rise in intracellular calcium leads to increased secretion of (pro)insulin
What are the effects of SUs?
Reduces HbA1c by 15-20mmol/mol (increasing insulin secretion)
Preventio of microvascular complications
Weight gain
Do sulphonylureas prevent from macrovascular complications?
No
Give some SE of SUs.
Hypoglycaemia
GI: anorexia, nausea, vomiting, diarrhoea, abdo pain
Weight gain
Headache
In what conditions should SUs b avoided in?
Severe renal or hepatic failure
What drugs can impede the effects of sulphonylureas?
corticosteroids
thiazide diuretics
What is Pioglitazone an example of?
Thiazolidinediones
What is the method of action of TZDs?
Binds to PPARgamma (whihc is already associated with RXR)
Activated PPARgamma-RXR complex binds to DNA to promote the expression of genes encoding several proteins involved in insulin signalling
What are the positive effects of TZDs?
- reduces HbA1c by 15-20mmol/mol by increasing insulin sensitivity
- Promote fatty acid uptake and storage in adipocytes, rather than skeletal muscle and liver
- Reduced hepatic glucose output
What are the disadvantages of the effects of TZDs?
Weight increase is inevitable (increased sucut fat and fluid retention)
Increased risk of heart failure (fluid retention)
Risk of fracture
Where exactly is GIP and GLP1 released from?
GIP - K cells in intestine
GLP1 - L cells in intestine
What is the method of action of GLP1 receptor agonists?
Binds to GPCR GLP1 receptors and increase cAMP concentration -> promoting insulin from pancreas without hypoglycaemia
Give 2 examples of GLP1 receptor agonists.
Exenatide and Liraglutide
When are GLP1 receptor agonists used?
Improve glycaemic control in obese adults with T2DM who are already on metformin and/or SU
(3rd line agent)
What are the effects of GLP1RA on weight?
Decrease gastric emptying - early satiety
act on hypothalamus to reduce appetite resulting in weight loss
Give 2 examples of DPP4 inhibitors.
Sitagliptin
Vildagliptin
What are the main effects of DPP4 inhibitors?
Promote insulin secretion from pancreas without hypoglycaemia
Suppresses glycagon
Weight neutral
What is the possible but rare side effect of DPP4 inhibitors?
Pancreatitis
What do SGLT2 inhibitors block and give some examples of this class of drug?
Sodium-glucose co-transporter-2 inhibitors
Dapaglifozin, Canagliflozin
Briefly describe the method of action of SGLT2 inhibitors.
Selectively block reabsorption of glucose at the SGLT2 channels (proximal tubule of the kidney nephron) deliberately causing glucosuria - enhance glucose excretion by the kidneys and lowers blood glucose
Does weight loss occur in the use of SGLT2 inhibitors?
yes up until a point when it plateaus
What are common side effects of SGLT2 inhibitors and why does this happen?
Thrush and urine infections caused by urinating more glucose
How does the glinide class of drug work?
Binds to SUR1 to close the KATP channel and trigger insulin release
Are glinide drugs fast or slow acting?
rapid onset/offest kinetics making them less likely to cause hypoglycaemia than SUs
Give examples of glinide drugs.
Repaglinide
Nateglinide
Why do alpha-glucosidase inhibitors work?
Theyd elay absorption of glucose thus reducing postprandial increase in blood glucose
When are alpha-glucosidase inhibitors used?
IN T2DM patients inadequately controled by lifestyle measures or other drugs
What are the side effects of alpha-glucosidase inhibitors?
Flatulence
Loose stools/ diarrhoea
Abdominal pain
Bloating
Compare when insulin is brought into ise in T1 and T2 DM
First drug choice in T1DM
Last option for T2DM
Should Metformin and SUs be continued when on insulin?
Yes - to maintain or improve glycaemic control
How is insulin most commonly administered?
Subcutaneous injection
Breifly describe the idea of a basal bolus regimen.
Aims to mimic normal endogenous insulin prduction
Underlying basal injection that lasts the full day
Bolus insulin injections at meals
For a basal bolus regimen in a newly diagnosed diabetic, what is the dosage of insulin that is started?
0.3units/kg body weight
divide it 50% bolus 50% basal
Give some sie effects of insulin therapy.
Hypoglycaemia Hyperglycaemia Local reaction at injection site (acute) Loss of fatty tissue at injection site (chronic) Insulin resistance
If a patient with diabetes also has renal failure, does their insulin dose increase or decrease?
Decrease - insulin is excreted by the kidneys
