Metabolism - Diabetes Drugs Flashcards
What is the mechanism of action of sulfonylureas?
- Promote insulin release from Beta cells in pancreas by blocking ATP sensitive K+ channels, resulting in depolarisation, Ca2+ influx and insulin exocytosis.
- May also reduce hepatic glucose production and increase peripheral insulin sensitivity
What are the major adverse effects of sulfonylureas? In which patients should you be cautious when prescribing these?
- Weight gain
- Hyperinsulinemia
- Hypoglycaemia
- Caution in hepatic or renal insufficiency since accumulation may cause hypoglycaemia
What is a Glinade? Names and function
- Insulin secretagogues but, unlike sulfonylureas, have rapid onset and short duration of action
- Categorised as post-prandial glucose regulators
- Repaglinide and Nateglinide
What are C/I for Glinides? What S/Es can occur?
- C/I: should not be used in combination with sulfonylureas due to serious risk of hypoglycaemia
- S/Es: hypoglycaemia and weight gain (incidence less than sulfonylureas)
What is a Biguanide? Give a name and mechanism of action
- Metformin: insulin sensitiser
- MoA: reduction of hepatic gluconeogenesis (main MOA) + increase glucose uptake and use by target tissues, decreasing insulin resistance.
- Do not promote insulin secretion t/f the risk of hypoglycaemia is far less than with sulfonylureas
What are S/Es and C/Is of Biguanides?
S/Es:
- slows intestinal absorption of sugars and improves peripheral glucose uptake and utilisation t/f weight loss may occur due to loss of appetite.
- Adserve GI effects
- Recommended as initial drug for T2DM
C/Is:
- Renal dysfunction due to risk of lactic acidosis
- Discontinue in acute MI, exacerbation of heart failure, sepsis and other disorders that can cause acute renal failure
- Should temporarily discontinue in pts undergoing procedures requiring IV contract
Thazolidinediones: names and MoA
- Pioglitazone: insulin sensitiser (do not promote insulin release t/f hyperinsulinaemia is not a risk)
- MoA: increase insulin sensitivity in adipose tissue, liver and skeletal muscle.
- Usually recommended as 2nd or 3rd line agent for T2DM
Thazolidinediones: S/Es
S/Es:
- Periodic LFT monitoring recommended due to small number of cases of liver toxicity
- Weight gain can occur due to the drug increasing subcut fat and fluid retention
- Associated with osteopenia and increased fracture risk, and may increase bladder cancer risk
C/Is:
-Avoid in pts with severe hearth failure
Alpha-glocusidase inhibitors: name and MoA
- Eg: Acarbose
- Alpha-glucosidase enzymes break down carbs into glucose and other simple surgars - this class of drug reversibly inhibits alpha-glucosidase enzyme, resulting in lower post-prandial glucose levels
Alpha-glocusidase inhibitors: S/Es and C/Is
S/Es
-Flatulence, diarrhoea, abdo cramping
C/Is
-Patients with IBD, colonic ulceration, or intestinal obstruction
DDP4 inhibitors: names and MoA
- Alogliptin, sitagliptin
- MoA: inhibit the enzyme DPP-4, which is responsible for the inactivation of incertain hormones (which promote insulin release) such as GLP 1. Prolonging the activity of increasing hormones increases insulin release in response to meals and reduces inappropriate secretion of glucagon.
DPP4 Inhibits: S/Es
SEs
- Weight neutral
- All except Linagliptin require dose adjustment in renal dysfunction
- Generally well tolerated - most common S/E are nasopharyingitis and headache
SGLT2 inhibitors: name and MoA
- Dapagliflozin
- MoA: SGLT2 is responsible for re-absorbing filtered glucose in the tubular lumen of kidney - these drugs decrease the reabsorption of glucose, increase urinary glucose excretion and lower BMs
SGLT2 inhibits: S/Es
- Most common: female genital mycotic infections - vulvovaginal candidiasis, UTIs, urinary frequency
- Can cause osmotic seizures and reduce systolic BP
What are the DVLA rules for DM?
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