Pharmacological treatments for T2DM Flashcards
- Detail how these drugs work (molecular mechanisms of action) - Name the main pharmacological treatments - Understand which treatments are suitable for each form of diabetes - Describe the molecular action of diabetes treatments
1
Q
Glucotoxicity
A
increases risk of developing long-term complications
2
Q
Why improve glycaemic control
A
- symptoms
- acute complications
- glucotoxicity
3
Q
Microvascular complications of glucotoxicity
A
neuropathy, nephropathy and retinopathy
4
Q
Macrovascular complications of glucotoxicity
A
CVD, cerebral and peripheral vascular disease
5
Q
Why can glucotoxicity not be treated with insulin
A
hyperinsulinaemia and insulin resistance
6
Q
Metformin
A
- mechanisms of action unclear
- target unknown
- does not increase insulin release
- does not require beta cells
7
Q
Main clinically important action of Metformin
A
- Restores hepatic glucose production in liver by inhibition of gluconeogenesis
- increases glucose uptake
8
Q
Sulphonylureas mechanism of action
A
- promote insulin secretion
- block ATP-sensitive K channel
- result in potentiation of glucose-induced insulin secretion
- meglitinides act on a different site of the same target
9
Q
Effects of sulphonylureas
A
- decrease in HbA1c with monotherapy
- rapidly effective
- weight gain
- hypoglycaemia
- will only work in patients with functioning islets and may stress islets further, which are already producing extra insulin to compact insulin resistance
10
Q
Effects of insulin
A
- no dose limit
- rapidly effective
- improved lipid profile
- monotherapy % decrease in HbA1c 1.5-3.5
- 1 to 4 injections daily
- weight gain
- hypoglycaemia
11
Q
TZD mechanism of action
A
- acts on adipose tissue, skeletal muscle, and liver
- increase glucose uptake into skeletal muscle
- decrease glucose release from liver
- does not require beta cells
- does not increase insulin release
- normalised dyslipidemia
- lipid normalising effects act through PPAR gamma but other targets such as AMPK, mitochondrial effects may be important
12
Q
Incretins
A
- GLP-1 agonists
- di-peptidyl peptidase (DPP)-4 inhibitors
- intestinal secretion of insulin
- GIP from K cells
- GLP-1 from L cells
13
Q
The incretin effect
A
insulin response is greater following oral glucose than IV glucose, despite similar plasma glucose concentration
14
Q
GLP-1 actions in humans
A
- GLP-1 is secreted when food is ingested
- beta-cell: enhances glucose-dependent insulin secretion in the pancreas
- alpha-cell: suppresses postprandial glucagon secretion
- liver: reduces hepatic glucose output
- stomach: slows the rate of gastric emptying
- brain: promotes satiety and reduces appetite
15
Q
GLP-1 receptor agonists
A
- two types: short acting (exenatide) or long acting (liraglutide)
- both drugs improve glycaemic control, reduce body weight, reduce systolic blood pressure, and low risk of hypoglycaemia
- long-acting receptor agonists produce superior glycaemic control compared to short-term, and temporary nausea
