Pharma 3 Diabetic Drugs Flashcards

1
Q

What is the action of insulin?

A
  • Activates GLUT4 to relocate to cell membrane and increase uptake of glucose into cells
  • inhibits glycogen breakdown and increases glucose uptake by liver and adipose
  • stimulates FA synthesis for transport as lipoproteins and inhibits lipolysis in adipocytes
  • Inhibitis proteolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the normal values in which glucose are kept in plasma?

A

3.8 - 6.5 mmol.L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the effect of diabetes mellitus ie hyperglycaemia?

A

In the short term - not much

In long term - macrovascular (increases risk of IHD, stroke, and PVD) and microvascular damage (increases risk of retinopathies, neuropathies, and nephropathies)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is type 1 and type 2 diabetes?

A

type 1 - autoimmune destruction of beta islet cells

type 2 - insulin resistance and decreased insulin output from beta cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How are type 1 diabetics treated? What are the varieties of treatment offered and how are these utilised to mimic physiological functioning?

A

insulin subcutaneous injections

Can be short, intermediate or long acting

Basal bolus regimen - uses long acting insulin in background and then a fast acting insulin with meals - 5 injections per day

Pre-mixed insulin regime - mix of fast and slow acting insulin - 2 times per day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the 5 classes of drugs on offer for type 2 diabetics?

A

Biguanides, thiazolidinediones, sulphonylureas, meglitidine, incretin based therapies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the mechanism of action of biguanides and give an example drug. How much can it reduce HbA1c by?

A

e.g. metformin

Works by increasing cell sensitivity to insulin and inhibits hepatic gluconeogenesis.

2%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the pros and contraindications of metformin?

A

Pros - well tolerated, weight neutral, cheap, good at lowering glucose

Contraindications - compromised renal function or resp disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the mechanism of action of thiazolidinediones (TZDs) and give an example drug. How much does it lower HbA1c by?

A

e.g. rosiglitazone or pioglitazone

Works by reducing gluconeogenesis and increasing glucose uptake in muscles. This is done by binding to a nuclear hormone receptor site which activates the RXR receptor, upregulating genes that affect glucose and lipid metabolsim

1-1.5%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the pros and cons of TZDs? What are the contraindications?

A

pros - long half life, cannot cause hypoglycaemia

cons - may cause oedema, increase LDL and HDL, binds to albumin causing PK and PD consequences, weight gain

Contraindication - heart failure patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the mechanism of action of sulphonylureas and give an example drug. How much do they reduce HbA1c by?

A

e.g. gliclazide

Act by binding to beta cells K+-ATP channel activity and increasing K+ conc within the cell and cause depolarisation. This results in increases of calcium ion entry into the cell and increases the insulin release from beta cells.

1-2%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the pros and cons of sulphonylureas? Contraindications?

A

pros - once a day

cons - can cause hypoglycaemia, bidns to albumin causing pk and pd consequences, weight gain and GI disturbances

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Give an example meglitidine and mechanism of action. How much does it reduce HbA1c

A

e.g. repaglinide

Same as sulphonylureas - Act by binding to beta cells K+-ATP channel activity and increasing K+ conc within the cell and cause depolarisation. This results in increases of calcium ion entry into the cell and increases the insulin release from beta cells.

1%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

pros of meglitidine?

A

pros - low risk of hypo, no weight gain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the order of therapy for type 2 diabetes?

A

lifestyle advice, metfomin, sulphonylureas, TZDs

If HbA1c levels not brough to 7% or below, move on to metformin and then sulphonylureas

if sulphonylureas doesnt bring down HbA1c to below 7.5% then go on to add a TZD, or start insulin therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Name 3 anti obesity drugs and how they work

A

orlistate - gastric and pancreatic lipase inhibitor

sibutramine - noradrenaline and serotonin reuptake inhibitor = appetite suppression

Rimonabant - cannabinoid antagonist

17
Q

What are the 2 incretin based therapies?

A

DPP-4 inhibitors (gliptins), and GLP-1 receptor agonists

18
Q

Give an example drug of a DPP-4 inhibitor

A

Sitagliptin

19
Q

Give an example GLP-1 receptor agonist

A

exenatide

20
Q

What are the physiological effects of GLP-1?

A
  • Brain - decrease hunger
  • Stomach - decrease gastric emptying
  • pancreas - increased insulin secretion, decreased glucagon secretion
  • liver - decreased glucose production
  • muscle - increase glucose uptake
21
Q

What is the mechanism of action of gliptins?

A

DPP-4 inhibitor inhibits breakdowns of incretins. Increatins stimulate increased insulin from beta cells and decreased glucagon from alpha cells.

22
Q

What are the pros and cons of incretin related therapies?

A

pros - weight neutral, modest HbA1c reduction

cons - high cost, some GI symptoms

23
Q

How do SGLT2 inhibitors work?

A

work by blocking SGLT2 in the proximal tubule which prevents glucose reabsorption

24
Q

Give an example SGLT2 inhibitor and the major con to using them.

A

e.g. dapagliflozin

increased risk of lower UTIs

25
Q

What is normal HbA1c levels?

A

6%