Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endocrinology > Lec14 Drug treatment of Type 2 DM > Flashcards

Lec14 Drug treatment of Type 2 DM Flashcards

1
Q

On which pathways does insulin have its effects on?

A

Insulin affects all major metabolic pathways:
Carbohydrate
Fat
Protein

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

What are the main target tissues of insulin?

A

Liver
Adipose Tissue
Muscle

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

What effect does insulin have on hepatic cells?

A

Insulin causes decrease in gluconeogenesis, glycogenolysis and ketogenesis

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

What effect does insulin have on muscle cells?

A

Increases GLUT4 translocation to the membrane and hence increase glucose uptake, glucose oxidation, glycogen synthesis, amino acid uptake, protein synthesis
Decreases glycogenolysis and proteolysis

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

What effect does insulin have on adipocytes?

A

Increase glucose uptake, increase triglyceride synthesis

Decrease FFA and glycerol release

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

What is the net effect on insulin?

A

To cause hypoglycaemia and increase fuel storage in muscle, fat tissue and liver

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

What factors contribute to hyperglycaemia that can be targeted with drugs?

A

Beta cell dysfunction
Insulin resistance
Loss of beta cell mass
Renal glucose absorption

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

What drug targets beta cell dysfunction?

A

Sulfonylureas - cause endogenous insulin release
e.g. Gliclazide
Glucagon Like Peptide 1 analogs (GLP1 analogs)
Dipeptidyl peptidase 4 inhibitors (DDP4 inhibitors)

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

What is the mechanism of action in sulfonylureas?

A

Sulfonylureas enter Beta cells via Glut2 receptors
They inhibit ATP sensitive K channels causing them to close
K builds up inside the cell causing the voltage inside the cell to become positive
Voltage dependent channels open - calcium enters
Vesicles containing insulin are released from beta cell by exocytosis

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

What are the therapeutic uses of sulfonylureas?

A

The only drug to stimulate endogenous insulin release
Best pt to use in:
over 40 years old (but also can give to under 40)
DM duration less that 10 years
Daily insulin if taking is less than 40 units

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

What is the major side effect of sulfonylureas?

A

Hypoglycaemia

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

Name 3 sulfonylureas?

A

Gliclazide
Glipizide
Glimepiride

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

Which class of drugs increases insulin sensitivity?

A

Biguanides - Metformin

Thiazolidinediones (TZDs) - Pioglitazone

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

How do biguanides work?

A

By increasing glucose uptake in muscle and decrease glucose production in the liver

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

What is an advantage of metformin?

A

It does not cause hypoglycaemia

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

What is the mechanism of action in biguanides?

A

Suppression of gluconeogenesis
Increases insulin sensitivity - improved insulin binding to insulin receptors
Increases peripheral glucose uptake
Increases fatty acid oxidation
Decreases glucose absorption from the GI tracts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Explain the mechanisms of action in further detail

A

Suppression of gluconeogenesis through AMP activated protein kinase (AMPK) dependent and independent pathways
Increases insulin sensitivity - improved insulin binding to insulin receptors
AMP is a second messenger for insulin
Metformin directly activates the AMPK pathway in hepatocytes
Increase of peripheral glucose uptake:
Increased GLUT4 translocation through AMPK - so skeletal muscle and adipose tissue is forced to use glucose and not FFA and other sources of energy
Metabolically changes the heart through p38 MAPCK and PKCdependent mechanisms to preferentially use glucose
Increases fatty acid oxidation
Decreases glucose absorption from the GI tracts - excites GI bacteria - may cause tummy upsets

18
Q

What other disease is metformin used to treat?

A

Polycystic Ovarian Syndrome

19
Q

Properties of metformin:

A

Orally active
Half life 1.5-4.5h
Does not bind plasma proteins - affects the genomic levels in hepatocytes
Decreased expression of the enzymes so the drug doesn’t need to be there all the time - can go a couple of days without

20
Q

List the adverse effects of metformin:

A

Lactic acidaemia (esp in pts with renal impairment)
Nausea, abdominal discomfort, diarrhoea, metallic taste, anorexia
Vit b12 and folate malabsorption with chronic use of metformin
MI or septicaemia

21
Q

Contraindications of metformin

A

Hepatic disease
PHx of lactic acidaemia - or renal impairment
Cardiac failure
Chronic hypoxic lung disease - causes metabolic acidosis

22
Q

What other class of drugs increase insulin sensitivity?

A

Thiazolidinediones - Pioglitazone only one still approved for use

23
Q

How do thiazolidinediones work?

A

They activate the peroxisome proliferator activated gamma receptors (PPAR-gamma) which are involved in transcription of insulin responsive genes and in regulation of adipocyte lipid metabolism

24
Q

What effect do thiazolidinediones have?

A

In the presence of endogenous or exogenous insulin, glitazones will:
Increase glucose uptake and utilisation in skeletal muscle
Decrease hepatic gluconeogenesis, glycogenolysis and triglyceride production in the liver
Increase glucose uptake in adipose tissue and decrease FFA metabolism

25
Q

What is a disadvantage of this drug?

A

It causes pts to put on weight

Diabetics are already overweight which is part of the problem

26
Q

What are the adverse effects of glitazones?

A

Fluid retention - causing oedema, mild anaemia
Dose related weight gain
Safety in pregnancy and lactation not determined
Can cause liver damage as it is metabolism by the liver - needs frequent tests

27
Q

Interactions of pioglitazone:

A

May lower the oral contraceptive levels containing ethinyl oestrodiol and norethindrone

28
Q

GLP1 analogs are:

A

Newer drugs

Designed to have fewer side effects

29
Q

Name a DLP1 analog

A

Exenatide

30
Q

How is exenatide administered?

A

Injected

Subcutaneously 30-60 mins before last meal of the day because it is a peptide and can be broken down in the GI tract

31
Q

How do DLP1 analogs like Exenatide work?

A

Augment the pancreas response - increase glucose dependent insulin secretion
Suppresses pancreatic release of glucagon to stop liver overproducing glucose
Slows down gastric emptying
Reduces appetite and promotes satiety
Reduces liver fat content

32
Q

Side effects of DLP1 analogs e.g. exenatide

A

GI effects e.g. acid, sour stomach, belching, diarrhoea, heartburn etc.

33
Q

What are Dipeptidyl Peptidase 4 (DPP4) inhibitors?

A

They are a class of drugs which increase insulin sensitivity

34
Q

How do DPP4 inhibitors work?

A

By inhibiting break down of incretins like GLP1 and GIP

35
Q

What is the effect of having increased incretins?

A

They suppress glucagon release from pancreas which stops liver overproducing glucose
Increased glucose-induced insulin secretion
Improved peripheral glucose utilisation
Reduce gastric emptying
Increases satiety

36
Q

Give examples of DPP4 inhibitors

A

Vildagliptin (reversible)
Sitagliptin (reversible)
Saxagliptin (covalently bound)

37
Q

What are the side effects of DPP4 inhibitors

A

Few side effects
Weight neutral no GI side effects
Cancer risk? - because DPP4 known to function as a tumour suppressor
no studies have shown it increases risk of cancer

38
Q

What factor contributing to hyperglycaemia do SGLT 2 inhibitors act on

A

Renal glucose absorption

39
Q

How do Sodium glucose transporter 2 inhibitors work?

A

100% Glucose has to reabsorbed in the kidney tubule

By inhibiting the sodium glucose transporter, glucose is excreted by the kidneys

40
Q

Give examples of SGLT2 inhibitors

A

Dapagliflozin

Canagliflozin

41
Q

Side effects of SGLT2 inhibitors

A

Rapid weight loss because you are peeing out the glucose
Tiredness
Osmotic diuretic so dehydration
Can worsen UTIs and thrush but generally doesn’t

Endocrinology (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions