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5 - Pharmacology > Diabetes Drugs > Flashcards

Diabetes Drugs Flashcards

1
Q

What is the normal range for blood glucose levels?

A

3.5 - 8 mmol/L

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2
Q

What are some of insulins actions?

A 
Increased:
- glucose uptake
- glycogenesis
- glycolysis
- lipogenesis
- esterification of FAs
- lipoprotein lipase activity
- amino acid uptake and protein synthesis
Decreased:
- gluconeogenesis
- lipolysis
- ketogenesis
- proteolysis
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3
Q

What are some of the actions of glucagon?

A 
Increased:
- glycogenolysis
- gluconeogenesis
- ketogenesis
- lipolysis
Decreased glygogenesis
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4
Q

How does insulin bring about action?

A

Circulates free in the blood plasma and binds to surface receptors which stimulates enzymes and proteins inside the cell to act.

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5
Q

How does glucagon bring about action?

A

Binds to glucagon receptors in cell membranes and stimulates adenylate cyclase, increase cAMP. This activates protein kinase A which phosphorylates and activates enzymes inside the target cell.

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6
Q

How can you describe diabetes mellitus?

A

An inability to regulate plasma glucose withing normal range.

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7
Q

Give some characteristics of diabetes mellitus

A
  • absolute/relative insulin deficiency
  • hyperglycaemia
  • glycosuria
  • polyuria- polydipsia
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8
Q

What is the first line of treatment when someone is diagnosed with type 2 diabetes?

A

Use diet and exercise to try and maintain adequate glucose control.

  • limit fat intake
  • increase intake of complex carbohydrates
  • reduce alcohol
  • stop smoking
  • increase amount of exercise
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9
Q

Give some of the major groups of oral hyperglycaemics

A 
Sulphonureas
Biguanides
Thiazolidinediones/glitazones
Gliptins/DPP-4 inhibitors
SGLT2 Inhibitors/Gliflozins
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10
Q

Describe the mechanism of action of sulphonylureas

A

They antagonise K+/ATPase activity of beta cells, causing depolarisation. VOCCs open and increase Ca2+ causes insulin vesicles to fuse with the membrane and release increased amounts of insulin.

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11
Q

Why can you only prescribe sulphonylureas in certain patients?

A

Patients need to have residual beta cell activity- helps to enhance the remaining activity.

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12
Q

What are some ADRs that can arise from taking oral suphonureas?

A

Hypoglycaemia
GI disturbance
Weight gain

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13
Q

Give some examples of some sulphonureas

A

Tolbutamide
Glibencamide
Glipizide

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14
Q

When would you not prescribe sulphonureas?

A

Breastfeeding women
Elderly
Patients with renal or hepatic insufficiency

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15
Q

Describe the mechanism of action of biguanides

A

Unclear mostly

  • increase insulin receptor sensitivity
  • enhances skeletal muscle and adipose uptake of glucose- inhibits hepatic gluconeogenesis
  • does not induce hypoglycaemia
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16
Q

Give an example of a biguanide

A

Metformin

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17
Q

When would you prescribe a biguanide?

A

In type 2 diabetes when there is endogenous insulin presence

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18
Q

When would you not prescribe a biguanide?

A

With compromised:

  • Heart function
  • Renal function
  • Hepatic function
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19
Q

Give some ADRs of biguanides

A 
GI disturbances (slow titration limits this)
Lactic acidosis
20
Q

Give the mechanism of action of Thiazolidinediones

A

PPAR-gamma agonist

  • binds to a nuclear hormone receptor site
  • reduces gluconeogenesis
  • increases glucose uptake into muscles(PPARG regulates FA storage and glucose metabolism)
21
Q

Give some examples of thiazolidinediones

A

RosiglitazonePioglitazone

22
Q

When would you prescribe a thiazolidinediones?

A

In uncontrolled, non-insulin dependent diabetes

23
Q

Give some ADRs for thiazolineinediones

A

GI disturbance

Weight gain

24
Q

Give a drug-druf interation for thiazolineinediones

A

Are heavily protein bound so could potentially be displaced

25
Q

Give the mechanism of action for meglitidines

A

K+/ATP antagonists on beta cells, causing depolarisation, calcium entry and fusion of insulin containing vesicles with the cell membrane

26
Q

Give some examples of meglitidines

A

Repaglinide

Nateglinide

27
Q

Why have insulin analogues been developed?

A
  • Do not have to rely on extraction of insulin from animals- can give an injection containing different types of insulin with varying characteristics e.g. rapid acting + intermediate acting + long acting. This helps to give the best control of blood glucose levels as possible.
28
Q

When would you use ultra rapid and short acting insulin?

A

Afters mealsWith acute hyperglycaemia

29
Q

When would you use intermediate and long acting insulin?

A

Basal insulinOvernight control

30
Q

What are the different types of insulin regimes?

A

Pre-mixed insulin - given twice a day with mealsIntermediate/long acting insulin + Fast or short acting insulin- intermediate insulin provides a basal level that acts overnight and short acting insulin is given with meals for an acute response.

31
Q

Which insulin regimen gives a better level of glycaemic control?

A

The mix of different insulins

32
Q

Describe the monitoring that must occur with acute treatment

A
  • Need to monitor several times a day with advanced diabetes- Helps to initially determine the dosing levels of insulin
33
Q

Describe the monitoring in chronic diabetes treatment

A

Glucose reacts with the terminal valine on Hb to produce glycosylated Hb (HbA1c). The HbA1c is a good indicator of how effective blood glucose control has been.

34
Q

How often do you need to measure HbA1c levels?

A

3 months - this is how long RBCs stay in the circulation

35
Q

What HbA1c percentage would be indicative of poorly controlled diabetes?

A

10% and above

36
Q

What are the main types of anti-obesity agents?

A

Orlistat
Sibutramine
Rimonabant

37
Q

Describe the mechanism of action of orlistat

A

Is an inhibitor of gastric and pancreatic lipase. This means there is a reduction in conversion of dietary fat to FAs and glycerol by 30%.

38
Q

Give some ADRs for orlistat

A

Soft fatty stools
Flatus
Faecal discharge/ incontinence

39
Q

Describe the mechanism of action for sibutramine

A

Is a noradrenaline and seratonin re-uptake inhibitor which causes appetite suppression and increased thermogenesis

40
Q

Give some ADRs for sibutramine

A

Increased heart rateIncreased blood pressure

41
Q

Describe the mechanism of action for rimonbant

A

Is an endocannabinoid antagonist- decreases body weight- helps regulate body-weight gain

42
Q

Give some ADRs for rimonabant

A

Depression – has been withdrawn from use by NICE

43
Q

Describe the mechanism of action for gliptins

A

DPP-4 inhibitors

  • block action of DPP-4, an enzyme which breaks down incretin
  • Increased incretin levels acts to stimulate insulin release
44
Q

Give some examples of glilptins

A

Sitagliptin

Anagliptin

45
Q

Give the mechanism of action of SGLT2 inhibitors

A

Inhibit SGLT2 channel in kidney, so there is less glucose reabsorption, causing a reduction in blood glucose levels.

  • increase insulin sensitivity
  • increase glucose uptake in muscles
  • decreased gluconeogenesis
  • improved first phase insulin release

5 - Pharmacology (17 decks)

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