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Pharmacology > Hypoglycaemic Agents > Flashcards

Hypoglycaemic Agents Flashcards

1
Q

What are the functions of insulin?

A

Facilitate diffusion of glucose into cells

Stimulate hepatic glycogen production

Stimulate hepatic fatty acid synthesis for transport of lipoproteins and increase the amount of free FAs in the circulation

Inhibit breakdown of far in adipocytes by inhibiting lipase

Can cause weight gain, is anabolic

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2
Q

Which cells produce insulin and glucagon?

A

Alpha cells produce glucagon

Beta cells produce insulin

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3
Q

Function of glucagon?

A

To increase glucose levels by stimulating glycogenolysis and gluconeogenesis in the liver

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4
Q

What needs to be changed about diet in type II diabetics?

A 
Reduce energy intake if overweight
Encourage carbohydrate complexes
Limit salt and alcohol intake 
Stop smoking
Start exercising
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5
Q

What are the classes of oral hypoglycaemics?

A

Insulin sensitisers

  • biguanides
  • thiazolidinedione

Beta cell stimulators

  • sulphonylureas
  • meglitidines

Appetite suppressants
-GLP-1 analogues

Weight loss agents

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6
Q

Give an example of a biguanide

A

Metformin

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7
Q

How do biguanides work?

A

Metformin
Mechanism not fully understood
-increase insulin receptor sensitivity, reducing resistance
-stimulate uptake if glucose in muscle and adipose tissue
-decrease absorption of glucose in gut

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8
Q

What effects can biguanides have on blood results?

A

Reduce HbA1c by up to 2%

Reduce VLDLs and LDLs

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9
Q

Extra benefits of biguanides (Metformin)?

A

Weight neutral
Lowers CVS risk
May have possible anti-cancer benefits
No risk of hypoglycaemia

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10
Q

What is the half-life of biguanides/Metformin? What affect does this have on dosage?

A

2-3 hours

Requires dosing 2-3 times a day

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11
Q

How is Metformin eliminated?

A

Entirely by the kidneys

-not metabolised

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12
Q

ADRs of Metformin?

A

GI symptoms in a third

  • increased wind
  • abdominal discomfort
  • loose stools/diarrhoea

Potential for lactic acidosis

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13
Q

Contraindications for Metformin?

A

Renal failure
Cardiac, liver and respiratory failure
Stop in intercurrent illness with risk of tissue hypoxia and contrast imaging

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14
Q

Give some examples of sulphonylureas

A

Gliclazide
Glimepiride
Glipizide

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15
Q

General action of sulphonylureas?

A

(Gliclazide)

Stimulates beta cells therefore requires some residual function

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16
Q

Mechanism of action of sulphonylureas?

A

Antagonise β-cell K/ATP channels
Potassium accumulates in the cell causing depolarisation
Allows Ca entry
Increases fusion rate of insulin vesicles with the beta-cell membrane and their release into the circulation

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17
Q

Half-life of sulphonylureas? Effect on dosing?

A

Gliclazide has a short half-life of 10-12 hours
Glimepiride has a longer half-life of 18-24 hours

Given once daily

18
Q

Adverse effects of sulphonylureas?

A

Hypoglycaemia - concern in elderly, missed meals or excess alcohol
GI disturbance
Weight gain - can limit use in obese patients

19
Q

Name some meglitinides

A

Repaglinide

Nateglinide

20
Q

Mechanism of action of meglitinides?

A

Same as sulphonylureas

-act on K+/ATP

21
Q

Half-life of meglitinides? Effect on dosing?

A

1-3 hours

Taken before meals for shorter-term control of post-meal glucose elevation

22
Q

Benefits of meglitinides?

A

Reduce HbA1c by 1%
Relatively lower risk of hypoglycaemia
Not associated with weight gain - extends utility in treating obese patients

23
Q

General mechanism of action of thiazolidinedione? (TZDs)

A

Insulin sensitisers
Increase glucose uptake in muscle
Increase glucose utilisation
Reduce gluconeogenesis in muscle, adipose tissue and the liver

24
Q

Mechanism of action of TZDs?

A

Agnostically bind to a nuclear hormone receptor site - peroxisome proliferator-activated receptor gamma (PRAR-γ)

This binds with another nuclear receptor - the retinoid X receptor (RXR)

The PRAR-γ/RXR complex upregulates genes important for insulin signalling - govern glucose and lipid metabolism

25
Q

Name some thiazolidinediones

A

Rosiglitazone

Pioglitazone

26
Q

Dosing of TZDs?

A

Once a day for prolonged control of glucose levels

-reach peak effects after 1-2 months

27
Q

ADRs of thiazolidinediones?

A

Weight gain
Possible bladder cancer
Fractures in post-menopausal women
Fluid retention and oedema

28
Q

Contraindications of TZDs?

A

Heart failure

29
Q

Do TZDs induce hypoglycaemia?

A

No

30
Q

Name a GLP-1 analogue

A

Exenatide

31
Q

Where is GLP-1 secreted from and when?

A

L-cells of the intestine

Upon ingestion of food

32
Q

Action of GLP-1?

A 
Stimulates beta cells to release insulin and decreases glucagon levels
Stops the liver from producing glucose
Decreases gastric emptying
Increases glucose uptake in muscle
Decreases appetite
33
Q

How are GLP-1 analogues administered?

A

Injected

34
Q

Extra benefits of exenatide/GLP-1 analogues?

A

Promotes weight loss

Lowers HbA1c

35
Q

Adverse effects of exenatide?

A

GI symptoms
Painful to inject
Nausea

36
Q

What drug class does acarbose belong to?

A

Alpha-glucosidase inhibitor

37
Q

How does acarbose work?

A

Inhibits breakdown of carbohydrates to glucose by blocking the enzyme glucosidase

38
Q

ADRs of acarbose?

A

Flatulence
Loose stools and diarrhoea
Therefore no longer used much

39
Q

Effect of NSAIDs on glucose levels?

A

Can cause hypoglycaemia with sulphonylureas

40
Q

What can diabetes be due to?

A

Genetic defects of beta cells
Genetic defects of insulin action
Drug-induced diabetes
Associated with other hormone disorders

41
Q

List the main treatment steps in type II combination therapy

A

Begin with lifestyle changes
Drug therapy - Metformin
If HbA1c levels go above 7% - sulphonylurea introduced
If HbA1c goes above 7.5% - add TZD or start insulin
If HbA1c goes above 7.5% again, tirade dose upwards

Pharmacology (23 decks)

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