DRUGS AND THEIR TARGETS IN T2DM - JP Flashcards

1
Q

Describe the steps in insulin secretion

A
  1. Increase in Blood Glucose
  2. Glucose enters pancreatic beta cells via GLUT-2 transporter.
  3. Glucose gets phosphorylated to Glucose-6-Kinase by Glucokinase
  4. Glycolysis of Gluco-6-Kinase yields ATP.
  5. Katp channels close causing membrane DEPOLARISATION.
  6. Depolarisation causes Ca2+ channels to open and Ca2+ to enter the cell triggering insulin secretion.
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2
Q

What are the 8 subunits of the Katp channel?

A

4 Potassium Inward Rectifier 6.2 Subunits (Kir6.2)

4 Sulphonylurea Receptor 1 Subunits (SUR1)

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3
Q

ATP binds to what part of the Potassium channel causing closure?

A

Kir6.2

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4
Q

What binds to SUR1 subunits to keep the channel open, maintaining the membrane potential?

A

ADP-Mg2+

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5
Q

What do Sulphonylureas bind to?

A

SUR1
Displacing ADP-Mg2+ and closing the Katp channel.
Causes depolarisation and insulin release

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6
Q

Name a Sulphonylurea?

A

Tolbutamide, Gliclazide and Glipizide

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7
Q

Why are Sulphonylureas known as ‘insulin secretagogues’?

A

They cause pancreatic beta cells to release insulin

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8
Q

Name some downsides of Sulphonylureas?

A

Weight gain

Hypoglycaemia (excessive insulin secretion)

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9
Q

What are Glinides?

A

Drugs that work similar to Sulphonylureas but don’t cause hypo’s

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10
Q

Name two incretins

A

GLP-1 (Glucagon Peptide Like-1)

GIP (Glucose Dependent Insulinotropic Peptide)

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11
Q

Where are incretins released from?

A

Enteroendocrine cells in the small intestine

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12
Q

How do incretins lower blood glucose?

A

Enhance insulin release from pancreatic beta cells (enhanced uptake of glucose)
Decreases glucagon release from pancreatic alpha cells (reduced production of glucose)

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13
Q

What does DPP-4 do?

A

Terminates the action of incretins (GLP-1 and GIP)

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14
Q

How do ‘Gliptins’ work

A

Inhibit the action of DDP-4, prolonging the action of GLP-1 and GIP

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15
Q

What do all DPP-4 names have in common?

A

All have gliptin in the name

I.e saxagliptin, vildagliptin, linagliptin and alogliptin.

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16
Q

What are incretin analogues?

A

Peptides that mimic the action of GLP-1 but are longer lasting.

17
Q

Name an incretin analogue?

A

Extenaide or Liraglutide

18
Q

Name a positive of incretin analogues?

A

Weight loss (loss of appetite)

19
Q

What does alpha-glucosidase do?

A

Break down starch and disaccharides to glucose

20
Q

Alpha-Glucosidase inhibitors are commonly/rarely used in the UK?

A

Rarely

21
Q

Metformin is an example of a … drug

A

Biguanide

22
Q

True/ False

Metformin is the first line treatment for T2DM?

A

FALSE HAHAHHAHA

Exercise is you FOOL

23
Q

What are the 2 main mechanisms of Metformin?

A

Reduces Hepatic Gluconeogenesis

Increases glucose uptake by skeletal muscle

24
Q

Positive aspects of Metformin? 5

A
Reduces microvascular risk
Oral administration 
Weight loss
No hypoglycaemia
Can be used with other agents
25
Q

Adverse effects of metformin?

A
GI upsets
Lactic acidosis (rarely)
26
Q

Name a class of new drugs that block reabsorption of glucose in the kidneys? (i.e makes you pee out glucose)

A

SGLT2 Inhibitors

27
Q

Name a SGLT2 inhibitor?

A

Anything with gliflozin in the name.

Dapagliflozin, canagliflozin or empagliflozin