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Pharmacology Y2 > Diabetes > Flashcards

Diabetes Flashcards

1
Q

Metformin: What is its primary mechanism of action?

A
  1. Metformin activates AMPK in hepatocyte mitochondria.
  2. This inhibits ATP production.
  3. This blocks gluconeogenesis and subsequent glucose output. It also blocks adenylate cyclase which promotes fat oxidation.
  4. Both help to restore insulin sensitivity.
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2
Q

Metformin: What does it target?

A

AMP activated protein kinase in Hepatocyte mitochondria

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3
Q

Metformin: What is its main side effect?

A

GI side effects with high doses (20-30% of patients)

e.g. Abdominal pain, decreased appetite, diarrhoea, vomiting)

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4
Q

Dipeptidyl-peptidase 4 (DPP-4) inhibitors: Give the name of one.

A

Sitagliptin

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5
Q

Dipeptidyl-peptidase 4 (DPP-4) inhibitors: What does it target?

A

DPP-4 (enzyme) in the vascular endothelium

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6
Q

Dipeptidyl-peptidase 4 (DPP-4) inhibitors: What is the role of DPP-4 enzymes?

A

Metabolism of incretins in the plasma. Therefore, these inhibitors increase incretin levels.

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7
Q

Dipeptidyl-peptidase 4 (DPP-4) inhibitors: What is the role of incretins?

A
  • stimulate the production of insulin when it is needed (e.g. after eating)
  • reduce the production of glucagon by the liver when it is not needed (e.g. during digestion)
  • slow down digestion
  • decrease appetite
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8
Q

Dipeptidyl-peptidase 4 (DPP-4) inhibitors: Where are incretins released from?

A

Enteroendocrine cells

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9
Q

Dipeptidyl-peptidase 4 (DPP-4) inhibitors: What are the main side effects?

A
  • Upper respiratory tract infections (5% of patients) Flu-like symptoms e.g. headache, runny nose, sore throat
  • RARE: Serious allergic reactions
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10
Q

Dipeptidyl-peptidase 4 (DPP-4) inhibitors: Who shouldn’t be given this drug?

A

patients with pancreatitis

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11
Q

Sulphonylureas: Give the name of a Sulphonylurea.

A

Gliclazide

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12
Q

Sulphonylureas: What does it target?

A

ATP-sensitive potassium channel in Beta pancreatic cells.

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13
Q

Sulphonylureas: What is its primary mechanism of action?

A
  1. Inhibits the ATP-sensitive potassium (KATP) channel on the pancreatic beta cell. Potassium can no longer leave the cells.
  2. This causes depolarisation which stimulates Ca2+ influx and subsequent insulin vesicle exocytosis.
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14
Q

Sulphonylureas: What are its main side effects?

A
  • Weight gain

- Hypoglycaemia

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15
Q

Sulphonylureas: How can weight gain be mitigated?

A

Concurrent administration of metformin

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16
Q

Sulphonylureas: What must be there to some extent for these to have any effect?

A

Some residual pancreatic beta-cell activity

17
Q

Sodium-glucose co-transporter (SGLT2) inhibitors: Give the name of an SGLT2 inhibitor.

A

Dapaglifozin

18
Q

Sodium-glucose co-transporter (SGLT2) inhibitors: What does it target?

A

SGLT2, in the proximal convoluted tubule of the kidneys.

19
Q

Sodium-glucose co-transporter (SGLT2) inhibitors: What is its primary mechanism of action?

A

Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the proximal convoluted tubule → reduces glucose reabsorption and increases urinary glucose excretion.

20
Q

Sodium-glucose co-transporter (SGLT2) inhibitors: What are the side effects?

A
  • Uro-genital infections due to increased glucose load in urine (5% of patients)
  • Slight decrease in bone formation
  • Can worsen diabetic ketoacidosis (stop immediately)
21
Q

Sodium-glucose co-transporter (SGLT2) inhibitors: For which groups of people would this treatment be less effective?

A
  • In patients with renal impairment

- People that are prone to UTIs

22
Q

Sodium-glucose co-transporter (SGLT2) inhibitors: What are its effects on weight and BP?

A
  • weight loss

- a reduction in BP

23
Q

Which anti-diabetic drugs don’t cause weight gain?

A
  • Metformin
  • Dipeptidyl-peptidase 4 (DPP-4) inhibitors
  • Sodium-glucose co-transporter (SGLT2) inhibitors
24
Q

What is the name of the specialised protein carriers that Metformin requires to enter tissues?

A

Organic cation transporter 1 (OCT-1)

25
Q

How is Metformin given?

26
Q

Describe the metabolism of Metformin.

A

Metformin is not metabolised in the liver → it comes in its active form.

27
Q

For whom should Metformin be carefully considered in the treatment of Diabetes?

A

People with Chronic Kidney Disease

28
Q

Why is Metformin contraindicated in individuals with renal impairment?

A

In kidney failure/disease, Metformin cannot be excreted adequately and instead may build up in the kidneys. This can lead to LACTIC ACIDOSIS

29
Q

What are the names of the drugs which increase insulin sensitivity?

A
  • metformin

- Thiazolidinediones

30
Q

What is the name of the drug which inhibits carbohydrate absorption in the gut?

A

alpha glucosidase inhibitor

31
Q

What drugs can boost insulin secretion?

A
  • Sulphonylureas
  • GLP-1 agonists
  • DPP4- inhibitors

Pharmacology Y2 (9 decks)

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