Lipids/ Diabetis/ BP drugs

Question 1

What is the MOA of metformin?

What is the effects on lipids?

Answer 1

• Enhances the effect of insulin via modification of the glucose metabolic pathways
  –> Inhibition of mitochondrial GDP
  –> Decrease in hepatic gluconeogenesis and intestinal glucose absorption
  –> Increases peripheral insulin sensitivity

Increase in HDL, lowering of LDL

Question 2

Is there current evidence that high intensity Blood pressure control (target under 120) is effectiveß

Answer 2

Yes! (control under 140) –> halves mortality

Question 3

Is there current clinical evidence in useing Evolovumab (PCSK9 inhibitor) on top of Statins to reduce CVS risk?

Answer 3

Not really –> no reduction in deaths, but reduction in MI and Cardivascular events and Triglicerides but expensive

Generally currently reserved for high risk

• very high lipid levels (especially Familiar)
• If statins are contraindicated

Question 4

What time of good diabetic control is needed until a difference in complications seen?

Answer 4

9-15 years

Question 5

Name some example of SGLT-inhibitors

Answer 5

**- gliflozin **

Dapagliflozin
Empagliflozin
Canagliflozin

Question 6

What are the effects of SGLT2 inhibitors on eGFR?

Answer 6

Similar to ACE inhibitors

–> initial drop, but after 1 year it is long-term protective

Question 7

What are the benefits of SGLT-2 inhibitors?

Answer 7

1. Weight loss
2. glycamic control
3. CVS protective (hypotension)
4. Renal protective
5. all protective

–> good

Question 8

What is the MOA of SGLT-2 inhibitors?

Answer 8

Blocking glucose resorption in kidney leading to glucose diuresis (via inhibition of Sodium-Glucose co-transporters)

Question 9

What are the main side-effects of SGLT2 inhibitors?

Answer 9

• UTIs
• potentially initial drop in eGFR
• increased incidence in normoglycaemic DKA

Question 10

Other than Metformin and SGL-2 inhibitors, what other 2 classes of drugs are now more commonly used in the control of Type 2 diabetis?

Answer 10

1. GLP-1 receptor agonist
2. DPP-4 inhibitor

Question 11

Name some examples of DDP-4 inhibitors. What is their MOA?

Answer 11

Gliptins
Sitagliptin, Linagliptin

MOA:
prevent break down of own GLP-1)
Indications/side effects same as FLP-1 analogue) Improve diabetic control and potentially weight loss (but usually no weight changes can be observed)

Question 12

What is the MOA of GLP-1 receptor agonists?

Answer 12

GLP 1 is

• Endogenous proteins that stimulate glucose-dependant insulin secretion and decrease glucagon secretion
• Reduce gastric emptying + appetite

Question 13

What are the benefits of using GLP-agonist in T2 diabetes control?

Answer 13

a) Weight loss
b) No risk of hypoglycaemia (so expecially good in patients with increased risk of hypoglycaemia)

+ Cardioprotective etc. (but not as good as SGLT2)

Question 14

What are the benefits of using GLP-agonist in T2 diabetes control?

Answer 14

a) Weight loss
b) No risk of hypoglycaemia (so expecially good in patients with increased risk of hypoglycaemia)

+ Cardioprotective etc. (but not as good as SGLT2)

Question 15

Name an examples of GLP-1 receptor agoinsts

Answer 15

Incretin (GLP-1 analogue –> peptide increasing insulin secretion )(-atide/- glutide)

Question 16

What are the main side-effects of GLP-1 agonists?

Answer 16

• GI complications, especially if already existing reduced gastric emptying.
  
  • Increased risk of pancreatitis and pancreatic cancer

Question 17

What type of drug is Gliclazide?

Waht is the main side-effect?

Answer 17

Sulphonylureas

Now used less and less frequently due to increaed risk of Hypos

Work by

1. Increased insulin secretion (Blockage of ATP-sensitive K+ channels on pancreatic beta cells) –> depolarisation of the cell membrane –> calcium influx–> increased insulin secretion
2. Decrease in hepatic gluconeogenesis and increase in peripheral insulin sensitivity

Question 18

Name the drug used for patients with type 2 diabetes which inhibits the enzyme alpha glucosidase in the brush border membrane of the small bowel.

Answer 18

Arcabose

Question 19

What type of drugs is thiazolidinediones?

What are they used for?

Answer 19

Insulin sensitisers tht could be used in monotherapy treatment of Type 2 Dieabets
Indiations

• severe renal failure
• and/or contraindication for insulin therapy

Question 20

What is the first-line treatment for patients with T2DM and CKD stage 4 (eGFR < 30ml/min)

Answer 20

Sulphonylureas (e..g Gliclazide)

Question 21

What do you need to consider regarding Metformin perscription and CKD?

Answer 21

Contraindicated if eGFR < 30ml/min
Caution if < 45 ml/min due to riks of lactic acidosis