Lipid Update

Question 1

describe the Optimal medical therapy for those with Coronary heart disease?

Answer 1

Intensive lifestyle modification

Aspirin (A)
High dose statin (A- Atorvastatin 40-80mg od)
Optimal blood pressure control - BC
Thiazides are almost free

Assessment for probable T2D (check HbA1c) - D

AABCD

Question 2

Aggressive management of which factors improves survival in CHD?

Answer 2

blood pressure and lipids

Question 3

optimum BP target in an elderly patient with CHD?

Answer 3

120/80

Question 4

Options for people with statin intolerance?

Answer 4

Ezetemibe - non statin lipid lowering drug

Plasma Exchange where available

Evolocumab (PCSK9 monoclonal antibody)

Question 5

which study has shown benefit for Aggressive management of BP and lipids in CHD?

Answer 5

SPRINT study

Question 6

which protein regulates the levels of the LDL receptor?

Answer 6

proprotein convertase subtilisin kexin 9 (PCSK9)

Question 7

Gain-of-function mutations in PCSK9 result in?

Answer 7

reduce LDL receptor levels in the liver, resulting in high levels of LDL cholesterol in the plasma and

increased susceptibility to CHD

Question 8

Loss-of-function mutations in PCSK9 result in?

Answer 8

higher levels of the LDL receptor, lower LDL cholesterol levels, and

protection from coronary heart dis

Question 9

patient is on atorvastatin but cholesterol needs further reduction. which drug to prescribe now?

Answer 9

Evolocumab

PCSK9 inhibition

Question 10

which drug added to atorvastatin DOES NOT reduce DEATH but does bring down LDL and major CVS events?

Answer 10

Evolocumab

Question 11

negatives of evolocumab?

Answer 11

horrendously expensive

reserve for high risk/ statin intolerant: e.g. hereditary hypercholesterolaemia

Question 12

Which study showed that aggressive control of blood glucose maintains a lower HbA1c through 15 years of follow-up

Answer 12

The UKPDS study : prospective diabetes study

T2DM

Question 13

what is the LEGACY EFFECT in blood glucose control?

Answer 13

mortality in the intensive treatment group remained low

after reverting back to loose treatment (their blood glucose control deteriorating to the same level as conventional treatment)

meaning they still see future benefit due to the years of good control

Question 14

Which study suggests that tight Blood glucose control increases mortality?

Answer 14

ACCORD study

suddenly aggressively controlling the blood glucose of people who have had poor control for decades leads to reduced complications but increased mortality

Question 15

the accord study recommends what after 20 years of tight BM control?

Answer 15

This is to say tight control is needed for 20 years then relax the therapy otherwise increased death

Question 16

empagliflozin is an example of ?

Answer 16

SGLT2 Inhibitor

Sodium-glucose cotransporter-2 (SGLT2) inhibitors

Question 17

role of SGLT2 Inhibitors?

Answer 17

These drugs are designed to make you pee out glucose

reduce BP and Blood glucose

Question 18

what is the MOA of SGLT2 Inhibitors?

Answer 18

Block the SGLT2 channels in the PROXIMAL TUBULE of nephrons

to reduce glucose reabsorption

Question 19

which study found EMagliflozin to Reduce MACE – major adverse cardiac events?

in patients with established CVD

Answer 19

EMPA - REG

Question 20

NEGATIVES about SGLT2 inhibitors?

Answer 20

EXPENSIVE

reduce eGFR - later resolves

Question 21

what is the role of GLP-1?

Answer 21

GLP-1 is secreted from the gut, and signals the pancreas to make even more insulin.

It also has a direct effect on appetite and gastric emptying

GLP-1 inhibits gastric emptying, acid secretion and motility collectively decreasing appetite.

Question 22

what is the incretin effect?

Answer 22

The incretin effect describes the phenomenon whereby oral glucose elicits higher insulin secretory responses than does intravenous glucose, despite inducing similar levels of glycaemia, in healthy individuals.

Because in the gut, incretins are released ; One of their many physiological roles is to regulate the amount of insulin that is secreted after eating.

Question 23

what hormone breaks down incretins e.g. GLP-1?

Answer 23

DPP4

Question 24

give some examples of GLP-1 analogues?

Answer 24

○ Exanatide
○ Liraglutide (Saxenda)
○ Semaglutide

Question 25

insulin is released from where in the pancreas

Answer 25

Beta cells in the islets of langerhans

Question 26

when you eat what is the response from the pancreas?

Answer 26

reduced glucagon from a cells

increased insulin from B cells

Question 27

when you eta what is the response from the liver and muscles?

Answer 27

reduced HPO from liver

increased peripheral muscle glucose uptake

Question 28

If a patient a tumour secreting excess GLP-1 what symptoms would we see?

Answer 28

hypoglycaemic episodes due to augmentation excess insulin production

Question 29

first line treatment for T2DM?

Answer 29

METFORMIN

Question 30

what happens if HbA1C target not met after 3 months of metformin?

Answer 30

add GLP-1 receptor antagonist

Question 31

what would be the role of a DPP-4 inhibitor?

Answer 31

inhibit DPP4 to prevent the breakdown of GLP-1 hence an up regulation in insulin production hence tighter BM control.

Question 32

patient with T2DM and established CVD. what to prescribe?

Answer 32

metformin +

SGLT2 inhibitors - empagliflozin
OR
GLP-1 analogue

Sglt2 and glp1 are preferred over dpp4 for adding to metformin

Question 33

how does Ezetimibe work?

Answer 33

blocks the critical mediator of cholesterol absorption;

the Niemann-Pick C1-like 1 (NPC1L1) protein

on the gastrointestinal tract epithelial cells

Question 34

Lipid soluble drugs require metabolism by the liver in two phases. What is Phase I

Answer 34

phase 1 - Oxidation by cytochrome P450