Chemical Pathology 19 - Lipid Update Flashcards
What is the statistical mortality benefit of adding a thiazide diuretic to outstanding BP medications, following an MI?
Worth it, as 2 in 100 will be prevented from a further MI in the next 5 years
What is the statistical mortality benefit of adding a PCSK9 inhibitor to outstanding BP medications, following an MI?
Decreases incidence of non-fatal MI, but does not reduce death
potentially useful in patients who are high risk (i.e. familial hypercholesterolaemia or statin-intolerant patients - BUT VERY EXPENSIVE DRUG
Give an example of a PCSK9 inhibitor medication, and how it works
Evolocumab
Inhibits PCSK9 enzyme, which would normally degrade the LDL receptor
*NB- LDL receptor is necessary to allow cholesterol recycling i.e. reduces cholesterol levels in the bloodd
inhibiting PCSK9 with mAbs can increase the removal of LDL cholesterol from the plasma
What did the UKPDS study show?
That early blood glucose control is important in reducing mortality/complications in patients with T2DM- even if later on their HbA1c increases
- it takes about 15 years before the benefits of good glucose control becomes apparent
**so it’s about control EARLY ON - AKA LEGACY EFFECT**
LEGACY EFFECT: mortality in the intensive treatment group remained LOW despite their blood glucose control deteriorating to the same level as conventional treatment
What did the Accord and Advance study show?
Slightly less intense intervention into glucose control actually reduce death compared to super-intense intervention
suddenly aggressively controlling the blood glucose of people who have had poor control for decades leads to reduced complications but increased mortality
- can precipitate tachycardia and kill patients
What did the Accord study show?
If you take someone who already has knackered coronary arteries and suddenly tighten glucose control, motality actually increases
What did the DCCT show?
Good control in type 1 diabetes improves outcome
What makes SGLT2 inhibitors such a fabulous drug class according to Meeran?
Reduce HbA1c, BP, weight, type 2 diabetes incidence and cardiovascular disease, with immediate effect!
What is the broad mechanism of action of SGLT2 inhibitors? + examples
They cause glycosuria by inhibiting SGLT2 in the kidney - reduces renal reabsorption of glucose
empagliflozin - main one
canagliflozin
dapagliflozin
Give an example of a GLP-1 analogue drug and MOA?
Semaglutide
Liraglutide- saxenda
Exenatide
**they try to mimic the incretin effect of endogenous GLP-1 - release of insulin following ingestion of glucose**
these are injections, injected once a week
MOA of DPP4 inhibitors
Example
They inhibit DPP4 enzyme which is responsible for breaking down GLP-1
(increases the amount of endogenous GLP-1- improved incretin effect by increased insulin release after ingestion
Example: gliptins - which can be taken orally
What is the optimal medical therapy for people with coronary heart disease/
- intensive lifestyle medication- bring down their risks (i.e. stop smoking)
- Aspirin
- High-dose statin (Atorvastatin 40-80mg OD)
- Optimal blood pressure control
- Thiazides are very CHEAP
- Assessment for probable T2DM (HbA1c)
- KEY POINT: aggressive management of blood pressure and lipids improves survival
WHat are some options for people with statin intolerance?
- ezetimibe
- plasma exchange
- evolocumab - PCSK 9 monoclonal antibody
* NOTE: PCSK9= Proprotein Convertase Subtilisin Kexin 9 - niacin - vitamin B3 - no longer available
MOA of ezetimibe
cholesterol absorption blocker (blocks NPC1L1)
How long does it take to see benefits of controlling glucose?
15 years
Overall summary of diabetes care
- metformin- trial for 3 months - FIRST LINE
- add either:
a) SGLT2 inhibitor - flozin (inhibits SGLT2 so causes glycouria and reduced absorption of glucose by kidneys)
KARIM MEERAN LOVES THIS DRUG
b) GLP-1 analogue - glutide (incretin effect- release of insulin in response to glucose)
c) DPP4 inhibitor - gliptin (inhibits DDP4 which prevents breakdown of GLP-1, so more GLP-1)
