ChemPath - Lipid update Flashcards
What are the conclusions of the SPRINT research study
Aggressive management of BP and lipids improve survival
Reducing BP further (140/80→ 120/80) greatly reduces deaths
Using thiazide diuretics to further lower BP in those with CHD → saves 2% over 5 years
What is the optimal medical therapy in people with coronary heart disease
- Intensive lifestyle modification
- Aspirin
- High dose statin (Atorvastatin 40-80 mg OD)
- Optimal blood pressure control
- Assessment for probable T2DM (HbA1c)
What medications can be given for lowering lipid levels
Statins
Ezetemibe (blocks NPC1L1 to reduce absorption)
Evolocumab (PCSK9 monoclonal antibody which removes PCSK9)
Plasma exchange
What is the MOA for evolocumab
PCSK9 monoclonal antibody
PCSK9 regulates the level of LDL receptor expression so if there a loss-function mutation, this increases the LDL-R receptors on the liver which reduces plasma LDL
What were the outcomes of the Fourier “PCSK9” study
Absolute reduction in LDL levels
Reduced major cardiovascular events, especially when added to statin therapy
Effect on mortality was insignificant
Therefore evolocumab is reserved for patients who are statin intolerance or have uncontrolled lipids
According to the UKPDS, how long does it take to see benefits of glucose control in T2DM patients
15 years
What is the legacy effect
Patients who had completed the UKPDS reverted back to poor glucose control on follow up, and HbA1c levels became similar to the control group
Mortality in the intensive treatment group remained low despite glucose control
What was the outcome of the Accord study
Looked at benefits of glucose control in those with cardiovascular complications in diabetes (USA/Canada)
Suddenly and aggressively controlling blood glucose in people with previous poor control leads to reduced complications BUT increased mortality (tachyarrhythmias)
How do SGLT-2 inhibitors work and give an example of a drug in this class
Reduce glucose re-uptake in the proximal tubules
Leads to osmotic diuresis (low glucose + BP)
Empagliflozin, canagliflozin
What were the conclusions of the EMPA-REG study
Significant and quick reduction in mortality after just 4 years
Also helped to treat heart failure and prevent nephropathy
Although will show an initial sharp reduction in GFR, followed by recovery
What were the conclusions of the following studies: CANVAS, OBSERVE-4D, DECLARE
CANVAS - canagliflozin increased amputation risk
OBSERVE-4D - no excess amputations with canagliflozin
DECLARE - no excess amputation risk with dapagliflozin
What is the MOA for GLP-1 analogues and give examples of drugs in this class
GLP-1 is a peptide secreted from gut L-cells that signal the pancreas to make insulin
This has a direct effect on appetite and gastric emptying
responsible for the incretin effect
GLP-1 is then broken down by DPP4
Exenatide, Liraglutide (Saxenda), Semaglutide
What is the MOA for Gliptins
Inhibits DPP4, which in turn prevents the break down of GLP-1 which can continue to signal insulin production
What are the options for medical management of T2DM (NICE)
- Single therapy with metformin
- Dual therapy with metformin + sulphonylureas, SGLT-2
- Triple therapy with metformin + sulphonylureas + fliptin, thiazolidinedione
- Triple therapy with metformin + sulphonylurea + GLP-1 analogue
Which diabetic control drug can cause hypoglycaemia (other than insulin)
Sulphonylureas e.g. glibenclamide
