ChemPath - Lipid update Flashcards

1
Q

What are the conclusions of the SPRINT research study

A

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

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2
Q

What is the optimal medical therapy in people with coronary heart disease

A
  • Intensive lifestyle modification
    • Aspirin
    • High dose statin (Atorvastatin 40-80 mg OD)
    • Optimal blood pressure control
    • Assessment for probable T2DM (HbA1c)
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3
Q

What medications can be given for lowering lipid levels

A

Statins
Ezetemibe (blocks NPC1L1 to reduce absorption)
Evolocumab (PCSK9 monoclonal antibody which removes PCSK9)
Plasma exchange

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4
Q

What is the MOA for evolocumab

A

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

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5
Q

What were the outcomes of the Fourier “PCSK9” study

A

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

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6
Q

According to the UKPDS, how long does it take to see benefits of glucose control in T2DM patients

A

15 years

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7
Q

What is the legacy effect

A

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

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8
Q

What was the outcome of the Accord study

A

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)

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9
Q

How do SGLT-2 inhibitors work and give an example of a drug in this class

A

Reduce glucose re-uptake in the proximal tubules
Leads to osmotic diuresis (low glucose + BP)

Empagliflozin, canagliflozin

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10
Q

What were the conclusions of the EMPA-REG study

A

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

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11
Q

What were the conclusions of the following studies: CANVAS, OBSERVE-4D, DECLARE

A

CANVAS - canagliflozin increased amputation risk
OBSERVE-4D - no excess amputations with canagliflozin
DECLARE - no excess amputation risk with dapagliflozin

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12
Q

What is the MOA for GLP-1 analogues and give examples of drugs in this class

A

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

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13
Q

What is the MOA for Gliptins

A

Inhibits DPP4, which in turn prevents the break down of GLP-1 which can continue to signal insulin production

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14
Q

What are the options for medical management of T2DM (NICE)

A
  1. Single therapy with metformin
  2. Dual therapy with metformin + sulphonylureas, SGLT-2
  3. Triple therapy with metformin + sulphonylureas + fliptin, thiazolidinedione
  4. Triple therapy with metformin + sulphonylurea + GLP-1 analogue
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15
Q

Which diabetic control drug can cause hypoglycaemia (other than insulin)

A

Sulphonylureas e.g. glibenclamide

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16
Q

Give an example of a drug from each class for diabetic control

A

Biguanide - metformin
Sulphonylurea - glibenclamide
Thiazolidinedione - pioglitazone
DPP4-inhibitor - gliptin
SGLT-2 inhibitors - empagliflozin
PCSK-9 inhibitors - evolocumab
GLP-2 analogues - liraglutide