Session 5 Flashcards
Brief overview of atherosclerosis?
I’d suggest looking at path as easy link here
LDL accumulation due to endothelial insult and the cells oxidise LDL accumulating monocytes inintima forming foam cells after engulfment. Sm cells proliferate forming the fatty streak. Disrupts vascular smooth muscle cells so platelets can bind.
How do statins work? Suggest revising MEH briefly here
2 examples?
Competitive inhibition of HMG-Coa reductase. Rate controlling enzyme in mevalonate pathway.
Low levels of cholesterol cause an up regulation of LDL receptors
Increasing LDL clearance/uptake from blood.
Atorvastatin,simvastatin
Benefits of statin therapy?
Lowers CVD risk
provides VEGF thus improved endothelium function
stabilisation of plaque as lower SM proliferation and increases collagen
Increases fibrinolytic and decreases platelet aggregation
Anti-inflammatory so less influx into plaque
Antioxidant
What is simvastatin and how activated?
Atorvastatin?
Side effects?
Don’t give if?
Pro drug activated by first pass metabolism
First pass metabolism into active derivatives
GI problems,headaches,nausea,myalgia,rhabdomyolysis
Renal impairment,pregnancy,breast feeding,amiodarone/amlodipine and CYP 3A4 is vital
When is primary prevention used with statins and dose?
Secondary prevention dose?
Example of fibrates?
10 year CVD risk of >10% using qrisk, 20 mg atorvastatin daily
80mg daily
Fenofibrate
What do fibrates do?
Result?
Side effects?
Don’t give with?
Activate nuclear transcription factor PPARa, regulates gene expression controlling lipoprotein metabolism increasing lipoprotein lipase production.
Increasing fatty acid uptake in liver, increase levels of HDL
Mylositis,cholelithiasis
Warfarin
What is ezetimibe? And dose?
What does it do?
What special about this pro drug?
Given adjunct to?
Side effects?
Don’t give if?
A cholesterol absorption inhibitor, 10mg SID
Inhibit NPC1L1 transporter, reducing cholesterol absorption in the gut, also increases LDL receptor expression.
Metabolised in liver and in the enterohypatic circulation, secretes by bile
Statins
Abdominal pain and GI upset
Hepatic failure
Target for those receiving secondary prevention for hyper cholesterol anemia?
Alirocumab?
Total cholesterol 4 and ldl 2 mmol/l
PCSK9 proteins bind to LDL receptors causing degradation.Alirocumab is a PCSK9 inhibitor reducing LDL cholesterol levels
Plant sterols do?
Work with?
Other good things for lowering cholesterol?
When might you combine statins and ezetimibe?
Lower ldl cholesterol naturally occurring in grains and legumes.
Statins not ezetimibe
Fish oils,Vit C/E
If tolerated low statin dose, they have a synergistic effect helping CKD and CVD
What stimulates insulin?
Inhibits?
Parasympathetics (M3)
Glucose incretins
Sympathetic (a2)
Glucagon
Cortisol
Diabetes symptoms?
Use of hba1c?
Random >11mmoll Polyuria Polydipsia Tired Thirst
Average sugar levels of past 12 weeks as it’s %of RBC’s with sugar coating
Why is insulin given paraenterally?
Half life?
Metabolised?
When might you have to change the route of administration?
Do what to insulin dose if taking with steroids?
To avoid protein digestion in the gut
5mins in plasma, thus conc highest after a few hours
Liver and kidney
Lipodystrophy
Increase dose
When should met for in be given in type 2?
Describe and example of biguanides?
Side effects?
Don’t take with?
HBA1c gets to 48mmol/mol (6.5%)
Metformin, lowers hepatic glucose output (glycogenolysis and gluconeogenesis). Also increases muscle utilisation and lowers appetite.
Nausea, GI upset/diarrhoea
Diuretics as they increase glucose so impair metformin action
What are sulfonylureas? And example?
Main issue?
Side effects?
Don’t take with?
Gliclazide, stimulate B cells to release insulin by blocking atp dependent k channels.
Weight gain through anabolic effects of insulin
GI,nausea,hypoglycaemia
Diuretics
Thiazilidinediones?
Issue?
Side effects?
Pioglitazone
Rosiglitazone
Increase sensitisation in muscle and adipose, lower hepatic output. Via activation of ppar-y involved in gene transcription.
Weight gain due to fat cell differentiation.
GI,hypoglycaemia
