Cholesterol + Drugs + IHD Flashcards
Lateral portion of left ventricle is supplied by which artery?
Circumflex
Anterior rounded section of a transverse cut heart is supplied by which artery?
left anterior descending
posterior descending artery supplies which segment of the heart?
posterior flattened area
LAD territory in the heart is where?
anterior 2/3 of heart
The circumflex artery supplies which heart segment?
Lateral
When does the myocardial blood usually flow?
during diastole
which heart area is most susceptible to ischaemia?
subendocardial muscle
additional oxygen supply to meet demand must be met by:
an increase in blood flow
What is Laplace’s relationship?
ventricular wall stress is proportional to pressure and radius
inversely proportional to wall thickness
Define Ischaemic heart disease
group of conditions where heart demand is not being supplied
Is stable angina acute or chronic?
chronic
Is unstable angina acute or chronic?
acute
What prevents stenosis in initial stages of atherosclerosis?
vessel remodelling to accomodate
How much percentage narrowing of a vessel do you need to get symptoms?
70%
If a vessel has atherosclerosis, what else is impaired in the endothelium?
vasodilators
Why do you get pain in Acute myocardial ischaemia?
no ATP = anaerobic resp = acidosis = products = stim the pain nerves
Key features of unstable angina?
pain at rest, increasing in frequency
Key feature in stable angina?
pain only upon exertion
Acute plaque event happens when what tears and exposes what?
Fibrous cap tears and exposes tissue factor = thrombus
if a thrombus starts, it’s it all or none?
Nope. It’s dynamic so there will be fibrinolysis too but the clotting may overtake and occlude the artery leading to infarction
Most common cause of Sudden Cardiac Death?
arrhythmic cardiac arrest d/t ventricular fibrillation/tachycardia = no blood pumped out = drop dead
Can the heart beat at 400-500 beats per minute?
YES. in Ventricular fibrillation. mind blown
What is a mechanical mechanism for sudden cardiac death?
haemopericardium = tamponade (ECG is present but no CO)
Do you always get an infarction with arrhythmic sudden cardiac death?
Not necessarily.
How long does it take to get irreversible myocite injury?
20-40 minutes of severe ischaemia
How long for MI to go transmural? where does it start?
up to 24 hours
99% cause of regional transmural MI is?
thrombosis post acute plaque event
Subendocardium get damaged in two shapes:
regional
circumferential (not common)
What would you look for in MI diagnosis on ECG?
ST elevation MI
Non-ST elevation MI
How many days can you detect CK-MB and Troponins in the blood post MI?
CK-MB: 2-3 days
troponins: about 6 days
You usually die from complications of MI, they are: 3 things:
ventricular fibrillation = sudden death
cardiac failure
acute pulmonary oedema
What can be ruptured in MIs? WHen do they usually occur?
papillary muscles
free wall of LV
Will a ventricular aneurysm risk bursting? what’s so dangerous about them?
Not likely to burst, but dilation increases risk of thrombus formation d/t decreased flow blood
3 other causes of ischaemic heart disease?
thromboemboli
vasculitis
aortic dissection
4 None-coronary artery ischaemic heart disease
LV hypertrophy
rapid tachycardias
hypoxemia
shock
two surgical treatments for ischaemic heart disease?
stents
coronary bypass
How is cholesterol transported in blood as?
lipoproteins (the carriers)
What is a waxy steroid metabolite found in cell membranes?
cholesterol
Chole- means?
Bile
stereos means?
solid
What is the principle sterol synthesized by animals?
Cholesterol. duh.
If the body is too hot or cold, what happens to cholesterol in the cell membrane?
Hot: fluidity/permeability increases too much
Cold: not fluid/permeable enough
What is the key component in vitamin D, steroid hormones and bile acids?
cholesterol
Name the 3 critical intermediates in cholesterol synthesis
HMG-CoA
Isoprene
Squalene
4 types of lipoproteins involved in cholesterol transport?
chylomicrons
VLDL
LDL
HDL
How does HMG-CoA reductase affect arteriosclerosis?
If it’s hyperactive due to genetics, then you’ll get more LDL cholesterol in blood
What is the genetic disease for increased cholesterol ?
Familial hypercholesterolaemia.
How many carbons in cholesterol ?
27
Which carbon is the OH on in cholesterol ?
3
describe cholesterol’s relationship with water
it’s amphiphilic. kinky.
Do plants make any cholesterol?
Nope. They have their own sterols
Where is VLDL cholesterol made?
liver
cholesterol in liver has 3 fates:
- ester formation, stored as VLDL
- bile (recycled usage)
- membranes
how much percent is cholesterol in the animal cell membrane?
8%
Where does cholesterol fit in the cell membrane’s Phospolipids?
In the cis-bond kink to decrease fluidity
What does cholesterol start off as?
Acetyl CoA
What has more energy? 1 ATP? or 1 NADPH?
NADPH yo.
Where in the cell is cholesterol made?
endoplasmic reticulum
What is ApoB-100?
protein that identifies LDL, attaches to receptor on liver
Lipoproteins have a phospholipid bilayer?
Naw. Monolayer!
HDL has what protein marker?
ApoA-I (HDL is good so it’s number one!)
VLDL and LDL has what protein marker?
ApoB-100 (LDL is bad so it’s b for bad)
what is the protein marker for chylomicrons and VLDL?
ApoC-II ( C for chylomicrons)
ApoC-II marks what?
Chylomicrons and VLDL
ApoA-I marks what?
HDL
Where do you find ApoC-II usually?
Outside of muscles to break down fat anuse it as energy
What’s the cholesterol donor?
LDL
What’s the cholesterol scavenger?
HDL
VLDL is created in liver, LDL is created?
In plasma from reminant chylomicrons
What and where does LCAT and ACAT enzymes come into play regarding cholesterol ?
LCAT - in plasma for HDL
ACAT - liver for VLDL
What’s in side LDL lipoprotein?
cholesterol ester, triacylglycerols, free cholesterol (no need to pay for them.)
HDL does what to macrophages?
prevents foam cell formation
What shape is Apo-AI
circular to make hydrophobic ring and round up cholesterol
How much percent does cardiovascular disease account for?
40%!
How much percent does cardiovascular disease account for?
40%!
3 kinds of dyslipidaemia are?
hypercholesterolaemia
hypertriglyceridaemia
mixed hyperlipidaemia
When are you considered high risk for hypercholesterolaemia?
> 7.5mmol/L cholesterol
Is cholesterol important for hormones?
Yes. precursor to steroid hormones
Whats the first statin discovered called?
Mevastatin
What do all statins do?
inhibit HMG-CoA
derease mevalonic acid
One dose of statin is great! TWO dose must double the effect right?
Nope.
What conditions to you use statins?
hypercholesterolaemia
mixed hyperlipidaemia
How long does it take for effect of statins?
1-2 years or use
Grapefruit juice doesn’t mix well with:
Statins
You need to be careful of these 3 things if you’re taking statins cause they’ll increase statin levels too much:
antibiotics
antifungals
fibrates
Common adverse effects of statins?
mild GI, headahce, insomnia, dizzy
When should you withhold statins? 3 scenarios:
infection
presurgery
post trauma
What drug binds bile acid to treat hypercholesterolaemia?
Resins like Cholestyramine
When should you give Resins if you have to give other drugs?
hours before or after resin
Whats Ezetimibe?
selective inhibition of cholesterol absorption in intestine via sterol transporter
does Ezetimibe affect bile acids, fat soluble vitamins, or cholesterol?
Cholesterol only, its like a cholesterol sniper.
Can you combine Ezitimibe?
Yes, like statins and other agents too
Which B-vitamin can you use to treat hypercholesterolaemia?
B3 - Niacin
What are some adverse effects of Niacin treatment for hypercholesterolaemia?
Flushing, vasodilation, hypotension, BUT tolerance develops
Would you use Niacin for hypercholesterolaemia alone?
Nope. Usually only in combos
What are fibrates used to treat?
Hypertriglyceridaemia
Gemfibrozil and fenofibrate are Hypertriglyceridaemia drugs, how do they work?
nuclear receptor agonistsm upregulate gene for lipoprotein lipase to lyse triglycerides in plasma
Are fibrates for Hypertriglyceridaemia first line?
Second line after dietary and lifestyle changes
Nausea, dry mouth, headache and rash are common side effects for which Hypertriglyceridaemia drug?
Fibrates
Can you treat Hypertriglyceridaemia with fish oils?
Yep.
What do you do if you have severe Hypertriglyceridaemia?
polytherapy: diet, fibrates, fish oils, statins, niacin, orlistat
What does decreased Q10 symptoms?
cardiac and skeletal muscle pain and complications
What’s the good thing that statins block out?
Q10 production
how do statins work?
competitive inhibitors of HMG-CoA reductase
how do you get elevated circulatory LDL in terms of a genetic reason?
Failure of LDL receptors to take LDL from circulation
What is a xanthoma?
cholesterol deposits = yellow under skin
Familial Hypercholesterolemia is suspected if? 2 things.
family history of early MI
>15mM choesterol
How do you treat Familial Hypercholesterolemia?
statins
What is mutated in Familial Hypercholesterolemia?
LDL receptor gene
In Familial Hypercholesterolemia, is it dominant or recessive?
Dominant
If you have Familial Hypercholesterolemia, what age can you get an MI?
mid twenties
Whats so important about the end product cholesteryl ester droplet after the cell takes in the LDL?
If provides feedback inhibition of HMG-CoA reductase
In Familial Hypercholesterolemia, what mechanism is messed up in the cholesterol production circuit?
HMG-CoA reductase is not inhibited and it just has a field day and over produces cholesterol
” Bro, I feel like my breast is being strangled.”
“Dude, you have angina pectoris, go to the hospital.”
What is variant angina?
coronary vasospasm at rest
unknown mediator
Any coronary reserve with angina?
Nope. All used up.
General drugs classes to affect:
Preload
Afterload
Mycardium
Preload: Nitrates
Afterload: Ca2+ blockers
Myocardium: B-adrenoceptor/Ca2+ blockers (Ivabradine)
How does nitrates decrease preload?
relaxes veins
how does nitrate decrease afterload?
relax large arteries
What’s the short acting nitrate given for acute symptoms of angina?
GTN (glyceryl trinitrate)
How do you administer GTN?
sublingually or transdermally
What’s finicky about GTN? 3 things:
light sensitive
needs to be in glass vial
1st pass metabolism
What’s the longer acting nitrate given for angina? how is it administered?
isosorbide dinitrate orally
do you only take nitrates reactively?
You can take them proactively too.
Why would you get reflex tachycardia with nitrate use alone? what can you do about it?
Baroreflex activates due to decrease in BP. So combine with B-blockers or Ca2+ blockers
Nitrate and viagra is bad why?
Viagra is a phosphdiesterase inhibitor, breaks down cAMP and you’ll get over cGMP production and could be fatal.
“I love GTN, I use it ALL the time Doc, that cool?”
“Bro, you’re gonna develop tolerance, your tissues are thiol depleted, here’s some N-acetyl cysteine, and take off the patch at night dummy.”
What kind of channels do Ca2+ blockers block?
L-type channels
What drugs to block Ca2+ into heart?
verapamil
diltiazem
What’s nifedipine and felodipine used for?
block Ca2+ entry into vessels
What’s verapamil
diltiazem used to do?
block Ca2+ into heart
Drugs to block Ca2+ entry into vessels?
nifedipine and felodipine
Should you combine verapamil and nifedipine in severe angina?
NO WAY. never combine two cardio depressive agents. You can combine it with a B-blocker instead Dr. House.
How are Ca2+ blocker normally used? Reactively? or?
Prophylactically
What type of Beta adrenoceptors are blocked?
Beta-1 adrenoceptors
Two areas of the heart the beta blockers effect:
Nodes
myocardium
Would you choose beta blockers or Ca2+ blockers for first line prophylaxis?
beta blockers
What is the selective beta-1 blocker?
atenolol
What’s a non-selective beta blocker?
propranolol
“I’m on nitrates, Ca2+, and B-blockers Doc, my heart disease is a-ok right?”
“Actually those drugs aren’t disease modifying, your risks of MI and mortality is exactly the same, you’ll just be more comfortable before you drop dead.”
Why is ivabradine so great?
‘pure’ heart rate reduction
selective inhibition of inward Na-K current in sinus node is done by which drug?
ivabradine
does ivabradine affect contractility, conduction, BP?
Nope. Just heart rate.
Why give ivabradine if it ‘only’ decreases heart rate?
It preserves endothelium-mediated vasodilation to there is improved exercise tolerance
What drug give you brightness in your visual field due to retinal effects?
ivabradine
Does ivabradine work if your HR is >70bpm?
Yes! only if it’s <70 bpm!
What is drug is contraindicated in variant angina?
B-adrenoceptor antagonists cause it may worsen the vasospasm
How would you treat unstable angina?
Nitrate, Ca2+/B-blocker, and also aspirin
