CV Drugs 2 Flashcards
What is Angina
It’s a symptom of coronary artery disease
William Heberden: ‘Disorder of the breast, choking of the breast’
What is Angina caused by
Build up of plaques narrows coronary arteries = decreased BF to heart - May cause chest pain (angina)
Burns was the first person to figure out what angina was caused by: Nutrient arteries of the heart are disease, impede the process of blood among them, Heart is sooner fatigued in the other parts.
So caused by Coronary Arteries becoming damaged - due to cholesterol-containing deposits (plaques) in your arteries and inflammation.
What is Atherosclerosis
The build-up of cholesterol-rich plaques (generally form in the proximal regions of coronaries, within 6cm of the Aorta) that causes stenosis of coronary Arteries
1 or more stenosis of coronary Arteries can cause Angina
Atherosclerosis has a fibrous cap (overlaying atheroma) - smooth muscle cells and connective tissue.
Also has Atheroma (yellowish/red) - soft pool of extracellular lipid, fell debris, activated immune cells. It progressively calcifies over time
Where is Atherosclerosis also common in, apart from Coronary Arteries?
Renal - Chronic Kidney Disease
Carotid Arteries - Stroke
Two types of Plaque?
Thin Fibrous plaque
- can rupture to get Thrombosis
- can progress to Acute Coronary Syndrome which is precipitated by a sudden decrease in coronary flow
Thick Fibrous plaque with small Atheroma
- lumen of Arteries are narrow - vasoconstriction, spasm
- leads to coronary flow reserve, so Stable angina. This is precipitated by an increase in myocardial O2 demand.
Types of Angina?
1) Angina of Effort
•symptoms: tightness, squeezing, crushing sensation in the chest
•Most common: Due to exertion/emotion, stops with rest or GTN
•results from increased O2 demand w resisted BF, due to fixed (Ather) stenosis
•decreased O2 in cardiac tissue -> release of protons, bradykinin -> Activation of TRPV1
2) Microvascular Angina
•chest pain, Normal Coronary angiogram, +ve exercise test; endothelial dysfunction,
•No stenosis. Do become ischaemic & develop Angina w effort
•occurs more commonly in women
3) Mixed Angina
•Unpredictable, develops at different levels of exercise
•Probably due to stenosis + vasospasm - thought to be v common
4) Vasospastic: dec O2 supply
•due to spasm of coronary artery
•occurs at rest, often at night
What are the Aims of drug treatment?
1) Limit the number, severity and sequelae of anginal attacks, thereby improving the quality of life
•main mechanism for the pharmacological treatment of Angina of Effort is to reduce cardiac O2 demand
•secondary mechanism is to increase O2 supply to the ischameic zone by reducing HR & increasing BF in Coronary Arteries
2)Protect against failure, potentially more lethal ischaemic syndromes (eg MI) and lower the risk of Atherosclerosis progression
State the different drugs available for Angina of Effort
->Cardiac O2 demand is a function of walls tension, contractility, and HR
- Nitrates
- B-Blockers
- Ca-channel blockers
- Katp channels activators
- Ivabrodine
- Ranolazine
NICE treatment pathway for Angina
*Use Short-acting Nitrate for immediate relief/short-term prevention
*For ongoing prophylaxis:
Step 1: B-blocker OR CCB
Step 2: B-blocker + Vascular selective CCB
Step 3: B-blocker + Vascular selective CCB + long-acting nitrate OR
Ivabradine OR
Nicorandil OR
Ranadazine
Clinical trial evidence demonstrating the superiority of any of these drugs is lacking!
Cellular + Hemodynamic mechanisms of Organic nitrates?
Cellular mechanism: NO donar
Hemodynamic mechanism: reduce venous pressure, increase coronary BF
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State the organic nitrate drug that’s taken?
Indication?
GTN taken sublingually.
Used for cutting short an angina attack or preventing a anticipated attack
State a longer acting organic nitrate
Are they effective?
Isoscorbide dinitrate
-taken on an ongoing basis (pills, ointments, patches)
Their effectiveness is limited by the development of tolerance after ~12hrs
•this can be avoided by a daily 8hr drug-free period (at night)
How do the organic nitrates break down to give rise to the desired product NO
High potency nitrates (GTN)
•when given low doses, they’re metabolized by an enzyme in the mitochondria called mtALDH. This gives rise to NO2- (nitrate). This is reduced to NO. The remaining molecule (dinitrate) GDN is further metabolized by cyt P450. This gives rise to more NO
Low potency nitrates (ISDN)
•mainly metabolized by Cyt P450 in the same way to give rise to NO
What’s the problem with the reduction process when producing NO?
The metabolism by enzyme results in production of reactive oxygens - in particular superoxide (O2-).
Superoxide binds to NO and reacts with it to form Peroxynitrate - does not give vasodilation. This is why TOLERANCE occurs (bc build of reactive oxygen)!
Hemodynamics: Major and minor actions
Major
Relax: venules + veins (preload) -> Arteries (afterload) -> Arteriole (BP)
So reduction in CVP + afterload -> reduction in cardiac wall tension -> reduction cardiac O2 demand
Minor
Dilate larger coronary arteries, increasing BF through coronary collaterals. May Also reduce TPR and afterlaod. Therefore reduction in cardiac O2 demand.
