Exam 1: Lecture 11, Angina Flashcards by Patryk Lasiuk

3 Types of angina

Stable
Unstable
Variant

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3 classes of drugs for angina

Organic nitrates
Calcium channel blockers
Beta blockers

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Nitrates: Prototype

Nitroglycerin

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Nitrates: MOA

Increase cGMP which decreases Ca that mediates contraction and dephosphorylates MLC’s leading to relaxation

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Nitrates: Applications

Angina, acute coronary syndrome

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Nitrates: notables

Undergoes large first pass effect, given sublingually to avoid

Tachyphylaxis - tolerance; decrease effect of same drug dose given repeatedly, so have to give it time

Interaction with sildenafil, don’t take together…space by 6 hours

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Which types of Angina can nitrates be used for?

Stable

Variant/Vasospastic/Prinzmetal’s

Unstable

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Beta-blockers: Prototype

Propranolol

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Beta-blockers: MOA

Competitive inhibitors of Ne and EPi at B1 (cardiac) and B2 (smooth muscle/lung) receptors, inhibit renin release

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Beta-blockers: Applications

Angina, hypertension, arrhythmias, migraine, performance anxiety

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How many generations of Beta-blcokers?

1st = non-selective
2nd = B1 selective
3rd = Vasodilatory

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Which types of Angina can Beta-blockers be used for?

Stable (mainly used here)

Unstable

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Beta-blockers notables

By using drugs that block B2 receptors, it leaves the vasoconstricting alpha receptors unopposed and potentially making angina worse

Have to be weened off, ~ 3 weeks

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Beta-blockers contraindicated in….

Asthma

Variant Angina

bronchospasm

AV/SA node dysfunction

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Ca Channel blockers: prototype

Verapamil (nondihydropyridine)

Nifedipine (dihydropyridine)

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Ca Channel blockers: MOA

Inhibition of L-type calcium channels,

Blocks calcium channels in the SR

Ca Channel blockers: Applications

Angina, hypertension, supraventricular tachyarrhythmias

Ca Channel blockers: notables

High 1st past effect,

High Albumin binding = cause for Drug-Drug interactions

Extensive metabolism, due to CYP450

Which types of Angina can Ca Channel-blockers be used for?

Stable

Variant/Vasospastic/Prinzmetals

unstable if pt refractory for other 2

MONA

Morphine, Oxygen, Nitroglycerin, Aspirin = treatment of Angina in ER

Monday disease and Nitrate tolerance

Those working in chemical plants or who get exposed to nitrates develop a tolerance during the week, then lose some of it over the weekend. When they return to work on Monday the exposure to nitrates can make them feel bad, but they regain tolerance and are better following days

Drugs to treat stable Angina

Nitrates, Ca Channel blockers, Beta-blockers

Drugs to treat Variant Angina

Nitrates, Calcium channel blockers

Drugs to treat Unstable Angina

Acute coronary syndrome must be treated with (anti platelets, aspirin, clopidogrel, heparin) plus nitrates and Beta-blockers

For refractory disease, calcium channel blockers used.

Most effective calcium channel blocker?

Verapamil in all aspects...ie Vasodilation, decreasing cardiac contractility, etc

Reperfusion

is when you have reoxygenation, when you reoxyenate it can trigger cell death by activating mPTP

Importance of Foam Cells

Macrophages that turn into these foam cells from collecting ApoB proteins. will then cause a build of of ApoB-Lp, instead of digesting them. foam cells = responsible for formation of plaques

What happens when foam cells die?

Apoptosis, then all the stuff in the cell will build up and a necrotic core will form. This fibrous cap is weakened, then thrombus comes and binds to ruptured region and will lead to blocked vasculature This is due to efferocytosis not being able to occur (clean up)

raynauds syndrome

cold sensitivity and poor circulation to extremities due to limited coruscation usually in women

Vasospastic/Prinzmetals Angina

increase vasoconstriction and decrease vasodilation

drugs increasing oxygen delivery?

Nitrates and Calcium channel blockers

Drugs decreasing oxygen demand?

Nitrates/beta blockers/calcium channel blockers

Beta blockers will..

decrease heart rate, blood pressure and contractility which decrease oxygen requirements at rest and exercise (effecting oxygen demand)

Main focus of beta blockeres

B1 receptor in cardiac cell... Beta-blockers will reduce ca moving into the cell/ and from SR B2 mediate vasodilation

Why beta-blockers not used in spastic angina/asthma?

By blocking beta receptors in vasculature, you'll have more alpha receptors open which cause vasoconstriction

Ranolazine

Not common in angina, but used in patients who don't respond to other options MOA: blocks Late sodium channel, preventing Na/ca exchange and decreases contraction

Aspirin

Rational = anti platelet activity COX1 inhibitor, it prevents cascade involved in platelet aggregation given to patients with unstable angina