Treatment of Coronary Heart Disease Flashcards by Uche PM

What are the 3 examples of nitrates that are used to treat heart disease?

Nitroglycerine
Nitroprusside
Isosorbide dinitrate

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What is the mechanism by which nitrates cause vasodilation? What is the mitochondrial enzyme involved in nitroglycerin formation of Nitric oxide?

Lead to nitric oxide formation, which activates cGMP with dephosphorylates the myosin light chain, leading to vasodilation
- mtALDH=mitochondrial aldehyde dehydrogenase

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What are the 2 types of vessels that are relaxed in response to nitrates? Why not all vessels?

Large arteries, veins

- Large and small arteries have different enzyme pathways for vasodilation

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Which of the nitrates forms nitric oxide completely Non-enzymatically?

Nitroprusside

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In addition to relaxation of vessels, what is another mechanism by which nitrates act to treat heart disease?

Block platelet aggregation

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Which of the nitrate undergoes a significant first pass hepatic metabolism? Which undergoes minimal first pass hepatic metabolism?

significant - nitroglycerin

minimal - isosorbide mononitrate

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What nitrate drug is a prodrug for isosorbide mononitrate? Which is the two (drug / prodrug) has a longer duration of action

isosorbide dinitrate

isosorbide mononitrate

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Which nitrate drug has a duration of action heavily dependent on formulation?

Nitroglycerin

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What is the major reason for diminished response (nitrate tolerance) when using nitrates? How can this be addressed?

Impaired biotransformation

Interrupt therapy for 8-12 hrs

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Headaches, orthostatic hypotension, dizziness, flushing, syncope are all side effects of _ class of drugs.

Nitrates

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How can reflex tachycardia from nitrates be addressed?

Add a beta blocker

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What type of drug is contraindicated in patients who use nitrates? Why?

Phosphodiesterase inhibitors

Excess cGMP, hypotension

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What are the 2 indicated uses for phosphodiesterse 5 inhibitors?

Erectile dysfunction

Primary pulmonary hypertension

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What are the 3 examples of phosphodiesterase 5 inhibitors available? What molecule in increased when using these drugs?

Sildenafil
Tadalafil
Vardenafil
cGMP

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What is the interaction between nitrates and phoshodiesterase 5 blockers?

nitrates increase cGMP, which causes vasodilation

PDE5 cycles cGMP to GMP, inhibiting PDE5 leads to too much cGMP, too much vasodilation

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Among the PDE5 inhibitors, which has the longest time to onset? Which has the shortest? Which is indicated for daily use?

Longest - sildenafil
Shortest - Tadalafil
Daily use - Tadalafil

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Besides nitrates, what other drug class can cause hypotension when combined with PDE5 inhibitors?

Alpha receptor blockers

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Sudden loss of hearing, increased vision loss, blurred vision and loss of blue/green discrimination are side effects associated with what drug class? What is responsible for the side effects of this drug class?

PDE5 inhibitors

Excess cGMP

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How do beta antagonist improve heart function?

Inhibit the sympathetic NS

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What is the effect of beta 1 blockade? Beta 2?

beta 1 - reduced HR and contractility, reduced renin

beta 2 - Increased vasoconstriction (usually counters alpha 1)

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What is a population that should not use beta 2 blockers?

Asthmatics

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Cardioselective beta blockers are likely functioning at what receptor subtype?

Beta 1 receptors

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What are the 4 examples of beta 1 selective antagonists provided?

Acebutolol
Atenolol
Esmolol
Metoprolol

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What are the 4 examples of non-selective beta Blockers provided?

Nadolol
Pindolol
Propranolol
Timolol

Among the beta blockers, which 2 have intrinsic sympathomimetic activity?

Acebutolol | Pindolol

What drug class is associated with bronchospasm, worsened type 2 diabetes, Hypoglycemia and hyperlipidemia?

Beta blockers

Impotence, sleep disturbance, cold extremities and myocardial depression is associated with what class of drugs?

Beta blockers

Beyond asthmatics, people what what 2 other diseases should avoid beta blockers?

peripheral vascular disease | insulin dependent diabetes

While beta blockers prolong survival in patients with | compensated heart failure by decreasing MVO2, what aspect of these drugs may worsen heart failure?

Their negative ionotropic effects

Regarding beta blockers, what is the rebound phenomenon? What is the mechanism? How can it be avoided?

- worsening ischemia with abrupt discontinuation of drugs - upregulation of beta receptors - gradual tapering of drug dosage

When calcium channel blockers are used for treatment of heart disease, what is the channel subtype targeted? What is the mechanism of these drugs?

L type calcium channels | Decrease cytosolic calcium

What are 2 calcium channel blockers that decrease HR? Which decreases cardiac contractility?

Diltiazem and Verapamil | verapamil

How do calcium channel blockers increase O2 supply to the heart?

Dilate epicardial arteries (and stenoses) | Block vasospasm

What are the 5 examples of dihydropyridines provided? Which is only used in subarachnoid hemorrhage?

``` Nifedipine Amlodipine Felodipine Nicardipine Nimodipine (subarachnoid hemorrhage) ```

In addition to heart disease and hypertension, what are 2 other uses of calcium channel blockers?

Supraventricular arrhythmias | Cerebral hemorrhage

Between beta blockers and calcium channel blockers, which is more effective for secondary prevention following MI? Which calcium channel blocker should be avoided following acute MI?

Beta blockers more effectove | Avoid nifedipine

Gingival inflammation and hyperplasia is associated with the use of _. Heart failure, brady cardia and heart block is associated with the use of what 2 drugs? Peipheral edema is associated with the use of what class of drug?

Nifedipine (other calcium channel blockers) Verapamil and diltiazem Didydropyridines

Calcium channel blockers should be avoided in heart failure. If they have to be used, what 2 are the best candidates?

Amlodipine and felodipine (both newest)

What are the 2 drug classes used to treat heart disease that inhibit the renin angiotensin system?

ACE inhibitors | Angiotensin receptor blockers

When used to treat heart disease, what are the 2 effects of ACE inhibitors and Angiotensin receptor blockers

Slow CHD progression | Prevent secondary MI

What is ranolazine? What is its effect on ATP production?

``` Newest antianginal (introduced in 2006) Shifts ATP production from fatty acid oxidation to glycolysis ```

What are 3 advantages of ranolazine?

No negative ionotropic or chronotropic effecrs Improved exercise tolerance Minimal effects of HR and BP

Ranolazine is reserved for what patient population?

Patients with chronic angina that are refractory to traditional antianginal agents

For stable coronary heart disease, what is the treatment for acute attacks? What is used for chronic treatment?

Acute - Sublingual nitroglycerin | Chronic - Beta blockers, aspirin

For unstable CHD, what are 3 treatments to reduce myocardial oxygen demand/prevent vasoconstriction?

Nitrates Beta blockers Calcium channel blockers

For unstable CHD, what are 3 treatments to stabilize atherosclerotic plaques?

Statins Antiplatelets therapy Anticoagulants

For unstable CHD, what are 3 (classes) of drugs used to prevent platelet aggregation?

– Aspirin – Thienopyridines - ADP antagonist – Glycoprotein llb/llla blockers

For unstable CHD, what are 2 drugs used to limit thrombus formation?

– Heparin | – Thrombin inhibitors (hirudin, hirulog)

For unstable CHD, what are 2 drugs used to prevent vasoconstriction?

– Nitrates | – Ca2+ channel blockers-vasospasm

What is the major drug used to prevent progression of CHD and secondary MI?

RAS inhibitors

Thienopyridines are used to prevent platelet activation. What are the 2 examples provided?

Prasugrel | Clopidogrel

Thienopyridines require hepatic biotransformation. Why? What is their target receptor? What do they displace?

They are prodrugs P2Y receptors Irreversibly replace ADP

What is the major side effect associated with clopidogrel?

Neutropenia

Between clopidogrel and prasugrel, which is likely to cause more bleeding? Why? Which has the longer half life?

Prasugrel Rapid absorption, near 100% metabolic activation, vs 15% for clopidogrel Prasugrel (see second point)

For the acute treatment of unstable CHD and MI, what is the MONA acronym?

Morphone,Oxygen, Notroglycerin and Aspirin

– Rapid onset of action – Easily titrated to achieve desired effect – Brief duration of action if adverse effects – No effects on cardiac contractility or conduction These are all advantages of using _ in the acute treatment of unstable CHD / MI

Nitroglycerin

What are the 2 interventional treatment for MI

PCI - Percutaneous Coronary Intervention | CABG - Coronary artery bypass graft

What are 2 drugs that can be used on stents? What are their functions?

– Paclitaxel (Taxol®)-antimicrotubule antineoplastic – Sirolimus (Rapamycin®)-inhibits cell cycle progression

What is microvascular angina? What causes it?

- Angina or angina-like discomfort with exercise, ST-segment depression or other signs of ischemia - Microvascular (endothelial) dysfunction (normal coronary vessels)