Angina

>400u/L

>5%

4-6 Hours

elevations to the 99th percentile

2-4 hours, less precise than CK but faster results, so now more widely used for the diagnosis of MI (you don't want to be waiting longer than needed to initiate therapy for a MI)

terminate angina attack, they do not reduce risk of ACS or prevent future attacks

A drug that reduces SA node firing rate in the heart, decreases pulse

A drug that reduces the heart's contractile force

Beta blockers and non DHP CCBs

non DHP CCBs are not selective to vascular smooth muscle, so they decrease contractility of the arterys and the heart muscle. DHP CCBs are more selective to arteries, meaning they will cause vasodilation but not reduce heart contraction or pulse.

The lols, metoprolol, carvedilol, propranolol, atenolol, ect

the dipines, amlodipine, nifedipine, felodipine, ect

Diltiazem, Verapamil

Nitrate therapy, long acting. Nitroglycerin is short acting and used for acute anginal attack, long acting nitrate therapy is used as a venodilator to reduce number and severity of attacks

DHP CCBs

Both DHP CCBs and nitrate, DHP CCBs work on arteries while nitrate works on veins, both are considered vasodilators. Vasodilators make it easier for blood to pump through the body, reducing the force the heart has to pump with.

It shifts substrate usage within the heart, decreasing myocardial oxygen demand without changing heart rate or force of contraction. Novel adjunctive anginal therapy.

They put dye into the blood to figure out where there are areas of >70% stenosis and insert a splint, which holds the vessel open and prevents it from becoming too blocked.

SL NTG tablets or spray, should stop attack within 3 tablets/15 minutes. If attack does not stop, it is indicative of unstable angina or a heart attack.

antiplatelets (stop platelets from functioning as well, reducing risk of blood clot formation) and statins, which will help to reduce the formation of atherosclerosis which are largely made of cholesterol deposits between the endothelium and the medial layers (smooth muscle)

Statins (stop formation of plaques and can reduce plaque buildup, leading to less often and less severe anginal attacks)
Negative chronotropic + ionotropic drugs (Beta blockers and non DHP CCBs)
Venodilators (nitrate therapy)
Arteriolar Dilators (DHP CCBs)
Ranolazine
PCI (percutaneous coronary intervention)

They reduce risk of clot formation, but clots are not what causes pain in angina attacks. Pain is caused by the heart not receiving enough oxygen due to clogged vessels caused by cholesterol plaques. Antiplatelets will help with preventing ACS (unstable angina and MI heart attacks) if that plaque tears and threatens to form a clot, but it wont help with the pain and reduced blood flow caused by the clot itself.

It is extremely fast acting and used for acute attacks cuased by excercise, anger, ect. It does not have a long lasting effect in the body and is not taken as a maintenence medication so it will not help to prevent future attacks.

ST segment DEPRESSION, chest pain triggered by excercise or anger than is relieved after no more than 30 minutes of rest or 3 SL NGL tablets.

ST segment DEPRESSION, chest pain that is not relieved after 30 minutes of rest or 3 SL NGL tablets

ST segment ELEVATION, chest pain that is not relieved after 30 minutes of rest of 3 SL NGL tablets, increased cardiac enzymes. Only 2 of these are needed for a diagnosis of MI, ususally that is ST segment elevation and chest pain that lasts longer than 30 minutes. However, in some cases of MI, ST segment depression can still be seen the same way as it is in unstable angina. In these cases, an initial diagnosis of unstable angina is made, however labs are always sent out to get cardiac enzyme levels, and if in a few hours those enzyme levels come back high the patients diagnosis is increased to MI and treatment for MI begins.

Aspirin - COX-1 inhibitor, decreases TXa2 in platelet

Clopidogrel, prasugrel, ticagrelor - P2Y12 ADP inhibitor

Studies say not to use both, no additional benefit with an increased risk of bleeding

1. SL NTG tablet for acute events, or spray for those with xerostomia (dry mouth, anticholinergic drugs or diseases that cause dry mouth)
2. Reduce ACS risk, antiplatelet therapy + lipid lowering therapy (high intensity statins atorvastatin 80 / rosuvastatin 40-80 +- ezetimibe +- PCSK 9 inhibitors (praluent and repatha))
3. Stop meds and treat conditions that exacterbate angina (stimulants, check TSH levels to ensure no hyperthyroidism (can cause rapid heartbeat) check catecholamine levels to ensure they are normal, for instance some tumors can excrete excess adrenaline, treating that can reduce anginal attacks)
4. Chronic pain reliever for anginal attacks, beta-blocker is preferred because it also helps with MI if the angina progresses that far, non DHP CCBs secondarily preferred. (Negative chronotropic and ionotropic drugs are first line compared to other angina attack treatments) Titrate to 50-60 BPM
5. If pain relief not enough, can add adjunctive DHP CCB or long-acting nitrate. DHP + non DHP CCB is not recommended. Beta blocker plus non-DHP CCB increases the heart block risk present with all beta blockers.
6. After all that, if pain relief is still not enough patient may benefit from revascularization, PCI or CABG. Does not increase lifespan or decrease risk of ACS, but provides pain relief.
7. Ranolizine used in patients already taking all these other therapies and have undergone revascularization and still have limiting anginal pain or if patient doesn't want to or cant undergo revascularization.

Steps 1-4 usually done for all patients, steps 5-7 are adjunctive

Reduces Txa2 (vasoconstrictor, pro platelet aggregation), which reduces risk of platelet aggregation

Increased risk of gastric ulcer formation due to COX-1 inhibition, COX-1 normally promotes PGE production which protects the stomach lining

Aspirin doses of 81-325 mg maximize COX-1 inhibition without much COX-2 inhibition

Reduces PGI in the endothelium of vessels, which increases risk of platelet aggregation

COX-2 inhibition found in higher doses of aspirin, typically over 650mg.

More inflammatory pain relief

COX-2 inhibition also caused by NSAID drugs, if patient is on chronic NSAID therapy, avoid aspirin use as this will further increase COX-2 inhibition and increase platelet aggregation risk

Active GI bleed, recent (within 4 weeks) peptic ulcer disease, hemophilia (already at increased bleed risk), history of NSAID induced bronchoconstriction (all NSAIDs contraindicated).

GI upset is not a contraindication, however if patient is throwing up asprin tablets then may be rectally administered with double the normal dose (50% bioavailability rectally)

If patient is having an ACS, EC aspirin should not be given as it takes longer to be absorbed, aspirin is EC because it can harm the stomach (gastric ulcer formation, also risk still present with EC formulations, they are kind of unescessary), however in an emergency like ACS we don't care about this risk. If EC aspirin is all that is available, have patient crush or chew the tablet before swallowing to destroy the EC.

during ACS, no loading dose needed for stable angina as it is ok if it takes a few days for drug levels to get up to therapeutic doses.

CYP2C19 substrate (needs activation)
don't use in patients who are poor CYP2C19 metabolizers

CYP3A4 substrate, PGP inhibitor (drug efflux pump of the liver, kidney, and small intestines), mild CYP3A4 inhibitor

avoid use with potent CYP3A4 inhibitors (additive effects of CYP3A4 inhibition and will not be metabolized as readily)

monitor digoxin serum levels closely (commonly used due to heart failure, overlapping indications) (due to PGP inhibition, may cause digoxin toxicity)

Substrate for multiple CYP enzymes, if one is blocked the others will metabolize it more extensively. Therefore no significant metabolic interactions and the best option for patients with multiple drug-drug interactions or with genetic metabolic mutations, however also has the greatest bleed risk and may increase risk of solid tumor formation.

Active GI bleed
DC 7 days before surgery due to bleed risk (however check with prescriber as risks of discontinuing may outweigh the benefits, could be worth dealing with increased bleeding during surgery)
Prasugrel in patients 75 or older or at an increased risk of intercranial hemmorage, due to increased bleed risk compared to other options
Ticahrelor can cause shortness of breath related to adenosine MOA, however this is transient and should dissapear within a few days.

History of NSAID induced bronchoconstriction is not a contraindication for P2Y12 ADP inhibitors as they are not NSAIDs

When patient is taking anticholinergics, (atropine, TCAs, phenothiazines (zine drugs, antipsychotics, chlorpromazine, fluphenazine, ect), first generation (sedating) antihistamines (diphenhydramine, dimenhydrinate, brom/chlorpheniramine, ect.)

Take when chest pain occurs and sit or lie down, this decreases oxygen demand and reduces risk of passing out / reduces harm of falling if the patient does pass out after administration

Do not shake spray container, use one spray or tablet under the tongue every 5 minutes as needed for anginal pain, if pain does not go away 5 minutes after taking the third dose (or after 30 minutes without NTG) do not take any more and go to the ED

For the SL tablets, take cotton out of container after opening but do not replace it, after removal it loses the nitrate gas it was infused with and may sap nitrate out of the tablets. Leave tablets in original container to protect them for light and moisture.

CYP3A4 substrate, avoid use with CYP3A4 inhibitors

Can cause QTc prolongation, risk is higher when taken with CYP3A4 inhibitors, may increase risk of Torsades de pointes (TdP), a tachycardic arrythmia

Azole antifungals (itraconazole, ketoconazole)
Macrolide antibiotics except for azithromycin (erythromycin, clarithromycin, telithomycin)
Non DHP CCBs (verapamil, diltiazem)
HIV protease inhibitors (ritanovir, saquinavir, indinavir)
Cyclosporin (immunosuppressant)
Amiodarone (antiarrythmic)
Dronedarone (antiarrythmic)
Nefazodone (antidepressant not commonly used due to liver damage, nefarious antidepressant)
Goldenseal
Grapefruit juice

Barbiturates (butalbitol, phenobarbitol, ect)
carbamazepine (another anti convulsant)
oxcarbazepine (another anti convulsant)
primidone (another anti convulsant)
phenytoin (closely related to barbiturates, another anti convulsant)
efavirenz (HIV treatment, ending in vir inhibits, containing vir induces)
nevirapine (another HIV treatment, ending in vir inhibits, containing vir induces)
rifabutin and rifampin (antibiotics)
St. John's Wort

DAPT (dual antiplatelet therapy (aspirin and a P2Y12 ADP inhibitor) for 3 months following a bare metal stent or 6 months following a drug eluting stent (drug that is eluted stops smooth muscle cells from prolipherating and forming a fiberous cap in the area of the stent, which can cause the stent to get closed off. However, this drug also slows the rate of healing, so a longer cours DAPT is required to ensure no additional clotting occurs during this elongated healing process.)

SGLT2 inhibitors (liflozins, canagliflozin, dapagliflozin, empagliflozin) or GLP1 receptor agonist (tides, dulaglutide, liraglutide, exenatide, ect.) in addition to the normal course of therapy for ASCVD. may reduce dosage of other therapies such as insulin or sulfonylureas, it is more important to take one of these treatments due to the reduced occurance of ASCVD events.

SGLT2 inhibitors are better are preventing renal and MI complications, while GLP1 receptor agonists are better for preventing stroke

Contraindicated in pregnancy and breast feeding
Higher levels of glucose excreted in urine, increases risk of fungal and bacterial UTIs, can also cause ketoacidosis and hyperkalemia
Canagliflozin may increase risk of bone fracture
Renal adjustments are required
Should be taken before the first meal of the day

Oral formulation is available

Unclear role in pregnancy, however it causes weight loss which is not recommended in pregnant patients
Concerns of medullary thyroid carcinoma and pancreatitis but not sure if is truly a risk
High cost and injectable only formulation may be a barrier and adherence risk for patients

Strong weight loss, particularly with longer acting therapies
Liraglutide (victoza) has most evidence for reducing MACE (major cardiovascular events)

Preventing platelet aggregation and the coagulation cascade is critical, if unstable angina continues it could develop into a MI (cell death)
Rapid reperfusion is helpful, primary PCI may be performed. Similar to an elective PCI, but instead of just looking for areas of stenosis, they find the area of clot formation, and before stent implantation they remove the clot surgically.

Thrombolytics (clot busters) not used in unstable angina, risks outweigh benefits, however they are used if patient progresses to MI.
Constant EKG monitoring and labs for cardiac enzymes, want to know immediatly if it progresses to MI.

SL NTG given for acute pain control (if primary PCI is not performed)
DAPT therapy initiated, aspirin plus P2Y12 ADP inhibitor (loding dose used due to ACS)
Anticoagulant therapy initiated (heparin + GP IIbIIIa antagonist (tirofiban and eptifibatide), bivalirudin (not heparin based, direct thrombin inhibitor, only used if primary PCI is performed as an alternative to heparin), enoxaparin (heparin based), or fonduparinox (low risk of HIT)

Indirectly inhibits factor X and II, needs endogenous antithrombin 3 to be effective

60u/kg IV loading dose, followed by 12u/kg/hour infusion for 48 hours

Draw aPTT (activated partial thromboplastin time) 6 hours after the loading dose (reading before this time are inaccurate), aPTT should be 1.5-2 times the control value, adjust heparin dose based on these finding

When heparin is administered with a primary PCI, aPTT is not used to monitor due to long lag after loading dose. Instead, ACT (activated clotting time) is used set to 200-300 seconds.

Bleeding, in modest bleeding, DC heparin and apply direct pressure or wait, in severe bleeding, DC heparin and administer protamine sulfate, the antidote to heparin, 1mg neutralizes 100u heparin. Administered over 2-3 minutes, can cause a feeling of warmth, hypotension, and transient bradycardia (adenosine like effect, similar to adenosine and ticagrelor)

If taking for greater than 3 months, risk of osteoporosis is increased

HIT (heparin induced thrombocytopenia), where the immune system recognizes endogenous platelet factor 4, UFH, and platelet when combined as a forgein body and begins and attack. This causes the platelets to activate, which in turn starts the clotting cascade and causing full body thrombosis, the exact opposite of what we are administering heparin to cause.

Usually only occurs after 5 days of treatment, usually after 7-10 days. Can occur quicker if there was heparin exposure within the last 6 months. Cross reactivity with LMWH, not fonduparinox however. Also no cross reactivity with direct thrombin inhibitors.

Treated by discontinuing UFH, give direct thrombin inhibitor such as the injectables argatroban, leprudin, until platelets reach at least 100,000 cells/mm^3

Factor X inhibition, much lower amounts of factor II inhibition compared to UFH.

Enoxaparin is the lowest molecular weight LMWH and the only one used in unstable angina

No monitoring of aPTT like with UFH, lower risk of HIT.

Factor X inhibition, no factor II inhibition at all
No risk of HIT
No aPTT monitoring

1 year after ACS event, and one antiplatelet indefinitely thereafter

ASA 81-325mg, 81 mg ticagrelor