Nitrates class?
- nitroglycerin (nitrostat, Nitroquick)
- isosorbide dinitrate (Isordil)
- isosorbide mononitrate (Imdur)
- transdermal patch (nitrodur)
Indications for Nitrates use?
- acute angina
- chronic angina
- CHF
MOA of nitrates?
- decrease O2 demand of heart
- decrease arteriolar and venous tone
- decrease preload and decrease afterload (at higher doses)
- cause vasodilation
- increases O2 to the heart
- decreases BP
In what diseases is preload increased?
- hypervolemia
- regurgitation of cardiac valves
- heart failure
In what diseases is afterload increased?
- HTN and vasoconstriction
increased after load = increased cardiac workload
What are short acting nitrates used for?
- dosage?
- immediate relief of anginal sxs
- sublingual nitro tablets or spray: 0.4 mg and repeat in 3-5 minutes if needed (up to 3)
- pain lasting more than 20 minutes should go to ED via EMS
What are the most common SEs from nitrates?
- HA
- dizziness (from lowering BP)
- Hypotension
- flushing
CIs to nitrates?
- hypotension
- aortic stenosis
- severe volume depletion
- acute RV infarction
- hypertrophic cardiomyopathy
- recent meds for ED: sildenafil (viagra), vardenafil (levitra), tadalafil (Cialis)
When are long acting nitrates used?
- added to B blockers or CCBs to control stable angina (not first line because you want to save nitrate for when angina can’t be controlled by other meds, don’t want to become tolerant)
- limited by development of tolerance
- need a nitrate free interval for 8-10 hours a day
Types of long acting nitrates?
- isosorbide dinitrate (Isordil)L 5-40 mg BID to TID
- Isosorbide mononitrate (Imdur - most common) 30-120 QD to BID
- transdermal patch (NitroDur): 0.1, 0.2, 0.4, 0.6 mg/hr (low dose for people with hypotension)
B blockers class?
- metoprolol (Lopressor, toprol)
- bisoprolol (zebeta)
- atenolol (tenormin)
- carvedilol (coreg)
Indications for B blockers use?
- HTN
- tachycardia
- CHF
- ischemic heart disease
NSTEMI
STEMI
unstable angina
chronic angina
B blockers are first line therapy for tx of what?
- tx of chronic angina
MOA of B blockers?
- blocks b receptors in heart causing a decrease in HR, decrease in force of contraction, decrease of AV conduction
- only antianginal agents that have been demonstrated to prolong life in pts with CAD post MI
- most commonly used is Metoprolol
B blocker CIs
- severe bronchospasm (asthmatics)
- bradyarrhythmias
- decompensated heart failure (in midst of acute exacerbation)
- may worsen Prinzmetal’s (variant) angina due to leaving alpha 1 receptors unopposed
Caution in B blocker use
- they may mask sxs of hypoglycemia (tachycardia, diaphoresis) - so caution in diabetics
- abrupt withdrawal may precipitate tachycardia, HTN crisis, angina or MI so it must be tapered off slowly (especially high doses) to prevent these sxs
Drugs in CCB class?
Amlodipine (Norvasc)
Nifedipine (Adalat, Procardia)
DIltiazem (Cardizem)
Verapamil
Indications for CCB use?
- HTN
- tachycardia
- chronic angina
- coronary vasospasm
- peripheral vasospasm
MOA of CCBs?
- decrease O2 demand
- decrease preload
- decrease HR (verapamil and diltiazem)
- decrease BP
- decrease contractility (verapmil, diltiazem)
- increase O2 supply
- cause coronary vasodilation
2 different subclasses of CCBs?
- dihydropyridines:
Amlodipine (Norvasc) - can be used in HF
Nifedipine (Adalat, Procardia) - Nondihydropyridines:
Diltiazem (Cardizem), and Verapamil
(have neg chronotropic rate and neg inatropic effect)>
Common SEs of CCBs?
- HA
- edema
- constipation
- hypotension
- dizziness
- bradycardia (nondihydropyridines)
CI for nondihydropyridines?
- systolic CHF: b/c low EF
- AV block or bradycardia
CI for all CCBs?
- caution when using in pt’s with peripheral edema or hx of hypotension (elderly), multiple drug interactions - metabolized by the liver (use caution)
What are anti platelet drugs function?
- interfere either with platelet adhesion and/or aggregation
goal: prevent initial clot formation
Fxn of fibrinolytic agents?
- degrade fibrinogen/fibrin
goal: eliminate already formed clots
Fxn of anticoagulants?
- inhibit clotting mechanism, goal: prevent progression of thrombosis
What are the antiplatet agents?
- aspirin
- clopidogrel (plavix)
- prasugrel
- Ticagrelor
- acute situations IV:
Abiciximab and Eptifibatide
MOA of aspirin?
- inhibits cox: this then inhibits synthesis of thromboxane A2, a potent stimulator of platelt aggregation
- irreversible platelet inhibitor
- prevents form. of clots by inhibition of platelet plug
- rapid absorption with peak effects in 1 hr
Dosing recommendations of aspirin and indication?
- primary prevention of CVA/MI: 81 mg daily
- 2nd prevention of CVA/MI: depends on other meds. acutely 325 mg daily for MI and CVA
- acute coronary syndrome: 325 mg chewed x 1
Is ASA beneficial in unstable angina?
- study showed that aspirin lead to a 51% reduction in CV events
Major SE of aspirin?
- always assess for GI bleeding
- H2 blockers or PPIs may decrease gastritis and GI bleeding
- administer with food to decrease GI disturbance
- Tinnitus at higher doses
- Resistance
- allergy
- stop 4 days before surgery
Class of P2Y12 antagonists of antiplatelet agents?
- clopidogrel (plavix)
- prasugrel (effient)
- ticagrelor (brilinta)
MOA of P2Y12 antagonists?
- inhibit binding of fibrinogen to activated platelets by blocking the P2Y12 receptor site as a result the GP IIb/IIIa receptor isn’t activated
- blocks receptor which is the binding site for fibrinogen, von WIllebrand factor and other ligands
- resulting in blockage of platelet aggregation and prevention of thrombosis
Indications for P2Y12 antagonists?
- unstable angina
- NSTEMI
- STEMI
- post intracoronary stent placement
- post stroke
- peripheral vascular disease
- No indication for primary prevention of MI/CVA unless pt is allergic to aspirin
P2Y12 drugs?
- clopidogrel (plavix): 300-600 mg loading dose - detected within 2 hours, platelet function returns to normal about 5 days after discontinuation
- prasugrel (effient): 60 mg loading dose: less than 30 minutes, platlet aggregation gradually returns to baseline values over 5-9 days after d/c
- ticagrelor (Brilinta)
180 mg loading doses: wthin 30 minutes, platelet fxn returns normal in 3 days
SEs of P2Y12 inhibitors?
- major: bleeding
- prasugrel not recommended for 75 and older, or those who weigh less than 60 kg - (LOPs) - = increased bleeding risk
- ticagrelor: 10-14% of pts = SOB first few days after initiating therapy
- no antidote for reversal of medication in event of significant bleeding
- some people have genetic variant and are resistant to clopidogrel
GPIIb/IIa antagonists?
- abciximab (Reopro)
- eptifibatide (integrelin)
MOA of GPIIb/IIIa antagonists?
- IV
- used for acute coronary syndrome
- during percutaneous coronary intervention
Onset of GPIIb/IIIa antagonists?
- immediate (IV)
- platelet fxn is restored to normal 4-8 hrs after d/c of infusions
(reversible)
SEs of GPIIb/IIIa antagonists?
- bleeding
- thrombocytopenia: reversible once d/c meds (takes a couple of days)
- allergy
Anticoagulants class for acute situations (MI)?
- enoxaparin (Lovenox - LMWH)
- Heparin (UFH)
- Bivalirudin (angiomax)
MOA of Heparin?
activation of anticlotting factors (especially antithrombin III)
- indirect thrombin inhibitor
- rapid onset of action and short half life
- dose adjusted by following aPTT
- given IV for acute tx, (SQ use for DVT prevention in post surgical pts)
CIs and complications of Heparin?
- CIs: anaphylaxis and recent major surgery
- adverse effects: bleeding, hypersensitivity rxns, transaminitis, HIT
MOA of Enoxaparin (Lovenox), indications
- inhibits Xa and antithrombin III
- indirect thrombin inhibitor
- stronger inhibition of Xa than UFH
- for use in MI pts: IV dose followed by SQ dose
MOA of Bivalirudin (angiomax)
- direct thrombin inhibitor
- immediate onset of action
- coagulation times return to normal about hour after d/c of infusion
- IV infusion only
Major SEs and CIs of Bivalirudin?
- SE: bleeding
- CIs: allergy or recent major surgery or trauma
Fibrinolytics class?
- tPA (activase)
- streptokinase (streptase)
- Urokinase (Abbokinase)
MOA of fibrinolytics?
- convert plasminogen to plasmin to breakdown fibrin strands
- short activation times and short half lives
Indications of fibrinolytics?
tx of existing clots:
- MI
- stroke
- Massive PE (life threatening)
- limb threatening ischemia
SEs of thrombolytics?
- massive life threatening bleeding
Absolute CIs of thrombolytics?
- previous intracranial bleeding at any time
- CVA within last 3 months
- closed head or facial trauma within 3 months
- suspected aortic dissection
- active bleeding diathesis
- uncontrolled HTN: SBP greater than 180 and DBP greater than 100
- known CV lesions
Relative CIs of fibrinolytics?
- current AC use
- invasive or surgical procedure in last 2 weeks
- prolonged CPR defined as more than 10 minutes
- known bleeding diathesis
- pregnancy
- hemorrhagic or diabetic retinopathies
- active peptic ulcer
- controlled severe HTN