Chapter 4. Cardiac Surgical Pharmacology

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Chapter 4. Cardiac Surgical Pharmacology

Synthetic lysine analogues: epsilon aminocaproic acid [EACA, Amicar], tranexamic

acid Attaching the lysine-binding site of the plasmin(ogen)

molecule, displacing plasminogen from fibrin: inhibit fibrinolysis

Decrease frequency of surgical re-exploration Decrease the proportion of pt receiving blood transfusion Did not increase the risk of peri-OP MI

Demopressin: no benefit for blood loss but increase the risk of peri-OP MI

Acquired functional platelet disorders : caused by Anti-platelet:

Clopidogrel (Plavix): selectively interferes with ADP-induced platelet

aggregation

Onset: 3~5days; effect disappear: 3~5days Half-life: 6~8hrs Bojar: DC for 5~7 days before elective cardiac surgery

Acquired functional platelet disorders : caused by Anti-platelet:

platelet glycoprotein (GP) IIb/IIIa complex: Have a role in platelet-mediated thrombus formation GP IIb/IIIa (IIb β 3) a receptor on plt that bind to

fibrinogen and vWF ( von Willebrand factor): allow cross-linkng of platelets and plt aggregation

platelet glycoprotein (GP) IIb/IIIa antagonists: interferes with ADP-induced platelet aggregation Inhibit plat participation in acute thrombosis Monoclonal Ab/abciximab (ReoPro); non-peptide fiban

molecule/tirofiban (Aggrastat); cyclic peptide/ eptifibatide (Integrelin)

ReoPro: shorter plasma half-life, but longer duration of action by binding to plt

Aggrastat and Integreslin: renal clearance, circulating plasma half-life 2~4hrs

Recommendations for managing patients receiving platelet inhibitors for cardiac surgery: Stop therapy. Do not give platelet transfusions prior to surgery

or revascularization. Give normal doses of heparin. Platelet transfusions as needed after

cardiopulmonary bypass.

Heparin: extract from bovine lung or porcine intestine Protamine: a histone and a basic arginine-rich

polypeptide extracted from salmon sperm reverse heparin immediately by nonspecific acid-base

interactions Dose: 1.3mg protamine/100U Heparin Possible anaphylactic reactions and adverse drug reactions Risk pt: (1) DM pt receving NPH [one kind of protamine-

containing insulin]: 0.6~2% [ 0.06% in other pt]; (2) prior vasectomy or fish allergy

Aprotinin: not approved, now forbidden Additional coagulation factors and platelets

may be acquired besides to inhibiting fibrinolysis to reverse the coagulopathy

For pt with… Hemophilia[Factor VIII or Factor IX deficiency], von Willebrand’s

disease (vWD), or acquired inhibitors to antihemophilic factor include antihemophilic factor concentrates, factor IX concentrates, factor VIIa concentrate, factor IX complexes, anti-inhibitor coagulant complexes, and desmopressin acetate

Recombinant activated factor VIIa (rFVIIa, NovoSeven, Novo Nordisk A/S) Recommended dose: 30~90μg/Kg

Tissue plasminogen activator [tPA], streptokinase, urokinase

Inactivate fibrinogen and other adhesive proteins Patients receiving these drugs within 24 hours of

surgery should be considered to be at high risk for coagulopathy, and fibrinogen levels should be measured

Chapter 4. Cardiac Surgical Pharmacology

Intensity of the effects of beta-blockers depends on….. Dose of the blocker The receptor concentrations of catecholamines [primarily

Epi and NE]

Beta-blockers V.S. catecholamines: competitive! Key to use Beta-blockers successfully:

(1) to titrate the dose to the desired degree of effect

Key to use Beta-blockers successfully: (2) give other type of drugs to reduce the activity of counterbalancing autonomic mechanisms that are unopposed in the presence of beta-blockers

Excessive bradycardia: give Atropine

Clinical trial: IV form Beta-blockers in the early phase of AMI may decrease 10% mortality!

Chronic PO form Beta-blockers decrease incidence of recurrent MI

Beta-blockers are Vaughan Williams class IIantidysrhythmics that primarily block cardiac responses to catecholamines Propranolol(Inderal), esmolol(Brevibloc),

acebutolol(Sectral)

Amiodarone, class III: exerts non-competitive alpha-and beta-adrenergic blockade

Sotalol, class III: non-selective beta

Beta-blockers + diuretics: initial drug of choice for uncomplicated HTN in pt <65 y/o

The primary goal in managing dissecting aneurysms: to reduce stress on the dissected aortic wall by

reducing the systolic acceleration of blood flow Beta blockers reduce cardiac inotropy and

ventricular ejection fraction. Beta blockers also may limit reflex

sympathetic responses to vasodilators that are used to control systemic arterial pressure.

Catecholamine-secreting tissue: release Epi/NE

Activation of the autonomic nervous system (ANS) and renin-angiotensin system (RAS) as compensatorymechanisms for the failing heart actually may contribute to deterioration of myocardial function

Mortality related to activation of ANS and RAS system

Beta-blockers and ACEI attenuate progression of myocardial dysfunction and remodeling

Carvedilol: contraindicated in severe decompensated heart failure and asthma pt

Carvedilol: Alpha : nonselective beta = 1:10 contraindicated in severe decompensated heart

failure and asthma pt In pt with Af and left-sided heart failure…… Improve EF; decrease incidence of death; and

hospitalization

Aluminum-coating antacids reduce GI absorption of beta-blockers

Increase biotransformation: phenytoin, phenobarbital, rifampin, smoking

Increase bioavailability due to decrease biotransformation: cimentidine, hydralazine