chapter 4. cardiac surgical pharmacology chapter 4...
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Chapter 4. Cardiac Surgical Pharmacology
R4 吳依璇
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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