Society of Cardiovascular Anesthesiologists

Drug Update

Drug Review: Fenoldopam

Reviewer: Rose Christopherson, M.D.

Reference: Medical Letter, Vol. 40, p. 7, 5/22/98.

Fenoldopam mesylate (Corlopam, Neurex) is a peripheral dopamine-1 agonist, approved for lowering blood pressure. It causes arteriolar vasodilation through stimulation of dopamine-1 receptors. Renal blood flow is increased despite reduced systemic blood pressure due to dilation of the renal vasculature. Fenoldopam also has direct natriuretic and diuretic properties due to effects on renal tubular cells. These effects are especially pronounced in patients with hypertension.

It is given intravenously by infusion (0.1-1.6mcg/kg/min). Onset is in 4-5 minutes. Plasma half-life is approximately 5 minutes. Duration of action is less than 10 minutes. A steady state is achieved after about 20 minutes of infusion. The reviewers suggest starting at the low end of the dose range, and titrating upward by 0.05-0.1mcg/kg/min increments at 15 minute intervals. The drug is rapidly metabolized in the liver into inactive compounds, which are excreted in the urine.

It can cause reflex tachycardia, and increased intraocular pressure. It should be used cautiously in patients with glaucoma. Other adverse effects are related to vasodilation, and include hypotension, flushing, dizziness, and headaches. Nausea and hypokalemia have also been reported.

No significant drug interactions have been reported so far. Although the drug is metabolized by the liver, the cytochrome P450 system is not involved.

Only one perioperative study was reported. Patients recovering from coronary artery bypass surgery were given fenoldopam to treat postoperative hypertension. Those who were on beta-blockers achieved their target blood pressure with lower doses of fenoldopam than required for those not on beta-blockers.

Comments: We have a variety of drugs for parenteral treatment of perioperative hypertension. However, most of them are associated with reductions of renal blood flow and urine output. An antihypertensive drug that increases urine output while increasing renal blood flow and improving or protecting renal function will be a welcome addition to our pharmacopoeia.

Drug Review: Abciximab

Reviewer: Sergio Gregoretti, M.D.

References: Rapid assessment of platelet function with a modified whole-blood aggregometer in percutaneous transluminal coronary angioplasty patients receiving anti-GPIIb/IIIa therapy. Mascelli MA, Worley S, Veriabo NJ, et al.. Circulation, 1997,96:3860-66

Pharmacodynamic profile of short-term abciximab treatment demonstrates prolonged platelet inhibition with gradual recovery from GPIIb/IIIa receptor blockade. Mascelli MA, Lance ET, Damaraju L, et al. Circulation, 1998,97:1680-1688

Abciximab (c7E3 Fab, Reopro.) inhibits platelet aggregation by engaging the glycoprotein (GP) Iib/IIIa receptors, thereby preventing the binding of fibrinogen and von Willebrand factor to activated platelets. The drug, already used during percutaneous coronary balloon angioplasty, has been recently shown to decrease substantially ischemic complications during coronary stenting as well. It is, therefore, likely that in the near future a larger number of patients under or shortly after treatment with abciximab will present to the anesthesiologist's care. Since the drug has a marked effect on coagulation, knowledge of its pharmacodynamics is of great importance and the papers by Mascelli et al., are very timely. The authors examined the extent of GP IIb/IIIa receptor blockade and the corresponding effects on ex vivo platelet aggregation of abcimibax administered at the standard doses used during percutaneous coronary interventions (0.25 mg/Kg bolus followed by an infusion at a rate of either 0.125 mg/Kg or 10 mcg/min for 12 hours). The effect of this treatment on platelet count was also studied. Throughout the drug administration period mean GP IIb/IIIa receptor blockade was 90% and platelet aggregation was inhibited by 90% or more. After cessation of therapy both receptor blockade and aggregation inhibition decreased fairly rapidly. At 12 and 36 hours after treatment, 67% and 57% respectively of receptors were blocked. The corresponding aggregation inhibition was 69% and 60%. At 72 hours, platelet aggregation inhibition was further decreased to 20%. Abciximab was detectable bound to circulating platelets up to 15 days after treatment, but the level of receptor occupancy was low and unable to affect platelet function. The presence of the drug on all circulating platelets for a time far in excess to the normal life span of the platelets suggest that the drug dissociates from the platelets removed from the circulation and binds onto the new ones released into it. Platelet counts monitored for 28 days after treatment remained within 10% of baseline values. The data indicate that abciximab treatment during percutaneous coronary intervention almost completely blocks platelet aggregation. After drug discontinuation, platelet function gradually recovers and is close to normal within 72 hours. Abciximab binds to the receptors in a reversible fashion and continuously equilibrates within the pool of GPIIb/IIIa receptors available in the circulation. Therefore, rapid reversibility of the platelet inhibition can be obtained by platelet transfusion. The drug will rapidly redistribute from platelets with fully saturated receptors to the new, transfused cells, thereby decreasing the overall level of occupancy of receptors per cell and, as a consequence, the degree of inhibition. Finally, the drug does not affect platelet count.

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