Transcript Brevibloc*?(Esmolol HCl)

Brevibloc
(Esmolol HCl)
ß-Adrenergic Receptor Activity
Site
ß1
ß2
Clinical Effect
 Heart Rate
Heart:
 Inotropy
 Conduction Velocity
 Excitability
Renin Release
Kidney:
Release of free fatty acids
Adipose tissue:
Peripheral Vessel: Arteriolar Dilation
Brochodilatatiion
Lungs:
Insulin Release
Pancreas:
ß-Blockers
• ß-adrenergic blocking agents
--- competitive antagonism
• Selectivity: ß1 cardio, ß2 broncho
• Indication
--- hypertension
--- arrhythmia
--- angina pectoris
--- myocardial infarction
--- glaucoma
Properties of Drugs
- Used Parentally to Control HR and/or BP
Indication
 HR
 BP
Peak Effect
(min)
Esmolol
Yes
Yes
2
9 min 10-20 min
1
Atenolol
No
Yes
2
6-7 h
12 h
1
Labetalol
No
Yes
5
5.5 h
3-5 h
1,1&2
Metoprolol
No
Yes
20
3-7 h
5-8 h
1
Propranolol
Yes
No
<10
4h
Variable
1&2
Diltiazem
Yes
No
2-5
3.4 h
1-3 h
Ca2+
Verapamil
Yes
No
3-5
2-5 h
1-2 h
Ca2+
T1/2
Duration
Receptor
Formulary Data
• Brevibloc (Esmolol Hcl)
• Bristol-Myers Squibb Company
• Ultrashort-acting, Cardioselective (ß1) Beta
blocker(IV)
• Indication:
--- Supraventricular Tachycardia
--- Atrial Fibrillation
--- Atrial Flutter
--- Peri-OP, Post-OP Tachycardia / Hypertension
--- Acute Myocardial Ischemia
Chemical Structure
Features
• ß1-selective Adrenergic Receptor Blocker,
ß1:ß2 = 40:1 (highly cardioselective)
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Very Soluble in Water
No Intrinsic Sympathomimetic Activity
No Membrane Stabilizing Activity
No Significant Drug Interaction
Rapid Onset: 2 mins
Ultra-short Action: 10-20 mins
Pharmacokinetics
• Distribution Half-Life: 2 mins
--- volume of distribution: 3.43 L/kg
(4 times the volume of central compartment )
--- Recovery within 10-20 mins (duration of action) when
infusion terminated
• Metabolism
--- Hydrolysis of the ester linkage
--- By esterase in the cytosol of RBC
• Elimination Half-Life: 9 mins
--- Not detected in serum in 30 mins when infusion terminated
• Total Body Clearance: 20 L/kg/Hr
--- greater than cardiac output
--- not limited or affected metabolism by hepatic or renal flow
Pharmacodynamics
• Decrease in
--- heart rate (peak effect in 60 sec)
--- blood pressure (peak effect in 2 min)
--- cardiac index
--- rate pressure product (RPP)
--- left and right ventricular ejection fraction
• Prolongation of
--- sinus cycle length
--- decrease AV node conduction velocity
--- decrease the rate of SA node activity
--- antegrade Wenckebach cycle length
--- the sinus node recovery time
--- increase AV nodal refractoriness interval
The Advantage of Brevibloc  I
• A Selective Approach:
– Targeted to the Heart
– Little effect on Bronchial Smooth Muscle
– Maybe used with caution in p'ts with asthma, COPD
• A Flexible Approach:
– Administer as long as indicated…..
– Maintenance infusions up to 48 hrs or short as you
want; rapid reversal of effect within minutes
The Advantage of Brevibloc
 II
• A Confident Approach:
– Easy to titrate upward or downward to desired
heart rate
– Allows maximum beta blockade while still
maintaining ventricular function
• An Effective Approach:
– Rapid control of atrial fibrillation,atrial flutter
and sinus tachycardia
The Advantage of Brevibloc
 III
Indication and Dosage
• Indication
- Supraventricular tachycardia (SVT)
- Peri-OP, post-OP Tachycardia / Hypertension
- Acute Myocardial Ischemia
• Dosage
Loading: 0.5 mg/kg, over 1 min
Maintenance: 0.05-0.2 mg/kg/min; *0.2 mg/kg/min
--- average effective dosage: 0.1 mg/kg/min
Dosage Guideline
Warnings?
• PATIENTS WITH BRONCHOSPASTIC
DISEASES SHOULD, IN GENERAL, NOT
RECEIVE BETA BLOCKERS.
--- YES for Brevibloc (ß1-selective; 40:1)
--- well-suited to many patients types,
including COPD, LVD
--- titratable
--- predictable
--- reversible
Reference (I) - Asthma
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J Clin Pharmacol 1986; 26: 169-174
Effects of Esmolol on Airway Function in P'ts with Asthma
Double-blind, randomized, cross-over study
Specific Airway Resistance (SRaw)
--- measured during (1) increasing dose of esmolol infusion, (2) dry air
provocation test, and (3) following IV isoproteronol infusion
• All p'ts were able to tolerate the maximum dose of esmolol
(0.3 mg/kg/min).
• Esmolol may be preferred over propranolol in p'ts with
asthma who require Tx with an IV beta-blocking agent.
Reference (II) - COPD
• Chest 1991; 100: 1215-1218
• Esmolol and ventilatory function in cardiac patients with COPD
• To assess the effects of acute cardioselective -blockade on ventilatory
function in p'ts with COPD and cardiac disorders
• 50 p'ts, Esmolol infusion: 8-24 mg/min
• Significant reduction in HR, SBP, and DBP (p<0.01)
• No significant effect on FEV1, peak flow, or forced vital
capacity
 Respiratory function was well preserved while esmolol
producing marked hemodynamic effects.
• No p'ts experienced dyspnea or wheezing with esmolol
• Acute -blockade with esmolol can be achieved in patients
with COPD and cardiac disorders with little risk of
bronchospasm.
Reference (III) - AF
• Am J Cardiol 1989; 63: 925-929
• Esmolol vs. Verapamil in the Acute Tx of AFs
• Efficacy:
Ventricular rate reduction, Conversion to sinus rhythm
--- both drugs produced a decrease in HR within 2 min
--- both drugs decreased HR in 30%; BP in 10%
--- 50% p'ts with new onset of AF who received ESMOLOL converted to sinus
rhythm.
• Safety: (Adverse Experiences)
Hypotension
--- Esmolol: resolved within 5-20 min after dosage was discontinued or reduced
--- Verapamil: required intervention (leg elevation, IV fluids) to resolve
• Esmolol compares favorably with verapamil with respect to both
efficacy and safety in acutely decreasing ventricular response during
atrial fibrillation or flutter.
• Conversion to sinus rhythm is significantly more likely with esmolol.
Reference (IV) - Modified Dosage
• J Am Coll cardiol 1994; 23: 302-306
• A New Dosing Regimen for Esmolol to Treat Supraventricular
Tachyarrhythmia in Chinese Patients ( Dr. Wen-Je Ko, NTUH)
• To find a safe dosing regimen for esmolol infusion to rapidly control
supraventricular tachyarrhythmia after cardiac surgery in Chinese p'ts
• Esmolol's Advantages:
rapid onset of action; ultrashort duration; metabolized by esterase in RBC; metabolism
not affected by renal or hepatic diseases; complete dissipation of side effects occurred
within 20-30 mins after infusion terminated
• Initial infusion rate: 150 or 100 g/kg/min, depending on p'ts age and BP
• Maintenance rate = Initial rate x (1- e-0.077t), t is the time period in minutes
required by the initial infusion to achieve the therapeutic effect without
experience of side effect of hypotension
• 5 min to therapeutic response, Maintenance = 1/3 Initial Dose
10 min, Maintenance = 1/2 Initial Dose
15 min, Maintenance = 2/3 Initial Dose
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