用户名： 密   码：
注册 | 忘记密码？
药品详细

Bupivacaine(布比卡因)

化学结构式图
中文名
布比卡因
英文名
Bupivacaine
分子式
C18H28N2O
化学名
1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
分子量
Average: 288.4277
Monoisotopic: 288.220163528
CAS号
2180-92-9
ATC分类
N01B 未知;N01B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

A widely used local anesthetic agent. [PubChem]

生产厂家
  • App pharmaceuticals llc
  • Hospira inc
  • International medicated systems ltd
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Link
  2. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB: Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006 Jul;105(1):217-8. Pubmed
  3. Picard J, Meek T: Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob. Anaesthesia. 2006 Feb;61(2):107-9. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Acetanilides
Substructures
  • Amino Ketones
  • Benzene and Derivatives
  • Acetanilides
  • Carboxylic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Anilines
  • Piperidines
适应症
药理
Indication For the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures.
Pharmacodynamics Bupivacaine is a widely used local anesthetic agent. Bupivacaine is often administered by spinal injection prior to total hip arthroplasty. It is also commonly injected into surgical wound sites to reduce pain for up to 20 hours after surgery. In comparison to other local anesthetics it has a long duration of action. It is also the most toxic to the heart when administered in large doses. This problem has led to the use of other long-acting local anaesthetics:ropivacaine and levobupivacaine. Levobupivacaine is a derivative, specifically an enantiomer, of bupivacaine. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both.
Mechanism of action Local anesthetics such as bupivacaine block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. Bupivacaine binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cells, which prevents depolarization. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone. The analgesic effects of Bupivicaine are thought to potentially be due to its binding to the prostaglandin E2 receptors, subtype EP1 (PGE2EP1), which inhibits the production of prostaglandins, thereby reducing fever, inflammation, and hyperalgesia.
Absorption The rate of systemic absorption of local anesthetics is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic solution.
Volume of distribution Not Available
Protein binding 95%
Metabolism
Amide-type local anesthetics such as bupivacaine are metabolized primarily in the liver via conjugation with glucuronic acid. The major metabolite of bupivacaine is 2,6-pipecoloxylidine, which is mainly catalyzed via cytochrome P450 3A4.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Bupivacaine
    		2,6-pipecoloxylidine Details
    Route of elimination Only 6% of bupivacaine is excreted unchanged in the urine.
    Half life 2.7 hours in adults and 8.1 hours in neonates
    Clearance Not Available
    Toxicity The mean seizure dosage of bupivacaine in rhesus monkeys was found to be 4.4 mg/kg with mean arterial plasma concentration of 4.5 mcg/mL. The intravenous and subcutaneous LD 50 in mice is 6 to 8 mg/kg and 38 to 54 mg/kg respectively. Recent clinical data from patients experiencing local anesthetic induced convulsions demonstrated rapid development of hypoxia, hypercarbia, and acidosis with bupivacaine within a minute of the onset of convulsions. These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions and emphasize the importance of immediate and effective ventilation with oxygen which may avoid cardiac arrest.
    Affected organisms
    • Humans and other mammals
    Pathways
    Pathway Name SMPDB ID
    Smp00393 Bupivacaine Pathway SMP00393
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 107-108 °C PhysProp
    water solubility 2400 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
    logP 3.41 HANSCH,C ET AL. (1995)
    pKa 8.1 Not Available
    Predicted Properties
    Property Value Source
    water solubility 9.77e-02 g/l ALOGPS
    logP 3.31 ALOGPS
    logP 4.52 ChemAxon
    logS -3.5 ALOGPS
    pKa (strongest acidic) 13.62 ChemAxon
    pKa (strongest basic) 8 ChemAxon
    physiological charge 1 ChemAxon
    hydrogen acceptor count 2 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 32.34 ChemAxon
    rotatable bond count 5 ChemAxon
    refractivity 90.19 ChemAxon
    polarizability 34.19 ChemAxon
    药物相互作用
    Drug Interaction
    Conivaptan Conivaptan may increase the serum concentration of CYP3A4 Substrates such as bupivacaine. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
    食物相互作用
    Not Available

    返回 | 收藏