Bupivacaine
Encyclopedia
Bupivacaine (icon) is a local anaesthetic drug belonging to the amino amide
group. AstraZeneca
commonly markets it under various trade name
s, including Marcain, Marcaine, Sensorcaine and Vivacaine.
, epidural
, and intrathecal
anaesthesia. Bupivacaine often is administered by epidural injection before total hip arthroplasty
. It also is commonly injected to surgical wound sites to reduce pain for up to 20 hours after the surgery. Sometimes, bupivacaine is co-administered with epinephrine
to prolong the duration of its action, fentanyl for epidural analgesia, or glucose
.
s (ADRs) are rare when it is administered correctly. Most ADRs relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, however allergic
reactions can rarely occur.
Systemic exposure to excessive quantities of bupivacaine mainly result in central nervous system
(CNS) and cardiovascular effects – CNS effects usually occur at lower blood plasma
concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. CNS effects may include CNS excitation (nervousness, tingling around the mouth, tinnitus
, tremor, dizziness, blurred vision, seizure
s) followed by depression (drowsiness, loss of consciousness, respiratory depression and apnea
). Cardiovascular effects include hypotension
, bradycardia
, arrhythmias, and/or cardiac arrest
– some of which may be due to hypoxemia
secondary to respiratory depression.
Bupivacaine has caused several deaths when the epidural
anaesthetic has been administered intravenously accidentally.
, a commonly available intravenous lipid emulsion, can be effective in treating severe cardiotoxicity secondary to local anaesthetic overdose, and human case reports of successful use in this way. Schemes to publicise this use more widely have been published.
, which prevents
depolarization
. Since pain transmitting nerve fibres
tend to be thinner
and either unmyelinated or lightly myelinated, the agent can diffuse more readily into them than into thicker and more heavily myelin
ated nerve fibres like touch, proprioception, etc. (Myelin is non-polar / lipophilic
).It should be noted, however, that bupivacaine also blocks specific potassium channels, an effect contributing to resting membrane potential depolarization.
is the (S)-(–)-enantiomer
of bupivacaine, with a longer duration of action and produces less vasodilation. Durect Corporation is developing a biodegradable controlled-release drug delivery system for post surgery. It is currently in Phase II.
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
group. AstraZeneca
AstraZeneca
AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...
commonly markets it under various trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....
s, including Marcain, Marcaine, Sensorcaine and Vivacaine.
Indications
Bupivacaine is indicated for local anaesthesia including infiltration, nerve blockNerve block
Regional nerve blockade, or more commonly nerve block, is a general term used to refer to the injection of local anesthetic onto or near nerves for temporary control of pain. It can also be used as a diagnostic tool to identify specific nerves as pain generators...
, epidural
Epidural
The term epidural is often short for epidural analgesia, a form of regional analgesia involving injection of drugs through a catheter placed into the epidural space...
, and intrathecal
Intrathecal
Intrathecal is an adjective that refers to something introduced into or occurring in the space under the arachnoid membrane of the brain or spinal cord...
anaesthesia. Bupivacaine often is administered by epidural injection before total hip arthroplasty
Arthroplasty
Arthroplasty is an operative procedure of orthopedic surgery performed, in which the arthritic or dysfunctional joint surface is replaced with something better or by remodeling or realigning the joint by osteotomy or some other procedure.-Background:Previously, a popular form of arthroplasty was...
. It also is commonly injected to surgical wound sites to reduce pain for up to 20 hours after the surgery. Sometimes, bupivacaine is co-administered with epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
to prolong the duration of its action, fentanyl for epidural analgesia, or glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
.
Contraindications
Bupivacaine is contraindicated for IV regional anaesthesia (IVRA) because of potential risk of tourniquet failure and systemic absorption of the drug.Adverse effects
Compared to other local anaesthetic, bupivacaine is markedly cardiotoxic. However, adverse drug reactionAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s (ADRs) are rare when it is administered correctly. Most ADRs relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, however allergic
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
reactions can rarely occur.
Systemic exposure to excessive quantities of bupivacaine mainly result in central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS) and cardiovascular effects – CNS effects usually occur at lower blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. CNS effects may include CNS excitation (nervousness, tingling around the mouth, tinnitus
Tinnitus
Tinnitus |ringing]]") is the perception of sound within the human ear in the absence of corresponding external sound.Tinnitus is not a disease, but a symptom that can result from a wide range of underlying causes: abnormally loud sounds in the ear canal for even the briefest period , ear...
, tremor, dizziness, blurred vision, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s) followed by depression (drowsiness, loss of consciousness, respiratory depression and apnea
Apnea
Apnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...
). Cardiovascular effects include hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
, arrhythmias, and/or cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
– some of which may be due to hypoxemia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
secondary to respiratory depression.
Bupivacaine has caused several deaths when the epidural
Epidural
The term epidural is often short for epidural analgesia, a form of regional analgesia involving injection of drugs through a catheter placed into the epidural space...
anaesthetic has been administered intravenously accidentally.
Treatment of overdose: lipid rescue
There is animal evidence that IntralipidIntralipid
Intralipid is a brand name for the first safe fat emulsion for human use, approved in 1962 in Europe and invented by Professor Arvid Wretlind, Sweden. The FDA initially would not approve the product due to prior experience with another fat emulsion. It was approved in the United States in 1972...
, a commonly available intravenous lipid emulsion, can be effective in treating severe cardiotoxicity secondary to local anaesthetic overdose, and human case reports of successful use in this way. Schemes to publicise this use more widely have been published.
Mechanism of action
Bupivacaine binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cellsNeuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
, which prevents
depolarization
Depolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...
. Since pain transmitting nerve fibres
Nociceptor
A nociceptor is a sensory receptor that responds to potentially damaging stimuli by sending nerve signals to the spinal cord and brain. This process, called nociception, usually causes the perception of pain.-History:...
tend to be thinner
and either unmyelinated or lightly myelinated, the agent can diffuse more readily into them than into thicker and more heavily myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
ated nerve fibres like touch, proprioception, etc. (Myelin is non-polar / lipophilic
Lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...
).It should be noted, however, that bupivacaine also blocks specific potassium channels, an effect contributing to resting membrane potential depolarization.
Developments
LevobupivacaineLevobupivacaine
Levobupivacaine is a local anaesthetic drug belonging to the amino amide group. It is the S-enantiomer of bupivacaine. Levobupivacaine hydrochloride is commonly marketed by Abbott under the trade name Chirocaine.-Clinical use:...
is the (S)-(–)-enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
of bupivacaine, with a longer duration of action and produces less vasodilation. Durect Corporation is developing a biodegradable controlled-release drug delivery system for post surgery. It is currently in Phase II.