Pseudocholinesterase deficiency
Encyclopedia
Pseudocholinesterase deficiency is an inherited blood plasma
enzyme
abnormality. People who have this abnormality may be sensitive to certain anesthetic
drugs, including the muscle relaxants succinylcholine and mivacurium
as well as other ester
local anesthetics. An exhaustive list of drugs that are normally metabolized
by the pseudocholinesterase enzyme can be found in the following section.
, India, on 22 men and women from this community showed that 9 of them had pseudocholinesterase deficiency, which translates to a prevalence that is 4000-fold higher than that in European and American populations.
. Eventually the muscle-paralyzing effects of these drugs will wear off despite the deficiency of the pseudocholinesterase enzyme. If the patient is maintained on a mechanical respirator until normal breathing function returns, there is little risk of harm to the patient.
However, because it is rare in the general population, it is sometimes overlooked when a patient does not wake-up after surgery. If this happens, there are two major complications that can arise. First, the patient may lie awake and paralyzed, while medical providers try to determine the cause of the patient’s unresponsiveness. Second, the breathing tube
may be removed before the patient is strong enough to breathe properly, potentially causing respiratory arrest
.
This enzyme abnormality is a benign
condition unless a person with pseudocholinesterase deficiency is exposed to the offending pharmacological
agents.
These drugs are commonly given as muscle relaxants prior to surgery. That means that victims of this deficiency cannot receive certain anesthetics.
A dose that would paralyze the average individual for 3 to 5 mins can paralyze the enzyme deficient individual for up to 2 hours. The neuro-muscular paralysis
can go on for up to 8 hours.
If this condition is recognized by the anesthesiologist early, then there is rarely a problem. Even if the patient is given succinylcholine, he can be kept intubated and sedated until the muscle relaxation resolves.
Drugs containing Mivacurium
- e.g. Mivacron
Mivacron is also a muscle relaxant that is used prior to inserting a tube for breathing.
Drugs containing Pilocarpine
- e.g. Salagen
Salagen is used to treat dry mouth. As the name suggests, dry mouth is a medical condition that occurs when saliva production goes down. There are lots of different causes of dry mouth including side effect of various drugs.
Drugs containing Butyrylcholine
Use of butyrylcholine
is not common. It can be used to treat exposure to nerve agents, pesticides, toxins, etc.
Drugs containing Huperzine A
and Donepezil
These drugs are used to slow the progression of Alzheimer's disease
.
Drugs containing Propionylcholine and Acetylcholine
Drugs containing Parathion
Parathion is used as an agricultural pesticide. Exposure to pesticides with Parathion should be avoided.
Procaine
drugs e.g. Novocaine
This drug is injected before and during various surgical or dental procedures or labor and delivery. Procaine causes loss of feeling in the skin and surrounding tissues.
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...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
abnormality. People who have this abnormality may be sensitive to certain anesthetic
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
drugs, including the muscle relaxants succinylcholine and mivacurium
Mivacurium
Mivacurium chloride is a short-duration non-depolarizing neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during...
as well as other ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
local anesthetics. An exhaustive list of drugs that are normally metabolized
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
by the pseudocholinesterase enzyme can be found in the following section.
Arya Vysyas
Multiple studies done both in and outside India have shown an increased prevalence of pseudocholinesterase deficiency in the Hindu Arya Vysya community. A study performed in CoimbatoreCoimbatore
Coimbatore , also known as Kovai , is the second largest city in the Indian state of Tamil Nadu. It is a major commercial centre in Tamil Nadu and is known as the "Manchester of South India"....
, India, on 22 men and women from this community showed that 9 of them had pseudocholinesterase deficiency, which translates to a prevalence that is 4000-fold higher than that in European and American populations.
Persian Jews
Pseudocholinesterase deficiency (anesthesia sensitivity) is an autosomal recessive condition common within the Persian and Iraqi Jewish populations. Approximately one in 10 Persian Jews are known to have a mutation in the gene causing this disorder and thus one in 100 couples will both carry the mutant gene and each of their children will have a 25% chance of having two mutant genes, and thus be affected with this disorder. This means that one out of 400 Persian Jews are affected with this condition.Effects
The effects are varied depending on the particular drug given. When anesthetists administer standard doses of these anesthetic drugs to a person with pseudocholinesterase deficiency, the patient experiences prolonged paralysis of the respiratory muscles, requiring an extended period of time during which the patient must be mechanically ventilatedMedical ventilator
A medical ventilator can be defined as any machine designed to mechanically move breatheable air into and out of the lungs, to provide the mechanism of breathing for a patient who is physically unable to breathe, or breathing insufficiently....
. Eventually the muscle-paralyzing effects of these drugs will wear off despite the deficiency of the pseudocholinesterase enzyme. If the patient is maintained on a mechanical respirator until normal breathing function returns, there is little risk of harm to the patient.
However, because it is rare in the general population, it is sometimes overlooked when a patient does not wake-up after surgery. If this happens, there are two major complications that can arise. First, the patient may lie awake and paralyzed, while medical providers try to determine the cause of the patient’s unresponsiveness. Second, the breathing tube
Medical ventilator
A medical ventilator can be defined as any machine designed to mechanically move breatheable air into and out of the lungs, to provide the mechanism of breathing for a patient who is physically unable to breathe, or breathing insufficiently....
may be removed before the patient is strong enough to breathe properly, potentially causing respiratory arrest
Respiratory arrest
Respiratory arrest is the cessation of breathing. It is a medical emergency and it usually is related to or coincides with a cardiac arrest. Causes include opiate overdose, head injury, anaesthesia, tetanus, or drowning...
.
This enzyme abnormality is a benign
Benign
A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...
condition unless a person with pseudocholinesterase deficiency is exposed to the offending pharmacological
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
agents.
Drugs to avoid
Drugs containing Succinylcholine - e.g. Quelicin & AnectineThese drugs are commonly given as muscle relaxants prior to surgery. That means that victims of this deficiency cannot receive certain anesthetics.
A dose that would paralyze the average individual for 3 to 5 mins can paralyze the enzyme deficient individual for up to 2 hours. The neuro-muscular paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
can go on for up to 8 hours.
If this condition is recognized by the anesthesiologist early, then there is rarely a problem. Even if the patient is given succinylcholine, he can be kept intubated and sedated until the muscle relaxation resolves.
Drugs containing Mivacurium
Mivacurium
Mivacurium chloride is a short-duration non-depolarizing neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during...
- e.g. Mivacron
Mivacron is also a muscle relaxant that is used prior to inserting a tube for breathing.
Drugs containing Pilocarpine
Pilocarpine
Pilocarpine is a parasympathomimetic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its...
- e.g. Salagen
Salagen is used to treat dry mouth. As the name suggests, dry mouth is a medical condition that occurs when saliva production goes down. There are lots of different causes of dry mouth including side effect of various drugs.
Drugs containing Butyrylcholine
Use of butyrylcholine
Butyrylcholine
Butyrylcholine is an acetylcholine-like molecule, with activation of some of the same receptors as acetylcholine. It is hydrolysed by acetylcholinesterase and butyrylcholinesterase , with butyrylcholinesterase being more efficient than acetylcholinesterase.Butyrylcholine is a synthetic compound and...
is not common. It can be used to treat exposure to nerve agents, pesticides, toxins, etc.
Drugs containing Huperzine A
Huperzine A
Huperzine A is a naturally occurring sesquiterpene alkaloid compound found in the plant firmoss Huperzia serrata. and in varying quantities in other Husperzia spp.including H. elmeri, H. carinat, H. aqualupian,...
and Donepezil
Donepezil
Donepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of mild to moderate Alzheimer's disease. Common side effects include...
These drugs are used to slow the progression of Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.
Drugs containing Propionylcholine and Acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
Drugs containing Parathion
Parathion
Parathion, also called parathion-ethyl or diethyl parathion, is an organophosphate compound. It is a potent insecticide and acaricide. It was originally developed by IG Farben in the 1940s. It is highly toxic to non-target organisms, including humans. Its use is banned or restricted in many...
Parathion is used as an agricultural pesticide. Exposure to pesticides with Parathion should be avoided.
Procaine
Procaine
Procaine is a local anesthetic drug of the amino ester group. It is used primarily to reduce the pain of intramuscular injection of penicillin, and it was also used in dentistry. Owing to the ubiquity of the trade name Novocain, in some regions procaine is referred to generically as novocaine...
drugs e.g. Novocaine
This drug is injected before and during various surgical or dental procedures or labor and delivery. Procaine causes loss of feeling in the skin and surrounding tissues.
Testing
This inheritable condition can be diagnosed by a simple blood test and managed by avoiding certain muscle relaxants. The test of pseudocholinesterase enzyme activity can be performed using the Acholest Test Paper. When a drop of the patient's plasma is applied to the substrate-impregnated test paper, a colorimetric reaction occurs. The time it takes the exposed Acholest Test Paper to turn from green to yellow is inversely proportional to the pseudocholinesterase enzyme activity in the plasma sample.| Reaction Time | Pseudocholinesterase Enzyme Activity |
|---|---|
| <5 min | Above normal |
| 5-20 min | Normal |
| 20-30 min | Borderline low |
| >30 min | Below normal |