Pseudocholinesterase deficiency

Genes encoding cholinesterase 1 (CHE1) and CHE2 have been mapped to 3q26.1-q26.2. One gene is silent, whereas the other is responsible for the defect in cholinesterase. Specifically there are sixteen possible genotypes, expressed as ten phenotypes, six of these phenotypes are associated with a marked reduction in the hydrolysis of succinylcholine. The plasma cholinesterase activity level is genetically determined by four alleles identified as silent (s), usual allele (u), dibucaine (d), or fluoride (f); also this allele can be absent (a).[2]

The inherited defect is caused by either the presence of an atypical PCE or complete absence of the enzyme. Cholinesterases are enzymes that facilitate hydrolysis of the esters of choline. Acetylcholine, the most commonly encountered of these esters, is the mediator of the whole cholinergic system. Acetylcholine is immediately inactivated “in situ” by a specific acetylcholinesterase in the ganglions of the autonomic nervous system (preganglionic and postganglionic in the parasympathetic nervous system and almost exclusively preganglionic in the sympathetic nervous system), in the synapses of the central nervous system, and in the neuromuscular junctions. The affinity of PCE is lower for acetylcholine, but higher for other esters of choline, such as butyrylcholine, benzoylcholine, and succinylcholine, and for aromatic esters (e.g., procaine, chloroprocaine, tetracaine). Normal PCE is produced in the liver, has a plasma half-life of 8 to 12 days, and can be found in plasma, erythrocytes, glial tissue, liver, pancreas, and bowel. When succinylcholine is used for anesthesia, its high plasma concentration immediately after intravenous injection decreases rapidly in normal individuals because of the rapid action of plasma PCE. In case of an atypical PCE or complete absence of PCE, the effect of the injected succinylcholine can last for up to 10 hours.[3]

For homozygosity, the incidence is approximately 1:2,000-4,000, whereas the incidence for heterozygosity increases to up to 1:500. The variant EaEa genotype, homozygous absent, is approximately 1:3200. The gene for the dibucaine-resistant atypical cholinesterase appears to be widely distributed. Among Caucasians, males are affected almost twice as often as females. The frequency for heterozygosity is low among black people, Japanese and non-Japanese Asians, South Americans, Australian aborigines, and Arctic Inuit (in general). However, there are a few Inuit populations (e.g., Alaskan Inuit) with an unusually high gene frequency for PCE deficiency. A relatively high frequency also was reported among Jews from Iran and Iraq, Caucasians from North America, Great Britain, Portugal, Yugoslavia, and Greece. [4]

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 ventilated. 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.[7]

These patients also may notify others in their family who may be at risk for carrying one or more abnormal pseudocholinesterase gene alleles.

Drugs to avoid

Drugs containing Succinylcholine

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.[8]

Drugs containing Mivacurium

Mivacron is also a muscle relaxant that is used prior to inserting a tube for breathing.

Drugs containing Pilocarpine

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 a variety of causes of dry mouth including side effect of various drugs.[8]

Drugs containing Butyrylcholine

Use of butyrylcholine is not common. It can be used to treat exposure to nerve agents, pesticides, toxins, etc.[8]

Drugs containing Huperzine A and Donepezil

These drugs are used to slow the progression of Alzheimer's disease.[8]

Drugs containing Propionylcholine and Acetylcholine[8]

Drugs containing Parathion

Parathion is used as an agricultural pesticide. Exposure to pesticides with Parathion should be avoided.[8]

Procaine

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.[9]

This inherited condition can be diagnosed with a blood test. If the total cholinesterase activity in the patient's blood is low, this may suggest an atypical form of the enzyme is present, putting the patient at risk of sensitivity to suxamethonium and related drugs. Inhibition studies may also be performed to give more information about potential risk. In some cases, genetic studies may be carried out to help identify the form of the enzyme that is present.[10]

Patients with known pseudocholinesterase deficiency may wear a medic-alert bracelet that will notify healthcare workers of increased risk from administration of succinylcholine, and use a non-depolarising neuromuscular blockade for general anesthesia, such as rocuronium.

Prognosis for recovery following administration of succinylcholine is excellent when medical support includes close monitoring and respiratory support measures.

In nonmedical settings in which subjects with pseudocholinesterase deficiency are exposed to cocaine, sudden cardiac death can occur.

• Cholinesterase Test - Lab Tests Online