The cholinergic crisis is triggered by an overdose of cholinesterase inhibitors. It is characterized by acute muscle weakness and nicotine-like side effects.
What is a cholinergic crisis?
A cholinergic crisis occurs when there is an oversupply of acetylcholine. Acetylcholine is a biogenic amine that acts as a neurotransmitter in the body. The neurotransmitter is found in both the central nervous system and the peripheral nervous system. Among other things, it works on the neuromuscular endplate, where it enables the skeletal muscles to move freely.
Acetylcholine also occurs as a signaling substance in the preganglionic neurons of the parasympathetic and sympathetic nervous system. When the action potential arrives, acetylcholine is released into the synaptic cleft. There it binds to the so-called cholinoceptors. These are receptors on the postsynaptic membrane. The binding to the receptor changes the ion permeability. This change can result in inhibition or excitement.
Then acetylcholine is split into acetic acid and choline in the synaptic cleft by the enzyme acetylcholinesterase. The neurotransmitter is produced in the terminal heads of certain axons. Acetylcholine is produced from choline and acetyl-CoA by the enzyme choline acetyl transferase and stored in small vesicles in the nerve cells.
Normally, no cholinergic crisis can be triggered by the body’s own synthesis processes. The main cause is an overdose of acetylcholinesterase inhibitors. By inhibiting the enzyme acetylcholinesterase, less acetylcholine is broken down, so that there is an oversupply. However, dosages of at least 600 milligrams of pyridostigmine per day are necessary for this.
Purely cholinergic crises are usually rather rare. More often, in poorly adjusted patients, signs of overdose are found mixed with symptoms that indicate an acetylcholine deficiency. Acetylcholinesterase inhibitors (AChE inhibitors) are used to treat Alzheimer’s disease.
Alzheimer’s disease is a progressive atrophy of the cerebral cortex. This is accompanied by a decline in cognitive, social and emotional skills. The affected patients suffer from forgetfulness, memory loss, a lack of language understanding, speech disorders and a lack of sympathy. By taking acetylcholinesterase blockers, the neuronal excitability should be increased. It does not cure the condition, but it does alleviate the symptoms.
Symptoms, ailments & signs
In the event of an overdose, too much acetylcholine remains in the synaptic gap. This leads to general muscle weakness. The patients suffer from shortness of breath due to weakness of the respiratory muscles. Difficulty breathing is exacerbated by excessive bronchial secretion. Due to the increased secretion, pulmonary edema can develop in an emergency.
Pulmonary edema is characterized by shortness of breath, strong cough and frothy sputum. The patients feel sick and vomit. Profuse sweating is also a typical symptom of the cholinergic crisis. It can also lead to gastrointestinal cramps and diarrhea. The heartbeat is slow and the blood pressure is too low (hypotension).
A slow heartbeat is also known as bradycardia in medical terminology. So-called fasciculations are typical of the cholinergic crisis. These are involuntary contractions of very small muscle groups. These are visible just under the skin, but usually do not lead to any movement. In many cases, these small muscle twitches can be provoked by pinching the muscle.
In addition to these small muscle movements, large and painful muscle spasms can also occur. Patients are afraid and may have cerebral symptoms. Other symptoms that can occur as part of a cholinergic crisis are increased salivation and constricted pupils. Nicotine-like side effects also include urination disorders.
Diagnosis & course
The diagnosis is usually made on the basis of the clinical picture. A brief medical history can quickly confirm the suspicion. In the X-ray – or CT picture a pulmonary edema can show depending on the severity of cholinergic crisis. The physical examination reveals the decreased blood pressure and pulse.
The cholinergic crisis must be differentiated from the myasthenic crisis in a differential diagnosis. Myasthenic crisis is a complication of myasthenia gravis disease. The myasthenic crisis is accompanied by almost the same symptoms. However, the muscarinic and nicotinic side effects are missing. In contrast to the cholinergic crisis, the myasthenic crisis does not lead to diarrhea or other gastrointestinal complaints.
In most cases, the cholinergic crisis results in very severe muscle weakness. As a rule, the patient is no longer able to carry out normal everyday activities and is therefore severely restricted. It can also lead to shortness of breath. Many people respond to breathlessness with a panic attack, which makes the condition even worse.
The shortness of breath itself is often associated with a cough. It is not uncommon for those affected to suffer from diarrhea and stomach problems that resemble gastrointestinal flu. The quality of life of the patient is extremely reduced by the cholinergic crisis and there are honest restrictions. The emptying of the bladder can often no longer be controlled and there is an increased flow of saliva.
Treatment is primarily aimed at combating breathing difficulties. This also stabilizes the circulation and prevents acute kidney failure. The patient must take antibiotics. In severe cases, an antidote can also be given. If the symptoms are recognized and treated early, there are usually no further complications.
When should you go to the doctor?
If muscle weakness and other signs of cholinergic crisis occur after taking cholinesterase inhibitors, seek medical advice immediately. If there is also shortness of breath and severe coughing, there is a risk of pulmonary edema – therefore alert the emergency services immediately. General symptoms such as gastrointestinal complaints and cardiovascular complaints should also be clarified quickly. Since the cholinergic crisis is always a medical emergency, a medical diagnosis must not be waited for.
People who regularly take cholinesterase inhibitors are particularly at risk. Appropriate medication is best taken under medical supervision. If this is not possible, the medication should be slowly adjusted to the desired level so that a cholinergic crisis does not occur in the first place. If the drug is overdosed: Do not wait for the symptoms mentioned, but go to the nearest hospital immediately. Under certain circumstances, neurological and intensive medical monitoring will be initiated there. If complaints then arise, the necessary measures can be taken immediately.
Treatment & Therapy
Cholinergic crisis is an emergency that requires immediate neurological and intensive care monitoring. The focus is on stabilizing breathing and circulation. Often it is only possible to maintain breathing through intubation. Artificial respiration may be required. The kidney function must also be considered, as kidney failure can also occur as part of the cholinergic crisis.
If an infection is suspected, antibiotic therapy must be initiated at an early stage. The muscarinic side effects such as diarrhea, increased salivation and increased sweating can be treated well with atropine as an antidote. An antidote is also called an antidote. Atropine is an alkaloid that in solanaceous plants like Engelstrompete, belladonna, Datura or henbane occurs.
It has a parasympatholytic effect, i.e. it reduces the effect of the parasympathetic nervous system. It also displaces the excess acetylcholine from the muscarinic receptors. If the cholinergic crisis was triggered by an overdose of acetylcholinesterase inhibitors, the patient must be re-adjusted immediately with medication.
Outlook & forecast
Without immediate emergency medical treatment, the cholinergic crisis leads to the death of the patient. Survivors in most cases suffer from lifelong health problems. In addition to muscle complaints and motor restrictions, fears arise as a result of the shortness of breath experienced. This can lead to psychological problems, which significantly changes the healing process.
The general physical condition of the patient often remains severely weakened and performance is reduced as a result. With immediate medical attention, some patients will experience full recovery after a few months of the emergency. The effects of intubation have subsided and ventilation is provided in a natural way. Therefore, the prognosis of a cholinergic crisis is not the same for all patients. However, there is seldom a full recovery.
Usually the person concerned suffers from another underlying disease that cannot be cured. Although the cholinergic crisis has been overcome in these patients, the underlying disease leads to permanent damage due to the already weakened state of health. Since the cause of the cholinergic crisis is usually an oversupply of acetylcholine or other substances, a new cholinergic crisis only occurs in rare exceptional cases. Medical treatment stabilizes the patient so that there is no relapse.
The cholinergic crisis can only be prevented with well-adjusted medication. Therefore, at the slightest sign of overdose, a doctor should be consulted. Warning signs include muscle twitching, headaches, and increased salivation. Diarrhea can also indicate an overdose of the acetylcholinesterase blocker.
In the follow-up care of the cholinergic crisis, it is important that the medication is adjusted correctly by the doctor. This means that patients need regular check-ups. This enables precise adjustment that can avoid later cholinergic crises or at least reduce the risk. In connection with the therapy, the dose should be strictly adhered to.
In the event of an overdose, patients should immediately consult a doctor or go to the hospital. Intensive medical and neurological monitoring takes place here, depending on the circumstances. Since the cholinergic crisis is often associated with other diseases, the corresponding therapeutic measures must also be carried out.
Otherwise, the underlying disease can aggravate it or even cause permanent damage to health. For this reason, medical treatment and care is essential. Relapses can also be avoided by stabilizing health. The close observation of the symptoms related to the illness is also part of the follow-up care.
If acute muscle weaknesses are feared at an inopportune time, it also makes sense to take certain measures to prevent accidents. Those affected should be careful with their own health. Less stress and strain help to contain the dangers in everyday life.
You can do that yourself
A cholinergic crisis is an emergency that usually requires immediate intensive care monitoring. Without immediate emergency medical intervention, life can even be in danger.
After a cholinergic crisis has been overcome, the further prognosis is not the same for all patients, and unfortunately a full recovery cannot be assumed in the majority of cases. Therefore, the patient’s complete education about the clinical picture and its main symptoms is of decisive prognostic importance.
The aim of intensive medical treatment is initially to stabilize, but also to keep the risk of relapse as low as possible. Here, the cooperation of the person affected in the sense of the prophylaxis of a new crisis is absolutely necessary.
First of all, a suitable individual medication must be put together, which is also tailored to other underlying diseases. The setting with the medication can only be successful if a patient strictly adheres to the prescription plan in the long term. Unauthorized discontinuation or change of medication could quickly lead to a new cholinergic crisis.
Overdosing must also be avoided at all costs. The acetylcholinesterase blocker, which is often used against the clinical picture, causes typical warning signs in the event of an overdose, which the patient must recognize in order to recognize a new cholinergic crisis at an early stage. These include, in particular, diarrhea, increased salivation, uncontrolled muscle twitching and headaches. The occurrence of just one of these symptoms should therefore be reason enough to consult a doctor as part of self-help.