What is Cinchonism?

Cinchonism refers to a range of symptoms caused by consuming substances derived from quinoline. Quinoline derivatives can have harmful effects on the nervous system, eyes, and ears. Typical symptoms of cinchonism include tinnitus (ringing sound in the ears), temporary or permanent hearing loss, face reddening (flushing), confusion, diarrhea, and vision problems, even permanent blindness in some cases. There are also some cases where lack of coordination (ataxia), shaking (tremors), and abnormal muscle contractions (dystonic reactions) are reported.

The term ‘cinchonism’ comes from the Cinchona tree, the source of quinine. The Cinchona tree’s bark was used by the Peruvian people to prevent chills, by making a tonic from the ground bark and sweetened water. The tree is named after the second countess of Chinchon in Peru. The Cinchona tree and its quinine were introduced to Europe by the Jesuits to manage malaria and was the first effective treatment against the most deadly form of malaria caused by Plasmodium falciparum.

The COVID-19 pandemic brought attention to hydroxychloroquine – another quinine derivative, as it can result in cinchonism. One must remember that the negative side effects related to dosage as hearing problems following hydroxychloroquine consumption could be either temporary or permanent. Notably, hearing damage caused by chloroquine has been seen to be irreversible in some cases.

Quinoline derivatives have various uses, including serving as a treatment for certain heart rhythm disorders, anti-malaria use, and some viral infections, including for a time, SARS-CoV-2 (the virus that causes COVID-19). This excerpt further discusses the broad impacts of cinchonism.

Lastly, quinine, a substance lying within this class, can directly harm the inner layer of the eye (retina). Even though there is usually some improvement over time, it’s not uncommon for some vision loss or narrowing of the field of sight to remain and sadly, vision may not always get better.

What Causes Cinchonism?

Cinchonism is a set of symptoms that occur from consuming substances called quinoline derivatives. The term “cinchonism” comes from the quinine source, which is the bark of the cinchona tree. Quinine use traces back to the 18th century when sailors and soldiers used it to prevent malaria. Today, medications containing these substances are used to treat several conditions including:

* Babesiosis, a parasite illness
* Heart rhythm problems
* Leg muscle cramping
* Malaria, a mosquito-borne disease
* Rheumatic conditions such as rheumatoid arthritis and systemic lupus erythematosus
* Various viral infections

Some of the quinoline derivatives used in these medications include but are not limited to:

* Chloroquine
* Hydroxychloroquine
* Quinidine
* Quinine sulfate
* Tonic water, which contains quinine

Risk Factors and Frequency for Cinchonism

Cinchonism, a condition caused by quinoline drugs, has been found to be directly related to the dose of the drug taken and any other medications taken at the same time. Regardless of gender or ethnicity, there doesn’t seem to be a specific group that is more at risk. In a study involving 61 volunteers receiving oral quinine and azithromycin for P. falciparum, almost everyone experienced some symptoms of cinchonism. Although the treatment was generally well-received and didn’t need to be stopped, it’s essential to be aware that these medications can result in symptoms to some extent.

Signs and Symptoms of Cinchonism

Cinchonism, a condition caused by an overdose of quinine, presents various symptoms. A comprehensive understanding of the drug’s type, dosage, and the length of use is crucial. It’s also important to have information about any previous medical conditions and the reasons for using the drug.

Once taken, quinine is absorbed rapidly, usually reaching peak concentration levels in the bloodstream between three to six hours. Nonetheless, its elimination from the body can extend up to 24 to 26 hours. The typical symptoms of cinchonism, such as nausea, stomach pain, vomiting, diarrhea, headache, sweating, deafness and tinnitus, tend to occur within three to six hours of ingestion.

  • Nausea
  • Abdominal pain
  • Vomiting
  • Diarrhea
  • Headache
  • Sweating
  • Deafness
  • Tinnitus

More severe toxic effects may lead to visual disturbances, starting with blurred vision and color vision problems, usually 6 to 15 hours after ingestion. These vision issues may signal the onset of heart issues indicated by changes in the electrocardiogram (ECG) reading, including extending the QT and QRS intervals. Other ECG abnormalities may include specific types of heart arrhythmias and possibly cardiac arrest. Neurological symptoms can include reduced alertness, seizures, and even a coma. There can also be metabolic and blood abnormalities such as low potassium levels, low platelet count, low blood sugar, and acute kidney damage.

The physical examination should look for specific signs:

  • Vital signs: Checking for unstable bodily functions, fast heartbeat, and low blood pressure.
  • General: Assessing cognitive functions, as cinchonism can cause encephalopathy, a brain disorder.
  • Eyes: A thorough examination of visual fields can reveal loss of peripheral vision (tunnel vision) if the optic nerve is affected. If the retina is involved, there may be central vision loss or even total blindness. Visual sharpness may also be generally reduced.
  • Ears: A Rinne/Weber test can uncover sensorineural hearing loss and tinnitus, a ringing in the ears.
  • Cardiovascular: Checking for a fast heartbeat.
  • Neurologic: Assessing a person’s walk can reveal a lack of muscle coordination or balance.

Testing for Cinchonism

If you’re suspected to have cinchonism, which is poisoning caused by an overdose of quinine or its natural source, the cinchona tree, certain tests would be useful.

Your doctor may order a basic metabolic profile to check your kidney function and electrolyte levels due to the diarrhea and vomiting frequently associated with cinchonism. To check if your liver function is causing any problems with medication clearance, liver function tests would also be done. You may also have your blood tested for quinine levels, where anything over 15 mg/L could increase the risk of lasting vision damage and irregular heartbeats.

In certain cases, further scans or studies may be needed. If you’re presenting signs of encephalopathy (a disease that affects your brain), then a computed tomography (CT) scan or magnetic resonance imaging (MRI) might be ordered to spot any issues in the brain.

Certain eye tests could also be done. A multifocal electroretinography (mfERG) test might show a reduced response at all points in your retina, and an optical coherence tomography can measure if the middle and inner layers of your retina have thinned by 25% to 35%, even though the layer of cells responsible for catching light and helping you see, known as photoreceptors, are intact.

Lastly, even though fast heart rates are typically not a symptom of cinchonism, your doctor might order an electrocardiogram (ECG) to measure your heart’s electrical activity. This test helps check for a condition called QT prolongation that can lead to a dangerous type of irregular heartbeat called torsades de pointes.

Treatment Options for Cinchonism

Managing cinchonism, a condition caused by the prolonged use of certain medications, generally involves stopping the use of the offending drug and providing supportive care. For patients who only have mild symptoms and will only use the offending drug for a short period, typically around 5-7 days, they can usually complete their treatment without experiencing worse or long-lasting side effects related to cinchonism.

Charcoal hemoperfusion is a method that has been trialled for treating cinchonism, but it’s had mixed success. Earlier studies, which suggested it was not very effective, believed the lack of effectiveness was because the drug was binding to proteins. Nevertheless, smaller sub-studies noted that this method did decrease the levels of the drug quinine in the blood, without causing additional harmful side effects. However, it’s important to note that the effectiveness of treatment methods such as charcoal hemoperfusion, hemodialysis, and exchange transfusion has not been proven to actually improve patients’ conditions, but is sometimes still used as therapy.

In terms of the blindness and visual impairments linked to the medications, several avenues have been explored. At first, it was thought that vision loss was primarily caused by blood vessels spasming. To test this theory, some patients were given stellate ganglion blocks, which reduce spasms in blood vessels. But later studies concluded that the main causes were more likely damage to the optic nerve and direct harm to the retina, so a stellate ganglion block wouldn’t actually help.

In tiny case studies, treating patients with hyperbaric oxygen appeared to lessen the impact of visual loss with good benefits and very few side effects. But more research needs to be carried out to confirm the usefulness of hyperbaric oxygen in treating cinchonism. For the time being, the only confirmed way to mitigate the severity of vision loss is to quickly stop taking the offensive medication. But it should be noted that, once a patient’s sharpness of vision decreases, the harm caused to their retina may be irreversible.

When diagnosing cinchonism – a condition caused by an overdose of quinine or its natural source, cinchona bark – doctors might first consider a range of other conditions that can produce similar symptoms due to the broad side effects of these medications. Therefore, knowing the patient’s medical history and conducting a physical exam is crucial. The conditions that could be mistaken for cinchonism include:

  • Drunkenness (which can cause unsteady movements)
  • Aspirin overdose (often causes ringing in the ears)
  • Issues with the mechanical carrying of sound waves to the inner ear, resulting in hearing loss
  • Brain inflammation, which can cause confusion
  • Problems with the stomach or intestines
  • Stroke or temporary disruption in blood flow to the brain, also known as a transient ischemic attack
  • Viral infections

It’s of utmost importance for physicians to explore these possibilities and perform the required tests to deliver a precise diagnosis.

What to expect with Cinchonism

The outlook for cinchonism, a condition caused by an overdose of quinine or its synthetic relative, is generally positive. It often depends on the specific drug taken and the amount of the drug present in the blood. Cinchonism itself doesn’t usually limit a person’s lifespan. However, fast and irregular heartbeats (ventricular tachyarrhythmias), which can be linked to similar drugs, may have serious, life-limiting effects. These outcomes are not discussed in greater detail here, as they are not specifically part of cinchonism.

Possible Complications When Diagnosed with Cinchonism

The main problem caused by cinchonism, a condition from excessive intake of quinine, is irreparable loss of eyesight. Quinine levels exceeding 15 mg/L in the bloodstream put a person at a higher risk for permanent damage to vision and irregular heartbeats. Vision problems may get better as long as the affected person hasn’t suffered any permanent vision loss. Typically, if the symptoms are mild and the person is not planning to take the medicine causing the issues for a long time (around 5 to 7 days), most patients can safely finish their treatment without experiencing an increase in or permanent side effects from cinchonism.

Preventing Cinchonism

Before starting a treatment with quinolone derivatives, it’s crucial for patients to understand the side effects these medications might cause. This information needs to be thoroughly explained by the doctor who prescribes the medication or a pharmacist well-versed in these medications’ properties. They should also discuss the benefits and potential alternatives, providing easy-to-understand literature outlining the drug’s nature, dosage, and frequency of use. The handouts should also list the side effects patients need to watch out for. A good way to ensure the patient understands the information is by using the ‘teach back’ method, where the patient explains back in their own words how they understand the medication is to be used.

Frequently asked questions

Cinchonism refers to a range of symptoms caused by consuming substances derived from quinoline, such as quinine. It can cause symptoms such as tinnitus, hearing loss, face reddening, confusion, diarrhea, vision problems, and even permanent blindness in some cases.

Cinchonism is common and almost everyone experiences some symptoms of cinchonism when taking medications containing quinoline derivatives.

The signs and symptoms of Cinchonism include: - Nausea - Abdominal pain - Vomiting - Diarrhea - Headache - Sweating - Deafness - Tinnitus More severe toxic effects may lead to additional symptoms such as: - Visual disturbances, including blurred vision and color vision problems - Changes in the electrocardiogram (ECG) reading, including extending the QT and QRS intervals - Specific types of heart arrhythmias and possibly cardiac arrest - Reduced alertness, seizures, and even a coma - Metabolic and blood abnormalities such as low potassium levels, low platelet count, low blood sugar, and acute kidney damage During a physical examination, specific signs to look for include: - Unstable bodily functions, fast heartbeat, and low blood pressure (vital signs) - Cognitive dysfunction, as cinchonism can cause encephalopathy, a brain disorder (general assessment) - Loss of peripheral vision (tunnel vision) if the optic nerve is affected, central vision loss or total blindness if the retina is involved, and reduced visual sharpness (eye examination) - Sensorineural hearing loss and tinnitus (ear examination) - Fast heartbeat (cardiovascular examination) - Lack of muscle coordination or balance (neurologic examination)

Cinchonism occurs from consuming substances called quinoline derivatives, such as quinine, chloroquine, hydroxychloroquine, quinidine, and tonic water.

The conditions that a doctor needs to rule out when diagnosing Cinchonism include: - Drunkenness (which can cause unsteady movements) - Aspirin overdose (often causes ringing in the ears) - Issues with the mechanical carrying of sound waves to the inner ear, resulting in hearing loss - Brain inflammation, which can cause confusion - Problems with the stomach or intestines - Stroke or temporary disruption in blood flow to the brain, also known as a transient ischemic attack - Viral infections

The tests needed for cinchonism include: - Basic metabolic profile to check kidney function and electrolyte levels - Liver function tests to assess liver function and medication clearance - Blood test for quinine levels to determine the risk of vision damage and irregular heartbeats - Computed tomography (CT) scan or magnetic resonance imaging (MRI) to evaluate the brain for signs of encephalopathy - Multifocal electroretinography (mfERG) test to assess the response of the retina - Optical coherence tomography to measure the thickness of the retina layers - Electrocardiogram (ECG) to measure heart's electrical activity and check for QT prolongation - Charcoal hemoperfusion, hemodialysis, and exchange transfusion as potential treatment methods, although their effectiveness is not proven - Stellate ganglion blocks and hyperbaric oxygen as experimental treatments for vision loss, with more research needed to confirm their usefulness.

Managing cinchonism involves stopping the use of the offending drug and providing supportive care. For patients with mild symptoms who will only use the offending drug for a short period, they can usually complete their treatment without experiencing worse or long-lasting side effects related to cinchonism. Treatment methods such as charcoal hemoperfusion, hemodialysis, and exchange transfusion have not been proven to actually improve patients' conditions, but are sometimes still used as therapy. In terms of the blindness and visual impairments linked to the medications, the only confirmed way to mitigate the severity of vision loss is to quickly stop taking the offensive medication.

When treating cinchonism, there can be side effects associated with certain treatment methods. However, it's important to note that the effectiveness of these treatment methods in improving patients' conditions has not been proven. The potential side effects include: - Charcoal hemoperfusion: This method has had mixed success and may not be very effective. It may decrease the levels of the drug quinine in the blood without causing additional harmful side effects. - Hemodialysis: The effectiveness of hemodialysis in treating cinchonism has not been proven. - Exchange transfusion: The effectiveness of exchange transfusion in treating cinchonism has not been proven. It should be noted that the main problem caused by cinchonism is irreparable loss of eyesight. Vision problems may get better as long as the affected person hasn't suffered any permanent vision loss. Once a patient's sharpness of vision decreases, the harm caused to their retina may be irreversible.

The prognosis for cinchonism, a condition caused by an overdose of quinine or its synthetic relative, is generally positive. Cinchonism itself doesn't usually limit a person's lifespan. However, fast and irregular heartbeats (ventricular tachyarrhythmias), which can be linked to similar drugs, may have serious, life-limiting effects.

A general practitioner or a specialist in internal medicine or toxicology.

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