Can dextromethorphan effectively treat repetitive itching in atopic dogs. How does this drug impact itch-scratch behaviors in canines with atopic dermatitis. What are the potential benefits and limitations of using dextromethorphan for canine pruritus management.

Understanding Atopic Dermatitis in Dogs

Atopic dermatitis is a prevalent cause of pruritus (itching) in dogs. This condition is diagnosed based on a combination of the dog’s clinical history, observable symptoms, and the exclusion of other potential causes of itching. The exact mechanisms underlying pruritus in dogs are not yet fully understood, adding complexity to the management of this condition.

Some veterinary professionals have observed that certain dogs appear to experience a combination of genuine sensory irritation and repetitive, self-directed behaviors. These cases are particularly challenging to differentiate from those involving pure sensory irritation. Dogs that become noticeably itchier when stressed are often suspected of falling into this category of combined sensory and behavioral pruritus.

Current Treatment Approaches for Canine Atopy

The treatment of atopic dermatitis in dogs varies depending on several factors:

• Severity of symptoms
• Seasonal or year-round nature of the condition
• Individual dog’s response to medical interventions
• Financial considerations of the pet owner

Many dogs undergoing immunotherapy for atopy also require concurrent antipruritic treatments, either on a long-term basis or intermittently as needed. This multi-faceted approach highlights the complex nature of managing atopic dermatitis in canines.

Dextromethorphan Study: Methodology and Design

A recent study evaluated the potential of oral dextromethorphan hydrobromide in treating repetitive itching behaviors associated with atopic dermatitis in dogs. The research involved 14 dogs diagnosed with atopic dermatitis by a veterinary dermatologist, all free from other complicating causes of pruritus such as mites or yeast infections.

The study design included:

• A three-week washout period to eliminate effects of previous medications
• A four-week, placebo-controlled, double-blind crossover study
• Administration of 2 mg/kg dextromethorphan in gelatin capsules every 12 hours
• A placebo phase for comparison
• Allowance of oatmeal soaks but no other therapies during the study period

How did researchers measure the effectiveness of dextromethorphan? The study relied heavily on owner-reported data, with pet owners recording the time spent with their dogs and the duration of observed itch behaviors. Additionally, a dermatologist conducted examinations at various points throughout the study to provide professional assessment.

Key Findings: Dextromethorphan’s Impact on Canine Pruritus

The study’s results revealed some promising outcomes regarding the use of dextromethorphan for managing repetitive itching behaviors in atopic dogs:

• Dogs receiving the placebo exhibited itch behaviors 8.7% of the observed time
• Dogs treated with dextromethorphan showed itch behaviors 6% of the observed time
• This 2.7% difference was statistically significant, representing a 31% decrease in observed itch behaviors

The dermatologist’s global assessment, which included pruritus, inflammation, and overall scores, was more favorable after the active treatment phase in 11 out of 12 dogs. Notably, the pruritus score during dextromethorphan treatment was significantly lower compared to both the placebo and baseline measurements.

Interpreting the Results: Potential Benefits and Limitations

While the study’s findings suggest that dextromethorphan may offer benefits in reducing repetitive pruritic behaviors in atopic dogs, several factors warrant consideration:

1. The potential influence of a placebo effect cannot be entirely ruled out.
2. The use of oatmeal soaks during the study may have contributed to overall skin improvement.
3. The 31% decrease in pruritus translates to a reduction from 23 minutes of itch-scratch behavior with placebo to 17 minutes with dextromethorphan – a difference that may not be perceived as significant by many pet owners.

Is a six-minute reduction in itching duration clinically meaningful? This question highlights the importance of considering both statistical significance and practical relevance when evaluating treatment outcomes.

Pharmacokinetics of Dextromethorphan in Dogs

A separate study investigating the pharmacokinetics of dextromethorphan in healthy dogs revealed several important characteristics of the drug:

• Short half-life
• Rapid clearance from the body
• Poor bioavailability when administered orally

These pharmacokinetic properties raise questions about the optimal dosing regimen and potential limitations of dextromethorphan as a long-term treatment option for canine atopic dermatitis. How can these challenges be addressed to maximize the drug’s therapeutic potential?

Practical Implications for Veterinary Practice

The findings from this study suggest that dextromethorphan may have a role in managing atopic dogs with habituated pruritic behaviors. However, veterinarians should consider several factors when contemplating its use:

• Individual patient response may vary
• The modest reduction in itching duration may not meet all pet owners’ expectations
• Pharmacokinetic challenges may necessitate frequent dosing or alternative delivery methods
• Potential side effects, as observed in the study (e.g., sedation, diarrhea)

How can veterinarians best incorporate these findings into their treatment protocols for atopic dermatitis? A balanced approach, considering both the potential benefits and limitations of dextromethorphan, may be most appropriate.

Future Research Directions

While this study provides valuable insights into the potential use of dextromethorphan for managing repetitive itching behaviors in atopic dogs, several areas warrant further investigation:

1. Optimization of dosing regimens to address pharmacokinetic challenges
2. Long-term safety and efficacy studies
3. Combination therapies incorporating dextromethorphan with other antipruritic treatments
4. Identification of specific subgroups of atopic dogs most likely to benefit from dextromethorphan treatment

What novel approaches could researchers explore to enhance the therapeutic potential of dextromethorphan in canine atopic dermatitis? Innovative drug delivery systems or time-release formulations might offer solutions to the pharmacokinetic limitations observed in current studies.

Exploring the Neurological Basis of Pruritus in Atopic Dogs

The potential efficacy of dextromethorphan in reducing repetitive itching behaviors raises intriguing questions about the neurological mechanisms underlying pruritus in atopic dogs. Dextromethorphan is known to have effects on the central nervous system, primarily as an N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist.

Could the observed reduction in itching behaviors be attributed to modulation of central nervous system pathways rather than direct effects on peripheral itch receptors? This hypothesis warrants further investigation and may open new avenues for targeting the neurological components of chronic pruritus in dogs.

Comparative Efficacy of Dextromethorphan and Traditional Antipruritic Treatments

To fully understand the potential role of dextromethorphan in managing canine atopic dermatitis, it would be valuable to conduct comparative studies with established antipruritic treatments. Such research could address questions like:

• How does the efficacy of dextromethorphan compare to commonly used antihistamines in reducing pruritus?
• Can dextromethorphan provide additive or synergistic effects when combined with traditional treatments like glucocorticoids or cyclosporine?
• Are there specific subsets of atopic dogs that respond better to dextromethorphan compared to other antipruritic medications?

By answering these questions, veterinarians could gain a clearer understanding of where dextromethorphan fits within the broader spectrum of treatment options for canine atopic dermatitis.

Investigating the Impact on Quality of Life

While the study focused on quantitative measures of itching behavior, it’s crucial to consider the broader impact of dextromethorphan treatment on the quality of life for both dogs and their owners. Future research could incorporate more comprehensive quality of life assessments, addressing factors such as:

• Sleep quality for both dogs and owners
• Overall skin condition and coat health
• Activity levels and willingness to engage in play or exercise
• Owner satisfaction with treatment outcomes

How might these quality of life measures correlate with the observed reductions in itching behaviors? Such insights could provide a more holistic understanding of the treatment’s overall impact and help guide clinical decision-making.

Exploring Potential Applications Beyond Atopic Dermatitis

The observed effects of dextromethorphan on repetitive itching behaviors in atopic dogs raise questions about its potential applications in other dermatological or neurological conditions characterized by persistent pruritus or compulsive behaviors. Areas for future exploration might include:

• Psychogenic pruritus or acral lick dermatitis
• Neuropathic itch associated with certain neurological disorders
• Post-operative pruritus following certain surgical procedures

Could the mechanisms by which dextromethorphan affects itching behaviors in atopic dogs have broader implications for managing other pruritus-related conditions in veterinary medicine? This line of inquiry could potentially expand the therapeutic applications of dextromethorphan beyond its current use.

Optimizing Drug Delivery and Formulation

Given the pharmacokinetic challenges associated with oral dextromethorphan administration in dogs, there is a clear need for research into alternative delivery methods and formulations. Potential areas of investigation could include:

• Transdermal delivery systems to bypass first-pass metabolism and improve bioavailability
• Extended-release oral formulations to prolong the duration of action
• Combination products incorporating dextromethorphan with other antipruritic agents or absorption enhancers

How might these novel formulations impact the efficacy and practicality of dextromethorphan use in veterinary practice? Addressing these pharmacokinetic limitations could significantly enhance the drug’s potential as a treatment option for canine atopic dermatitis.

Elucidating the Mechanisms of Action

While the study demonstrated a reduction in repetitive itching behaviors with dextromethorphan treatment, the precise mechanisms underlying this effect remain unclear. Further research is needed to elucidate:

• The specific neuroreceptors and pathways involved in mediating the antipruritic effects
• Potential impacts on inflammatory mediators associated with atopic dermatitis
• Interactions between dextromethorphan and the complex immunological processes underlying canine atopy

A deeper understanding of these mechanisms could not only optimize the use of dextromethorphan but also pave the way for the development of more targeted and effective treatments for canine pruritus.

Addressing Individual Variability in Treatment Response

The study results suggest that not all dogs respond equally to dextromethorphan treatment. Investigating factors that influence individual treatment response could greatly enhance clinical decision-making. Key questions to explore include:

• Are there genetic markers or biomarkers that predict a favorable response to dextromethorphan?
• How do factors such as age, breed, or concurrent health conditions impact treatment efficacy?
• Can specific characteristics of the atopic dermatitis (e.g., localization, severity, duration) predict the likelihood of response to dextromethorphan?

By identifying predictors of treatment success, veterinarians could more effectively target dextromethorphan therapy to those dogs most likely to benefit, optimizing patient outcomes and resource utilization.

Long-Term Safety and Efficacy Considerations

As with any chronic condition, the long-term management of canine atopic dermatitis requires careful consideration of both efficacy and safety. Future research should address:

• The safety profile of dextromethorphan with extended use in dogs
• Potential for the development of tolerance or habituation with long-term treatment
• Interactions with other medications commonly used in the management of atopic dermatitis
• Strategies for monitoring and managing potential side effects in long-term users

How can veterinarians balance the potential benefits of dextromethorphan against any long-term risks or side effects? Answering this question is crucial for establishing dextromethorphan as a viable long-term treatment option for canine atopic dermatitis.

Integrating Dextromethorphan into Multimodal Treatment Approaches

Given the complex nature of canine atopic dermatitis, most effective management strategies involve a multimodal approach. Future research should explore how dextromethorphan can be optimally integrated into comprehensive treatment plans, considering:

• Potential synergies with other pharmacological interventions
• Interactions with non-pharmacological management strategies (e.g., dietary modifications, topical treatments)
• Role in supporting the efficacy of immunotherapy or other long-term management approaches

By understanding how dextromethorphan complements other treatment modalities, veterinarians can develop more effective and personalized management strategies for dogs with atopic dermatitis.

As research in this area continues, the veterinary community may gain valuable insights into novel approaches for managing the challenging and persistent problem of pruritus in atopic dogs. The exploration of dextromethorphan’s potential in this context represents an exciting development in the ongoing effort to improve the lives of dogs affected by atopic dermatitis and their owners.

Can dextromethorphan be used to treat repetitive itching and scratching in atopic dogs?

January 1, 2005

Karen A. Moriello, DVM, DACVD

In a recent study, oral dextromethorphan hydrobromide was evaluated in 14 dogs with atopic dermatitis to determine whether the drug had any effect on repetitive behaviors associated with or suggestive of pruritus.

Atopic dermatitis is one of the most common causes of pruritus in dogs. It is diagnosed based on a dog’s history and clinical signs and the elimination of other causes of pruritus.

The pathogenesis of pruritus in dogs is still not well understood. To further complicate matters, some clinicians speculate that certain dogs have a combination of sensory irritation (true itch) and repetitive behaviors (self-directed itch), though these dogs are hard to differentiate from dogs with purely sensory irritation. But the dogs that are most suspected of having this combination are those that clients describe as becoming itchy when stressed.

Treatment options for atopy vary depending on a variety of factors, including the severity of signs, whether the signs are year-round or seasonal, the dog’s response to medical treatment, and the owner’s financial constraints. Dogs receiving immunotherapy often also receive concurrent antipruritic therapy on either a long-term or intermittent basis.

In a recent study, oral dextromethorphan hydrobromide was evaluated in 14 dogs with atopic dermatitis to determine whether the drug had any effect on repetitive behaviors associated with or suggestive of pruritus (e.g. self-licking, self-chewing, self-biting).1 A veterinary dermatologist diagnosed atopic dermatitis in the dogs, and all of the dogs were free of other complicating causes of pruritus (e.g. mites, yeast). After a three-week washout period from any drugs the dogs may have been receiving before the study, the dogs were randomly enrolled in a four-week, placebo-controlled, double blind crossover study. The dogs received 2 mg/kg dextromethorphan in a gelatin capsule every 12 hours and a placebo for two weeks each. During the study, oatmeal soaks were allowed, but no other therapies. Twelve dogs completed the study; two dropped out because of adverse effects (sedation, diarrhea). Because of a lack of compliance with data collection, the investigators were only able to evaluate data from 10 dogs. An important component of the study was the owners’ scoring of their dogs’ pruritus. The owners were required to record how much time they spent with their dogs and the amount of time the dogs exhibited certain itch behaviors. In addition, a dermatologist examined the dogs at various points in the study.

The investigators used a calculation called the itch percent to evaluate the data. The itch percent was calculated based on the time the owners spent with their dogs and how much time the dogs were observed to be involved in itch-scratch behaviors during these periods. Dogs receiving the placebo were observed to exhibit itch behaviors 8. 7% of the time; dogs receiving dextromethorphan exhibited itch behaviors 6% of the time. The difference (2.7%) was statistically significant and represents a 31% decrease in observed itch behaviors. A global dermatology score was calculated for all the dogs, which consisted of three components of the dermatologist’s assessment (a pruritus score, an inflammation score, and an overall score). The dermatologist’s global assessment was more favorable after the active treatment phase in 11 of the 12 dogs, and the pruritus score during dextromethorphan treatment was significantly less compared with the placebo and baseline. The investigators concluded from these findings that dextromethorphan was beneficial in reducing the time the dogs spent licking, chewing, and self-biting.

Commentary

The findings in this study suggest that dextromethorphan may be clinically useful in atopic dogs with habituated pruritic behaviors. However, a placebo effect may still have been a factor. Moreover, the investigators stated that the oatmeal soaks might have contributed to some of the overall gross improvement in the skin. And the 31% decrease in pruritus represents 23 minutes of itch-scratch behavior when the dogs received the placebo vs. 17 minutes when they received dextromethorphan. I’m not sure that the average client would find a decrease of six minutes of itching to be a great improvement. Finally, in a recent study on the pharmacokinetics of dextromethorphan after intravenous and oral administration in healthy dogs, the investigators found that the drug had a short half-life, was rapidly cleared, and had poor bioavailability.2 The authors of this pharmacokinetics study concluded that the drug’s erratic absorption, short elimination half-life, and rapid clearance limit its potential usefulness when administered orally long-term.2

If there is a true benefit from dextromethorphan, it suggests that some central component to pruritus or at least to the repetitive behaviors that clients and veterinarians interpret as pruritus (e.g. licking, biting) exists. Opioid antagonists have been successfully used in other species to treat repetitive behaviors. 3,4 For example, dextromethorphan has been effective in treating crib-biting in horses.5 It is hypothesized that dextromethorphan works by N-methyl-D-aspartate blockade and not by opioid blockade. The exact mechanism of action is unknown, but N-methyl-D-aspartate receptors are found in the spinal cord and brain and are involved in learning and memory, tolerance, and sensitization.

When new findings regarding a drug’s antipruritic effects are reported, it is tempting to prescribe it as a first-choice drug; however, newer is not always better or appropriate. The long-term safety of dextromethorphan is unknown, and the dogs in this study received the drug for only two weeks. Clients should be aware that this drug is not free of side effects, which include sedation, vomiting, and diarrhea.

Treating dogs with chronic atopy will always require vigilant monitoring for breakthrough infections and secondary parasitic infestations. Traditional therapies for pruritus (immunotherapy, antihistamines, glucocorticoids, and cyclosporine) are indicated initially. Dextromethorphan may be useful in patients with no obvious signs of inflammation or in cases of a suspected repetitive behavior. But it is important to note that no studies are available documenting the existence of habitual pathogenesis. Perhaps there is a place for a drug such as dextromethorphan in the treatment of atopy, but for now my recommendation is to focus on traditional antipruritic therapies and monitoring of underlying disease.

REFERENCES

1. Dodman NH, Shuster L, Nesbitt G, et al. The use of dextromethorphan to treat repetitive self-directed scratching, biting, or chewing in dogs with allergic dermatitis. J Vet Pharmacol Ther 2004;27:99-104.

2. Kukanich B, Papich MG. Plasma profile and pharmacokinetics of dextromethorphan after intravenous and oral administration in healthy dogs. J Vet Pharmacol Ther 2004;27:337-341.

3. Dodman NH, Shuster L, Court MH, et al. Investigation into the use of narcotic antagonists in the treatment of a stereotypic behavior pattern (crib-biting) in the horse. Am J Vet Res 1987;48:311-319.

4. Kenny DE. Use of naltrexone for treatment of psychogenically induced dermatoses in five zoo animals. J Am Vet Med Assoc 1994;205:1021-1023.

5. Rendon RA, Shuster L, Dodman NH. The effect of the NMDA receptor blocker, dextromethorphan, on cribbing in horses. Pharmacol Biochem Behav 2001;68:49-51.

“Dermatology Update” was contributed by Karen A. Moriello, DVM, DACVD, Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Dextromethorphan: MedlinePlus Drug Information

pronounced as (dex troe meth or’ fan)

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Dextromethorphan is used to temporarily relieve cough caused by the common cold, the flu, or other conditions. Dextromethorphan will relieve a cough but will not treat the cause of the cough or speed recovery. Dextromethorphan is in a class of medications called antitussives. It works by decreasing activity in the part of the brain that causes coughing.

Dextromethorphan comes as a liquid-filled capsule, a chewable tablet, a dissolving strip, a solution (liquid), an extended-release (long-acting) suspension (liquid), and a lozenge to take by mouth. It is usually taken every 4 to 12 hours as needed. Follow the directions on the package or prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.

Dextromethorphan should only be used according to the label or package directions. Do not take more than the recommended amount of dextromethorphan in a 24-hour period. Refer to the package or prescription label to determine the amount contained in each dose. Taking dextromethorphan in large amounts can cause serious side effects or death.

Dextromethorphan comes alone and in combination with antihistamines, cough suppressants, and decongestants. Ask your doctor or pharmacist for advice on which product is best for your symptoms. Check nonprescription cough and cold product labels carefully before using 2 or more products at the same time. These products may contain the same active ingredient(s) and taking them together could cause you to receive an overdose. This is especially important if you will be giving cough and cold medications to a child.

Nonprescription cough and cold combination products, including products that contain dextromethorphan, can cause serious side effects or death in young children. Do not give these products to children younger than 4 years of age. If you give these products to children 4-11 years of age, use caution and follow the package directions carefully.

If you are giving dextromethorphan or a combination product that contains dextromethorphan to a child, read the package label carefully to be sure that it is the right product for a child of that age. Do not give dextromethorphan products that are made for adults to children.

Before you give a dextromethorphan product to a child, check the package label to find out how much medication the child should receive. Give the dose that matches the child’s age on the chart. Ask the child’s doctor if you don’t know how much medication to give the child.

If you are taking the liquid, do not use a household spoon to measure your dose. Use the measuring spoon or cup that came with the medication or use a spoon made especially for measuring medication.

If you are using the dissolving strips, place them on your tongue and swallow after they melt.

If you are taking the chewable tablets you can allow them to melt in your mouth or you can chew them before swallowing.

If you are taking the extended-release suspension, shake the bottle well before each use to mix the medication evenly.

If you are taking the lozenges, allow them to slowly melt in your mouth.

Stop taking dextromethorphan and call your doctor if your cough does not get better within 7 days, if your cough goes away and comes back, or if your cough occurs with a fever, rash, or headache.

This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking dextromethorphan,

• tell your doctor and pharmacist if you are allergic to dextromethorphan, any other medications, or any of the ingredients in the product you plan to take. Check the package label for a list of the ingredients.
• do not take dextromethorphan if you are taking a monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate), or if you have stopped taking an MAO inhibitor within the past 2 weeks.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.
• tell your doctor if you smoke, if you have a cough that occurs with a large amount of phlegm (mucus), or if you have or have ever had breathing problems such as asthma, emphysema, or chronic bronchitis.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking dextromethorphan, call your doctor.
• if you have phenylketonuria (PKU, an inherited condition in which a special diet must be followed to prevent damage to your brain that can cause severe intellectual disability), you should know that some brands of chewable tablets that contain dextromethorphan may be sweetened with aspartame, a source of phenylalanine.

Unless your doctor tells you otherwise, continue your normal diet.

Dextromethorphan is usually taken as needed. If your doctor has told you to take dextromethorphan regularly, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Dextromethorphan may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dizziness
• lightheadedness
• drowsiness
• nervousness
• restlessness
• nausea
• vomiting
• stomach pain

If you experience any of the following symptoms, call your doctor immediately:

• rash

Dextromethorphan may cause other side effects. Call your doctor if you experience any unusual problems while you are taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website (http://goo. gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services at 911.

Symptoms of overdose may include:

• nausea
• vomiting
• drowsiness
• dizziness
• unsteadiness
• changes in vision
• difficulty breathing
• fast heartbeat
• hallucinating (seeing things or hearing voices that do not exist)
• seizures
• coma (loss of consciousness for a period of time)

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• Alka-Seltzer Plus Day Non-Drowsy Cold Formula^® (containing Acetaminophen, Dextromethorphan, Phenylephrine)
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• PediaCare Children’s Fever Reducer Plus Cough and Runny Nose^® (containing Acetaminophen, Chlorpheniramine, Dextromethorphan)
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• PediaCare Children’s Fever Reducer Plus Flu^® (containing Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylephrine)
• PediaCare Children’s Fever Reducer Plus Multi-Symptom Cold^® (containing Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylephrine)
• Robitussin Cough and Chest DM^® (containing Dextromethorphan, Guaifenesin)
• Robitussin Cough and Cold CF^® (containing Dextromethorphan, Guaifenesin, Phenylephrine)
• Robitussin Cough and Cold Long-Acting^® (containing Chlorpheniramine, Dextromethorphan)
• Robitussin Night Time Cough, Cold, and Flu^® (containing Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylephrine)
• Sudafed PE Cold/Cough^® (containing Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine)
• Sudafed PE Day/Night Cold^® (containing Acetaminophen, Dextromethorphan, Diphenhydramine, Guaifenesin, Phenylephrine)
• Theraflu Cold and Cough^® (containing Dextromethorphan, Pheniramine, Phenylephrine)
• Theraflu Daytime Severe Cold and Cough^® (containing Acetaminophen, Dextromethorphan, Phenylephrine)
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• Tylenol Cold and Cough Daytime^® (containing Acetaminophen, Dextromethorphan)
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• Tylenol Cold Multi-Symptom Nighttime^® (containing Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylephrine)
• Tylenol Cold and Mucus Severe^® (containing Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine)
• Vicks Children’s NyQuil Cold and Cough^® (containing Chlorpheniramine, Dextromethorphan)
• Vicks DayQuil Cold and Flu Relief^® (containing Acetaminophen, Dextromethorphan, Phenylephrine)
• Vicks DayQuil Cold and Flu Symptom Relief Plus Vitamin C^® (containing Acetaminophen, Dextromethorphan, Phenylephrine)
• Vicks DayQuil Mucus Control DM^® (containing Dextromethorphan, Guaifenesin)

Last Revised – 01/15/2022

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Dextromethorphan is – causes, symptoms, signs, stages, consequences, treatment

Many cough medicines contain dextromethorphan. In doses recommended by the doctor, the drug is safe and has a good therapeutic effect.

When used in large doses, the substance has a stimulating effect, which young people use to get positive emotions.

Pharmacy drugs, which include dextromethorphan, have a pronounced sedative, hypnotic, relaxing effect and can cause drug intoxication.

Dextromethorphan – description, composition, effect, properties

Dextromethorphan is a codeine-like synthetic substance that is an ingredient in many cough medicines. Despite the similarity to morphine, it does not have an opiate effect.

The substance depresses the cough center, affecting the nervous system. Softens cough of various etiologies and has a mild sedative effect.

Preparations containing dextromethorphan include: Grippex, Glycodin, Alex Plus, Tussin Plus, Coldrex Night, etc. They are available in the form of syrup, tablets, capsules.

The drug should be taken at the dosage prescribed by the attending physician: 90-120 mg per day, in divided doses. Before use, you should read the instructions for use, which indicate possible adverse reactions and conditions in which the drug should not be taken.

The use of dextromethorphan is contraindicated in:

• bronchial asthma;
• bronchitis;
• impaired renal and hepatic functions;
• heart and respiratory failure;
• pregnancy, breastfeeding period;
• hypersensitivity.

Should not be taken concomitantly with mucolytics.

The effect of the drug

When used in high doses, dextromethorphan has a psychotropic effect, reminiscent of the effect of small doses of ketamine or LSD (hallucinogenic drug).

The effect on the body of dextromethorphan can be different, depending on the dose taken: from a weak stimulating effect and pleasant experiences to a state of excitement, disorientation in the environment, intense hallucinations, impaired thinking and loss of consciousness.

With an increase in intoxication, the rise in the psycho-emotional state and euphoria are replaced by fear, increased anxiety, depression, insomnia and other painful symptoms.

There are violations of the cardiovascular system, respiratory organs, gastrointestinal tract. Dangerous consequences are respiratory depression and cardiac arrest.

The use of a substance in excessive amounts is dangerous to the body due to its stimulating effect on the central nervous system. This leads to poor physical and mental health.

Drug dependence

The state of euphoria and mental well-being causes the addict to repeat the drug, constantly increasing the dose.

The transition from episodic to regular drug use, the emergence of addiction to drug intoxication leads to the formation of a persistent dependence on dextromethorphan.

There are 4 degrees of drug intoxication.

The first degree is characterized by increased mood, a feeling of cheerfulness, energy, anxiety, dizziness, hallucinatory disorders.

The second is manifested by an increase in activity, pronounced auditory and visual deceptions of perception.

Signs of using the third degree:

• deterioration of the functions of vision and hearing;
• confusion;
• slow reactions;
• impaired memory and ability to perceive information;
• feeling of fear, panic reactions.

The last degree is characterized by impaired coordination of movements, depression of consciousness, severe psychotic disorders.

Symptoms to look out for include pale skin, weight loss, blood pressure fluctuations, changes in pupil size, and unsteady gait.

The action begins 30 minutes after ingestion and lasts up to 6-8 hours.

When it enters the stomach, the active substances are quickly absorbed. Metabolism occurs in the liver tissues with the formation of dextrorphan. The maximum concentration in the blood is detected after 2 hours.

Dextromethorphan is excreted mainly through the kidneys in an unchanged form and in the form of decay products. The half-life is 2-4 hours.

Stages and types of drug dependence

Drug addiction is manifested by a pronounced need to take a substance, the inability to control drug intake. The addict continues to use the drug, despite the harmful effects and deterioration in well-being.

Psychological dependence on dextromethorphan is characterized by an irresistible desire to take the substance to obtain positive emotions. The absence of the drug affects the mental state. Patients experience severe discomfort, a sense of dissatisfaction, anxiety, emotional stress.

Physical dependence develops when abrupt discontinuation leads to deterioration and a severe pathological condition – withdrawal syndrome (abstinence). Dependence on a drug of this kind is mild and occurs against the background of prolonged abuse in some cases.

Against the backdrop of cancellation a few days after the last dose, muscle pain, impaired stool, decreased mood, lethargy, insomnia, increased sweating are possible.

Side effects of this drug

Regular use of the drug in high dosages causes significant harm to health.

Due to chronic intoxication, the work of all body systems, the central nervous system is disrupted, sleep, appetite worsen, memory and attention suffer.

There are mental disorders, panic states, depression, delusional experiences, hallucinations, suicidal thoughts.

Continuous use of the drug requires an increasing dose to obtain the desired effect. Depending on the amount taken, various negative manifestations are possible: drowsiness, tachycardia, dizziness, nausea, vomiting, diarrhea, etc.

Poisoning and overdose of dextromethorphan is manifested by the following symptoms:

• psychomotor agitation;
• disorientation in space and time;
• shallow breathing;
• arrhythmia, palpitations;
• lowering blood pressure;
• dyspeptic disorders;
• confusion, coma;
• seizures;
• involuntary movements of the eyeballs;
• itching and rashes on the skin;
• problems with speech, coordination of movements;
• tremor of limbs;
• feeling of fear, anxiety;
• hallucinatory experiences.

An overdose of dextromethorphan is an emergency and, if left untreated, can be fatal.

Combination of the drug with other substances

To get more vivid sensations, addicts often combine several drugs. This has a negative effect on the entire body and poses a serious threat to human life.

The use of dextromethorphan and alcohol enhances the effect of ethyl alcohol and the psychotropic effect of the drug, causing severe intoxication and severe poisoning.

The sedative effect is greatly increased when the substance is taken simultaneously with benzodiazepines and barbiturates, which can lead to respiratory arrest and death.

Co-administration of dextromethorphan with antidepressants causes serotonin syndrome, which is characterized by confusion, fever, anxiety, tremors, and other symptoms. This condition can lead to death.

Long-term and systematic substance abuse affects the mental state and leads to a deterioration in physical health.

The family and loved ones of the patient suffer greatly from the consequences of addiction. Conflicts arise at work, at home, social life. The patient cannot live a normal, fulfilling life.

To successfully get rid of addiction at all stages of treatment, you need to be patient and strictly adhere to the rules of behavior with an addicted person. An important role is played by the constant support, respectful attitude and help of relatives.

At the first signs of drug addiction, changes in behavior and the identification of suspicious drugs, it is recommended to contact an experienced specialist – a mental health clinic psychiatrist-narcologist as soon as possible.

You need to contact only specialized medical centers. Highly qualified doctors will draw up an individual treatment plan and help overcome addiction.

You should not self-medicate, use traditional medicine, contact “healers” without a medical education and relevant work experience. This can lead to irreversible consequences.

Diagnosis and treatment

An accurate diagnosis is established only by a clinic specialist after diagnosing Dextromethorphan addiction.

Diagnosis includes taking an anamnesis, talking with the patient and his close circle, and a thorough examination. It is important to pay attention to the appearance and behavior of the patient, the nature of speech and other manifestations of dependence.

It is mandatory to conduct tests for the presence of the drug in the biological fluids of the body, laboratory blood and urine tests.

According to the indications, consultations of narrow specialists are prescribed.

Dextromethorphan addiction treatment is a lengthy therapeutic process that requires an integrated approach, specialized medical care and constant support from relatives at all stages of treatment.

It is impossible to get rid of dextromethorphan addiction on your own, without special therapy and psychotherapeutic assistance. Long-term use of the drug affects the physical condition, psyche and consciousness of the patient. Only complex therapy and the desire of the addict to become healthy can guarantee a positive result.

Treatment is carried out in a specialized clinic under the supervision of experienced professionals. For each patient, an individual program of therapeutic and rehabilitation measures is drawn up, taking into account all the features.

The first stage is a detoxification therapy aimed at removing toxins, cleansing the body and alleviating withdrawal symptoms.

Then follows the stage of drug treatment, the purpose of which is the restoration of impaired functions of internal organs, symptomatic therapy, improvement of mental state and elimination of complications.

Psychotherapeutic assistance includes working with a psychologist, conducting individual and group psychotherapy. Sessions contribute to the elimination of negative attitudes from the patient’s consciousness, the conscious rejection of the drug. As a result, new life values ​​are formed, motivation for a healthy lifestyle appears.

The length of the recovery period depends on many factors and can take several months.

When completing the full course, the former addict returns to a healthy life in society, can work and build relationships in the family.

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Prevention or advice

After drug therapy and a period of rehabilitation, in order to prevent breakdowns and relapses of addiction, it is necessary to create an optimal microclimate, to review the patient’s social circle.

At this stage, in addition to special psychotherapeutic programs, it is important to observe the daily routine, eat right, ensure proper sleep, and exercise. Restoration of professional skills, support of relatives and organized work of specialists play an important role.

Recommendations for prevention of dependence on dextromethorphan:

• dextromethorphan should only be taken as directed by a doctor;
• it is not recommended to exceed the allowable dosage;
• do not self-medicate;
• inform the specialist about any changes in the condition.

The use of narcotic substances causes irreparable harm to health and poses a danger to life.

The first step in the treatment and prevention of the disease is to contact a competent doctor of a specialized clinic.

References:

1. Abuse of dextromethorphan: clinical effects and treatment. / Romanelli F., Smith K.M. / J Am Pharm Assoc (2003). 2009 March-April; 49 (2)
2. Pharmacokinetics and pharmacodynamics of dextromethorphan: clinical and forensic aspects. / Silva A.R., Dinis-Oliveira R.J. / Drug Metab Rev.2020 May
3. Dextromethorphan/bupropion: A novel oral NMDA (N-methyl-d-aspartate) receptor antagonist with multimodal activity. / Stahl SM. / CNS Spectr. 2019 October
4. Ivanets N.N., Anyukhina I.P., Vinnikova M.A., Narcology. National Guidelines 2008

Dextromethorphan (DXM) | Addictionlink.fi

Published on 19.1.2011.

Dextromethorphan has been widely used worldwide since the 1950s as a cough suppressant because it reduces cough irritation by acting on central nervous system function. In Finland, preparations containing dextromethorphan are, in particular, mm. Resilar®, Redol Comp® and Sir Ephedrin®, which are only available in pharmacies. Some of these drugs are available only by prescription from a doctor. Abroad, the drug has several slang names – such as CCC, Robos, Skittles – derivatives of the trade names of drugs containing dextromethorphan. In Finland, the corresponding name “Ressut” is known.

As a psychoactive substance (SAS), dextromethorphan has not been widely used for decades, but since the early 2000s, its use as a psychoactive substance has steadily increased worldwide. As a surfactant, this compound is used mainly by young people aged 12–20 years. At high doses, dextromethorphan exhibits effects somewhat similar to ketamine, phencyclidine (PCP), or LSD. According to the latest information, in addition to the psychological dependence, physical dependence can also occur in addition to the drug. There is not enough information about the nature, prevalence and intensity of addiction. Dextromethorphan is obviously not addictive very easily. It is known that the tolerability of the drug increases, therefore, in order to achieve the desired effect, it is necessary to take larger doses over time. At the same time, the risk of harmful influences increases.

Dextromethorphan can be considered a safe surfactant due to its long-term presence in the market and easy availability in pharmacies (at least in the US). Also, the price is considered acceptable, and the need for the so-called. illegal trade on the streets. Harmful effects when the compound is used in high doses or regularly, however, are not well known, giving a false impression of the safety of dextromethorphan. Particularly due to the rise in abuse of the drug, recent articles on dextromethorphan suggest questioning the availability of the drug over the counter.

Mechanism of action

Dextromethorphan ((+)-3-methoxy-N-methylmorphinan) was previously classified as a synthetic opioid with a structure similar to codeine. At present, dextromethorphan should not be classified as an opioid because its primary effects are not mediated through opioid receptors. When using the drug as a surfactant, it is assumed that the mechanism of action is associated with the NMDA receptor, the functions of which are blocked. This, in turn, prevents the influence of glutamate, which activates the central nervous system, which leads to a violation of the functions of the central nervous system. It is also assumed that the binding to the sigma-1 receptor and its activation are important elements of the mechanism of action. At high and very high doses, dextromethorphan can bind to opioid receptors, reduce the return of serotonin to cells, increase dopamine levels and cause adrenergic effects (including increased blood pressure and accelerated heart rate).

The compound is well absorbed when taken by mouth for about 30 minutes. When used as a cough suppressant, the action usually begins in 15-30 minutes. When used as a surfactant, the action is likely to start later. Dextromethorphan has a significant first cycle metabolism in the liver, which reduces the useful component of its action. The half-life in the body is 2-4 hours. The compound continues to act for 3-8 hours, depending on the size of the dose taken. Due to the individual characteristics of liver function, some users can achieve a state of intoxication at lower doses than others. The duration of exposure may also vary, and harmful effects, incl. nausea, less common.

Effects and harmful effects

Adult doses for cough suppressant are 90–120 mg/day. in the form of several doses (30 mg / time). At such doses, there is no intoxicating effect, euphoria or dependence. With a small overdose, no harmful effects are usually observed.

Dextromethorphan and its metabolite, dextrofan, are so-called. dissociative compounds. This includes, for example, feelings of alienation from one’s body (out-of-body). Hallucinations of various kinds are also common and are thought to be similar to those caused by LSD, phencyclidine (PCP), and ecstasy (MDMA). According to some users, dextromethorphan-induced hallucinations may differ significantly from LSD-induced hallucinations. According to them, dextromethorphan causes variegated moving formations (the so-called closed-eye visual hallucinations), which are visible especially when the eyes are closed or in a dark room. The effects of the compound depend on the person, the dose taken, individual tolerance, as well as other surfactants taken simultaneously with it. Table 1 contains different degrees of intoxication (or categories, in English plateau or stage). The effects of lower levels are not necessarily felt at higher levels, as is the case with dextromethorphan.

Table 1. Possible effects of dextromethorphan on different degrees of intoxication.

In addition to the effects listed in Table 1, the following possible effects are named in the literature, depending on the source:

• Brain damage
• Changing the perception of time
• Energetic or warm feeling
• Psychopathological re-experiencing (Flashback)
• Respiratory failure
• Dizziness
• Lack of ability to concentrate
• High blood pressure
• Coma
• Convulsions
• Dry mouth
• Itching
• Impaired coordination of movements
• The feeling of flying
• Liver failure
• Changes in the sense of self
• Renal failure
• Pulse acceleration
• Vomiting
• Nausea
• Psychosis
• Speech disorder
• Changing pupil size
• Nystagmus
• Changes in the functioning of the senses
• Drowsiness
• Trembling
• Fatigue

The most serious harmful effects are more pronounced when higher doses are taken. Also, constant or frequently repeated use increases the risk of serious harmful effects. Judgment is also endangered, which in the worst case can lead to permanent injury or even death. There are a few cases of death caused by dextromethorphan in the literature, but even at high doses they are not frequent. It should be noted that in the literature there is a lot of conflicting information regarding the ability of dextromethorphan to cause, for example, respiratory failure.

Excipients and combined preparations

When using dextromethorphan as a surfactant, excipients contained in compounds with dextromethorphan (including ethanol, sweeteners) and other active ingredients of combined preparations (in Finland, for example, salbutamol and ephedrine). The more dextromethorphan is required for intoxication, the more other unwanted compounds enter the body. These unwanted compounds can cause very strong harmful effects and in some cases even be more dangerous than dextromethorphan itself. Therefore, some consumers process preparations with dextromethorphan chemically, in particular, with the help of gasoline. Processing, of course, can remove some of the unwanted constituents, but at the same time, processing without proper experience can lead to exposure to other compounds (gasoline) or other hazards (variation in drug concentration).

In Finland, dextromethorphan is often available in the form of a salt containing bromine. In the literature, bromine poisoning is considered possible with prolonged use of the drug, but not a single case of dementia has been noted.

Addiction

Studies have shown that dextromethorphan causes physical dependence. The development of withdrawal symptoms obviously involves long-term use of large doses. According to one study, symptoms do not appear until 3 days after stopping dextromethorphan. Symptoms may be similar to those of opioid withdrawal, for example:

• Feeling cold
• Anxiety
• Muscle pain
• Depression
• Vomiting
• Loose stools
• Sleep disturbance
• Night sweats

Joint effects

Several synergies with other drugs have been shown. The main drug groups are MAO inhibitors (eg moclobemide) and SSRI drugs (eg fluoxetine). They increase the risk of serotonin syndrome, the typical symptoms of which are, in particular, fever, trembling, clouding of consciousness, anxiety. Serotonin syndrome develops with a delay of a couple of hours and in a pronounced form can be life-threatening. Alcohol, lithium, tricyclic antidepressants, clonazepam, pethidine, ecstasy (MDMA), tryptophan, and St. John’s wort are considered harmful when taken with the drug. Also, medicinal substances that affect metabolism via the CYP2D6 enzyme (eg bupropion) increase the risk of serious adverse effects. There is little or no information available on interactions with other surfactants, so any form of combined use should be considered hazardous and should be avoided.

Overdose

Overdose symptoms are often expressed as symptoms of agitation, but possibly also sluggishness and drowsiness. In case of overdose, treatment is symptomatic and there is no specific antagonist. Activated charcoal or gastric lavage may help if help is given promptly. Inducing vomiting is not recommended due to the risk of vomit entering the lungs. There is no certainty about the benefits of naloxone.

The American recommendation (Chyka et al., 2007) advises going to the emergency room if the dose of dextromethorphan exceeds 7.5–10 mg/kg body weight. For a man, this means a dose of dextromethorphan of about 600–800 mg. It should be noted that according to Pharmaca Fennica, the human lethal dose of dextromethorphan is about 500 mg. In reality, the lethal dose is much higher. For example, according to the Erowid database, the average dose is 200–400 mg, and the high dose is 300–600 mg. Individuals who have taken a low dose and who develop more than mild symptoms – fever, decreased levels of consciousness – should also go to emergency room or at least a poison information center. In the case of co-administration of other drugs, there are more serious reasons for going to emergency care.

Veli-Matti Surakka
Pharmacist

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Alaspää A: Lääkemyrkytykset. Lääkärin käsikirja, 2009.

Bankena JA, Fosterb H: Dextromethorphan. An Emerging Drug of Abuse. Annals of the New York Academy of Sciences 1139: 402–411, 2008.

Chyka PA, Erdman AR, Manoguerra AS ym.: Practice guideline: Dextromethorphan poisoning: An evidence-based consensus guideline for out-of-hospital management. Clinical Toxicology 45:662–677, 2007.

Hendrickson RG, Cloutier RL: Selected Topics: Toxicology: “Crystal Dex”: Free-base dextromethorphan. The Journal of Emergency Medicine 32(4):393–396, 2007.

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The Vaults of Erowid: DXM. Viimeksi muokattu 22.9.2010. Haettu internetistä 10.1.2011 osoitteesta: https://www.erowid.org/chemicals/dxm/.

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