When to start taking pain medication?

When to start taking pain medication?

How many times have you looked in the medicine cabinet for painkillers, without seeing your doctor about the pain first? We know, a lot.

Analgesics, or painkillers, have been around for a long time and are used by many people since they do not require a medical prescription and are not that expensive.

For example, aspirin (acetylsalicylic acid) is one of the oldest known medicines, which dates back to Ancient Egypt. Yes, you read that right, Ancient Egypt!

On the other hand, analgesics have sparked a lot of debate surrounding their indiscriminate use.

Everyone reacts differently to different medications and the effect they have on the body can vary significantly, which means that two people can experience completely different side effects from the exact same medication.

Currently, the most common types of medication for treating pain are:

1. Nonsteroidal anti-inflammatory drugs (NSAIDs), the most common being ibuprofen, naproxen and acetylsalicylic acid.

2. Corticosteroids

3. Opioids

4. Antidepressants

5. Anticonvulsants/ anti-seizure medication

This article includes:

  1. Types of pain medication
  2. Alternative treatments for pain

The World Health Organization (WHO) has developed a scale for formulations for managing pain (WHO Pain Scale):

  • Mild pain: recommended to be treated using NSAIDs and/or contributor drug (corticoid, antidepressant, anticonvulsant)
  • Moderate pain: use of mild opioids is recommended and/or medication such as those listed above.
  • Severe pain: potent opioids as well as medication such as those listed above.
  • Chronic pain that is difficult to manage: evaluate the need for intervention with anesthesia (nerve blocks).

Types of pain medication

1.    Nonsteroidal anti-inflammatory drugs (NSAIDs)

What are nonsteroidal anti-inflammatory drugs and how do they work?

For the most part, the so-called nonsteroidal anti-inflammatory drugs (NSAIDs) used today inhibit the activity of cyclooxygenase (cox-1). This is found in various tissues and it measures physiological reactions (production of gastric juices, platelet aggregation, regulate kidney function).

Cyclooxygenase 2 (cox-2) is found naturally in a few tissues, but, in the case of an injury, it is  found in the injured tissue.

Cox-2 inhibition regulates the unwanted effects of inflammation, but simultaneous Cox-1 inhibition causes collateral effects due to the decrease in the synthesis of prostaglandins, prostacyclins and thromboxanes, reducing pain.

NSAIDs include various compounds that, although not chemically related, do share therapeutic and collateral effects.

This vast group includes anti-inflammatory, analgesic and antipyretic drugs, and its antiplatelet effect should also be included in its pharmacology.

Most NSAIDs inhibit both cox-1 and cox-2, however, new medications are usually selective inhibitors of cox-2 so they present fewer adverse effects.

In addition to the most well-known active ingredients (acetylsalicylic acid, naproxen, acetaminophen and ibuprofen), which are available over the counter, there are also NSAIDs that are only available with a prescription.

Main chemical groups of NSAIDs

a) Salicylates:

   ASA (acetylsalicylic acid)

   Diflunisal

b) Pyrazolone derivatives:

   Aminophenazone (dipyrone or metamizol)

   Phenylbutazone

   Azapropazone

c) P-aminophenol derivatives:

   Acetaminophen (paracetamol or tylenol)

d) Acetic acid derivatives:

   Indomethacin

   Sulindac

   Glucametacine

e) Carboxylic and pyrrole derivatives:

    Etodolac

   Ketorolac

f) Phenylacetic acid derivatives: :

  Diclofenac (voltaren)

  Aceclofenac

  Tolmetin

  Fenclofenac

g) N-acetylanthranilic acid derivatives:

    Mefenamic

   Niflumic

   Meclofenamic

   Lysine clonixinate

h) Propionic acid derivatives:

   Ibuprofen, Naproxen, Ketoprofen

   Flurbiprofen, Fenoprofen, Oxaprozin

i) Enolic acid derivatives

  Piroxicam

  Meloxicam

  Tenoxicam

j) Nimesulide, sulfonanilide

k) Naftilalcanone group:

   Nabumetone

What are nonsteroidal anti-inflammatory drugs used for?

If you have a headache, are suffering from a sprain, or have symptoms of arthritis, you could try NSAIDs, so long as you respect the recommended dosage for your case. If you feel any discomfort, stop taking the medication and talk to your doctor.

It is important to consider that although some of these drugs are available over the counter and are easily accessible, they are not harmless. As chemical compounds, not only can they cause serious side effects, but they may also be prohibited for certain health conditions.

What are the dangers and side effects of nonsteroidal anti-inflammatory drugs?

Gastrointestinal: ulceration, perforation and bleeding (2-4%). Greater risk in patients with a history of peptic ulcers, intolerance to other NSAIDs, heart disease, esophagitis, pancreatitis, discrete hepatic biochemical changes, and those who are over 65. This effect is less common with the use of acetaminophen or paracetamol.

Renal: renal insufficiency, papillary necrosis, nephrotic syndrome, interstitial nephritis and renal failure. Increased risk in congestive heart failure, cirrhosis, renal failure and the elderly. Especially with propionic acid derivatives (ibuprofen, naproxen).

Cardiovascular: high blood pressure and secondary hypertension, myocardial infarction and cerebrovascular accidents. Increased risk in patients who use beta-blockers (metoprolol, carvedilol, propranolol). Talk to your doctor, as many drugs used in cardiology pose an increase in their effects upon taking NSAIDs, meaning if you take antihypertensive drugs as well as NSAIDs, this may reduce blood pressure even more.

Encephalic: greater risk of stroke, which increases when taken at a high dose over extended periods of time.

Hematological: hemorrhages due to interference with antiplatelet function of platelets, neutropenia and other cytopenias due to marrow failure, mainly with indomethacin and phenylbutazone. This effect is produced by drugs such as acetylsalicylic acid (ASA), especially when combined with other NSAIDs, other than paracetamol (acetaminofen).

Respiratory: in patients that suffer from asthma or rhinitis they can increase symptoms.

Dermatological: erythema multiforme (Steven-Johnson), toxic epidermal necrolysis, angioedema, photosensitivity, urticaria. Be especially careful with oxicam derivatives (piroxicam, meloxicam).

Central nervous system: headaches, depression, confusion, hallucinations, personality disorders, memory loss, irritability, due to interactions with other medication.

Despite being considered safe, NSAIDs can cause the side effects mentioned above when taken at high doses over a long period. Therefore, always consult your doctor before starting any treatment plan with this type of medication. Your pharmacist can provide you with guidance, but your doctor is the best person to talk to about starting this type of medication.

When should you avoid taking nonsteroidal anti-inflammatories?

Some people are allergic to NSAIDs and may have difficulty breathing after taking this medication. If this is the case for you, you should know that you are more likely to be allergic to other types of NSAIDs as well as that which caused you the reaction in the first place.

If you have asthma, you should take NSAIDs in moderation, as you are more likely to experience a serious allergic reaction.

Most NSAIDs are not considered safe during early pregnancy, so if you are or believe you could be pregnant, it is recommended that you avoid taking any medication without a prescription.

You may also like:

Do I have chronic pain? Differences between chronic and acute pain

2. Corticosteroids

What are corticosteroids and how do they work?

Corticosteroids imitate the effects of hormones that your body produces naturally in the adrenal glands, which are the small glands found in the upper part of the kidneys.

When they are prescribed in doses that exceed the normal levels in the body, corticosteroids suppress inflammation. This can reduce the signs and symptoms of inflammatory disorders, such as arthritis and asthma.

Corticosteroids also suppress the immune system, which can help control illnesses in which the immune system attacks its own tissues by mistake.

The way corticosteroids work depends on their potency, which is measured by their produced effect and how long the concentration lasts in the body. Steroids are classified as follows:

  • Glucocorticoids: those molecules that preferably act on carbohydrates and inflammation. The most important human glucocorticoid is cortisol.
  • Mineralocorticoids: those molecules that affect sodium and potassium and do not have an analgesic effect. The principal mineralocorticoid hormone is aldosterone.

What are corticosteroids used for?

They treat inflamed areas of the body to alleviate swelling, redness, itching and allergic reactions.

Corticosteroids are used to treat chronic inflammation such as rheumatoid arthritis, lupus, asthma, allergies, psoriasis and many other illnesses like acute and chronic adrenal insufficiency (e.g. Addison’s disease), sclerodermia, nephrotic syndrome, autoimmune nephritis, organ rejection following a transplant, chronic obstructive pulmonary disease (COPD), severe bronchospasm, urticaria, contact dermatitis and are contributors in the treatment of leukemia and some lymphomas.

Corticosteroids can be administered:

  • Orally. Tablets, capsules and syrups can help treat inflammation and pain associated with certain chronic illnesses, such as rheumatoid arthritis and lupus.
  • Using an inhaler or nasal spray. These help control inflammation associated with asthma and allergies that affect the nose.
  • Topically. Creams and ointments can help cure many skin diseases.
  • By injection. Often used to treat signs and symptoms in muscles and joints, including pain and inflammation from tendonitis.

They have two mechanisms of action:

  1. Non-genomic mechanisms: high dose and fast action
  2. Genomic mechanisms: low dose and slow action

Which medications belong to this group?

Short-acting medications (8 to 12 hours):

  • Cortisol
  • Hydrocortisone

Intermediate-acting medications (12 to 36 hours):

  • Prednisolone
  • Metilprednisolone
  • Deflazacort
  • Triamcinolone

Long-acting medications (12 to 36 hours):

  • Betamethasone
  • Dexamethasone

What are the dangers and side effects of corticosteroids?

Corticosteroids can cause a huge variety of side effects and should, therefore, be taken in the lowest dose possible. Given that these side effects accumulate over time, corticosteroids are more suitable for short-term use (1 to 3 weeks).

However, it is common to use steroids in palliative care, like in the case of cancer patients. If this is the case, your doctor may prescribe them to you for more than three weeks and you should be even more cautious of any unexpected reactions.

The side effects most commonly associated with corticosteroids are:

  • Weight gain (round face, extra deposits of fat in the chest, but slender arms)
  • Stomach issues
  • Headaches
  • Mood swings
  • Trouble sleeping
  • Weakened immune system
  • Reduced bone density
  • Glaucoma
  • Water retention
  • High blood pressure
  • Insulin resistance; this can lead to diabetes
  • Thinning of the skin
  • Inflammation in the legs
  • Reduced concentration and testosterone levels in men
  • In women they can suppress the secretion of estrogen and progesterone, which can alter ovulation and menstruation.

When should you avoid taking corticosteroids?

In any case, corticosteroids should be taken with caution.

By combining nonsteroidal anti-inflammatory drugs with a steroid, you are 15 times more likely to experience gastric bleeding; therefore, this combination should be avoided, especially among older people.

In order to gain the most benefit from corticosteroids with the least amount of risk, follow these steps:

  • Try smaller or intermittent doses. The newest forms of corticosteroids come in different concentrations and work for different durations. Talk to your doctor about the possibility of switching to a low dosage of this medication for a short time period, or taking corticosteroids every two days instead of daily.
  • Try other forms of corticosteroids that are not administered orally. Inhaled corticosteroids for asthma, for example, directly target the surface of the lungs, reducing exposure to the rest of the body and therefore, causing fewer side effects.
  • Make healthy choices throughout treatment. If you are taking corticosteroids over a long period of time, talk to your doctors about the ways you could minimize side effects. Lead a healthy lifestyle and participate in physical activities that help you maintain a healthy weight and strengthen your muscles and bones.
  • Consider taking calcium and vitamin D supplements. Long-term treatment with corticosteroids can cause loss of bone density (osteoporosis). Talk to your doctor about taking calcium and vitamin D substances to help protect your bones.
  • Take care when coming off of treatment. If you have been taking oral corticosteroids over a long period, your adrenal glands may produce lower amounts of steroid hormones naturally. In order to give your adrenal glands time to recover this function, your doctor may gradually reduce your dosage. If the dosage is reduced too quickly, it is possible that your adrenal glands may not have enough time to recover and you could experience fatigue, pain and dizziness.
  • Use a medical alert bracelet. It is recommended that you wear some form of identification such as this if you have been using corticosteroids over a long period.
  • Get regular checkups. If you are undergoing long-term treatment with corticosteroids, you should see your doctor regularly to assess whether it is causing any side effects.

3. Opioids

What are opioids and how do they work?

Opioids are a broad group of analgesic or painkiller medications that interact with the opioid receptors on nerve cells. Opioids are derived from a natural compound. They can be made from the poppy plant, such as morphine for example, (Kadian, MS-Contin and others), codeine and nospaine. They can also be synthesized in a laboratory, known as opiates, such as fentanyl (Actiq, Duragesic and others), buprenorphine, methadone.

When opioids are distributed around the body through the blood, they attach to opioid receptors in the brain and cells release signals that muffle your perception of pain and increase the feeling of pleasure.

Opioids are also the most controversial pain medication. They are narcotic drugs containing natural, synthetic or semi-synthetic opiates. They are only available by prescription.

In general, they are used to treat acute pain, such as pain following surgery. Below are some examples of common opioids:

  • Morphine
  • Fentanyl
  • Oxycodone
  • Codeine
  • Hydrocodone
  • Hydromorphone
  • Meperidine
  • Tramadol

They can be classified:

  1. According to their chemical composition into:
    1. Phenanthrenes (codeine, morphine, hydrocodone, oxycodone and oxymorphone)
    2. Phenylethylamines (methadone and propoxyphene)
    3. Phenylpiperidines (alfentanil, fentanyl, meperidine, sufentanil)
    4. Morphines (levorphanol)
  2. According to their analgesic potency:
    1. Weak opioids: codeine, dextropropoxifeno, tramadol, nalbufina
    2. Potent opioids: morphine, pethidine, fentanyl, buprenorphine, oxycodone, methadone.

Opioid analgesics attach to the nerve cell receptors in the brain that increase the pain threshold (the amount of stimulation required to feel pain), thus reducing the feeling of pain.

What are opioids used for?

These drugs can be effective for reducing pain, but they should only be used if your pain is severe and should not be combined with other pain medication. Unlike other types of pain medication, opioids do not cause bleeding in the stomach, or anywhere else in the body.

They should not be used for more than 3 or 4 months, so if you suffer from chronic pain, this is not the best option for you.

They are administered in the following cases:

  • patients with a clear diagnosis
  • the intensity of their pain is above a 5 on the Visual Analogue Scale
  • they have exhausted other possibilities of targeted treatment
  • Moderate to severe chronic pain, which impacts the functional capacity and quality of life of the patient and where the benefits outweigh the risks.

What are the dangers and side effects of opioids?

Narcotic drugs can vary in intensity, but they are rarely prescribed for longer than 4 months. It is unusual for people to become addicted to opioids if they only use them for a short period. Using opioids to treat chronic pain has become rather controversial, given that their long-term use has a high risk of causing addiction.

Side effects of opioids can include:

  • Constipation
  • Nausea
  • Dizziness
  • Drowsiness or fatigue
  • Itching
  • Vomiting
  • Abdominal pain
  • Headaches
  • Dry mouth
  • Feeling of fullness
  • Diarrhea
  • Confusion
  • Difficulty breathing
  • Chest wall rigidity
  • Delirium

Eventually, the indiscriminate use of narcotic drugs can cause death. Other serious consequences of abusing this type of drug include:

  • Addiction
  • Difficulty breathing
  • Chest pain
  • Arrhythmia, or an abnormal heartbeat
  • Cardiac arrest

Opioid addiction

If you take any type of opioid  for a long period, even a prescribed opioid, you can become addicted, which means that, if you stop taking them, you may experience withdrawal symptoms, such as a strong desire for the medication, yawning, insomnia, anxiety, mood swings or diarrhea.  

Addiction is a chronic disease characterized by overwhelming cravings, compulsive drug use and the inability to control one’s drug use. It can have fatal consequences.

The indiscriminate use of opioids has become a huge public health problem in some parts of the world, including the U.S.  

According to the Centers for Disease Control and Prevention (CDC), in the US alone, opioid derivatives caused the deaths of 33,000 people in 2015. This number includes deaths caused by heroin and illegal opioids, but almost half of these cases involved prescription opioids.

Addiction cases that do not end in death can lead to serious heart infections (endocarditis) and narcotic bowel syndrome.

When should you avoid taking opioids?

The best thing to do is to talk to your doctor about any questions or worries you may have before starting any type of treatment with pain medication or opioids.

As we mentioned earlier, the use of this type of medication for controlling chronic pain is reasonably controversial and research has revealed many risks associated with its long-term use.

If you have started taking any type of narcotic medication, remember that drowsiness is a very common side effect, so you should avoid operating any type of heavy machinery or doing any activity that requires your extreme attention or poses a risk to your physical safety. You should also never mix narcotic medication with alcohol.

After a few days of adjusting to the medication, drowsiness should subside.

Narcotic drugs can also interact with other medication, which could prove fatal. Do not mix this type of analgesic with any other pain medication without talking to your doctor first.

4. Antidepressants

What are antidepressants and how do they work?

Depression appears to be associated with low levels of certain neurotransmitters in the brain, such as serotonin, noradrenaline or dopamine. Therefore, antidepressant medications try to increase some of these substances in the brain through different ways.

There are almost thirty in total, which fall into five categories:

* SSRIs (Selective Serotonin Reuptake Inhibitors)     

* SNRIs (Serotonin and Noradrenaline Reuptake Inhibitors)     

* Tricyclic     

* MAOIs (Monoamine oxidase inhibitors)

* Tricyclics and MAOIs are less common these days, they are generally only prescribed by specialists.

The analgesic action of these drugs is independent of the antidepressant or sedative effect, it is measured through the boosting of these actions from the serotonergic pathways (which generate the feeling of pleasure) and affect nociception.

Furthermore, experimental studies suggest that antidepressants boost the power of endogenous opioid systems. They are also of great use in situations in which the pain is a symptom of depression.

How do antidepressants work with respect to pain?

Research suggests that antidepressants work best for chronic neuropathic or nerve pain, headaches (such as migraines), menstrual cramps, facial and pelvic pain. They are also effective against pain caused by fibromyalgia and lower back pain.

Neurological pain:

– Diabetic neuropathy

– Phantom limb pain

– Headaches

– Facial arthralgia

– Peripheral neuropathy

– Central pain syndrome

Rheumatological pain:

– Chronic arthralgia

– Fibromyalgia

– Cervicalgia (neck pain)

– Dorsalgia (back pain)

– Lumbalgia (lower back pain)

What are the dangers and side effects of antidepressants

Compared to other types of pain medication, antidepressants actually have fewer long-term effects. In general, SSRIs and SNRIs have fewer effects than tricyclic antidepressants.

Usually, side effects of antidepressants include:

  • Blurry vision
  • Constipation
  • Trouble urinating
  • Dry mouth
  • Fatigue
  • Nausea
  • Headache
  • Monoamine oxidase inhibitors (MAOIs)
    • Low blood pressure
    • Drowsiness or jitteriness
  • Heterocyclic antidepressants
    • Confusion
    • Delirium
    • Memory difficulties
    • Problems concentrating among patients over 50 years old.
    • Reduced effect of anticonvulsant medication which could cause the onset of seizures
    • Alteration in the frequency, rhythm and contractility of the heart (sinus tachycardia)
  • Selective serotonin reuptake inhibitors (SSRIs).
    • Nausea, vomiting
    • Nervousness
    • Agitation
    • Altered sleep

Research has shown that antidepressants are associated with a mild risk of suicidal thoughts and actions. If you are taking this type of medication and you feel depressed or have suicidal thoughts, do not ignore them. Talk to your doctor immediately.

When should you avoid taking antidepressants?

Whilst they may not cause serious side effects, antidepressants do require a degree of caution, especially regarding their interaction with other medication.

Do not combine an antidepressant with another type of medication without consulting your doctor first. Two types of antidepressants should never be administered at once, and they should never be combined with alcohol.

As a general rule, you should always talk to your doctor first before taking any new medication to ensure it is taken responsibly.

5. Anticonvulsants

What are anticonvulsants and how do they work?

Also known as anti-epileptic or anti-seizure drugs, anticonvulsants are normally used to treat seizure disorders. However, research has shown that they may also be useful for treating chronic pain.

Some studies have suggested that anticonvulsants are a cornerstone of this type of treatment and tend to produce fewer side effects in the long term.

Others argue that other types of medication interventions should be researched before prescribing anti-seizure drugs.

The exact way in which anticonvulsants actually treat pain is still unknown, but they are believed to minimize the effects of the nerves that cause pain.

There are only a few anticonvulsants that have been approved by the FDA (U.S. Food & Drug Administration) for treating chronic pain, such as carbamazepine and gabapentin, which both require a prescription.

What are anticonvulsants used for?

Anticonvulsants can also be particularly effective for combating different types of chronic pain, such as neuropathic and back pain, fibromyalgia, headaches and migraines.

Anticonvulsants, like topiramate and divalproex sodium, are sometimes used to help prevent pain caused by migraines.

Uses:

  • Chronic neuropathic pain (gabapentin)
  • Trigeminal neuralgia (carbamazepine)
  • Diabetic neuropathy
  • Migraine prophylaxis
  • Postherpetic neuralgia

What are the dangers and side effects of taking anticonvulsants

There has only been a small number of studies on the effectiveness of anticonvulsants in the long-term treatment of chronic pain. Therefore, you should be wary of unexpected reactions to this type of medication.

Generally, anticonvulsants are well tolerated, but older people may be particularly sensitive to this type of medication. Their most common side effects include:

  • Drowsiness
  • Dizziness
  • Fatigue
  • Nausea
  • Dry mouth
  • Constipation
  • Difficulty concentrating
  • Swelling of arms, calves or ankles
  • Changes in weight (gain or loss)

When to avoid taking anticonvulsants?

Though in general they present a low risk and have few side effects, many anticonvulsants can interact with common over-the-counter and prescription medication.

Anticonvulsants can prevent some medication from working properly, and other medication may have the same effect on the anti-epilepsy medication. Take care when taking anticonvulsants, as both of these situations can be very dangerous.

Some anticonvulsants reduce the effectiveness of the oral contraceptive pill, increasing the breakdown or metabolism of estrogen and progesterone in the liver. If you are a sexually active woman on the pill, ask your doctor whether this treatment is right for you.

As we mentioned above, older people are more likely to experience side effects when taking these drugs. If you are an older person, you should be very cautious and tell your doctor if you feel any discomfort.

Alternative treatments for pain

Analgesics are an important part of a pain management plan, but they are not the only way to free yourself from your pain.

There are many things you can do to help alleviate pain without the risk of suffering from side effects.

If your pain has been persistent or debilitating in some way, consult a specialist about how to manage your pain. Doctors specialized in pain management may try other treatments, such as certain types of physiotherapy and biofeedback, among others.

Check out our article on treatments for the most common types of chronic pain  to find out more about this topic.

The wide range of alternative medicines for treating pain includes acupuncture, neural therapy, osteopathic or homeopathic medicine and the use of medicinal cannabis, among others.

Read more:

Are you experiencing chronic pain? The difference between acute and chronic pain

Top tips for preventing and relieving back pain

Bibliography:https://www.mayoclinic.org/es-es/steroids/art-20045692
https://www.mayoclinic.org/es-es/diseases-conditions/prescription-drug-abuse/expert-answers/what-are-opioids/faq-20381270
http://www.sepsiq.org/file/Royal/1-Antidepresivos.pdf

http://www.farmacologia.hc.edu.uy/images/Antidepresivos_-_EUTM.pdf

http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0034-75072002000200004

https://www.webmd.com/pain-management/guide/pain-relievers#1

https://medlineplus.gov/ency/article/007489.htm

https://medlineplus.gov/painrelievers.html

http://www.elsevier.es/es-revista-farmacia-profesional-3-articulo-antidepresivos-13081504

https://www.verywellhealth.com/types-of-opioids-chronic-pain-medications-2564496

https://www.verywellmind.com/ten-most-addictive-pain-killers-22506

https://mix995wjbr.com/2018/01/01/12-common-prescription-pain-medications-classified-opioids/

https://www.medicinenet.com/narcotic_analgesics-oral/article.htm

https://www.mayoclinic.org/es-es/chronic-pain-medication-decisions/art-20360371

https://www.mayoclinic.org/es-es/healthy-lifestyle/childrens-health/in-depth/acetaminophen/art-20046721

https://www.mayoclinic.org/es-es/steroids/art-20045692

https://en.wikipedia.org/wiki/History_of_aspirin

https://www.getreliefresponsibly.com/use-pain-medicine-safely/adult-nsaid-dosage-chart

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001922/

https://es.wikipedia.org/wiki/Prostaglandina

https://www.bbc.com/mundo/noticias-internacional-41755400

https://www.mayoclinic.org/es-es/pain-medications/art-20045647

https://es.wikipedia.org/wiki/Inhibidor_de_la_recaptaci%C3%B3n_de_serotonina_y_noradrenalina

https://bpac.org.nz/bpj/2007/march/interactions.aspx

https://www.webmd.com/pain-management/explore-seizure-meds

https://www.webmd.com/epilepsy/features/tip-sheet-avoiding-epilepsy-drug-interactions

https://www.verywellhealth.com/anti-seizure-medications-for-chronic-pain-2564494http://www.colombiancannabis.co/cannabis-detalle.php?L=D&id=NQ==&p=Mw==