Epilepsy & drugs

Discussion in 'Pharmacology' started by Alfa, Jun 16, 2006.

  1. Alfa

    Alfa Productive Insomniac Staff Member Administrator

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    Now and then the topic of epilepsy & drugs has been touched, but never discussed to the full extent. Epilepsy is very comon. In fact many people are not even aware they have a mild version of epilepsy. Some will never find out. There are mild, severe versions of epilepsy and everything inbetween.
    Certain drugs can provoke a epileptic seizure. But which and why?

    Please post info on this, so this can become the central thread about epilepsy & drugs.

    Here are some related threads:
    Epileptic attack
    If u seizured on acid would u drop again?
    Weed and Seizures
     
    1. 4/5,
      Interesting topic, overlooked by most
      May 19, 2008
    2. 3/5,
      Important and useful topic, hope this thread gets a lot of posts.
      Jun 24, 2007
  2. old hippie 56

    old hippie 56 Gold Member

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    My friends partner was diaganosed with progressive MS with a seizure disorder. The only drug that brought on a seizure was meth. She hasn't touch meth in years, still has minor seizures that is brought on by stress. Hadn't had a major seizure in a couple of years.
     
    Last edited: Jun 16, 2006
  3. Jatelka

    Jatelka Psychedelic Shepherdess Platinum Member & Advisor

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    An Overview of Epilepsy (specifically drug-related stuff will be posted later)

    Seizure: The physical manifestation of uncontrolled electrical activity in the brain

    The important thing to realise is that ANYONE can have a seizure (under the “correct” circumstances). This does NOT necessarily mean they have epilepsy. Common causes include high temperature (common in children: febrile convulsions), diabetics with a low blood sugar, other metabolic disturbances, infections, hypoxia, and alcohol withdrawal, to name a few. Seizures can also be caused by structural brain lesions.

    Epilepsy: “A group of disorders in which there are recurrent episodes of altered cerebral function associated with paroxysmal excessive and hyper-synchronous discharge of cerebral neurones”

    In health the firing of neurones of the cerebral cortex is “held in check” by inhibitory neurotransmitters such as GABA. There are also a large number of excitatory neurotransmitters (acetylcholine, glutamate and aspartate). In epilepsy it is likely that there is both a reduction in inhibition and an increase in excitation (although the exact mechanisms are poorly understood).

    Types of Epilepsy: The chief division is into partial/focal and generalised seizures.

    Partial seizures

    The paroxysmal neuronal activity is limited to one part of the brain.
    If the activity remains localised awareness is preserved, and the seizure is termed “simple”. If the activity spreads to involve the reticular activating system, then awareness is lost and the seizure is termed “complex partial”. If the activity spreads further then a generalised seizure results (partial seizure with secondary generalisation).

    Partial seizures can be further subdivided according to the area of brain affected. They can be motor – rhythmic jerking of the opposite side of the face, arm or leg. They can be sensory – tingling or electric sensations on the opposite side of the body. They can be visual – Occipital foci cause simple visual hallucinations whereas temporal foci cause more formed hallucinations (E.g.: faces). Temporal foci can also cause alterations of mood, memory and perception – déjà vu, jamais vu, and complex hallucinations of smell, taste, vision and emotional changes (feeling of impending doom, sexual arousal etc) and visceral sensations (nausea and abdominal pain).

    Complex partial seizures are often preceded by an “aura” (essentially a simple partial seizure). The person then loses awareness of their surroundings, and they are unresponsive. Autonomic movements (lip-smacking, swallowing, fidgeting) may occur.

    Generalised

    The excess neuronal activity involves large areas of both cerebral hemispheres simultaneously and synchronously.

    Tonic/Clonic (Grand-Mal): There may be a pro-dromal phase (which can last for hours/days) encompassing irritability and unease. An aura may occur. There is a tonic phase (stiffening of arms and legs, respiratory muscle spasm causing the person to cry out and loss of consciousness) which lasts approx 30 seconds. This is followed by a clonic phase (violent jerking of arms and legs, tongue-biting, and incontinence). This usually lasts 1-5 minutes. IF IT LASTS FOR MORE THAN 5 MINUTES THEN URGENT MEDICAL HELP SHOULD BE SOUGHT. The final phase is post-ictal: The person is unconscious with flaccid limbs. This can last from minutes to hours. As the person regains consciousness headache, confusion, autonomic and violent behaviour may occur.

    Absence Seizures (Petit-Mal): Relatively uncommon and mostly seen in children. During an attack the person stops activity and stares into space. There may be rolling of the eyes or excessive blinking. They are unresponsive to commands. Attacks typically only last a few seconds, and hundreds may occur during the course of a day. The person is unaware that an absence has happened and will continue with their previous activity.

    Causes of Epilepsy (In a majority NO cause is found)

    Generalised

    Primary/Idiopathic: Usually Tonic/Clonic and Absences. Genetic factors play a part (but epilepsy is NOT directly heritable)
    Diffuse Cerebral Insults: Hypoxia, Encephalitis
    Metabolic Disturbance: Hypoglycaemia, hyponatraemia, hypocalcaemia, renal and liver failure.

    Partial

    Cerebral Trauma: Birth injury, head injury, strokes.
    Structural lesions: AV malformations, cysts, aneurysms, tumours.
    Infections: Meningitis, cerebral abscess, HIV, TB
    Inflammatory: Multiple Sclerosis, Lupus


    Sometimes “triggers” can be identified for seizures. Some common ones include:

    Sleep deprivation, emotional stress, infections/fever, flickering lights (Eg: Strobe, TV/Computer screens), missed meals, loud noises, hot environments, drug or alcohol ingestion or withdrawal.
     
    Last edited by a moderator: Sep 9, 2017
    1. 5/5,
      good read
      Jun 17, 2006
    2. 4/5,
      Very informative jatelka. ;)
      Jun 16, 2006
  4. Jatelka

    Jatelka Psychedelic Shepherdess Platinum Member & Advisor

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    Withdrawal Seizures

    Alcohol

    Alcohol withdrawal commonly results in tonic/clonic seizures. With prolonged intake alcohol potentiates GABA (an inhibitory neurotransmitter). It is thought to do this by reducing the number of GABA receptors (so less GABA is taken up) and by altering the GABA receptor sub-type profile. When alcohol is withdrawn the potentiating effect is lost and reduced levels of GABA result in seizures. In chronic alcohol intake glutamate (an excitatory neurotransmitter) is suppressed. On withdrawal, glutamate levels increase, again, this can result in seizures. Another neurotransmitter involved is NMDA (excitatory). Prolonged alcohol intake causes an increase in the number of NMDA receptors, and also alters the function of those receptors. Although the mechanism by which this change induces withdrawal seizures is not clear, NMDA receptor antagonists (Eg: Dizocilpine) are highly effective anticonvulsants in alcohol withdrawal (in animal studies). The A9 allele of the DAT (Dopamine transporter) gene has also been found to increase the likelihood of withdrawal seizures. Calcium channels also appear to be implicated in alcohol withdrawal seizures: The calcium channel blocker Nitrendipine has been found to reduce the frequency and severity of seizures on withdrawal.

    Alcohol intoxication can also cause seizures. Interestingly, acutely high levels of alcohol INHIBIT NMDA receptors rather than causing up-regulation. This results in increased levels of NMDA.

    Barbiturates

    Barbiturates also exert their effects by potentiating GABA. They are sometimes still used as anticonvulsants (often in older people who have been stable for years). It is the loss of potentiation on withdrawal which can result in seizures. There is some evidence that NMDA is also involved, however the evidence is less clear than for alcohol.

    Benzodiazepines

    Again, these potentiate GABA. There is some evidence that calcium channel blockade can reduce the frequency of withdrawal seizures. Benzodiazepine withdrawal seizures occur more frequently in people withdrawing from short-acting drugs and in those who also drink alcohol.

    GHB

    GHB is an immediate precursor to GABA. There are also specific GHB receptors in the brain. At low doses GHB acts primarily at GHB receptors and causes the release of excitatory neurotransmitters including dopamine, glutamate and acetylcholine. At higher doses, or with frequent/prolonged dosing it acts mainly at GABA receptors and has an inhibitory effect. Because of it's short half-life dosing needs to be very frequent (every 2-3 hours) to induce a life-threatening withdrawal syndrome Tonic/Clonic activity occurs because of loss of inhibitory influences.

    For a paper on the Neurobiological basis of alcohol withdrawal seizures see here…

    https://drugs-forum.com/forum/local_links.php?catid=38&linkid=520

    For a paper on GHB withdrawal syndrome see here...

    https://drugs-forum.com/forum/local_links.php?catid=38&linkid=524
     
    Last edited by a moderator: Sep 9, 2017
    1. 4/5,
      Exellent information!
      Jun 17, 2006
  5. Micklemouse

    Micklemouse Platinum Member & Advisor

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  6. Micklemouse

    Micklemouse Platinum Member & Advisor

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    From http://www.emedicine.com/NEURO/topic417.htm

     
    1. 5/5,
      very informative. purrr
      Jul 10, 2006
  7. Richard_smoker

    Richard_smoker Gold Member

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    Interesting topic. Definitely something that needed to be included on this forum.

    Just to add a little--I didn't see a clear explanation as such about how seizures are often caused by drugs and other events that essentially throw off the normal balance of energy/metabolism in the brain, so here goes...

    Essentially, everyone has a 'threshold' level for triggering seizure activity in their brains. Just like a light switch has a threshold level--flip it up an inch, and BAM--the light turns on. Likewise, our neurons have a 'switch' that is effected by our genes, our environment, our sensitivities to light/sound, and drugs.

    In general, one can think of a seizure as being a random spasm of neurons within the brain. Just about any type of CNS STIMULANT will lower the seizure threshold... meaning that it becomes EASIER to trigger this type of abherent firing of neurons.

    Think: amphetamines, welbutrin (& other stimulating psychoactive pharms). Other possibilities: LSD, Mushrooms, ritalin, ecstacy, RCs, etc.

    Also: when the body becomes accustomed to SEDATIVES (alcohol, benzos, barbituates, etc.), the brain's equilibrium metabolic rate becomes changed so that the resting metabolic rate is REVVED-UP! (this is why people who are addicted to xanax/valium/etc have a DIFFICULT time with anxiety and sleep when their xanax/valium runs out.

    SOOooo, when you suddenly take away the sedative drug, the person's threshold for seizures has changed, making any person FAR more susceptible to seizure activity.

    These are 2 very simple examples that pretty much sums up the topic of seizures for the average person. People with epilepsy and other seizure disorders are usually just born with a much lower-than-normal threshold for firing off seizures.

    -Dick
     
    1. 4/5,
      good points made
      May 19, 2008
    2. 5/5,
      good info
      Jul 25, 2006
  8. Jatelka

    Jatelka Psychedelic Shepherdess Platinum Member & Advisor

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  9. Paracelsus

    Paracelsus Platinum Member & Advisor

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    List of drugs and other factors which reduce the seizure threshold

    Ressurrection.

    I thought the following list would be helpful for determining possibly risky combinations of drugs, as well as drugs which epileptics and other persons with high risk of seizures shouldn't use. I'm sure there's much to add, so any input is appreciated.

    Seizure threshold-reducing factors

    Non-drug factors:

    -withdrawal from sedatives (alcohol, barbiturates, benzodiazepines, GHB and analogs, etc.)
    -listening to brainwave generators, binaural waves, etc.
    -watching TV (looking at CRT monitors)
    -stress
    -sleep deprivation
    -menstruation
    -infections, fever

    Seizure threshold-reducing drugs (STRDs):

    Stimulants - practically all

    -Amphetamines: street amphetamines, amphetamines used in ADHD treatment (amphetamine and dextroamphetamine, methamphetamine, methylphenidate, etc.), those used as slimming aids (phentermine, fenfluramine, diethylpropion, sibutramine, etc.), propylhexedrine, 4-fluoroamphetamine (4-FMP), l-methamphetamine, etc.
    -Cocaine and coca
    -Khat
    -Caffeine (alertness aids, caffeinated soda, energy drinks, cofee, guarana, kola, tea, yerba, etc.)
    -Ephedra and ephedrine
    -Pseudoephedrine, phenylpropanolamine and other stimulant decongestants
    -Aminophylline, theophylline and maybe other bronchodilators (albuterol, etc.)

    Opiates

    -Pethidine (same as meperidine)
    -Fentanyl
    -Tramadol

    Antidepressants - practically all

    -SSRIs (fluoxetine, paroxetine, sertraline, etc.)
    -MAO inhibitors (iproniazid, moclobemide, etc.)
    -Tricyclic antidepressants (amitriptyline, etc.)
    -Nefazodone

    Seizure risk in increased in the first 2-6 weeks of treatment.

    Antipsychotics

    -Chlorpromazine
    -Clozapine
    -Flupenthixol
    -Fluphenazine
    -Haloperidol
    -Olanzapine
    -Pimozide
    -Risperidone
    -Thioridazine
    -Thiotixine
    -Trifluoperazine

    Hormonal preparations

    -Oral contraceptives
    -Hormone replacement therapy
    -Anabolic steroids (unsure)

    Seizure risk is increased in the first 1-4 weeks of treatment.

    Immunomodifiers

    -Cyclosporine

    Anaesthetics

    -Enflurane, isoflurane
    -Propofol

    Antiarrhytmics

    -Lignocaine
    -Mexiletine

    Antibiotics

    -Penicillins
    -Cephalosporins
    -Amphotericin
    -Imipenem

    Antihistamines (H1 antagonists)

    -Azatadine
    -Cyproheptadine
    -Chlorpheniramine, brompheniramine, pheniramine
    -Methdilazine
    -Promethazine

    Antimigraine drugs (5HT antagonists)

    -Sumatriptan (possibly also other triptans)

    High-risk categories

    -Epileptics
    -Persons with a history of seizure(s)
    -Persons with a recognized risk of seizures

    Even ‘normal’ person can experience seizures, if two or more factors of the above are combined (like listening to brainwave generators while on an amphetamine binge and not having slept for three days). Of course, combining two or more factors of the above doesn’t always result in seizures; the risk of seizures varies from person to person and is dose-dependent (in the case of seizure threshold-reducing drugs).
     
    Last edited by a moderator: Apr 30, 2017
  10. toe

    toe Gold Member

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    Lithium can cause seizures, particularly if levels aren't well-monitored or interactions pop-up.

    Bupropion is notorious for causing seizures.
     
  11. seeingred

    seeingred Silver Member

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  12. stoneinfocus

    stoneinfocus Silver Member

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    Tramadol because it´s an opiat that hinderes the re-uptake of serotonin and noradrenaline at the pre-synaptic gap, serotonin is suggested to be the causing factor, but it remains still unkown why exactly, but pob. 5-HT.
     
    Last edited: May 4, 2008
  13. Politicalchalk

    Politicalchalk Titanium Member

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    For Seroquel, are you sure it's a seizure? It's an atypical-antipsychotic (one Swim's been on), and so many typical reactions are things like dystonias and tardive dyskiesia, which can look an awful like a seizure. Although it very well may have seizure inducing activity
     
    Last edited: May 3, 2008