Mefloquine - antagonists of 5-HT3

This one of the reasons, I am opposed to anti-depressants. Although, this paper was published in 2007, it is still very relevant!!

The antimalarial drugs quinine, chloroquine and mefloquine are antagonists at 5-HT3 receptors
A J Thompson,1 M Lochner,1 and S C R Lummis1*
1Department of Biochemistry, University of Cambridge, Cambridge, UK
*Author for correspondence:
Received November 1, 2006; Revised January 3, 2007; Accepted January 5, 2007.

Abstract
Background and Purpose:
The antimalarial compounds quinine, chloroquine and mefloquine affect the electrophysiological properties of Cys-loop receptors and have structural similarities to 5-HT3 receptor antagonists. They may therefore act at 5-HT3 receptors.

Experimental Approach:
The effects of quinine, chloroquine and mefloquine on electrophysiological and ligand binding properties of 5-HT3A receptors expressed in HEK 293 cells and Xenopus oocytes were examined. The compounds were also docked into models of the binding site.

Key Results:
5-HT3 responses were blocked with IC 50 values of 13.4 μM, 11.8 μM and 9.36 μM for quinine, chloroquine and mefloquine. Schild plots indicated quinine and chloroquine behaved competitively with pA 2 values of 4.92 (K B=12.0 μM) and 4.97 (K B=16.4 μM). Mefloquine displayed weakly voltage-dependent, non-competitive inhibition consistent with channel block. On and off rates for quinine and chloroquine indicated a simple bimolecular reaction scheme.

Quinine, chloroquine and mefloquine displaced [3H]granisetron with K i values of 15.0, 24.2 and 35.7 μ M. Docking of quinine into a homology model of the 5-HT3 receptor binding site located the tertiary ammonium between W183 and Y234, and the quinoline ring towards the membrane, stabilised by a hydrogen bond with E129. For chloroquine, the quinoline ring was positioned between W183 and Y234 and the tertiary ammonium stabilised by interactions with F226.

Conclusions and Implications:
This study shows that quinine and chloroquine competitively inhibit 5-HT3 receptors, while mefloquine inhibits predominantly non-competitively. Both quinine and chloroquine can be docked into a receptor binding site model, consistent with their structural homology to 5-HT3 receptor antagonists.

Keywords: 5-HT3 receptor, Cys-loop receptor, binding site, ligand docking, malaria, quinine, chloroquine, mefloquine, antagonist.....

Conclusion

Cont/.....

In summary, we have used a combination of electrophysiology, ligand binding, homology modelling and simulated docking to define the mechanisms by which quinine, chloroquine and mefloquine inhibit the 5-HT3 receptor response. Our observations further extend the number of receptors known to be affected by these compounds and the growing diversity of targets may account for the broad spectrum of side effects that have been reported by patients receiving them (Luzzi and Peto, 1993; Palmer et al., 1993; Taylor and White, 2004). Inhibition of the 5-HT3-mediated current could have wide-ranging effects in the nervous system, as 5-HT3 receptors can modulate a variety of neurotransmitter responses such as those to GABA, dopamine and cholecystokinin (Thompson et al., 2006b).http://tinyurl.com/ny2zqv

Serious Side Effects of Anti-Depressants

A few more videos and one more article, after which, a break from writing about Anti-Depressants.

There is a strong movement of psychiatrists who are opposed to promoting psychotropics. They are campaigning for a paradigm shift in psychiatry. Neuroscientists are coming closer to showing "mental illnesses" are biological. It is known for a long time that CNS can be triggered by ADRs from prescribed medications, trauma injury to the head, stroke, hypothyroidism, infectious pathogens, mycotoxins, heavy metals, hormonal imbalance and more. We know very little, about neuronal circuitry. At this time, it is conjectural to imply for any drugs to improve brain function, alleviate depression, cure or improve psychiatric symptoms. The science does not support such claims. What is taught at Universities in text books of Psychology, Psychiatry and Neuroscience, is not supported by claims made by Pharmaceutical companies.

Thomas Szasz, http://www.szasz.com/a famous psychiatrist, Nobel Prize winner and Professor Healy, Professor Ashton, Dr David Permlutter and other famous psychiatrists, and neuroscientists, have written important articles and books on this matter.

If staying away from benzos and anti-depressants, these symptoms will resolve, in time.

Incidentally, most prescriptions for Klono is 0.2 mg and 0.5 mg, and very difficult to stop, for many, even after one week of starting. The options are to up the dosage or start tapering, under supervision of a medical professional.

Klonopin carries with an insert warning that it should not be taken longer than a few weeks, yet, it is highly addictive, from the first pill.

Why are doctors renewing prescriptions when manufacturers are saying themselves, it is highly addictive and should not be taken for more than a few weeks.

Again, it is about profit. The pharmaceutical industry make a yearly profit of approximately $40 billion a year!! Why should we bump up their shares whilst making ourselves ill and poorer??

Who suffers? The patient...

For those of you taking Benzos, such as Klonopin, suffering from symptoms as described below, please seek help.

Lastly, many of us suffered all the torturous symptoms as listed below from floxing and from Lariam or other meds, we recovered by abstaining from taking anti-depressants and psychotropics.

It is very important to seek help if displaying these symptoms whilst on Klono. The consequences can be very serious, both mentally and physically.

Below is a list of symptoms as reported by those who are taking Benzos and other psychotropics. Those drugs prolong CNS symptoms, and could trigger life threatening side effects. For thos who wish to switch, taper or wean, in your own time, when you are ready, (under supervision of your doctor), see this excellent guide written by world renowned psychiatrist, Professor Heather Ashton http://lonelylinks.com/download/Chapter1.pdf

An E- Support group organizing conferences, chaired by MDs, Psychiatrists etc. www.april.org.uk

Visual perceptual

Derealisation, Depersonalisation, Distortion of body image, Feeling like legs and arms are not attached to body
Psychotic symptoms


Auditory hallucinations, Catatonic episodes, Compulsive suicidal ideation, Confusion, Delusional thinking, Disorientation, Formication (sensation that I had fleas/spiders crawling over me)



Mood

Aggression, Anger, Agoraphobia, Agitation, Akathisia, Anxiety, Apathy, Anhedonia (inability to experience pleasure), Crying and feeling weepy, Deep depression, Despair, Dysphoria, Extreme dispassion, Fear, Fear of dying, Fear of losing control and going insane, Fearing symptoms are not withdrawal, Fearing that you will never get better, Fear of life, Fear that symptoms are permanent, Feeling emotional, Feeling frightened, Feeling hopeless, Feeling like jumping out of skin, Feeling that the world is about to cave in on you, Frustration, Gittery, Gloom and doom, Inability to appreciate humour and laugh, Inability to feel emotions, Inability to feel joy, Inability to feel pleasure, Internal feeling of anxiety with no corresponding external cause, Irrational fears, Irrational rage, Irritability, Lonliness, Low mood, Nervousness, No feelings of fun or laughter, Obsessive thoughts, Overwhelmed feeling, Rapid mood fluctuations, Sensitive feelings, Severe negative looping thoughts, Sudden sadness, Terror, Void of normal emotions



Mental status

Difficulty in distracting oneself, Feeling disconnected, Feeling drugged, Feeling freaked out, Feeling like a zombie, Feeling like being on a bad LSD acid trip, Feeling numb, Feeling scared, Feeling that you're just going crazy, Feeling traumatised, Feeling unreal, Getting worried over small things, Hallucinations, Horrid visions, Hypomania, Images and songs keep repeating in mind, Inability to relax or sit still, Intrusive thoughts, Jumpiness, Loss of sense of identity, Misperceptions, Morbid thoughts, Morning madness, Not knowing who you are, Obsessive and compulsive thinking (OCD), Overwhelming feeling that you are going to die, Pacing, Panic attacks, Paranoia, Racing thoughts, Reduced stress tolerance, Suicide attempts, Suicidal thoughts, Thinking you are mentally ill, Unwarranted feelings of guilt, Visual hallucinations, Vivid dreams, Weird thinking, Wired feeling


Eyes and ears

Bloodshot eyes, Blurry vision, Dark-dim vision upon exertion or sunlight, Difficulty seeing, Drooped eyelids, Dry eyes, Eye twitching, Flashes of light in the eyes, Fuzzy eyes, Glassy eyes, Impaired vision, Occasional right eye pain, Pressure in the inner ear and outer ear, Red burning eyes, Sore eyes, Swollen eyes, Tearing eyes, Uncontrolled eye movement, Visual distortions preceding a migraine


Behavioural

Constant need to be occupied, Avoiding friends and people, Inability to occupy oneself


Visual perceptual

Derealisation, Depersonalisation, Distortion of body image, Feeling like legs and arms are not attached to body
Psychotic symptoms
Auditory hallucinations, Catatonic episodes, Compulsive suicidal ideation, Confusion, Delusional thinking, Disorientation, Formication (sensation that I had fleas/spiders crawling over me)


Cardiovascular

Chest pains, Fast heartbeat, Heart palpitations, Heart pounding, Low blood pressure, Premature ventricular contractions (irregular heart beats), Pulsating all over my body(also visable), Pulse thudding, Racing heart, Severe pain chest, Skipping heart beats, Tightness in chest


Cognitive symptoms

Can't do tasks like make food, Difficulty reading, Difficulty thinking, Forgetting names of family members, Hard time with words, Impaired cognitive skills, Impaired communication skills, Inability to focus, Inability to function, Inability to learn, Jumbled thoughts, Lack of concentration, Memory and comprehension problems, Poor judgement, Poor memory, Short-term memory problems, Slow thinking processes, Spaciness


Muscular

All muscles moving, All muscle tone feels flacid, Body feels twisted, Cranial tightness (felt my head was decompressing), Difficulty walking due to weakness and shaking, Face spasms, Inner tension, Inner vibrations, Jaw clenching (can't open or close mouth properly due to the spasms and pain), Jaw Spasms, Legs and arms shake, Muscle twitching, Muscle spasms, Rigidness and jerks, Muscle aches, Muscle cramping, Muscle tension, Muscle wasting, Muscle weakness (especially in the legs, arms and hands), Jelly legs, Restless legs, Stiff arms and legs, Stiff muscles, Stiffness in back, Teeth chattering, Tension in neck, Tight achy muscles, Tight jaw and temple, Tight head, Tight muscles in left leg, Tight muscles in neck and shoulders, Trembling and shaking, Tremors, Weakness, "jelly legs"

Nerves

All nerves firing off, Ankles reflexes diminished
Eyes and vision
Eye fluttering and twitching, Eye pain, Pain in eyes
Bone
Skeletal aches
Joints
Joint pain
Urinary
Difficulty urinating

Gastrointestinal

Bloating, Constipation, Choking, Diarrhea, Dry heaving, Fast and fine vibrations of the stomach, Gas, Knot in stomach, Loss of appetite and weight loss, Malabsorption, Nausea and vomiting, Severe pain in stomach, Slow heart rate, Swelling-bloating, Tachycardia, Weight gain


Mouth

Acid reflux, Dental pain (tooth pain), Dry mouth, Sore tongue, Metallic taste, Sore gums, Sore mouth, Too much saliva

Pain

Abdominal pain, Aching pain in legs, Bladder ache, Body aches, Headaches, Jaw pain, Lower back pain, Muscle and joint pain, Nail Pain, Neck pain, Nerve pain (hitting non-specific areas of the body randomly, but for short bursts), Pain in hands and feet, Pain in previous surgical sites, Severe bone pain, Severe head pain, Sore tongue and throat, Stinging pain, Teeth pain (felt like I had braces on), Throbbing pains, Throbbing legs, Waves of pain

Respiratory

Breathlessness, Chest discomfort and tightness, Difficulty breathing, Hyperventilation (overbreathing), Shallow breathing


Sensitivity

Chemical sensitivity, Cold extremities, Creepy crawlies on hands and arms, Feel cold even in hot weather, Food sensitivity, Intolerance to cold and heat, Intolerance to music, Photosensitivity, Sensitive to music, Sensitive to loud noises, Sensitive to light and stress, Sensitivity to smells, Very cold especially hands and feet


Sensorary

Brain nerve pain, Burning feet and legs, Buzzing throughout body, Chills, "Electric shock" sensations, Electric static shooting around body, Food doesn't have much taste, Head sensations, Heavy sensation in forehead and eyes, Heightened sense of smell, Hypersensitivity to light, Hypersensitivity to odors, Hypersensitivity to sound, Hypersensitivity to stimuli, Intense burning head/brain, Intense burning scalp, Intense burning spine, Itchy head and face, Numbness and tingling in face, Numbness and tingling in feet, Numbness and tingling in hands, Numb area on bottom of left foot, Numbness in arms, Numbness in face and left side, Numbness in fingers, Numbness in head, Numb right foot, Numbness in lip and tongue, Pins and needles, Sensory disruption, Soapy taste in mouth, Stabbing pains in limbs, Tingling on scalp, Tinnitus


Skin

Burning patches, Chapped skin, Cold sweats, Dermatographism, Dry itchy skin, Eyebrow loss, Feeling hot, Hair loss, Hives, Itching and stinging from head to toe, Itching sensation under my skin, Lashes falling out, Night sweats, Rashes, Rash under brows, Skin sensitivity, Sweating, Tingling skin, Very oily skin and hair


Sleep

Anxiety dreams, Frequent awakenings during the night, Horrific nightmares, Hypnagogic hallucinations, Jolts that wake you up, Lack of deep sleep, Poor sleep, Rebound REM sleep, Severe insomnia and tiredness, Sleep paralysis, Twilight sleep, Waking early, Weird dreams


CNS

Adrenaline jolts, Brain fog, Dizzy, Frozen feeling (like I need to get up and do something but can't do the action), Hypervigilence about symptoms, Impaired vigilance, Increased nicotine craving, Lack of energy, Lack of motivation, Light-headedness (especially when I stand too quickly), Loss of balance, Loss of sex drive, Mental and physical exhaustion, Migraine headaches, Pounding in my head, Pressure in head, Pulsating in right temporal area especially upon exertion, Restlessness, Room spinning, Seizures, Severe fatigue, Thirst, Vertigo, Voice weak


Immune system

Fevers, New allergies, Ulcers in mouth, Worsening of allergies


Female

Irregular Menstrual Cycle


Body

Feeling as if been punched in gut and chest, Feeling heavy legged, Feeling unwell, Flu like symptoms, General malaise, Going from hot and sweaty to cold and clammy, Hot and cold flushing, Increased number and severity of infections, Severe body pain, Water Retention


1. ACUTE:

- aggression
- anxiety
- agoraphobia
- apathy
- ataxia
- breathlessness
- chest discomfort and tightness
- choking
- constipation
- convulsions (muscle usually)
- dental pain
- depersonalisation
- depression
- derealisation
- diarrhoea
- distortion of body image, misperceptions
- dry, itchy skin
- "electric shock" feelings throughout the body
- dysphoria
- excitability
- fasciculations
- flushing
- formications
- head sensations
- heart palpitations
- hyperacusis
- hypersensitivity to stimuli
- hyperosmia (sensitive sense of smell)
- hyperpyrexia (overheating)
- hyperventilation (overbreathing)
- insomnia
- intrusive thoughts
- irrational rage
- irritability
- jumpiness
- metallic taste
- nausea
- nightmares
- obsessions
- panic attacks
- perceptual disturbances and distortions
- photosensitivity
- psychotic symptoms (usually transient and
confined to rapid withdrawal)
- restlessness
- seizures (on abrupt discontinuation)
- sensory disruption
- scalp burning
- sore tongue
- sweating, night sweats
- tinnitus
- tremor
- vomiting
- weakness, "jelly legs"
- weight gain
- weight loss (this may be quite rapid)

Cold Turkey

Symptoms usually confined to 'cold turkey' or rapid
withdrawal from high doses of benzodiazepines:
- confusion
- delirium
- fits
- hallucinations
- psychotic symptoms
- seizures

2. PROTRACTED:

- abnormal muscle tone
- anxiety
- aching joints
- ataxia
- allergic reactions
- back pain
- blepharospasm (eye twitching)
- breast pain
- apathy
- constipation (often alternating with diarrhoea)
- cravings
- dehydration
- dental pain
- depersonalisation
- depression
- derealisation
- diarrhoea (often alternating with constipation)
- dry, tickly cough
- dysphagia
- fluctuations in blood pressure
- "electric shock" feelings throughout the body
- fasciculations
- formication (sensation of bugs crawling over skin)
- gait disturbance (the ground seems to move underfoot)
- gastritis
- glassy eyes
- hair loss
- heartburn
- heart palpitations
- heavy flu-like symptoms
- hyperacusis
- hyperaesthesia (sensitivity to stimuli)
- hyperosmia
- insomnia
- iris colour changes
- kakosmia
- joint pains
- leukonychea (whitening of nails)
- libidinal changes
- malabsorption
- menstrual irregularity
- muscular cramps
- muscular rigidity
- muscular spasms
- muscular (and bone) weakness
- myoclonic convulsions (muscle/nerve spasms)
- nausea
- neurological problems (topical nerve anaesthesia)
- nose bleeds
- oedema (especially of ankles and face)
- oesophagitis
- paraesthesiae (numbing, burning and tingling; pins and needles)
- poor concentration
- poor short-term memory
- perspiring, night sweats
- severe headaches
- sinusitis
- skin insensitivity
- sore, itchy eyes
- spine (burning sensation)
- stomach cramps
- thirst
- thrush-like symptoms
- tremor
- tinnitus (ear buzzing, popping, ringing, hissing)
- tiny pupils
- urinary problems (bladder either 'all on' or 'all off')
- vertigo
- visual disturbances (blurred, double, vivid)
- vomiting
- water retention

3. PARADOXICAL:

- acute hyperexcited state
- agitation
- aggressive behaviour
- anxiety
- breathlessness
- excitability
- fear
- hallucinations
- hostility
- hyperactivity
- increased muscle spasticity
- irrational rage
- insomnia
- nervousness
- nightmares, vivid dreams
- phobias
- rage
- restlessness
- restless legs, arms
- sleep disturbances
- tension
- tremor
- panic attacks

4. TOLERANCE EFFECTS (including toxicity):

- anxiety
- apnea (night)
- breathlessness
- dyspnea (breathing problems)
- fibrositis
- fatigue
- gait disturbance
- impotence
- leaden heaviness
- lethargy
- libido disturbances
- loss of self-confidence
- menstrual irregularity
- neurological problems
- panic attacks
- phobias
- severe muscle rigidity
- short-term memory impairment
- vasovagal attacks
- vertigo

5. SIDE EFFECTS:

- abnormal behaviour or false beliefs
- aches and pains (muscle tension)
- aggressiveness
- agitation
- agoraphobia and claustrophobia
- anger
- anti-social behaviour
- apathy
- ataxia
- blood disorders (resulting in severe tiredness
and possible infections)
- blurred vision
- bradycardia (slow heartbeat/pulse)
- breast enlargement
- changes in appetite
- changes in libido
- changes in salivation
- chemical sensitivities, allergies
- cognitive impairment
- confusion
- daytime drowsiness
- depression
- diarrhoea and constipation
- diplopia
- dizziness
- dry, itchy skin
- dysarthria
- dysphoria
- emotional blunting
- exhaustion
- fatigue
- feeling afraid
- feeling unreal
- feelings of anger and anxiety
- flu-like symptoms
- hair loss
- hallucinations
- headaches
- hypotension
- IBS (Irritable Bowel Syndrome)
- inability to pass urine/holding of urine in the bladder
- impairment of motor co-ordination
- incontinence
- insomnia
- irritability
- jaundice
- jaw pains
- lack of concentration
- lack of confidence
- lethargy
- many people wonder why they have changed from being happy
and outgoing, to being over-anxious and unconfident
- memory loss or forgetfulness
- mild hypertension
- muscle weakness, spasticity, cramps, abnormal tone
- nausea
- nightmares
- numbed emotions
- oedema
- panic attacks
- personality changes
- poor muscle control
- problems with vision
- psychomotor impairment
- rashes
- reduced alertness
- reduced blood pressure
- restlessness
- shivering
- skin problems, rashes
- sleep problems
- slurred speech
- stomach and bowel problems
- stomach upsets
- suicidal behaviour
- thyroid disturbances
- tolerance
- tremor
- urinary retention
- vertigo
- violence
- water retention
- weight gain
- xeroderma (dry skin)

6. CATEGORIES OF SYMPTOMS:

CARDIOVASCULAR:

Fluctuations in blood pressure
Mild hypertension
Shivering, feelings of extreme cold or hot
Heart palpitations

DERMATOLOGICAL:

Allergic reactions
Chemical sensitivities
Dry, itchy skin
Dry throat, sore tongue, and thrush
Formications (sensation of crawling on skin)
Glassy eyes
Hair loss
Leukonychea (whitening of nails)
Nosebleeds
Oedema
Paraesthesiae (numbness, tingling)
Perspiring, night sweats
Rashes, blotches

GASTROINTESTINAL:

Bladder incontinence
Constipation (sometimes alternating with diarrhoea)
Diarrhoea
Dyspepsia (indigestion)
Gastritis
Heartburn
Nausea
Oesophagitis
Stomach cramps

GENITOURINARY:

Impotence
Libido disturbances
Menstrual irregularities
urinary problems (continence or incontinence)
Encopressia (faecal incontinence)

MUSCULOSKELETAL:

Aching joints
Blepharospasm (eye twitches)
Formication (sensations of bugs crawling on skin)
Gait disturbance
Jaw, tooth, neck and shoulder pain
Muscle wasting
Muscle spasms
Rapid weight loss
Severe headaches
Severe muscle rigidity
Tremor or feeling of inner vibration
Vertigo

NEUROLOGICAL:

Blurred vision, seeing spots, flashes, vivid vision
Bruxism (teeth grinding)
Dysphagia (difficulty eating or swallowing)
Electric shock feelings
Fatigue, leaden heaviness
Hypersensitivity to light, sound, and other stimuli
Neurological problems (e.g. topical anaesthesia)
Severe muscle rigidity
Speech difficulty
Thirst
Tinnitus (ear buzzing, popping, ringing, hissing)
Tiny pupils
Tremor

PARADOXICAL:

Agitation
Aggressive behaviour anxiety
Breathlessness
Excitability
Fear
Hostility
Hyperactivity
Irrational rage
Insomnia
Nervousness
Nightmares, vivid dreams
Phobias
Restlessness

PSYCHIATRIC:

Apathy
Anxiety
Delirium
Depersonalisation
Depression
Derealisation
Distortions or hallucinations
Dysphoria (inability to feel pleasure or happiness)
Fear
Hyperventilation
Hyperreflexia (‘jumpiness’)
Hypnologic hallucinations sleepwalking)
Lack of concentration
Nightmares
Obsessions
Paranoia
Phobias (hydrophobia, agoraphobia, monophobia,
acrophobia, anthropophobia and others)
Rapid mood changes
Suicidal thoughts
Short-term memory impairment

RESPIRATORY:

Breathlessness
Choking
Dry, tickly cough
Dyspnea (breathing difficulty)
Hyperventilation (overbreathing)
Inability to draw satisfying breath
Night apnea
Sinusitis

http://benzowithdrawal.com/forum/index.php exellent forum

http://www.non-benzodiazepines.org.uk/

http://www.benzo.org.uk/ (excellent site)

there are other helpful sites

Books re: psychotropics

For those who started on Psychiatric drugs, but wish to wean and taper, books such "Brain Book" by Dr David Permlutter, Neuroscientist and "Coming off psychiatric Drugs, by Peter Lehmann, Judi Chamberlin, Pirkko Lahti, and Loren R. Mosher are helpful.

Professor Ashton's Manual concerning Benzodiazepines, on how to switch to Diazepam, and taper and wean is a must read. The Manual emphasizes safety. http://www.benzo.org.uk/manual/bzsched.htm

There are many books, written by psychiatrists and Neuroscientists, concerning psychotropics, avoidance, alternatives, withdrawal, tapering and weaning safely.

Caution: weaning and tapering should be under the supervision of your psychiatrist.

A number of meds and indeed diseases, can induce sudden or delayed, neuropsychiatric symptoms. Fluoroquinolones antibiotics, Lariam/Mefloquine, beta blockers, Anti depressants, analgesics, anesthetics (both general and local) and many more.

Conditions such as hypothyroidism, Huntington's Disease, Lyme Disease, infectious pathogens, mercury and other heavy metals accumulation, changes in hormones, etc.. are also known to cause neuropsychiatric symptoms.

Below is an article, alerting about asthma drug suspected of causing neuropsychiatric symptoms in children. I suspect this is also happening to adults. Nasacort for sinusitis and rhinitis, can also cause neuropsychiatric symptoms.

If your or a member or family suddenly or over a period of time, display psychiatric symptoms, please, investigate.

Often, there is an underlying cause as mentioned above. Avoid psychiatric drugs, see vids posted below.

Asthma Drug linked to suicide attempts, thoughts of self-harm

By Bradley Bouzane, Canwest News ServiceJuly 7, 2009

OTTAWA — The side-effects of a popular asthma medication that has been sold in Canada for 12 years has been linked to suicide attempts and thoughts of suicide, as well as feelings of depression and hostility.

The July 2009 issue of the Canadian Adverse Reaction Newsletter from Health Canada cites montelukast sodium — which has been marketed in Canada since 1997 as Singulair — as having several connections to the alarming reactions.

Between its introduction to the Canadian market and Jan. 31, 2009, Singulair has been linked to two suicide attempts in Canada and 11 cases where users had thoughts of suicide or self-harm. In 29 other cases, 14 of which were labelled as "serious adverse reactions," those affected suffered from depression, hostility or other psychosis. No deaths have been linked to the drug's side-effects.

Karen Liberman, executive director of the Mood Disorders Association of Ontario, said the side-effects are disturbing, given how common asthma is.

"It's kind of like a perfect storm," Liberman said. "Asthma is so prevalent, and depression and bipolar (disorder) and anxiety are more prevalent.

"One of the things we know about these illnesses is they are susceptible to stress on the body, whether it's chronic pain, life stress or relationship stress. If you carry the genetic vulnerability to depression, these are the things that can trigger it. As you can imagine, if you are someone with a chronic disease like asthma, and you take medication that's supposed to help, and it precipitates something like depression, that would be very troubling."

Between September 2007 and July 2008, the list of adverse reactions stemming from the drug was amended in Canada, which warns patients that "if suicidal thoughts and actions occur, montelukast should be discontinued and a physician or pharmacist contacted immediately."

In eight reported cases, thoughts of suicide or self-harm subsided once the dose was reduced or stopped completely, while the same adverse reaction returned in one case when the dose was restarted.

In the 29 less severe cases, the reactions were eliminated by lowering the dose or stopping use of the drug in 19 of those cases. Upon reintroduction, the symptoms returned in four cases.

More than half of the reported cases — 26 of 42 — were in people under the age of 18.

The drug is used to treat asthma in people older than age two, as well as patients age 15 and older who suffer from severe seasonal allergies. Cont...http://www.leaderpost.com/news/Asthma+drug+linked+suicide+attempts+thoughts+self+harm/1768232/story.html

Popular Asthma Medicine Singulair Associated With Psychiatric Disorders In Children

New Medical Journal Article Follows June 2009 FDA-Required Warning For Singulair About Neuropsychiatric Events

(Posted by Tom Lamb at DrugInjuryWatch.com)

On June 12, 2009 the FDA announced a new warning about an increased risk of neuropsychiatric events for the asthma medicine Singulair (montelukast)-- as well as some other less popular leukotriene inhibitors, Accolate (zafirlukast) as well as Zyflo and Zyflo CR (zileuton).

http://www.drug-injury.com/druginjurycom/drug_safety_alerts/

This blog is about recovering from Adverse Drug \Reactions/Side Effects, (inc vaccines). Published articles concerning pharmacodynamics and pharmacokinetics, damage to mitochondria & methylation (caused by medicines), epigenetics, phytochemistry, Ayurvedic medicine, and other validated alternatives therapies such as Orthomolecular medicine, (vitamins and supplements) referenced from various scientific medical/ journals.

Topical comments pertaining to this blog are welcome.

For those of you suffering from an Adverse Reaction/Side Effects, there is hope. There are vitamins and supplements which are very helpful to help detoxing, such as magnesium orotate, magnesium citrate for palpitations, Vitamin E, Fish Oil containg EPA/DHA, ALA, NAC etc.. I will write an article concerning these.

If you are suffering from neuropsychiatric symptoms(CNS) as side effects, avoid psychotropics.

They are extremely addictive, may cause more damage, and are not a cure, not even temporary. Benzodiazepines (Benzos) are extremly addictive, and very difficult to wean off for most. Look up Benzodiazepines Withdrawal on You Tube before taking one!! There are alternative neuroscientists and psychiatrists using vitamins and supplements, herbs and NeuroFeedback. Most neuropsychiatric symptoms subside, with time. For some, it may take a few weeks, others a few years.

I will write more about CNS symptoms and various safe coping strategies. Meanwhile, look up "Altering Brain Chemistry" on http://noquinolones.proboards.com/index.cgi?board=treat&action=display&thread=1192 Listed are some remedies, validated with scientific research such as Ashwaganda, Bacopa and Heel's homeopathic remedies, and more.

Avoid Neurotonin, Cymbalta and other benzos type of pain killers. They belong to the same class of drugs as Benzos attaching themselves to Benzos receptors, causing even more long term damage. Often, those suffering from an ADR causing neuropathic pains, nerve fibers will heal in time. If taking strong listed analgesics, these nerve fibers may suffer more damage, delaying recovery, and may not heal.

Vids concerning Benzos withdrawal:

Warnings about Fluoroquinolones antibiotics:

New Vids by MrFloxed

Regardez bien le vid sur les fluoroquinolones antibioques!!
Avant d'en prendre, renseignez vous.
Effets secondaires, n'attendez pas,
regardez ce site et les vids sur le "Video Bar"

http://quinolones.free.fr/AVQ/projets.html
www.favc.info

Bevor Sie fluoroquinolones Antibiotika nehmen, informieren Sie sich über Risiken.
Wenn Sie die Antibiotika nehmen, die unter Nebenwirkungen leiden, betrachten Sie jene "Videos Bar" und Sites: www.favc.info

Se lei porta un antibiotico di fluoroquinolone e sospetta una reazione avversa, uno sguardo su quei video sulla "Video Bar" e questo luogo: www.favc.info

Si usted toma un antibiótico de fluoroquinolone y sospecha una reacción adversa, la mirada arriba esos vídeos "Video Bar" en la barra vídeo, y en este sitio: www.favc.info

Om du tar en fluoroquinolone antibiotika och misstänker en motsatt reaktion, blick upp de video "Video Bar" på video stången, och denna plats: www.favc.info

Hvis du tager et fluoroquinolone antibiotikum og mistænker en ugunstig reaktion, udseende op de videoer på videoen stangen, og dette sted : www.favc.info

Jos otat fluoroquinolonen antibioottia, ja epäilee nurjaa reaktiota, etsii nuo videot videobaarissa, "Video Bar" ja tämä paikka: www.favc.info

Εάν έχετε πάρει μια fluoroquinolone αντιβιοτικά και ύποπτων η παρενέργεια, εξετάσει τις βιντεοταινίες σε βίντεο bar, και αυτό τόπο: www.favc.info

もしfluoroquinolone抗生物質を取って、拒絶反応を疑っていれば、ビデオバー〔棒/法廷〕と、このサイトのそれらのビデオを調べてください：www.favc.info

如果你在送一種 fluoroquinolone 抗生素和懷疑一種不利的反應，查閱那些關於視訊的條，本網站的錄像：www.favc.info

यदि आप ले रहे हैं और एक fluoroquinolone प्रतिजीवाणु प्रतिकूल संदिग्ध प्रतिक्रिया में देखना शुरू करने पर उन वीडियोज़ वीडियो बार, और यह स्थान: www.favc.info

Ha ön figyelembe véve a fluoroquinolone antibiotikum és a gyanús egy nemkívánatos reakció, felnéz a videók a video bar, és ez a hely: www.favc.info

Ако сте като на fluoroquinolone антибиотичните и съмнителни неблагоприятна реакция, проверявам тези клипове на видео бар, и този сайт: www.favc.info

Pokud jste přijetím fluoroquinolone antibiotického a podezření na nežádoucí reakce, pohle�e až ty videa o video bar, a to stránkách: www.favc.info

Indien u neemt een fluoroquinolone antibioticum en een ongunstige reactie verdenk, blik op die video's op de videobar en deze plaats: www.favc.info

Hvis du tar et fluoroquinolone antibiotikum og frykter en ugunstig reaksjon, titt opp de videoene på videoen bar, og dette stedet : www.favc.info

Se toma um antibiótico de fluoroquinolone e suspeita uma reacção adversa, olhar para cima esses vídeos na barra de vídeo, e este local: www.favc.info

Ako ste preuzimaju fluoroquinolone antibiotika i sumnja da je negativnih reakcija, gledati one video video Bar, i ovaj sajt: www.favc.info

If you are alan fluoroquinolone antibiyotik ve şüpheli bir olumsuz tepki, başınızı bu prodüksiyon on the video bar, ve bu site: www.favc.info

만일 당신이 취하고 있는 용의자 fluoroquinolone 항생제와 반응하는 부작용이 사람들을 찾는 비디오 동영상을 표시줄, 이 사이트: www.favc.info

ADR nightmare from Paul C sent to my Email.

Copied and Posted with his permission. Unedited:

Floxin Horror Chronology in Brief

Paul C

April 1998: was prescribed 10 days Floxin, 300 mg. 2/day

10 days

Day 11: woke up both ankles swollen

inflammation increased daily within both tendons/calves

Met with Podiatrist

Tried to Meet with original Dr. Again/emergency Told cannot see me without appointment...

Saw other dr. in his office. Was told I have Ryders Syndrome/Lyme Disease

Called Johnson and Johnson: told to rest.. No help\

Saw other Podiatrist... did not know what was happening

Doctor in Podiatrist office gave me Lyme disease med. Without confirmation of lyme disease.

New Lyme specialist at Hosp. Of Spec Sugergy: told NO

Lyme disease

Saw Rhymatologist Hosp spe. Sug: said it was like a baseball bat hit my legs.... I was crying in pain.

Went to surgery area Hosp. Spe surg: told to walk but no

pounding activity

few days later: 2 ruptures in 2 tendons

Was put in hard CAST for one month

Incredible Pain.... Cyring at home ttype of pain

In legs swelling but in cast and told not to take cast off

and use ice.. Which would have been smart... best doctors

in NY did not treat this correctly. 1998

While at home... found sympathetic chiropractor in CA

I talked with every day to keep me going.

Physical Therapy for 6 months

OPERATION 1999

Tumor developed behind toe of right foot.

Morton’s Neuroma Surgery 1999: Dr. Waller

More phy. Therapy: hand problems developed

Dr. Wolffe sports Phy. Therapy carpal tunnel

1999: Intence pain in both calves continued.

Saw Dr. Pfaffle, Madison Medical Group.

Intense Pain both legs Put me on steroids and Pain Meds

1999 saw Dr./ Rho Lenox Hospital

Intense terrible pain both calves ongoing. Torturous

Did EMG exam in both legs... so painful.. Nerves

damaged... hit doctor to stop test !

Test revealed autonomic nerve damage.

Tried various meds and acupuncture... no help.

Continued to work with pain meds.... Flexible

schedule.

Series of misunderstanding my doctors:

Dr. Waller Morton Neuroma surgery: pressed down

on tendon hard to test me... I screamed in pain... this still hurt? HA then he said.. If u take pain meds... need more and more you know... Then how do I deal with pain?

He also once said when I asked him in 2002 about

constant leg pain 24/7: he said I just have to relax.

No affirmation of extreme damage I’m suffering from.

Saw Urologist of friends who prescribes Levaquin: suggested I just take Citrocal 2/day. And I’d be fine.

"I know a woman with bad legs.. One month vitamins

and she was fine. "Did she have quinolone damage?" NO !!

In a desperate state in 2000:

Went to "Friends in Deed" a crisis center in NY for primarily cancer victims

Referred to pain doctor: Dr. Alan Leff

2006 MRI left and right feet: tendon tears still evident in

both legs and numerous sections of calves with fluid retention problems, tendinopathies, etc.

2006: Just could not work anymore.

Long term disability began 2006

2007: Spontaneous Tendon Rupture in Right Elbow area.

Treating that now as well.

Rhymatologist and Endocrinologist reports 2009

Low Growth Factor from Pituitary found

MRI showed small pituitary: shrank?

Low Bone density

Low testosterone

Hypoglycemic. High Blood Pressure... Weight Gain

Vit D deficiency

Chronic Hands swollen.

Possible rhymatoid Arthritis set in./ Memory Problems

Concentration Problems...

This is the tip of the iceberg of how my life has been

ruined by one 10 day course of an antibiotic

Much is written in medical journals about medications causing damage to the mitochondria, altering or DNA deletions and cell apoptosis.(see articles below) These can manifest as fatigue, exhaustion, allergies, diabetes, heart failure, and a multitude of other diseases including those for which there are no dognosis/tests available. Meds cause DNA mutations, in most cases causing ill health! Symptoms can be immediate causing allergic reactions, side effects or Adverse Drug Reactions (ADRs), or delayed reactions, which can manifest years later.

There is strong evidence linking the rise in medication prescriptions, (and off the counter meds (OTC) invasive investigations/surgeries, vaccines, with a steep rise in chronic illness/diseases, amongst children, and adults alike. The generation born in the late 1950s AND early 1960s suffer serious illness in their forties and fifties, on the rise, disabilities and limitations occurring much earlier than the generation born after WWI and WWII.

Reliable sources published articles, concerning generation X, and future generations, suffering chronic illnesses at an earlier age, greater disabilities, and shorter life span. All linked to vaccines and medications, environmental illness and unnecessary surgical procedures.

The damage occurs at cellular level causing damage to ATP/ADR conversion, and various biochemical dysfunction. is well documented.

ADRs symptoms are denied by doctors as being "rare", causing despair and distress to patients. Overall, it is an uphill struggle with medical professionals.
Widespread denial and collusion perpetuate the myth that Adverse Drug Reaction are "rare"... far from it. Most people do not make the connection with a prescribed or over the counter drug they took. Delayed reactions can take years to manifest as in the case for auto-immune illnesses which can take years to develop (caused by meds).

Unaware for instance that Aspirin can trigger tinnitus, or some prescribed diuretics can trigger diabetes? Read on:

An excellent article concerning medications affecting mitochondria This is totally different from hereditary mitochondrial diseases.

"Medications have now emerged as a major cause of mitochondrial damage, which may explain adverse reactions......"

http://www.montanaim.com/pubs/Medication-induced_mitochondrial_damage_and_disease.Neustadt-Pieczenik.pdf

For those interested in the correlation between mito cytopathies and meds, and there is a correlation between these two.

Worth noting that often those cytopathies manifest themselves, months to years later. ( I can't take meds, even if I wanted to. I simply could not be more iller, barely hanging by a thread as it is). Honest MDs advised not to take any meds, and if having to as in life/death situation, to take minute dosage and increase over a period of several months..

This may explain the overlap with ADRs to meds, vaccines, CFS, GWVs, floxies etc... Those who are severely affected, suffer similar symptoms and disease process.

Someone I met in a local CFS support group, developed stomach cancer. Before passing away, he told us that severe symptoms from CFS were far worse than his cancer. I suspect that he too suffered from an ADR...

Medication-induced mitochondrial damage and disease.
Neustadt J, Pieczenik SR.
Montana Integrative Medicine, Bozeman, MT 59718, USA. drneustadt@gmail.com

Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health and disease. Damage to mitochondria is now understood to play a role in the pathogenesis of a wide range of seemingly unrelated disorders such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis.

Medications have now emerged as a major cause of mitochondrial damage, which may explain many adverse effects. All classes of psychotropic drugs have been documented to damage mitochondria, as have statin medications, analgesics such as acetaminophen, and many others.

While targeted nutrient therapies using antioxidants or their precursors (e. g., N-acetylcysteine) hold promise for improving mitochondrial function, there are large gaps in our knowledge. The most rational approach is to understand the mechanisms underlying mitochondrial damage for specific medications and attempt to counteract their deleterious effects with nutritional therapies.

This article reviews our basic understanding of how mitochondria function and how medications damage mitochondria to create their occasionally fatal adverse effects.

Delivery of Drugs and Macromolecules to Mitochondria

This article is indicating how many miles scientists have to go yet, how difficult it is to repair things at cell level in the human body. Abstract Mitochondria is where the bulk of the cell’s ATP is produced. Mutations occur to genes coding for members of the complexes involved in energy production. Some are a result of damages to nuclear coded genes and others to mitochondrial coded genes. This review describes approaches to bring small molecules, proteins and RNA/DNA into mitochondria. The purpose is to repair damaged genes as well as to interrupt mitochondrial function including energy production, oxygen radical formation and the apoptotic pathway. Keywords: Mitochondrial DNA, Mitochondrial disease, Translocators, Protein and RNA import, Membrane insertion, Lipophilic cations Full text: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2267434 http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2267434&blobtype=pdf For those who are keen on taking antibiotics, read about mitochondria cytoxicity, which meansm, essentially, DNA damage. There are several articles posted on the FAVC, http://noquinolones.proboards.com/index.cgi?board=theories&action=display&thread=318&page=1 worse offenders are, antibiotics, (Fqs, macrolides, tetracyclines, clyndamicin, Rifamopin) anti-depressants and NSAIDs.. This study is well designed and discusses glycation, cell death, lactic acidosis etc.. It mentions about high dose of these. I have yet to come accross a published paper about the toxicity of low dosage of Fqs or any other meds, LOL. It is known, that many who took just ONE lariam or Fq, or Diclofenac, have died of sudden cardiac death, triggered by cardiac electrical conductivity dysfunction, caused by a med!! http://aac.asm.org/cgi/reprint/AAC.00729-05v1.pdf Well illustrated and easy to read article re: mitochondria and its role in disease processes. http://www.ceri.com/mito.htm A lecture from Professor Leona Samson at MIT. Over my head, but, there were a few interesting facts. Watch the vid here: How much progress since this lecture in 2006?? Forget cigarette smoking (well, not completely). The really bad news, says Leona Samson, is that by virtue of the act of living, a human body will be exposed to destructive threats from the environment, and from within itself. Charbroiled burgers, sunlight, pollution, and even how our bodies use oxygen all pose what Samson calls “insults” to the DNA of our cells. Our success in fending off these inevitable DNA-damaging agents in the environment depends a lot on inheritance, Samson tells us. For instance, victims of the rare disease Xeroderma pigmentosum don’t have the capacity to repair DNA that’s been corrupted by UV radiation from the sun. Children with Xeroderma pigmentosum develop skin cancers. In the larger population, such cancers tend to occur much later in life. The reason, Samson says, is that most of us have a formidable array of mechanisms within our cells for detecting and mending defective DNA. Cells with flawed DNA that goes un repaired must either die, or go on to mutate in often dangerous ways. Samson wants to figure out how to protect cells against carcinogenic effects in the environment, and whether a tumor cell will be susceptible to treatment. She has been painstakingly studying the Saccharomyces cerevisiae yeast organism, trying to identify all the factors that determine whether or not DNA damaging agents kill or mutate cells. She interrogated each of this organism’s 5,800 genes, “asking one by one, which of you is making a product that’s important to helping a cell recover from damage.” In what was a “huge surprise,” Samson learned that there are more than 2,000 gene products involved in helping a yeast cell repair itself, “from areas of the cell never suspected before for being important” in this way. Now Samson must elucidate the complex cellular pathways that “talk to each other” when DNA is damaged -- and figure out “how to extend to humans, ultimately.”

Interesting article concerning the connection between ion channels in the brain, and dysfunction of these causing CNS symptoms, yet, BIG PHARMA continue to manufacture "happy pills' which do not work, except for a a few hours, are addictive and cause even more damage to the fragile system of neuronal circuitry. After all, anti-depressants alone, is worth a revenue of $40 billions a year!!

Not only, there is no science behind the production of anti-depressants and most strong analgesics, such as Neurotonin, (which are nothing more than mind altering drugs), but, BIG PHARMA is jumping on the gravy train, preparing to manufacture "drugs" to treat dysfunction in potassium ion channels, hum, can't wait to see the results.

Key Potassium Ion Channel Modulating Proteins Discovered

New York (MedscapeWire) Feb 8 — A family of proteins has been identified called potassium channel interacting proteins (KChIPs) that associate with and regulate the activity of certain potassium ion channels, called "A-type" channels, according to a study in the February 3 issue of Nature. These A-type potassium channels are thought to be involved in the control of the electrical signals of the brain and other excitable tissues. Abnormalities in the electrical signals of these tissues may form the basis for a variety of disorders including anxiety, depression, ischemia, and epilepsy.

The article believed to be the first publication to identify a modulator of the function of these key potassium channels. Prior to this discovery, the activity of the isolated channel was found to be significantly different from the natural activity measured in the brain. These KChIPs are believed to be important missing components of native A-type potassium channels which helps explain the difference. The identification of these additional components may allow for the development of new drug screens to identify compounds that modulate A-type potassium channels in a tissue-specific manner. This may allow for the development of therapeutics for CNS disorders that do not cause unwanted adverse effects in nonbrain tissues such as the heart.

Cont/...

http://www.medscape.com/viewarticle/411593