What drug side-effects might tell us about the Brain…

Some clues to brain and behavior are found not only in how medications are supposed to work, but in their undesired side effects.   If a drug works (more or less) in most people, but has the exact opposite effect in others, then this may tell us that the minority has a biochemistry that differs in some important way.
There is even a term for this effect: it is “Paradoxical reaction” This is an adverse reaction to a substance, almost always to a drug, that is exactly the opposite of the intended effect.  In other words a seemingly contradictory reaction to a drug that is nonetheless very real.
For instance, a psychotic patient can be treated with the ‘anti-psychotic’ Haldol (Haloperidol) that supposedly works by decreasing excitement in the brain.   In some people, however it causes hallucinations and paranoia.   We might stop and wonder why less activity causes effects that at least I would have associated with a fevered mind.  As an unlikely guess – maybe we have a ‘sanity checker’ on our ideas that gets inhibited when brain activity is decreased.  But then – why only inhibited in a minority of patients?
Haldol also causes a loss of interest in sex for many people – and this, instead of being a drawback,  conceivably could be an asset in the treatment of sex offenders who wish to reform.
Benzodiazepines, a class of psychoactive drugs called the “minor” tranquilizers, have varying hypnotic, sedative, and anti-anxiety properties, but they may create the exact opposite effects in some patients. Susceptible individuals may respond to benzodiazepine treatment with an increase in anxiety, or an increase in aggressiveness, a loss of impulse control, and talkativeness.
Imagine – a drug that makes you want to talk.
In addition, for an extremely weird effect, it can lead to criminal behavior in susceptible individuals.
If you could cure sex-offenders with a drug, and conversely, make normal people into criminals with another drug, does this have implications for how we judge individuals?
paradox
We don’t like mothers who are nasty to children, but:
mothers…taking a combination of benzodiazepines and tricyclic antidepressants said that instead of feeling less anxious or depressed, they became more hostile and openly aggressive towards the child.
This suggests that psychiatrists who prescribe drugs are in uncharted territory, and don’t really know the mechanism of action of these drug cocktails.
I remember telling a person who knew about mental health issues that I had read that antidepressants could cause suicide in some patients, but this person was skeptical – saying the patients were depressed to begin with, and the drug may not have worked, and so the patients lost the motivation to live and killed themselves.   However, the skeptics are not correct in all cases, because:
anti-depressants can rarely make users obsessively violent or have suicidal compulsions, which is in marked contrast to their intended effect.
There are drugs that have effects on the minds of a minority of people, that are not necessarily paradoxical, but are quite interesting.
Here are reports from the web:
Person A: I flipped out on the painkiller, some morphine derivative, until they loaded me up with Valium. ….and reacting with hyperactivity paranoia and violence is something i have never heard of as a retain to a painkiller …
Person B: Thank you for responding I have had the same response to pain medication my whole life. I was 8 when I broke both bones in my left arm, they gave me Darvon before they tried to set the bones back together. I swore they were not real people anymore, and I KNEW they were going to kill me. I ran out of the treatment room and screamed and fought and bit anyone that got near me. It was a real freak show from what I understand.

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Person C in replying to the above suggests that a doctor use brain scans on people who respond in such adverse ways, and I (the blogger) think that is worth a try.
A very strange reaction is to a drug called Compazine. Compazine is a drug given intravenously in hospitals for nausea and/or for migraine headaches. Approximately one out of five people have a weird reaction to Compazine that then requires the administration of intravenous Benadryl – (a commonly used antihistamine) to resolve.
 Patients become restless, agitated and can’t sit still. In many cases, they actually do not know what is going on- all they know is that they ‘Want to Go Home.” They will repeatedly state that they want to go home or that they, “Have to get out of here” over and over.
According to Kerri Knox, an RN  in San Francisco:
I can distinctly remember working as a nurse in a small emergency room when our unit secretary came in on her day off because she was dehydrated after several days of vomiting. I started an intravenous line to give her fluids- and gave her a dose of Compazine as per the doctor’s order. Soon, she was stating, “I Want to go home now.” Because I had given her a sedative drug, the hospital could not allow her to drive herself home and I called her boyfriend to come and pick her up. After I tended to another patient and returned to my coworker, she was gone and the ambulance door was closing. I opened the ambulance door and saw her running away towards the main street, IV pole being pushed in front, hospital gown billowing out behind. We had to call the police department to get her back. Once she had some Benadryl, she agreed to stay and get the rest of her intravenous fluids. Now THAT is a Paradoxical Reaction! Once I began to recognize the reaction, I dubbed it the ‘I Gotta Go’s’ because that’s what everyone with a paradoxical reaction says.
With these few examples, we see that intriguing questions are raised, and perhaps avenues of investigation, by unwanted side effects of drugs.  One problem with drugs as far as the brain is concerned is that it is hard to target them – you are bathing the whole person in these drugs, which is not the way neurotransmitters usually work in the brain.

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