Why?
My doctor gave me a prescription for Ativan, a tranquilizer. It had no effect on me. I can also take Benadryl with no drowsiness.
Okay, so I’m a freak. But why? What’s the actual mechanism by which you and I are affected differently by various drugs and why does it exist? How different can people really be chemically?
People can be very different chemically. Just try injecting a random person’s blood into your arm and see what happens - most of the time, you reject the blood, form clots and die. This is based on the different antigens and receptors (or lack of receptors) in blood.
Receptors are used in many other contexts in biology, such as the transport of chemicals across cell walls. If a person lacks receptors or their receptors are damaged or blocked, they may not respond the way they should. Type II diabetes appears to be a problem of that sort, where cells stop responding to insulin - even when that same person had a normal response earlier in their life.
Many psychological problems are linked to problems in the production, uptake and/or responsiveness to normal neurotransmitter chemicals. To oversimplify an example: If your depression is caused by low serotonin, increasing levels of serotonin will help cure the depression. If your problem is low or blocked serotonin receptors, taking more will not help. (Since the depression symptoms look the same either way, you can see how one person might respond to a medication that doesn’t affect the other).
Sickle cell anemia results from a single codon error, which produces an incorrect protein and malformed blood cells when a person has two copies of the gene. The condition is dangerous when expressed, but it does protect against malaria even when not expressed (i.e. when you have one good gene and one bad one).
I don’t think anyone knows how sickle cell genes protect you, and that’s a part of the answer to your question too. To a large extent, we can only observe that person A reacts differently from person B, but we don’t know why that is.
Okay, that’s fair enough.
Do Ativan and Benadryl work in remotely similar ways?
It was kind of a funny conversation with my doctor. I’m on two medications and at least one of them is making me incredibly sleepy and also disrupting my sleep though neither is really supposed to make me drowsy. But the two drugs that are supposed to make nearly everyone drowsy–Ativan and Benadryl–have no effect. It’s opposite chemistry!
IIRC from school, sickle cell trait protects because when malaria infects a red bllod cell it sickles, commiting suicide as it were to halt the progression. With sickle cell anemia this happens randomly, and to large numbers of cells.
jsgoddess drugs that affect the central nevous system often do so by binding to neurotransmitter receptor sites in the synaptic gap between neurons, or between neurons and muscles. Different types of neurotransmitters are released to send different signals, and land on different types of receptor sites. Guess how the opiate and nicotinic receptor sites got their name. However people vary in terms of how many receptors they have, a 30% variation in not unknown. Some mood disorders may be linked to abnormal numbers of receptors, or it can greatly impact your sensitivity to a drug. A serum concentration of X will affect someone with 30% less receptors much differently than the average.
Also, GI track absorbsion, and kidney and liver clearance of a drug can significantly affect how quickly or how long you have a serum concentration of X. I’m sure there a other reasons
ETA paradoxical reactions are not fully understood, but well described, witness adderal/ritalin etc for ADHD. Benadryl is well known to cause paradoxical agitation. Milage varies.
I don’t have an answer for you, just wanted to add that Ativan and Benadryl don’t really make me drowsy either, so that makes two of us.
But you’re obviously a freak. You’re a trapezoidal jellyfish, and that just ain’t normal. 
I started a thread like this a while back . . . So many people take Tylenol for headaches, but no matter how much I take it has absolutely no effect on me. Same for my mother and brother. Individual body chemistry can be complex. And it can of course be affected by other meds you are taking.
A lot of different drugs are metabolized by different CYP450 enzyme isotypes. A difference in the amount of CYP450 enzymes that are produced can change the way and speed that a drug is metabolized. So, if you produce a lot of a particular CYP450 isotype you might clear the drug from your system before it takes effect, or if you don’t produce enough the drug could build up in your system and cause all sorts of toxic effects… Or, it might cause the drug to do absolutely nothing if it is a prodrug.
Tailoring a patients treatment to their genetic makeup is starting to become an important part of how medicine will progress in the future. Using large population genome sequencing programs, scientist are starting to identify groups of people that respond better to specific drugs, and can pinpoint responsible genes. In the future, some simple genetic testing will occur before treatment to identify the best approach.
Exciting stuff.
Si
I wrote out a longer post, but the boards ate it. So just google “pharmacogenetics” and go nuts.
Well, my NSAID of choice is ibuprofin, naprosyn/alieve might as well be M&M candies for the amount of good they do me. I can do parafon fortis, vicodin, codeine with anything and flexoril until the cows come home and not get sleepy, codeine just plain doesnt do anything except make me slightly constipated … and I can see the attraction of morphine but will not take it any longer than I absolutely need to.
I have a fairly high pain tolerance for chronic pain [i’m still a baby about acute pain if I am not expecting it. if I have warning and can get myself psyched up for it I can take a fair amount of acute pain.] I apparently have the gene that makes naprosyn not work for me, as does mrAru.
I have discovered that I do have to be a bit careful with my meds because the jackasses who make the meds like to put tylenol in the damnedest places.
Many times even the drugs that DO work on a particular person quit working over time. The body tries to return to it’s original state and adapts to the treatment. So the Doc has to change your meds. Pretty common with blood pressure treatment.
I am bipolar and very much under control now for years. Before that, doctors gave me antidepressants which are contraindicated for most bipolar people. Antidepressants make me suicidal within a week and those prescriptions almost killed me (it is a known effect). Plain vanilla bipolar drugs like lithium work like a charm. That is another example of how people differ strongly to different medication although no one really knows why in that case.
Bendaryl doesn’t do a thing to me UNLESS I’ve had even a single drink.
Then it puts me to sleep, whether I like it or not.
Ignoring biochemistry for a second. If youre extremely tense then a weak benadryl or small dose of ativan wont do much. Atiban is a benzodiampene, like valium. Im certain 5mg of a different stronger benzo like Klonopin will knock you right out. Youre not immune, youre just on the wrong drug and on a low dose. Your doctor gave you ativan because its safe and has a low half-life.