How'd it go today?
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Knotorious
That Guy With The Face
The following is my best effort to make pharmacology sound exciting to the layperson...because I have zero life and way too much free time. If you don’t like thinking very hard, then you should probably move to the next post. If anyone actually reads this to completion, please give yourself a firm hug and say, “I’m amazing!”
I’ve been having a ton of anxiety lately and I’m convinced it has to do with one of my medications. My usual pharmacy was out of my usual brand of Ritalin this month and so I was forced to go elsewhere and acquire pills from a different manufacturer.
“But Knotorious, why would this cause you to have a different experience? Aren’t pharmaceuticals regulated and held to the highest of standards with regard to continuity of synthesis, production and strength?”
Well, sort of. The reality is that any given drug of the same type, per FDA regulations, is allowed to differ in strength and synthesis by as much as 20%. For example, you might have version A of Ritalin, made by manufacturer A, at a strength of 10mg which actually contains 10mg of the active ingredient.
But then one day you are forced to try version B of Ritalin, by manufacturer B, and it may either have as much as 20% less of the active ingredient OR it might have a synthesis (production method) which has a up to 20% deviation relative to the FDA standards. Inversely, you might find that a different drug has up to 20% more active ingredient and/or alteration of synthesis. One can see how 20% differences in each drug might either dramatically improve or worsen a psychiatric, or even physiological, condition.
In my case, the drug that I have received this time around does not appear to be less potent, however, it does appear to have been manufactured via a different synthesis. Ritalin (methylphenidate) is what is known as an NDRI, or norepinephrine and dopamine reuptake inhibitor. It increases concentrations of both catecholamines via prevention of either’s ability to reuptake (reabsorb) into the presynaptic cleft of the brain. In other words, it doesn’t generate those neurotransmitters, it potentiates them.
The Ritalin I received, with its different and inferior production method, resulted in a mixture of the drug that has a much higher concentration of the levorotary salt (which increases concentrations of norepinephrine) versus the dextrorotary salt (which increases dopamine concentrations).
It is well established that norepinephrine and the levorotary salt predominantly influences the PNS (peripheral nervous system), whereas dopamine and the dextrorotatory salt mostly influences the CNS (central nervous system). It is also known that PNS stimulation, when in excess, can lead to restlessness, agitation, tachycardia, and anxiety, etc. Most psychiatric drugs are designed to potentiate effects in the CNS because the effects are significantly more therapeutic and tolerable.
While norepinephrine receptors are important targets for drugs which treat ADHD, it is dopamine which is considered mostly responsible for the paradoxical calming effect of this particular stimulant, a member of the cathinone family.
In summation, I believe that the Ritalin I recently received has been produced differently than the variant I am used to. As a result, I am experiencing unusual anxiety due to believed higher concentrations of the levorotary enantiomer of methylphenidate, resulting in a sub-therapeutic product with an excess of noradrenergic activity.
Thanks for letting me be myself! Now let’s end this message with a "transparent rickroll”…
EDIT: If my f*cking Ritalin was working normally, I'd be too focused on actually accomplishing something instead of writing excruciatingly lengthy messages.
I’ve been having a ton of anxiety lately and I’m convinced it has to do with one of my medications. My usual pharmacy was out of my usual brand of Ritalin this month and so I was forced to go elsewhere and acquire pills from a different manufacturer.
“But Knotorious, why would this cause you to have a different experience? Aren’t pharmaceuticals regulated and held to the highest of standards with regard to continuity of synthesis, production and strength?”
Well, sort of. The reality is that any given drug of the same type, per FDA regulations, is allowed to differ in strength and synthesis by as much as 20%. For example, you might have version A of Ritalin, made by manufacturer A, at a strength of 10mg which actually contains 10mg of the active ingredient.
But then one day you are forced to try version B of Ritalin, by manufacturer B, and it may either have as much as 20% less of the active ingredient OR it might have a synthesis (production method) which has a up to 20% deviation relative to the FDA standards. Inversely, you might find that a different drug has up to 20% more active ingredient and/or alteration of synthesis. One can see how 20% differences in each drug might either dramatically improve or worsen a psychiatric, or even physiological, condition.
In my case, the drug that I have received this time around does not appear to be less potent, however, it does appear to have been manufactured via a different synthesis. Ritalin (methylphenidate) is what is known as an NDRI, or norepinephrine and dopamine reuptake inhibitor. It increases concentrations of both catecholamines via prevention of either’s ability to reuptake (reabsorb) into the presynaptic cleft of the brain. In other words, it doesn’t generate those neurotransmitters, it potentiates them.
The Ritalin I received, with its different and inferior production method, resulted in a mixture of the drug that has a much higher concentration of the levorotary salt (which increases concentrations of norepinephrine) versus the dextrorotary salt (which increases dopamine concentrations).
It is well established that norepinephrine and the levorotary salt predominantly influences the PNS (peripheral nervous system), whereas dopamine and the dextrorotatory salt mostly influences the CNS (central nervous system). It is also known that PNS stimulation, when in excess, can lead to restlessness, agitation, tachycardia, and anxiety, etc. Most psychiatric drugs are designed to potentiate effects in the CNS because the effects are significantly more therapeutic and tolerable.
While norepinephrine receptors are important targets for drugs which treat ADHD, it is dopamine which is considered mostly responsible for the paradoxical calming effect of this particular stimulant, a member of the cathinone family.
In summation, I believe that the Ritalin I recently received has been produced differently than the variant I am used to. As a result, I am experiencing unusual anxiety due to believed higher concentrations of the levorotary enantiomer of methylphenidate, resulting in a sub-therapeutic product with an excess of noradrenergic activity.
Thanks for letting me be myself! Now let’s end this message with a "transparent rickroll”…
EDIT: If my f*cking Ritalin was working normally, I'd be too focused on actually accomplishing something instead of writing excruciatingly lengthy messages.
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Knotorious
That Guy With The Face
Because I keep it scholarly...
Read the highlighted text.
pubmed.ncbi.nlm.nih.gov
Read the highlighted text.
Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic-guided dosing of replacement therapy in haemophilia A? - PubMed
It is not necessary to take potency differences into account when applying PK guidance of FVIII concentrates in haemophilia A patients. However, when the patient is switched to another FVIII batch after PK-guided dosing, trough levels may deviate ±20% from calculations based on label dose.
pubmed.ncbi.nlm.nih.gov
Kaveman
Treehouser
0600 was to early for all that phara talk. My brain hurts now, and I've the whole day ahead of me.
But at least my only prescription is to be set on fire...
But at least my only prescription is to be set on fire...
Treeaddict
Treehouser
Off work today due to approximately 6” of snow. Roads not cleared until later in the day. Dug my parents out again but in 2 sessions as it seems easier to push more often than “shovel” once. I was glad to see one of their younger neighbors clearing my parents sidewalk. I expressed gratitude.
Rigged a sled with a rope to the truck. The sled was about 25’ behind the tailgate. Gave my kids and a few of the neighborhood kids rides at 15mph up and down our street which is petty quiet (nearly dead when it snows). Neighborhood kids had to get their parents permission. Made em fish tail a little too! They loved it.
Rigged a sled with a rope to the truck. The sled was about 25’ behind the tailgate. Gave my kids and a few of the neighborhood kids rides at 15mph up and down our street which is petty quiet (nearly dead when it snows). Neighborhood kids had to get their parents permission. Made em fish tail a little too! They loved it.
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I noticed the streets here had snow for quite awhile the last few days. In recent history, they seemed to clear them lightning fast. Leaving snow was more like when I was a kid. We all used to sled on the good road hills. We also sled offroad, but the road was the best. Get a few cars to pack down the snow, and you'd really fly.
Treeaddict
Treehouser
Yeah, and they haven’t seemed to apply brine as much. I used to know there was a forecast for snow by the brine solution on the roads a day ahead of time.
You probably sled down that large hill across Red Pump opposite of Marywood. There’s a stream under a bridge at its bottom. Can’t remember the road name. Took Honeysuckle Dr to get to it.
Marywood postdated my sledding career. It was actually around here. There's a real good hill at the end of the subdivision you could get a lot of speed on. Getting to that hill was a moderate hill that didn't provide a ton of speed, but you got a lot of ride time. One of the neighbors had a short, but extremely steep hill, and the path went between two trees on a slight bank so you got some air time going between the trees. I guess it was kinda dangerous, but I don't think anyone ever hit the trees.
Man, winter was always the best. A day off school, and play in the snow all day. Well, that, and sitting in front of the fireplace watching cartoons. Life doesn't really get much better than that :^)
Man, winter was always the best. A day off school, and play in the snow all day. Well, that, and sitting in front of the fireplace watching cartoons. Life doesn't really get much better than that :^)
stikine
Treehouser
Just curious, what was the sled of choice for you back then?
stikine
Treehouser
I was hoping you would say the flexible flyer! What a classic. I got my mom's when I was a kid and it was amazing. Unfortunately I don't know where it ended up after all the years.
It's the one thing I want to ride again... just one more time. (Sad moment) ☹️
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Cobleskill
Treehouser
Yes. Progressed to standing up on 2 man tobaggen. Me and a bud could steer and rarely go down. Probably would have liked snow boarding, but too old for that now.
pigwot
M's, Juniper's, Lowen’s, and Inge’s Grandpa
pigwot
M's, Juniper's, Lowen’s, and Inge’s Grandpa
Had to work today. Can you believe that shit?! :^D
Temps were nice, but perhaps a little too warm. Had to stake a house in a grubbed out forest clearing, and there were pockets of what was once standing water, but kind of frozen over and covered in snow. "Kind of frozen" is the key phrase. You couldn't see what was going on under the snow, and I'd sometimes break through into soft mud and water. Also a lot of time on my knees in the snow, so my legs got pretty wet. Wished I had my filson chaps. They're good for mud protection without adding a ton of warmth. Add in the usual headache of dealing with the boss on the gun, and it was a pretty meh day. Could be worse I guess.
Temps were nice, but perhaps a little too warm. Had to stake a house in a grubbed out forest clearing, and there were pockets of what was once standing water, but kind of frozen over and covered in snow. "Kind of frozen" is the key phrase. You couldn't see what was going on under the snow, and I'd sometimes break through into soft mud and water. Also a lot of time on my knees in the snow, so my legs got pretty wet. Wished I had my filson chaps. They're good for mud protection without adding a ton of warmth. Add in the usual headache of dealing with the boss on the gun, and it was a pretty meh day. Could be worse I guess.
davidwyby
Desert Beaver
57 and raining good. can you believe it? Gonna be a muddy world for a few days.
CurSedVoyce
California Hillbilly
Raining here too. Clearing out tomorrow. Promised Levi we would tinker on his car.
Posting here cause it doesn't warrant it's own thread...
I was looking at wesspur's clearance rope section, and they have 5' of ⅝" amsteel blue for $22.56. Can anything be made with that little bit of rope? I was thinking maybe a soft shackle, but you'd be pretty close to using all the 5', no?
I was looking at wesspur's clearance rope section, and they have 5' of ⅝" amsteel blue for $22.56. Can anything be made with that little bit of rope? I was thinking maybe a soft shackle, but you'd be pretty close to using all the 5', no?
Kaveman
Treehouser
Dog leash?
CurSedVoyce
California Hillbilly
Too short for splice unless you might make a soft shackle out of it
Kaveman
Treehouser
5/8ths feels better in the hand when he hits it than most dog leashes. That's why I buy horse leads for big dogs. I've got the pattern second from the right on top lol.
flushcut
TreeHouser
I have two leashes made out of 5/8” Bluewater static. The loops are just whipped together no lock stitching, pretty strong, nice feel in the hand.
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