Does anyone have a good physiological explanation why increased pressure increases the effects of some medications? I've got some students with a medical background and they want more detail. Thanks!
diving with meds
- Thread starter whitedragon13
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Nope, I don't have a physiological explanation, though DAN might.whitedragon13:
I do however have a personal account. I take a medication for a back injury that has a potential side effect of causing nausea and vomiting, among others. At sea level or above, I don't have any side effects at all. On two seperate occasions I took 1/2 the normal dose before I did some shallow (one to ~60', one to ~40') dives. Both times I became extremely nauseous under water. Upon surfacing from the 60' dive, I vomited several times and had to sit for a good 20 minutes before I could hike back from the exit point.
I no longer take the medication when I'm going to go diving.....
OP
I'm theorising that it's because some meds react with oxygen and since you inhale more dense air, the meds react faster, but that's a total guess.
pharmguy
Contributor
There are 2 key effects I would consider likely/plausible:
1. Some effects are potentially gas-related (i.e. partial pressure) as whitedragon13 postulated.
Changing the partial pressure around a membrane can change the permeability of molecules (drugs) moving across a membrane. Think nitrous gas in a dentist's office.
Patrial pressure can also change physiological pH (especially in the blood where CO2 is is buffered by a complex system). Drug/molecule ionization is dependent upon the relative pH - change the pH and you change the ionization. Drug binding ability is dependent upon ionization - drugs that are more ionized may bind more readily to certain receptors causing a greater reaction and vice versa.
2. Some effects can be explained by physical pressure. The body is a semi-solid fluid. Molecules are not rigid stick-and-ball constructions but instead have movement. Drug binding sites are often in crevices or pockets and are highly dependent upon 3D structure. If pressure can change the 3D structure of a large molecule then the binding site can be changed to the extent that receptor of the molecule is unable or less able to interact with the "drug". An experiement was done whereby an apple (or a steak?) was subjected to very high pressure (I think 500 atm equivalent). Bacteria on the apple were found to have their ribosomes (essential proteins that are needed for numerous functions) separated - ribosome are 2 proteins that fit together (change the fit and you change the association). By using pressure alone the scientists found a way to preserve an apple by killing all the bacteria (without ribosomes bacteria cannot continue to live).
Now the amount of pressure is extreme but it shows that a change in pressure can affect the function of large proteins (which happen to be a major site for drug action).
Sorry for the long post.
1. Some effects are potentially gas-related (i.e. partial pressure) as whitedragon13 postulated.
Changing the partial pressure around a membrane can change the permeability of molecules (drugs) moving across a membrane. Think nitrous gas in a dentist's office.
Patrial pressure can also change physiological pH (especially in the blood where CO2 is is buffered by a complex system). Drug/molecule ionization is dependent upon the relative pH - change the pH and you change the ionization. Drug binding ability is dependent upon ionization - drugs that are more ionized may bind more readily to certain receptors causing a greater reaction and vice versa.
2. Some effects can be explained by physical pressure. The body is a semi-solid fluid. Molecules are not rigid stick-and-ball constructions but instead have movement. Drug binding sites are often in crevices or pockets and are highly dependent upon 3D structure. If pressure can change the 3D structure of a large molecule then the binding site can be changed to the extent that receptor of the molecule is unable or less able to interact with the "drug". An experiement was done whereby an apple (or a steak?) was subjected to very high pressure (I think 500 atm equivalent). Bacteria on the apple were found to have their ribosomes (essential proteins that are needed for numerous functions) separated - ribosome are 2 proteins that fit together (change the fit and you change the association). By using pressure alone the scientists found a way to preserve an apple by killing all the bacteria (without ribosomes bacteria cannot continue to live).
Now the amount of pressure is extreme but it shows that a change in pressure can affect the function of large proteins (which happen to be a major site for drug action).
Sorry for the long post.
whitedragon13:
What medications are you referring? For the most part, pressure doesn't affect the medication, rather it affects the physiological condition for which the medication is being taken, or actually, increases the risk factors associated with those conditions. There is no general explanation. Each medication has to be considered individually.
OP
Divaholics:
Divaholics, I didn't say the pressure affects the medication, I said the pressure increases the effects of the medication.
I don't think, as you say, that it affects the physiological condition itself. It's the medication that is of concern-drowsiness is enhanced etc. I think pharmguy had a pretty good guess.
whitedragon13:
My bad. I worded my response wrong. I did mean pressure increases the effects of the medication. I stand by my response, though. I haven't been able to find any information that states medication effects are increased by pressure. If you're taking medication that causes drowsiness, then you shouldn't be diving after taking that medication. There are no studies that indicate medication effects are increased when diving. All the caveats are based on the general side effects of the medication itself. A general rule to follow is if you shouldn't be driving on the medication, you shouldn't be diving either.
The following is an excerpt from an article on the DAN website:
"The interaction between the physiological effects of diving and the pharmacological effects of medications is usually an educated, yet unproven, assumption. Each situation requires individual evaluation: no general rule applies to all. Currently, there are no specific studies that indicate the safety or danger associated with drugs and diving."
The full article can be found at http://www.diversalertnetwork.org/medical/articles/article.asp?articleid=39
OP
cool, thanks for the link.
I'm not trying to take meds and dive or even suggesting it, I'm just trying to figure out why increased pressure increases the effects. Is the converse true? That if you're taking certain meds in space, you have to take larger doses?
I'm not trying to take meds and dive or even suggesting it, I'm just trying to figure out why increased pressure increases the effects. Is the converse true? That if you're taking certain meds in space, you have to take larger doses?
pharmguy
Contributor
whitedragon13:
As Divaholics said it depends on the medication and the effect.
In space I believe NASA has fine-tuned the atmosphere such that the partial pressures are constant. There is no change in physiological pH because in space the gases are kept constant (think rebreather). The astronauts will not likely experience any deviance from what would be expected on Earth (but this depends on what the medication is/does).
As far as pressure goes - increased pressure can alter binding sites but decreased pressure (i.e. a vacuum) would not have any real effect as the proteins will move with the same or more freedom and so the binding sites are not inihibited.
OP
Prior to space-walk, the astronauts have to "decompress" by pre-breathing O2. The suits are much lower pressure than the spaceship itself. One of the major initiatives is build higher pressure suits/ships/stations without adding much weight.
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