Pdohlen
Member
- Joined
- Jul 27, 2018
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- 59
What do you all think of this article?
Tox and Hound - Unconscious Uncoupling - Managing pH in Salicylate Overdoses
From the article you get the impresiion that overdosing is somewhat common.
The author describes the uncoupling from aspirin as a depletion of atp, and thus a needed upregulating of metabolism in order to restore balance. It seems to me that this could be a dangerous game of balancing?
I would be grateful if someone could help with an explanation to why and at what doses this could be a problem.
Sodium bicarbonate to the rescue?
Tox and Hound - Unconscious Uncoupling - Managing pH in Salicylate Overdoses
From the article you get the impresiion that overdosing is somewhat common.
"So, what do uncouplers do? They uncouple electron flow from ATP formation. Salicylate is a great example of an uncoupler. It works by grabbing protons and shuttling them back across the inner mitochondrial membrane. It can also open up pores in the membrane but the effect is the same, it shorts out the battery. This causes less ATP formation. Now the body doesn’t take kindly to having less ATP. In response, it revs up the engine sending more and more electrons through the system. This results in big increases in metabolism, glycolysis, the TCA cycle, and all those processes that feed into this. So, what happens clinically when you rev up a system without producing more work? You get heat. This is why patients who overdose on uncouplers can get profoundly hyperthermic.5 This is akin to what happens if you sit in your car and floor the gas while the engine is in neutral. Lots of energy is consumed, but no work is produced – the engine overheats. Clinically this is also one of the ways that aspirin contributes to death. The lack of ATP targets the brain and the heart (they are so needy) causing the famous life-threatening dyad of a really bad aspirin overdose – cerebral and pulmonary edema."
The author describes the uncoupling from aspirin as a depletion of atp, and thus a needed upregulating of metabolism in order to restore balance. It seems to me that this could be a dangerous game of balancing?
I would be grateful if someone could help with an explanation to why and at what doses this could be a problem.
"
- At high concentrations salicylate uncouples oxidative phosphorylation
- Uncoupling decreases ATP formation
- ATP consumption > ATP production
- ATP imbalance causes hypermetabolism and metabolic acidosis
- Hypermetabolism stimulates ventilation
- Metabolic acidosis is balanced by respiratory alkalosis
- The patient is sedated and paralyzed, stops ventilating
- Acidosis worsens, pH goes down
- Salicylate rapidly moves into the brain and heart
- You fill out another death report "
Sodium bicarbonate to the rescue?