Toxic gases and metabolic poisons Flashcards
carbon monoxide mechanism, endogenous role, biomarker, and treatment
CO binds 220x tightly than O2 to the iron in haemoglobin. also binds to components of the mitochondria respiratory chain. leads to oxygen radical production, oxidative stress, lipid peroxidation, and inflammatory casacades (effecting CNS).
Biomarker is seen as high lactate in the blood.
Treated by hyperbaric oxygen.
CO also has a cytoprotective role through the stimulation of mitochondrial biogenesis. CO is produced endogenously by haemoxygenase.
cyanide sources
they are nitriles. also can be metabolised into cyanates and thiocyanates (seen in small amounts endogenously).
cyanide is regularly created as a byproduct of combustion (smoking) and is found bound to sugars in some food.
cyanide can also be released from sodium nitroprusside metabolically or through its decomposition
Cyanide is also seen to be produced endogenously in small amounts by myeloperoxidase, but its function is unknown
cyanide mechanism
inhalation of hydrogen cyanide or oral sodium cyanide and cyanogenic glycosides.
They inhibit cytochrome oxidase enzyme, the terminal oxidase of the mitochondrial respiratory chain. causes NADH accumulation and ceasation of ATP production.
cyanide treatments
Cobalt edetate to chelate cyanide
hydroxycobalamin (hydroxy-vit B12)
amyl nitrite converts haemoglobin to methemoglobin. methemoglobin can then bind to cyanide, and consequently sodium thiosulfate can react with cyanomethemoglobin (catalysed by rhodenase) to produce the less toxic sodium thiocyanate.
hydrogen sulphide mechanism and treatments
produced by decay processes. also produced endogenously by cystathionine-beta synthase and cystathionine gamma lyase. Also found in small amounts in durian, but is seen to be beneficial to health
It inhibits cytochrome oxidase (same as cyanide) while also being a potassium channel opener and an inhibitor of PDE5.
amyl or sodium nitrite convert haemoglobin to met-haemoglobin which then binds to H2S. the nitrite may also displace the H2S from cytochrome oxidase.
Hyperbaric oxygen, cobinamid (hydroxycobalamin precursor) and vasopressor agents (like NA) can also be used as treatments
mustard gas mechanisms, treatment and alternative use
it is highly lipophilic and is quickly absorbed through the skin or mucous, causing itching, blistering, chemical burns, pulmonary oedema, and even death.
It is highly reactive, alkylating DNA.
NAC and diethylnetriamine (deactivates mustard gas) are used to treat.
nitrogen mustards have also been used as early chemotherapeutics. E.g., Mustine
Lewisite mechanisms, treatment
a blistering warfare gas that causes respiratory distress, stinging, burning and liver necrosis.
BAL - british anti-lewisite (dimercaprol) was developed as a treatment, but has also been found to treat heavy metal poisonings. It was made to bind to the arsenic atom in lewisite.
Phosgene mechanisms
causes choking, oedema and is a possible carcinogen.
it is highly reactive with amines, -OH, and -SH.
methylisocyanate effects and example
Bhopal disaster
Causes coughing, pulmonary oedema, and even death
it is highly reactive
Radon mechanism
a leading cause of lung cancer
it is a radioactive gas, with the 222 isotope being of concern.
it is an alpha particle emitter, that causes oxidative stress, DNA strand breaks, and carcinogenesis.
sodium azide mechanism
an explosive gas used in air bags.
an inhibitor of cytochrome oxidase and also a strong stimulator of cGMP generation. This causes low blood pressure - collapse and even death
CS gas mechanism
used in riot control.
causes coughing and pulmonary damage. Activates TRPA-1 causing pain.
while “safe”, deaths have occurred following exposure
