CNS toxicity

Question 1

describe the mechanism of ammonia toxicity and antidotes

Answer 1

Ammonia
Reaches astrocytes in CNS
ammonia + glutamate = glutamine (enzyme: glutamine synthetase.)
Glutamine is osmotically active which leads to astrocyte swelling and cerebral oedema.
Once inside the astrocyte it is converted back to ammonia in mitochondria.
Ammonia activates NMDA receptors leading to excitotoxicity and neuronal cell death.
Can lead to neuropsychiatric disorders, alzheimer’s, cerebral oedema, mental retardation and hepatic encephalopathy (because liver generates excess ammonia by failure of conversion into urea)
Antidotes: glutamine synthetase inhibitors, NMDA antagonists, Lactulose (acidifies gut to form NH4 which is non transportable)