The cranium and its constituents (blood, CSF, and brain tissue) create a state of volume equilibrium, such that any increase in volume of one of the cranial constituents must be compensated by a decrease in volume of another. *This concept only applies to adults, as the presence of fontanelles and open suture lines in infants that have not yet fused means there is potential for a change in size and intracranial volume. The principal buffers for increased volumes include CSF and, to a lesser extent, blood volume. These buffers respond to increases in volume of the remaining intracranial constituents. For example, an increase in lesion volume (e.g., epidural hematoma) will be compensated by the downward displacement of CSF and venous blood.The Monro–Kellie hypothesis is named after Edinburgh doctors Alexander Monro and George Kellie. Diagnosis
The most definitive way of measuring the intracranial pressure is with transducers placed within the brain. A catheter can be surgically inserted into one of the brains lateral ventricles and can be used to drain CSF (cerebrospinal fluid) in order to decrease ICPs. This type of drain is known as an external ventricular drain (EVD). This is rarely required outside brain injury and brain surgery settings.In situations when only small amounts of CSF are to be drained to reduce ICPs (e.g. in IIH), drainage of CSF via lumbar puncture can be used as a treatment. Non-invasive measurement of intracranial pressure is being studied. Treatment
The treatment for ICP depends on the cause.
Interactions
Only in vitro interaction studies are available. In these, trifluridine used the concentrative nucleoside transporter 1 (CNT1) and equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2), and tipiracil was transported by the solute carrier proteins SLC22A2 and SLC47A1. Drugs that interact with these transporters could influence blood plasma concentrations of trifluridine and tipiracil. Trifluridine, being a thymidine phosphorylase inhibitor, could also interact with substrates of this enzyme such as zidovudine. Pharmacology
Mechanism of action
The drug consists of the cytotoxin trifluridine and the thymidine phosphorylase inhibitor (TPI) tipiracil. Trifluridine is incorporated into DNA during DNA synthesis and inhibits tumor cell growth. Trifluridine (TFT) is incorporated into DNA by phosphorylation by thymidylate kinase (TK) to TF-TMP;  TF-TMP then covalently binds to tyrosine 146 of the active site of thymidylate synthase (TS) inhibiting the enzymes activity. TS is vital to the synthesis of DNA because it is an enzyme involved in the synthesis of the deoxynucleotide, thymidine triphosphate (dTTP). Inhibition of TS depletes the cell of dTTP and causes accumulation of deoxyuridine monophosphate (dUMP), which increases the likelihood that uracil gets misincorporated into the DNA. Also, subsequent phosphorylations of TF-TMP cause an increased level of TF-TTP within the cell, which results in it being incorporated into DNA. Even though the exact mechanism of how TFT causes DNA damage is not completely understood, it is hypothesized that the incorporation TF-TTP in DNA leads to DNA strand break formation.Tipiracil prevents the degradation of trifluridine via thymidine phosphorylase (TP) when taken orally and also has antiangiogenic properties.