Impact of Secondary Liver Cancer on Pharmacokinetics of Chemotherapy Medications

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Consider Smith’s secondary liver cancer – how might this impact on the pharmacokinetics
of his chemotherapy medications? Ensure that you include appropriate consideration of
hepatic first-pass metabolism in your answer.
Pharmacokinetics is the movement of medicines into, through and out of the body
(Versypt, Harrell and McPeak 2017). The existence of a malignancy alters several parameters in
the body, and therefore, the pharmacokinetics of anti-cancer drugs cannot be extrapolated from
healthy persons to people with cancer. Pharmacokinetic drug-drug interactions are because of
changes in absorption, distribution, metabolism along with the elimination of medications
(Versypt, Harrell and McPeak 2017).
Absorption of chemotherapy medications and its distribution in the body might be altered
by advanced liver cancer resulting in abnormal bioavailability. The decreased plasma protein
binding also affects penetration of medications into tissues and drug distribution. As a result of
advanced liver cancer, bile acid is reduced in the intestines which may impair the absorption of
chemotherapy medications. Furthermore, protein binding of medications might be affected by
increases in the bilirubin along with bile acids in plasma concentrations hence impacting
distribution of drugs along with metabolism (Sane and Sinz 2017).
Medicine metabolism has the highest effect on clearance for most medicines, and it is
thus probable to significantly affect a person's beneficial along with adverse reaction at a
prescribed dosage. The lung cancer spread to the liver resulting to secondary liver cancer, and
this impact the pharmacokinetics of chemotherapy in that when administered the cancer cells
develop drug resistance through changes in drug transportation resulting in decreased
intracellular drug accumulation.

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In secondary liver cancer, reduction in blood flow in the organ along with diversion of
blood via collateral varices declines clearance of high-clearance medications (Almazroo, Miah
and Venkataramanan 2017). In liver metastasis, there is capillarization of the sinusoid, that is, the
sinusoidal endothelial cells which line the hepatic microcirculation mislay their fenestrae and
create a basement membrane. Capillarization generates a barrier to diffusion of oxygen, which
results in a substantial decrease in hepatic adenosine triphosphate along with oxidative
metabolism.
Drug metabolism is not globally reduced in liver metastasis, but the metabolism of
chosen medications may be markedly affected (Almazroo et al., 2017). Serum albumin may
reduce, which will change the disposition of medications which are highly bound to albumin.
Cationic chemotherapy medications might be preferentially bound to α1-acid glycoprotein,
which is always increased in cancer people rather than to albumin. Extensive replacement of
liver tissue may result in a decline in metabolic capacity. Bile flow disruption by malignancy
invasion of intrahepatic bile ductules or via extrahepatic biliary obstruction can reduce the
elimination of medications which are primarily excreted into bile (Almazroo et al., 2017).
Describe how his chemotherapy medications can be useful in treating his lung cancer.
Anti-cancer medicines can only be useful if they can kill the tumor cells and cease them
from replicating. Lung cancer is the main source of mortalities due to tumors and around 75
percent of individuals are untreatable at recognition (de Castria, da Silva, Gois and Riera 2013).
The common type of lung being non-small cell is around 90 percent of all cases of lung tumor.
For most of the individuals, chemotherapy is a better therapy choice and it is affiliated with
prolonged endurance along with an exclusive life. Nonetheless, therapeutics for persons with
progressive non-small cell lung cancer is reassuring in the sense that it gives relaxation from

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discomfort along with other upsetting manifestations (de Castria et al., 2013). Medications which
include cisplatin plus another drug of which Mr. Smith uses docetaxel are the most broadly
utilized medication combinations although they can be affiliated with inadmissible noxiousness.
Therefore, it would be sensible to have a therapy which is effectual but with less contamination
(de Castria et al., 2013).
Docetaxel is among the drugs that are called mitotic inhibitors. It is categorized as a
taxane, a plant alkaloid, and an anti-microtubule agent (Ravichandra, Ramesh, Swamy,
Purushotham and Rudramurthy 2018). It is a cytotoxic anti-microtubule agent which attaches to
the β-tubulin subunit of microtubulin leading to preserving microtubules and impeding
depolymerization that results in hindrance of microtubule dynamics along with cell cycle arrest
and finally apoptotic cell death (He, Li, Wu and Yang 2015). Microtubules are part of the cell’s
apparatus for dividing and multiplying itself (Heuer et al., 2017). Impeding these structures
ultimately leads to the death of cells and stops cancer cells from replicating. Moreover, they
prevent the body from producing the proteins which cancer cells require to develop hence
treating cancer effectively (Szczyrek et al., 2017).
Cisplatin is categorized as an alkylating agent, and alkylating agents are most operational
in the resting stage of the cell. It offers a correct instance of how minor alterations in molecular
structure can result in extreme contrasts in biological action (Alvarado-Luna and Morales-
Espinosa 2016). Within a cell, cisplatin mislays its two chloride ions, generating a sensitive
species which form a connection with DNA bases (Messori and Merlino 2016). Due to the comic
geometry of the relationships, the cisplatin quickly creates crosslinks amid bases. Here, Cisplatin
interferes with the replication of DNA, or DNA repair mechanism leading to DNA distortion and
consequently actuating apoptosis in cancer cells.