Lung Cancer: Pathophysiology, Pharmacokinetics, and Treatment

This paper provides a critical analysis of the pathophysiology of lung cancer, pharmacokinetic effect of intravenous chemotherapeutic, mechanism of chemotherapeutic drugs, adverse effects of morphine and management.

Running head : LUNG CANCER
Name of the Student
Name of the University
Author Note

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Introduction:
With the global burden of the disease, lung cancer is highlighted as one the majority
non- communicable disease which increased the morbidity rate. In Australia, lung cancer is the
fifth most common form of cancer which affects a significant number of individuals in Australia.
Each year, approximately 11,500 Australians are diagnosed (O'byrne et al. 2016). Considering
the prevalence of the disease, it more common in men compared to female where smoking is one
of the common contributors to the development of lung cancer (Kubota et al. 2017). The world
health organization suggested that each year 1350000 new cases are reported in the clinical
setting. The most common symptoms of the disease are chest pain, cough, unexpected loss of
appetite, shortness of breath and prevalence of lung infection such as pneumonia and bronchitis
(O'byrne et al. 2016). Every number the number of the new cases are increasing exponentially,
indicating poor prognosis and high prevalence of the disease. The researchers suggested that in
men, the common form of lung cancer is non-small cell lung cancer where epithelial cells of
lungs become affected. This paper will focus on a case study where a 78 years old man, Nigel
was diagnosed with primary stage 4 non-small lung cancer which further caused metastasis to the
liver. He was experiencing pain which further made him uncomfortable. He was administrated
with an active regimen of a combined drug such as Cisplatin and docetaxel using intravenous
infusion every three weeks. He was administrated with morphine to reduce the pain he was
experiencing. This paper will provide critical analysis of the pathophysiology of cancer,
pharmacokinetic effect of intravenous chemotherapeutic, mechanism of chemotherapeutic drugs,
adverse effects of morphine and management.

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Discussion:
Pathophysiology of lung cancer associated with the symptoms:
While lung cancer can be classified into two groups such as small cell lung cancer and
non-small cell lung cancer, the highest prevalence of non-small cell lung cancer is higher in men
compared to women. As discussed by Muller et al. (2016), there are certain risk factors evident
in the lung cancer patients such as smoking, exposure to asbestos, tar and soot, chromium,
arsenic and nickel, genetic factors are the contributor of non-small cell lung cancer. In patients
exhibiting these risk factors are often live with non-small lung cancer where epithelium cell line
of lungs produce tumor and damaged lung tissues (Böttger et al. 2019). The damage of the lung
tissues is manifested as an array of symptoms where shortness of breath and live metastasis are
highlighted, inpatient. Taking in an insight into the situation it can be said that the tumor
produced in the lung cancer narrow the down or airway resulted in lack of adequate oxygen level
in lungs and eventually facilitate the enlargement of the right side of the heart (Böttger et al.
2019). Hence, the patient was experiencing dyspnea or shortness of breath and makes him
uncomfortable.
Considering secondary cancer, the patient was experiencing liver metastasis which
affected his pharmacological interventions. The metastatic tumors of the lungs are the cancers
which are developed at other places when spread from lungs. As discussed by böttger et al.
(2019) in the advance or last stages of lung cancer, the malignant cells break cell to cell
junctions and spread through the blood or lymphatic system. In the current context, since the
lungs are situated close the lungs in the right upper quadrant in stage four metastatic cells
spread through blood or lymphatic system to the liver and damage the tissues of the liver

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(O'byrne et al. 2016). Hence, the patient was suffering from substantial liver metastasis which
resulted in pain in the right upper quadrant.
Impact on the pharmacokinetics of chemotherapeutic drugs:
The case study highlighted the primary stage four non-small lung cancer of patient which
has been spread to the liver, developing liver metastasis. While metastatic cells can affect any
organs, the liver was affected in the case of Nigel which further affects the normal metabolism
process of the body. As discussed by Zhang, et al. (2016) since the liver is the crucial organ
which facilitates the process of metabolism of the pharmacokinetics of drugs have a major
impact when drugs enter the liver. The process by which drug metabolized to active form is
defined as first pass metabolism and the hepatic system is the key player in the successful
accomplishment of drug metabolism. In the current context, the patient was administrated with
chemotherapeutic drugs such as Cisplatin and docetaxel in order to cure cancerous lungs (Kubota
et al. 2017). If these drugs were orally administrated to the patients then these drugs had to pass
through hepatic first metabolism. After oral administration of drugs, by following ADME
principle, every drug is absorbed by the gastrointestinal tract which further travels immediately
to the hepatic system through the portal vein (Sodhi et al. 2017) . In the hepatic system, the
significant amount of drugs is metabolized into an active form of drug which is sufficient for
performing localized action (Muller et al. 2016). Hence, when the drug is metabolized through
the liver, the bioavailability of drugs reduced to 20% to 30 % (O'byrne et al. 2016). However,
considering the secondary liver cancer of patient where the normal function of the liver was
disrupted, the health professionals administrated these two chemotherapeutic drugs using the
intravenous infusion. As discussed by Gazdar et al. (2017), the intravenous infusion process is
undertaken in patient to avoid the first pass metabolism of drugs. In intravenous infusion, the

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drugs were injected directly into the vein of patients which circulated through the blood and
directly show the mechanism of the action on the target organ (George et al. 2015). While the
bioavailability of the drug in oral administration is minimal, the intravenous infusion provides
the highest bioavailability (Kulasinghe et al. 2018). Hence, there will be no impact on the
pharmacokinetics of drugs such as Cisplatin and docetaxel. The drug will directly act on the
lungs through blood circulation.
Role of Cisplatin and docetaxel in curing lung cancer:
As observed in this case study, the patient was suffering from stage four non-small
cell lung cancer which spread throughout the lungs and caused liver metastases. To cure lung
cancer and avoid the first pass metabolism, the patient was administrated with intravenous
infusion of a combined drug such as Cisplatin and docetaxel. Cisplatin is a platinum-based
chemotherapeutic drug used for treating an array of cancer such as lymphomas, sarcomas and
germ cell tumor (Goldstraw et al. 2016). As discussed by Borghaei et al. (2015) the patients with
non-small cell lung cancer are often administrated with Cisplatin. Cisplatin is an antineoplastic
in the family of alkylating agent and it shows three different mechanisms to inhibit the growth of
cancer. The first mechanism is incorporating alkyl groups to DNA which further fragment
DNA by repair enzyme when the enzyme attempt to repair the base which further leads to
miscoding of the DNA and disrupts downstream processes(Goldstraw et al. 2016) . The second
mechanism is inducing the formation of cross-linking in the guanine bases which further hinder
the process of cell division and transcription. The third mechanism is the mechanism of
impairing of nucleotide (Wu et al. 2015). However, .in advance stage of cancer, this drug is
failed to inhibit the growth of cancerous cells and combined with another drug. In order to
enhance the activity of Cisplatin , docetaxel is used (Goldstraw et al. 2016).. The researchers

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reported that this combination is an active regimen to treat severe stages of the non- small lung
cancer. The researcher suggested that this drug shows synergistic effects for cisplatin to reduce
the growth of cancerous cells (Senan et al. 2016). The docetaxal binds to the tubulin reversibly
in 1: 1 manner and induced assembly of microtubule from the tubulin. This phenomenon further
facilitates the depolarization process followed by interrupting the interphase process of the cell
cycle. The response rate, in this case, is 30 to 50% for the patients who are suffering from small
lung cancer (Goldstraw et al. 2016).
The comparison between nivolumab and Cisplatin and docetaxel:
Taking an insight into the situation, in order to reduce the symptoms of the lung cancer
the patient was administrated with a venous infusion of a combined drug such as Cisplatin and
docetaxel. While cisplatin works in the DNA level and docetaxel works in chromosome level.
However, drawing a comparison between nivolumab and Cisplatin and docetaxel it can be said
that while the target site of this combination of drugs is a molecular system, nivolumab target
immune system (Brahmer et al. 2017). Cisplatin is a platinum-based chemotherapeutic drug
which disrupts three different mechanisms to inhibit the growth of cancer. Three mechanisms
are such as incorporating alkyl groups to DNA which further leads to miscoding of the DNA,
disrupting the process of cell division by the formation of cross-linking and of impairing of
nucleotide which leads to mutation (Thatcher et al. 2015). On the other hand, docetaxel is also
anti-neoplastin given to the patients after failure of prior chemotherapy. As discussed above that
the drug Binds to the tubulin reversibly in 1: 1 manner and induces the assembly of microtubule
from the tubulin, disrupting the interphase process of the cell cycle (Wu et al. 2015).
However, compared to these two antineoplastic drugs, nivolumab is human IgG4
antibody which targets the immune checkpoint of program cell death. The drug was grafted

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onto the kappa and igG4 FC region with a mutation S228P. The researchers suggested that
nivolumab blocks the immune checkpoint PD-1 which is cd28 T cell receptor. When chronic
antigen stimulation was observed in the body, this receptor is highly up-regulated in cells (Garon
et al. 2015). The tumor cells express both of PD1 ligands and produce inhibitory signals in t
cells followed by inhibiting the immune responses. This drug retrieves the immune response of t
cells which will inhibit the growth of tumor cells. While the response rate of combined drug
discussed above is 30 to 50% the response rate of nivolumab is 45 to 70% (Jänne et al. 2015).
This research further indicates that nivolumab can be a better replacement therapy for the
combined drug with better efficacy.
The reason behind the side effect of chemotherapeutic agent:
In the case study, it was observed that he was administrated with Cisplatin, docetaxel to
manage the symptoms of lung cancers in the intravenous pathway. However, researchers
documented that despite having the potential of curing non-small lung cancer, these
chemotherapeutic drugs such as Cisplatin, docetaxel, and nivolumab show an array of side
effects such as nausea and vomiting( Vendetti et al. 2015) . Chemoreceptors triggered zone is
the most crucial player in inducing the sensation of nausea and vomiting. The intravenous
method was avoided by the health professionals in order to avoid the first metabolism
considering secondary liver cancer and achieve the highest concentration of the drug (Thatcher
et al. 2015). However, since the drugs were given intravenously, the drugs circulated in the
blood to show mechanism on the lungs. While through systematic circulation, the blood
containing a high concentration of chemotherapeutic drugs enters into the gastrointestinal tract
and it further sent a signal to the brain (Nascimento et al. 2017)). This signal is sent by the
chemoreceptors which are present in the intestinal wall and the information further has been

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forwarded to vomiting center, chemoreceptors triggered zone. This chemoreceptor triggered zone
is situated in the medulla of the brain and takes part in other activities (Sun et al. 2016). This
zone has a specific barrier which is used as a receptor for detecting molecules which can
threaten the normal function of the body. This defensive zone generally detects the blood
containing toxins, chemotherapeutic agents, microbes and copper sulfate (Sun et al. 2016).
When chemotherapeutic drugs are detected in blood at high concentration, main stimulus factors
which stimulate chemoreceptor trigger zone are dopamine and serotonin. After activation of the
zone, the zone, in turn, activated integrated emesis center which is the key player behind the
feeling of nausea and vomit (Li et al. 2016). The integrated emesis center is activated by the
release of another neurotransmitter such as acetylcholine. The release of the neurotransmitter
simultaneously induces the vomiting reflex by afferent pathway. Therefore, the patient when
administrated with chemotherapeutic drugs such as Cisplatin and docetaxel even after
administrated using the intravenous technique, he was feeling nauseous. In order to manage
nausea and vomiting, Nigel was administrated with Ondansetron which is serotonin type 3
receptor and acts as an antagonist for this receptor (Thatcher et al. 2015).
Adverse reaction of morphine:
In order to reduce the pain and discomfort of the patient, he was administrated with
morphine which is a conventional drug for reducing pain. As discussed by morphine is
analgesic and psychoactive drug which targets the central nervous system for reducing the
feeling of pain and discomfort that he was feeling at the right upper quadrant. In the current
context, the patient was experiencing shortness of breath because of morphine. The intravenous
morphine when administrated in patient, it causes respiratory depression and systematic dilations
which further induce high blood pressure. In order to manage the feeling of shortness of breath

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and side effects of morphine, he was administrated with Naloxone that manages naloxone. The
researchers suggested that naloxone directly works on the central nervous system to reduce high
blood pressure. It is an antidote which is acts as a competitive antagonist of the receptor which
facilitates high blood pressure. In order to reduce the blood pressure, he can be supported with
additional interventions such as proper nutritional diet which will be devoid of NaCl and
vegetables that will stabilize normal blood pressure.
Conclusion:
Thus it can be concluded that lung cancer is highlighted as one the majority non-
communicable disease which increased the morbidity rate. While lung cancer can be classified
into two groups such as small cell lung cancer and non-small cell lung cancer , the highest
prevalence of non-small cell lung cancer is higher in men compared to women. The risk factors
for lung cancer include environmental factors such as exposure to radon, asbestos and , air
pollution and certain dietary . This paper will focus on a case study where a 78 years old man,
Nigel was diagnosed with primary stage 4 nonsmall lung cancer which further caused metastasis
to the liver. He was experiencing pain which further made him uncomfortable. He was
administrated with an active regimen of a combined drug such as Cisplatin and docetaxel using
intravenous infusion every three weeks. Considering the pathophysiology, the tumor produced
in the lung cancer narrow the down or airway resulted in lack of adequate oxygen level in lungs
which causes shortness of breath and since liver present adjacent to the lungs, it causes
metastasis. The pharmacokinetics of drugs given to him would not be affected since he was
administrated with intravenous drug where the drugs directly would work on the lungs. The two
chemotherapeutic drugs such as Cisplatin and docetaxel where Cisplatin inhibits DNA
synthesis, docetaxel works on the chromosome. Compared to these two drugs, nivolumab target

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the immune system for the management of cancer. However, he was feeling nauseous which can
be managed through Ondansetron. He was also administrated with morphine which showed side
effects of high blood pressure. It can be managed through dietary intervention and naloxone.

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