Exam (elaborations)
PHM 450 exam 2 Questions With Complete Solutions
- Course
- PHM 450
- Institution
- Florida State University
PHM 450 exam 2 Questions With Complete Solutions
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PHM 450 exam 2 Questions With Complete SolutionsAcetaminophen Correct Answers Acetaminophen (APAP or
paracetamol) is a commonly used analgesic (pain relieving) and
antipyretic (fever reducing) drug sold under a number of brand
names, including Tylenol. At recommended doses,
acetaminophen is considered to be generally safe and well
tolerated. Acute overdose (>150 mg/kg/day) causes rapid
centrilobular hepatic necrosis, making acetaminophen overdose
the leading cause of drug-induced liver failure in the United
States.
Acetaminophen Interactions Correct Answers Acetaminophen
can also be toxic as a result of the body's response to other
medications. A classic example is consumption of ethanol,
which induces hepatic levels of CYP2E1. Co-administration of
acetaminophen under such conditions can lead to elevated
production of the cytotoxic NAPQI; thus it is often
recommended that other analgesics be used by alcoholics or for
hangovers. Similar induction of CYP2E1 is observed with the
anti-tuberculosis medicine isoniazid, and is thought to contribute
to the increased risk of hepatotoxicity when the two medications
are co-administered.
Acetaminophen is metabolized by the following Phase I
enzyme: A) Glucuronyl transferase B) CYP2E1 C) CYP3A4 D)
None of the above Correct Answers b
Acetaminophen Species Specificity Correct Answers
Acetaminophen is a good example of species differences in
toxicity. Cats are extremely sensitive to acetaminophen toxicity,
,due to a lack of glucuronyl transferase enzyme required for
acetaminophen detoxification through glucuronidation. In
contrast, rats are relatively insensitive to acetaminophen-induced
liver damage, and thus resemble the majority of the human
population in terms of acetaminophen sensitivity. Mice and
hamsters, on the other hand, are relatively sensitive to
acetaminophen-induced hepatotoxicity, and metabolize
acetaminophen at a similar rate to a highly sensitive
subpopulation of humans who exhibit high sensitivity in an
idiosyncratic manner.
Acinar Zones Correct Answers Zone 1 is the periportal region
immediately surrounding the portal tract.
Cells in this region receive first contact with sinusoidal blood
that is rich in oxygen and nutrients, as well as first contact with
compounds that will undergo hepatic metabolism.
Hepatocytes in Zone 1 contain the highest level of several
metabolic enzymes (such as glutathione and alcohol
dehydrogenase), and play a role in fatty acid oxidation,
gluconeogenesis and ammonia detoxification.
Outside of Zone 1 is Zone 2 (the mid-zonal region) and then
Zone 3 (the centrilobular region).
Cells in Zone 3 are exposed to much lower levels of oxygen,
bile acids and nutrients than cells in Zone 1 or Zone 2, and
contain the highest concentration of cytochrome P450 enzymes
(CYP450) in the body
Activation of Sinusoidal Cells Correct Answers Sinusoids are
the channels that run between hepatocytes that carry blood
through the liver. In addition to the hepatocytes that line the
sinusoids, there are cells called Kupffer cells, which are a
, special kind of macrophage that reside in the liver. Macrophages
are cells that scavenge particles by engulfing the particles and
destroying them internally. The sinusoids also contain Ito cells,
which store fat, synthesize collagen, and store Vitamin A.
Several lines of evidence indicate that activation of sinusoidal
Kupffer and Ito cells can be a primary or secondary factor in
toxicant-induced liver injury: 1) Kupffer and stellate cells often
change their morphology or shape into an activated form after
exposure to hepatotoxicants 2) Pre-activation of Kupffer cells
before exposure to a hepatotoxicant will often increase the
severity of the liver damage 3) Activated Kupffer cells secrete
significant amounts of soluble cytokines, including reactive
oxygen species, that are known to cause cellular damage, and 4)
Acute and chronic exposure to alcohol directly or indirectly
affects sinusoidal cells
Acute Renal Failure Correct Answers Refers to a sudden and
usually reversible loss of renal function, which develops over a
period of days or weeks. >50% loss of GFR over period of hours
to days ARF is characterized by an abrupt decline in glomerular
filtration rate (GFR) with resulting azotemia (elevated levels of
nitrogencontaining compounds, such as urea and creatinine, in
the blood).
Aflatoxin Correct Answers Naturally occurring mycotoxin
(toxin produced by fungi) produced by Aspergillus (mold on
foodstuffs) Causes DNA damage by forming a reactive epoxide
intermediate after bioactivation by CYP450 - epoxide
intermediate covalently binds to guanine Targets p53 gene As
mutations accumulate, increased risk of developing into
cancerous cells Human hepatocellular carcinoma
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