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BMS291 – Pathophysiology and Pharmacology 1

code: 201815

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1: Pharmacology Report Part B

By: Joshua

no: 11630807

Lecturer: Dr Natalia Bilton

count: 1493

submitted: 06/10/2017






Part B Atorvastatin Questions (each question is worth 5

Read the definition section of this source:!po=21.5909 and look up any words
you do not recognize, until you think you understand the meaning of this text.

Cover, or hide the text and write down the
important details in this section of text in your own words, as if you were
explaining it to a classmate.

Cholesterol, triglycerides, and
high-density lipoproteins are important parts of the lipid percentage in the human
body. Cholesterol is essential for the normal function of the body and is a
fundamental element of their cell membranes. It also stores critical substances
need to produce hormones and bile acids. Triglycerides are an ester (a chemical compound derived from an acid with an
alkoxy part) derived from glycerol (The main backbone of lipids) and it makes
up the main parts of the body fat in humans.


and triglycerides, being nonpolar lipid substances (insoluble in water), need
to be transported in the plasma associated with various lipoprotein particles. The
levels of plasma lipids in the blood have a bell-shaped distribution in the
general population.


After you have finished writing, check your
writing against the original and ask yourself the following question:


Have I accurately presented this information
using my writing style?

To an extent, I Have presented the main information from the
definition but have lost most of the detail. Only the first paragraph has retained
most of its information though being subject to simplification and the rest I
could only really remember the first line. After reading it a couple of times
and then writing, I realised how poor my memory is.


Have I simply changed words around in the
original sentences?

Perhaps in the last sentence yes, and in some parts I remembered
most of the sentence and failed to simplify because it was difficult to do so.



2.     Read the Technique section of this source!po=21.5909 and fill in the blanks in this statement using the words in the
word bank. Include this statement (with the blanks filled in of course!) in
your word doc that contains the rest of your assessment.


“Cholesterol is measured by taking
a sample of a person’s Blood. This
sample should be taken after a period of Fasting, because it takes 12 hours for Chylomicrons to be cleared from the person’s circulation. The samples are
analysed at clinical laboratories and
compared to Reference values. ”
Word bank: fasting, clinical, chylomicrons, reference, blood


3.        Read the Basic Science – Endogenous Pathway section of this source!po=21.5909 and using the paraphrasing technique answer the following


What does the liver synthesise?

The liver synthesises triglycerides by using the
substrates free fatty acids and carbohydrates.

What are VLDL particles and what do they do?

Very-low-density lipoprotein
particles (VLDL), is a type of lipoprotein made by the liver and is one of the five major groups of lipoproteins. It
allows fats and cholesterol to move within the
water-based solution (due to it being similar to extracellular water) of the
bloodstream (Cox RA, 1990).

How are LDL particles created?

LDL particles are created when VLDL particles are stripped of
triacylglycerol making them denser. These particles are remodelled in the liver
and converted into LDL (Cox RA, 1990).

What is the function of LDL particles?

LDL’s function is to deliver cholesterol to cells, where it is
used in membranes, or for the synthesis of steroid hormones.


 Read the
Treatment Guidelines and HMG-CoA Reductase inhibitors section on pages 791-792
of the prescribed textbook and answer the following
questions in your own words.

Lipid-lowering drugs are prescribed to patients
only after which interventions are tired first? 

Before Lipid-lowering drugs are prescribed to patients,
Interventions such has aerobic exercise and dieting are tried due to the side
effects of lipid-lowering drugs.


Describe the mechanism of action of

Atorvastatin works by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A
(HMG-CoA) reductase, an enzyme found in liver tissue
that plays a key role in production of cholesterol in the body (Becker ML,

What is the function of the enzyme HMG-CoA Reductase?

This enzyme catalyses the conversion of HMG-CoA to mevalonate in the
cholesterol synthesis pathway. By limiting the rate of cholesterol
biosynthesis, an upregulation of
LDL-receptors and increased hepatic uptake of LDL-cholesterol from the circulation
occurs (Becker ML, 2013).


Read the Drug Interactions and Adverse drug
Reactions on page 795 of the prescribed textbook and answer the following

Why should grapefruit juice be avoided when
taking atorvastatin? In your answer make sure you describe the following:

What does grapefruit juice bind to?

and other citrus fruits contain Furanocoumarins which are a specific group of
secondary metabolites. The biosynthesis of these furanocoumarins, reduces the presystemic felodipine metabolism
in the body through selective post translational down regulation of the
cytochrome P450 3A4 (CYP3A4) enzymes in the wall of the intestines (David G.
Bailey, 2013).

What is the consequence of the above binding?

The enzyme CYP3A4 which is responsible for the metabolism of
stains such atorvastatin is inhibited due to the furanocoumarins resulting in a
higher frug concentration in the body (David G. Bailey, 2013).

Detail how grapefruit juice affects the drug’s

One whole grapefruit or 200 mL of grapefruit
juice is sufficient enough to cause increased systemic drug concentration and
adverse effects. Grapefruit can increase a drug’s oral bioavailability from a low
(< 10%) to an intermediate (> 30%–70%) intrinsic oral bioavailability (David G.
Bailey, 2013).  


Describe the most common adverse effect of this
drug and its underlying mechanism.

Myalgia (muscle pain) is a common averse effect from taking the
drug Atorvastatin or any statin medication. The cause of the pain has been show
to originate from the gene atrogin-1. Statin medications induces the expression
of atrogin-1, a key gene involved in skeletal muscle atrophy, in humans with
statin myopathy; however, the mechanisms of muscle injury by statins are poorly
understood (Hanai JI, 2007).

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