BMD225: Biomedical Pharmacology Workshop 3

EXERCISE 1
A NEW HORMONE THAT KEEPS POTASSIUM IN CHECK
In the year 2030, a new hormone, is discovered and named hormone Z. Molecular
investigations reveal that hormone Z is a 32kDa glycoprotein hormone with a plasma half-life
of 2 hours. Detailed analysis of urinary metabolites indicate that this novel hormone is
inactivated by an endopeptidas enzyme that cleave the dibasic peptide bond between
sequential arginine residues at positions Arg48 and Arg49 and that the peptide fragments are
further metabolised by the hepatic CYP enzymes prior to elimination in the urine.
The plasma concentration of hormone Z is reported to range between 10 and 50 nmol L-1 in
the systemic circulation. This glycoprotein activates G-protein-coupled receptors (GPCR) in
the kidney to induce kaliuresis and so lowers the plasma potassium concentration,
maintaining plasma [K+] between 3.5 and 5 mmol L-1.

In April 2032, the first patient (Patient 1) is reported with symptoms that appear to be
attributable to a change in the physiology of hormone Z. The patient presents with
hyperkalaemia (plasma potassium concentration of 10 mmol L-1) and circulating levels of
hormone Z between 180 and 220 nmol L-1.

Over the next 3 years, a further four patients are identified and reported with different
symptoms:

• Patients 2 and 3 both have hyperkalemia (plasma potassium concentrations greater

than 10 mmol L-1) and plasma concentrations of hormone Z of less than 5 nmol L-1.
• Patient 4 has severe hypokalemia (plasma potassium concentration of 2 mmol L-1)
and a plasma concentration of hormone Z greater than 300 nmol L-1 (the upper limit
of the assay for this hormone).
• Patient 5 also has severe hypokalemia (plasma potassium concentration of 2 mmol
L-1) but with a plasma concentration of hormone Z of only 10 nmol L-1.

Drawing on basis principles of homeostasis and endocrine physiology, drugs are designed
and developed to treat all five patients. Patients 2 and 3 are both treated with the same drug
which returns the plasma potassium concentration to normal (between 3.5 and 5 mmol L-1)
in Patient 2, but has no effect in Patient 3. Patient 2 is 37 years of age, 172 cm tall, and
weighs 68 kg. Patient 3 is 62 years of age, 165 cm tall, weighs 92 kg, and is prescribed
metformin.

Q1. What appears to be happening for Patient 1?

 A. Deficiency of hormone Z
B. Excess of hormone Z
C. Resistance to hormone Z
D. Constitutive activation of receptors for hormone Z

Q2. What appears to be happening for Patients 2 and 3?

A. Deficiency of hormone Z
B. Excess of hormone Z
C. Resistance to hormone Z
D. Constitutive activation of receptors for hormone Z

Q3. What appears to be happening for Patient 4?

A. Deficiency of hormone Z
B. Excess of hormone Z
C. Resistance to hormone Z
D. Constitutive activation of receptors for hormone Z

Q5. What appears to be happening for Patient 5?

A. Deficiency of hormone Z
B. Excess of hormone Z
C. Resistance to hormone Z
D. Constitutive activation of receptors for hormone Z

Q6. Why does the drug that treats hormone Z deficiency in Patient 2 not work in Patient 3?

Q7. For recombinant hormone production, in which cells would you express the gene
encoding hormone Z (and why)?

Q8. How could you modify the structure of synthetic hormone Z to extend its half life in the
circulation?
EXERCISE 2:

Self-medicator with a gut problem

Livia Perrera, a 24-year-old woman, comes to the pharmacy looking for a remedy for her heartburn.
She has had occasional heartburn about once a week or few years, but for the past few weeks since
her return from a holiday in South Asia it has become more frequent and is now occurring almost
daily after a meal. She complains of an acidic taste in her mouth and a burning feeling in the throat
and stomach when she is sleeping, and this keeps her awake at night. She does not complain of any
other related symptoms, such as pain when swallowing. She has given up hope on visiting her GP
because of the long waiting time for an appointment and therefore has been self-medicating with
over-the-counter medicines such as Rennie chewable tables and Gaviscon syrup after seeing their TV
adverts. However, since starting these medications, she has been suffering from nausea, bloating,
wind, abdominal cramping, and diarrhoea (for which she started taking Imodium daily, but this is not
working well anymore). She is convinced that she might also have irritable bowel syndrome, and is
therefore holding a packet of Bucospan and about to buy it.

As the pharmacist, how would you respond?

What is/are the active ingredient(s) of the drugs mentioned and how do they work?
What are their possible side effects?

Rennie and Gaviscon:

Imodium:

Bucospan:

What alternative drugs could you recommend? Give examples and explain how they work