Case Study: Antiparkinsonian Agents

HT, a white, 59-year-old male was diagnosed with idiopathic Parkinsonism 6

months ago. He complains to you that his medicine (Laradopa; L-dopa,
Compound 1) no longer controls the tremor in his left hand.
Upon inquiry regarding other medication, you discover that HT has recently
decided to take ProstaKit, a product he purchased through the internet because
he was concerned about the “health of his prostate gland”.
ProstaKit contains three separate products. Formula 1: Palmitol containing saw
palmetto berries (Compound 2), zinc (50 mg), and vitamin B6 (120 mg,
Compound 3). Formula 2: Flax-O-Mega containing cold pressed flaxseed oil
(Compound 4) and Formula 3: Pro-Essence containing burdock root, juniper
berry, prickly ash bark, slippery elm bark, and uva ursi. Is HT experiencing an
advancement of his Parkinsonism or is something else taking place here?

11. Identify the therapeutic problem(s) where the pharmacist's intervention

may benefit the patient.

• Mr Ht is a 59yr old, white man that has recently been diagnosed with
Iodiopathic Parkinson’s disease (PD). This is a neurodegenerative
disorder associated with a decrease in dopamine in parts of the brain.
• He was diagnosed 6 months ago and has been treated with L-Dopa. His
symptoms started reappearing recently, characteristed by the tremors in
his left hand.
• Mr HT has recently been worried about his prostate health and has
purchased and started using a product called Prostakit. This contains
herbal extracts that are causing drug drug interactions with L-Dopa.
• L-Dopa is not the first line treatment for PD, it is usually a dopamine
agonist.
12. Identify and prioritize the patient specific factors that must be
considered to achieve the desired therapeutic outcomes.

• Mr HT is 59yrs old and knows that he could be prone to prostate cancer

due to his age.
• Mr HT was prescribed and given only L-Dopa, without a L-amino acid
decarboxylase inhibitor, eg. Carbidopa.
• The Prostakit that Mr HT is taking consists of: Formula 1- Vitamin B6 and
palmetto berries (these are co factors for aromatic L-amino acid
decarboxylase).
• Formaula 2: contains prussic acid which also a neurodegenerative agent,
causing a progression in Mr HT’s condition.
• L-Dopa effectiveness tends to decrease as the disease progresses.
1
23. Conduct a thorough and mechanistically oriented structure-activity
analysis of all therapeutic alternatives provided in the case.
COMPOUND 1 – L-Dopa aka Levodopa
• It is a bioprecusor prodrug of Dopamine. Dopamine cannot cross the
blood brain barrier (BBB) and is thus not useful pharmaceutically.
Whereas Levodopa is lipophilic enough to cross the BBB and once in the
brain it is thus converted to Dopamine .
• Levodopa is metabolized by an enzyme called aromatic L-amino acid
decarboxylase. This enzyme is found in very high concentrations in the
peripheral nervous system, more so than that which is found in the brain.
Due to this high amount of enzyme in the periphery, the Levodopa is
metabolized extensively in the periphery, leaving a low amount to cross
the BBB, and act in the brain.
• Due to this, if levodopa is administered on its own a high dose is required
to achieve a therapeutic outcome.
COMPOUND 2 – PALMITOL
• This compound is made up free fatty acids and ethyl esters of fatty acid
and sterols. This compound is thus very lipid soluble and attributes to its
pharmacological effects.
• This compound has been found to be very effective in the treatment of
benign prostatic cancer.
• It is found to inhibit the enzyme that converts testosterone to
dihydrotestosterone, called 5-alpha-reductase enzyme. It has some
inflammatory properties and may also inhit some growth factors.
COMPOUND 3 – VITAMIN B6
• Pyridoxine aka Vit B6, is readily absorb from the gut, and is converted to
pyridoxal phosphate and pyridoxamine phosphate. These areatored in the
liver.
• L-amino acid decarboxylase is dependant on pyridoxine, this enzyme is
also responsible for the metabolism ( decarboxylation) of Levodopa. This
compound will increase the peripheral dercarboxylation of Levodopa
which will leave even less amount of Levodopa available to cross the
BBB, thus decreasing its effects.
 COMPOUND 4 – FLAXSEED OIL
• This is a highly unsaturated oil, also known as linseed oil.
• It is made up of triglycerides: stearic acid and palmitic acid (saturated
acids) , oleic acid, linoleic acid and omega 3 fatty acid, α-linoleicc acid.
• it is an ester with numerous double bonds which makes it highly lipophilic,
making it eay to cross the BBB.
• This product is used as antiseptic, anti-inflammitory, laxative and many
others.
• This flaxeed oil contains lignans and these are the ones responsible for
decreasing the risk of cancer.

• Levodopa complexes with iron in its ferrous and ferric states. Levodopa
increase the rate of oxidation of iron from its ferrous to the ferric state. The
ferric form of iron binds levodopa strongly. Levodopa and the ferric form of
iron form a 3: 1 levodopa :iron complex. With this it has been found that
administration of ferrous sulphate with levodopa leads to a 51% decrease
in levodopa bioavailability and a 55% decrease in peak levels in healthy
subjects (Campbell & Hasinoff, 1989).

4. Evaluate the SAR findings against the patient specific factors and
desired therapeutic outcomes and make a therapeutic decision.
Formular 2 should not be given as it contains agents that are neurodegerative,
which will cause his condition to progress much faster.

Compound 1 –levodopa
• Levodopa is not in combination with Carbidopa (l-amino acid
decarboxylase inhibitor) in this preparation Laradopa, this would thus
require a higher dose of Levodopa (3-6g daily), which would lead to an
increase in side effects.
• With out the Carbidopa and a lower dose of Levodopa would lead to a
decrease in expected concentration of Levodopa that reaches the brain,
as extensive metabolism by peripheral enzymes.
• Generally when given incombination with Carbidopa there is a high
concentration available to reach the brain.
• Sinemet® is an example of a combination drug that contains both
carbidopa and levodopa.
• A Catechol-O-methyl transferase(COMT) inhibitor can also be given with
Sinemet®, this will decrease the breakdown of dopamine in the brain.
Increasing the therapeutic outcomes.
• An anticholinesterase drug also decreases the motor effects of tremor and
can also be given as additive treatment.
VITAMIN B6
• Is an inducer of the enzyme that breaks down levodopa, this would thus
increase its metabolism peripherally and decrease the amount of levodopa
available to fross the BBB.
• When levodopa is administered with Carbidopa, these effects of Vit B6 is
reduced greatly and Vit B6 can be given.
 Formular 1 and 3 can be given if Mr HT’s PD treatment is changed from just
L-dopa do a combination like Sinemet®, then he can continue to use the
Prostakit.

5. Counsel your patient.

• It must be explained that medically PD can only be managed and not

treated, and reassured that the treatment available will make life more
comfortable.
• Patient should be advised that self medication including herbal products
should first be discussed with his doctor or pharmacist.
• There are side effects to all medication and if Mr HT experiences
something abnormal he should contact the pharmacist.
• Operating heavy machinery and cars are not advisable immediately after
the dose
• Mr HT may continue to use the Prostakit although only formula 1 and 3
may be used.
• Formula 2 must not be used.
•
• Pharmacist required to advise patient on safe protective treatment.
Pharmacist to determine if there is an immediate need for protective
therapy – if there is existing history of prostate cancer in the patients
family.
•