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• 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.
• 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.