Parkinsons disease: medication

Parkinsons diseaseAnna Matthews, Claudia Li, Queenie LauIntroductionProgressiveCannot be cured One person in every 500 suffers from Parkinson's DiseaseCommon nervous system disorder amongst the elderly One in 20 sufferers are under the age of 40

CausesLoss of dopamine in the substantia nigraAs the cells die, less dopamine is produced Can result from genetic and environmental factors

Genetic FactorsVast majority are not directly inherited (~15-25%)An affected first-degree relative results in a 4-9% increased risk of developing the diseaseGenemutations include PINK1 and LRRK2

Environmental FactorsExposure to toxins e.g. pathogens, toxic chemicals and heavy metals Severe head injuries, such as repeated traumaDrug induced e.g. antipsychotics and MPTPOthers

Main SymptomsMain symptoms: Tremor (Shaking)Slowness of movementRigidity (Stiffness) Early symptoms: feeling tired and weak; poor hand co-ordination

Physical SymptomsSpeech and communication problemsSwallowing problemsBladder and bowel problemsEye problemsFalls and dizzinessFatigueFreezingPainRestless legs syndromeSkin, scalp and sweating problems

Mental Health SymptomsAnxietyDementiaDepressionSleep disturbanceHallucinations and delusionsMemory problems

Case StudyPatient: Mr BeattieSituation: The patient is asking for some nicotine patches, as he has heard they can be used to treat ParkinsonsHis shakes from his Parkinsons Disease are getting worse and the medicines do not seem to workHe used to be very physically active and feels caged in that he cant do what he used toHe is getting increasingly dependent on his wifePatients medical history: Parkinsons Disease for 19 yearsFamily history: Father suffered from PDPMR: Madopar CR 125mg caps2 each morning and 2 at nightMadopar 125 mg caps 4 times a day (in between the Madopar CR caps)Entacapone 200 mg tablets 1 taken 6 times dailyRopinirole 3 mg tablets 1 taken 3 times a day

As Claudia said earlier, the substantia nigra are dopamine producing cells. Diminished substantia nigra as seen in Parkinsons disease means that dopamine, which acts as a neurotransmitter in the brain, is not present in sufficient quantities in the basal ganglia of parkinsonian patients. There are a variety of treatments available to slow the progression of Parkinsons, but so far there is no cure.11

The first type of medication well discuss is Madopar. This contains levodopa, which is a dopamine precursor. It is used as a prodrug to increase dopamine levels since it is able to cross the blood-brain barrier whereas dopamine itself cannot. Once levodopa has entered the central nervous system, it is metabolised to dopamine by aromatic L-amino acid decarboxylase.After administration, levodopa is rapidly decarboxylated to dopamine in extracerebral as well as cerebral tissues. As a result, most of the levodopa administered is not avaliable to the basal ganglia, and the dopamine produced peripherally frequently causes unwanted effects. It is therefore particularly desirable to inhibit extracerebral decarboxylation of levodopa. This can be achieved by simultaneous administration of levodopa and benserazide, a peripheral decarboxylase inhibitor, preventing the peripheral breakdown of levodopa.

12Madopar CR capsules125mg2 each morning and 2 at night

Madopar 125mg capsulesFour times a day in between Madopar CR capsules

Each capsule contains 100mg of levodopa...... and 25mg benserazideLevodopaThe pharmacokinetic properties of Madopar CR differ from those of standard madopar capsules. The active ingredients are released slowly in the stomach. Maximum plasma concentrations of levodopa, which are 20-30% of those achieved with the standard dosage forms, are reached about 3 hours after administration. The plasma concentration-time curve shows a longer half life than with standard madopar. The benefit to using controlled release capsules as well as standard ones is that it enables the patient to keep a steady plasma concentration of levodopa during the day and night. Taking madopar CR before going to bed can reduce stiffness throughout the night.13

Catechol O-methyl transferases are enzymes that degrade catecholamines such as dopamine. COMT inhibitors such as Entacapone prevent the breakdown of dopamine.14Entacapone 200mg tabletsOne tablet six times a day

COMT inhibitorEntacapone is a selective, reversible catechol-O-methyl transferase (COMT) inhibitor for the treatment of PD. The mechanism of action of entacapone is believed to be through its ability to inhibit COMT in peripheral tissues, altering the plasma pharmacokinetics of levodopa. When entacapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as benserazide, plasma levels of levodopa are greater and more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that at a given frequency of levodopa administration, these more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to a greater reduction in the manifestations of parkinsonian syndrome.15

The final line of treatment for Parkinsons is the use of a dopamine agonist. As the disease progresses, neurons die, so the effect of levodopa administration decreases with time as there is a limit on how much levodopa can be converted to dopamine.

16Ropinirole 3mg tabletsOne tablet three times a day

Dopamine agonistRopirinole has effects similar to those of natural dopamine, so it helps to reduce the symptoms of PD.

17

18Effects of nicotineInhibits MAOMay block the damaging processes causing PDIncreases the levels of dopamineReduce L-DOPA-induced dyskinesias Withdrawal can cause down-regulation of the production of dopamineDecrease the sensitivity of nicotinic acetylcholine receptors

Therapies for Parkinsons DiseaseOccupational therapySpeech and Language therapyPhysiotherapySeeing a dietitianComplementary therapies

Complementary TherapiesDetermined by 6 different aspectsCommon aspects:- Alexander technique- Bowen technique- Feldenkrais Method- Massage therapy

Role as a CarerAdapting to ParkinsonsUnderstanding the medication for the patientSupport from other healthcare professionals and carers