Medications Used in the Treatment of Parkinson’s Disease.

 

Three common medications used in the treatment of PD.

•          Levodopa – Replaces - Gold Standard

•          Dopamine Agonist - Look-a-Like

•          Enzyme Inhibitors – Prevent Breakdown of dopamine

•          Others: Anticholinergics and Amantadine – used for treatment of tremor

 

Levodopa

    The gold standard treatment

    Replaces dopamine.  Approximately 7% of l-dopa is successfully converted to dopamine and reaches the brain

    Stalevo, Madopar, Sinemet, Duodopa

Dopamine Agonists

    Act directly on dopamine receptors

    Mimic the action of dopamine

    Used as a monotherapy and in combination with l-dopa

    Requip, Mirapexin, Neupro, Apo-go

MAOB Inhibitors

    Prevent the breakdown of dopamine in the brain

    Used as a monotherapy and in combination with l-dopa

    Eldepryl & Azilect

COMT Inhibitors

    Can increase the amount of l-dopa that reaches the brain to 15%

    Comtess

 

Levodopa:

Most effective drug in the treatment of PD

Available for over 40 years

Large, neutral amino acid – crosses into blood through the gut (jejunum)

Combined with Decarboxylase Inhibitor to prevent breakdown prior to crossing Blood-Brain barrier

Common side effects: nausea/vomiting, postural hypotension, later on dyskinesias and motor fluctuations.

**It is essential that Levodopa is given 30-40 minutes prior to meals, or at least 1 hour after meals, with a full glass of water, or any fluid, just not milk. Levodopa uptake is disrupted by the protein from food and diet, so if given with or directly after meals, they will not be effective. This could result in increasing your work load, as when a dose fails, the person with PD will need more assistance, so giving the medication at the right time will benefit the patient and the staff.

Dopamine Agonists

Directly stimulate dopamine receptors

No absorption delay from competition with dietary
amino acids

Longer half-life than levodopa

Mono-therapy or adjunct therapy

May delay or reduce motor fluctuations & dyskinesias associated with levodopa

May be neuroprotective

Standard side effects: Nausea/Vomiting, Postural Hypotension, Headaches, Drowsiness

More literature on less common, but potentially devastating side effects:

Impulsive Compulsive Behaviours / Impulse Control Disorder / Dopamine Dysregulation Syndrome

Impulse Control Disorder:

Thought to be possible side effect of PD meds.

Uncontrollable urge to carry out a certain activity, often repetitively, which can result in causing harm to themselves or others.

Impulsive and Compulsive Behaviours include, but not limited to, gambling, binge eating, shopping excessively or an increase in sexual thoughts or desire.

Approx 17% of people on Dopamine Agonists will have some form of ICD, and 7% of people on Levodopa.

 

Dopamine Dysregulation Syndrome:

Dopamine Agonists can cause DDS, a disorder in the control of dopamine, in a very small but important group of patients. However, it is usually associated with Levodopa.

A Typical Patient is

Male (80%)

Diagnosed with PD at a young age

A risk taker

Takes more medications than prescribed, may hoard tablets

Dyskinetic

May have history of Alcoholism, Depression or Psychiatric problems

Why Does this Happen?

Dopamine is the chemical that controls the feelings of reward and motivation, so the artificial dopamine can result in these people being motivated to carry out certain tasks which will give them an instant reward, ie gambling or shopping. This reward seeking behaviour is associated with reward anticipation, and is not reliant on the actual reward.

COMT Inhibitors

Boost the function of levodopa by reducing the breakdown of the drug by enzymes in the body.

Known to colour stools and urine (orange colour)

MAOB Inhibitors

     Prevent the enzyme MAOB from breaking down the dopamine, keeping the remaining dopamine there longer.

     Thought to have neuroprotective properties

 

Drugs to avoid

Some drugs can bring on Parkinson’s-like symptoms and should be avoided, unless they’re recommended by a specialist.

These are some (but not all) of the drugs to avoid:
 

•         haloperidol (Serenace®/Haldol®)

•         metoclopramide (Maxolon®)

•         prochlorperazine (Stemetil®)

•         chlorpromazin (Largactil®)

•         fluphenazine (Modecate®)

•         fluphenazine with nortriptyline (Motival®)

•         perphenazine (Fentazin®/ Triptafen®)

•         trifluoperazine (Stelazine®)

•         flupenthixol (Fluanxol®/Depixol®)

 

Domperidone (Motilium®) is the anti-sickness drug of choice to prevent and treat nausea and vomiting caused by levodopa.Other anti-sickness drugs that are generally considered useful include cyclizine (Valoid®) and 5-HT₃ receptor antagonists like ondansetron.

 

 

 

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