What is Drug Interaction?

Medicines are used to treat certain conditions or illnesses, but when two or more medicines are used simultaneously, they may interact with each other and cause complications or unwanted side effects. Drug interactions may occur with prescription drugs, over-the-counter (OTC) medicines, herbal remedies, or dietary supplements, so it is important that the patient realizes the dangers of mixing drugs without consulting a doctor.

Parkinson’s Disease Medicines

The drug therapy most commonly used in Parkinson’s disease usually consists of the following :

• Levodopa
• Levodopa + peripheral decarboxylase inhibitors such as carbidopa and benserazide.
• Dopamine receptor agonists – pramipexole, ropinirole, and rotigotine.
• MAO-B inhibitors – selegiline and rasagiline.
• COMT inhibitors – entacapone
• Anticholinergics – benzhexol and orphenadrine
• Amantadine.

Drug Interactions with Parkinson’s Disease Medicines

Levodopa

Since this is the most widely used medicine in Parkinson’s disease, its drug interactions should be understood by all Parkinson’s patients. Certain medicines decrease effectiveness of levodopa hence the dose of levodopa may have to be adjusted if used together. These include

• Anticholinergics – sometimes used in addition to levodopa for treatment of symptoms in Parkinson’s disease. Over-the-counter cough and cold medicines contain anticholinergics such as diphenhydramine, chlorpheniramine, and phenylephrine.
• Antispasmodics used for treating stomach or uterine cramps also contain anticholinergics such as dicyclomine and hyoscyamine.
• Anti-allergic medicines (like anti-histamines)
• Antiepileptic drugs such as phenytoin
• Sedatives such as diazepam, lorazepam and alprazolam.
• Multivitamins, specially vitamin B-6 or pyridoxine, and minerals such as iron.
• Tricyclic antidepressants such as amitriptyline
• Metoclopramide – used to control nausea and vomiting.

Certain medicines help to increase the effect of levodopa. They include

• Medicines containing acetaminophen, used for pain, headache, and fever.
• Antacids and other medicines containing aluminum, calcium, and magnesium.

The above medicines should not be used to enhance the effect of levodopa.

Levodopa may potentiate the action of antihypertensives, causing excessive lowering of blood pressure when used concurrently. Levodopa may cause severe hypertensive reactions if taken by patients treated with MAO (monoamine oxidase) inhibitors such as furazolidone or procarbazine within the last 14 days.

Other Parkinson’s Drugs

Similar drug interactions are possible with all other medicines used in Parkinson’s disease. In addition,

• Alcohol intake may cause CNS depression when used along with Parkinson’s disease medicines.
• Antibiotics such as ciprofloxacin, norfloxacin, and ofloxacin may cause drug interactions with pramipexole, ropinirole, or rotigotine.
• Entacapone may react with antibiotics such as ampicillin, erythromycin, and chloramphenicol.
• Narcotic pain relievers such as codeine may react with entacapone or other drugs.
• Quinine or quinidine may interfere with renal clearance of amantadine.

Various other drug interactions are possible and you should consult with your doctor before taking any other medication or supplement, whether an OTC (over-the-counter) medicine, scheduled drug or a herbal remedy.

Types of Parkinson’s Drugs

Levodopa

Various drugs have been used for the treatment of Parkinson’s disease but the most effective treatment so far is a combination of levodopa and a peripheral acting dopa-decarboxylase inhibitor. Levodopa is a natural substance in our body which is converted to dopamine in the brain. However, if taken orally, about 90% of it is converted to dopamine outside the brain and only a small proportion of it reaches the brain. This causes side effects like nausea and vomiting, which can be offset by combining levodopa with peripheral decarboxylase inhibitors like carbidopa. Levodopa is especially effective in improving bradykinesia and rigidity of Parkinson’s disease, and tremor to a lesser extent, but initial treatment with levodopa should be delayed because of the long term side effects such as involuntary movements, depression, hallucinations and delusions. With long term use, the effect of levodopa shows some fluctuation in response, known as the ‘on-off phenomenon’ where there is unpredictable action of the drug. This can be treated by variations in dose.

Dopamine Receptor Agonists

These drugs are not as effective as levodopa in the treatment of Parkinson’s disease but their action lasts longer and they help considerably during the on-off effect of levodopa. Side effects such as dose fluctuations or dyskinesia (involuntary movements) are rare, although once dyskinesia develops, dopamine agonists tend to make them worse. Other side effects are nausea, vomiting, confusion and hallucinations. Pramipexole and ropinirole are administered as oral preparations while rotigotine can be used in patch form. Pergolide and bromocriptine are not used because of causing problems in heart valves. Apomorphine injection maybe used to give rapid short term relief.

Monoamine Oxidase B (MAO-B) Inhibitors

Drugs like selegiline and rasagiline are mildly effective. There may be drug reaction with other medications, especially narcotics and antidepressants.

Catechol-Omethyl Transferase (COMT) Inhibitors

COMT inhibitors like entacapone can be used with levodopa by helping to reduce its dose and thus reduce the instance of motor fluctuations caused by levodopa.

Anticholinergics

Anticholinergics like benzhexol are effective in controlling tremor and rigidity but not bradykinesia, hence they may be used in the early stage of the disease. The side effects are confusion and hallucinations, especially in the older age group, in whom these drugs are best avoided. The other side effects are blurred vision, dryness of mouth, constipation and retention of urine.

Amantadine

Amantadine can be used in early stage of Parkinson’s disease before starting with stronger drugs, and in the later stage along with carbidopa-levodopa preparations to offset side effects such as involuntary movements. The side effects of this drug are confusion, seizures, ankle edema.

These drugs are currently used in Parkinson’s disease but ongoing drug research to isolate compounds to reduce the severity of Parkinson’s symptoms offers hope for more effective drugs in the future.

When medication has ceased to be effective or the side effects from them have become no longer tolerable, surgery might be an option your Doctor will consider and advise to help alleviate your symptoms and improve your quality of life. However not all sufferers of Parkinson’s will be a candidate for surgery, an example would be a person who didn’t respond very well to Levodopa treatment.

Of all the people suffering from this disease it is thought that only around 10% of them could be classed as possible suitable candidates for surgery. Another factor to consider when thinking of surgery is that while improvements could be gained there is also the risk factor to take into account that surgery of any kind has.

There is also the risk that the surgery might not make any improvements and could in fact make the symptoms worse. There are three main types of surgery which can be used in the treatment of Parkinson’s disease; these are ablative, stimulation, deep brain stimulation, transplantation and restorative surgeries.

Ablative surgery

This type of surgery aims to locate, target and then destroy the defined area of the brain which is affected by the disease. The aim is get rid of all the tissue which produces the abnormal electrical or chemical impulses which in turn produce the symptoms of tremor in the patient.

This type of surgery is performed by inserting an electrode into the part of the brain affected by the disease; this method is often very difficult to guess correctly for if too much tissue is taken then it could lead to stroke or paralysis while if too little is taken the tremor might not be eliminated or could return.

The patient will remain awake during this procedure with a local anaesthetic being given to dull the feeling in the outer part of the brain. The brain itself cannot feel pain so it can be probed without any discomfort to the patient.

Deep brain stimulation

This type of surgery specifically targets the subthalamic nucleus; it is a part which is extremely difficult to reach and is found below the thalamus. This type of surgery doesn’t destroy tissue but instead renders it inactive.

An electrode is connected via a wire which is inserted below the skin and attached to a stimulator and battery pack in the patient’s chest. The operation is totally reversible and the risk of stroke is reduced and allows for more precise control of symptoms.

Transplantation or restorative surgery

This type of surgery relies on the implantation of dopamine producing cells being implanted directly into the striatum. Cells used for this process are taken from a variety of sources which include the patients own body, human embryos and pig embryos.