Drugs useful in Parkinson

Parkinson or Parkinson-like syndromes may be Idiopathic, Drug-induced or Post-surgical, Post-infective (Post-encephalitic), or Post-traumatic.

Parkinsonism may be associated with dopamine hypoactivity and/or acetylcholine hyperactivity.

So,Pharmacologic Treatment of Parkinson involves two aspects:

1. Helping Dopamine
2. Blocking Acetylcholine

Special Points

1. Name an anti-parkinson as well as antiviral agent:

Amantadine

2. Drug of choice for drug-induced Parkinson:

Anticholinergics (Atropine Substitutes) and  Antihistamines

SAQ/LAQ/Viva

Classify drugs used in Parkinsonism with examples

(A)Drugs affecting Dopamine (DA) system (Dopaminergic system)

1. Dopamine presursor: Levodopa

2. Peripheral DOPA decarboxylase inhibitors: Carbidopa, Benserazide

3. Direct DA agonists: Bromocriptine, Pergolide, Piribedil, Ropinirole, Pramipexole
4. COMT inhibitors: Tolcapone, Entacapone
5.  MAO-B inhibitors: Selegiline
6.  Dopamine facilitator: Amantadine

(B)Drugs affecting Acetylcholine (Ach) system (Cholinergic system)

1. Central anticholinergics: Trihexyphenidyl (Benzhexol), Procyclidine, Biperiden, Benztropine

2. H1-Antihistamines: Promethazine, Orphenadrine, Diphenhydramine

[Remember: These drugs – Anticholinergics (Atropine substitutes) and Antihistamines are the drugs of choice for treatment of drug induced Parkinson]

SAQ/Viva

Explain the rationale of using Levodopa-Carbidopa combination in Parkinsonism.

If levodopa is used alone, almost 95% of it gets metabolized in the periphery by the enzyme dopa decarboxylase. Hence very less levodopa is actually available for entry into the brain, and for getting converted into dopamine.

Carbidopa/Benserazide  are peripheral dopa-decarboxylase inhibitors.  They do not enter the brain, and only peripherally they prevent the breakdown of levodopa into dopamine. So more amount of levodopa is preserved to enter the brain. Thus effectively more levodopa is available to enter the brain and further to get converted into dopamine.

Thus carbidopa / Benserazide increase the bioavailability of levodopa into the brain.

So there is decrease in the dose requirement of levodopa.

Further its dose-related adverse effects are minimized.

And hence the tolerance to levodopa is delayed.

LAQ/SAQ/Viva

Mention the advantages of Levodopa-Carbidopa combination.

Carbidopa is a peripheral dopa-decarboxylase inhibitor. It inhibits the enzyme dopa decarboxylase in the periphery, and inhibits peripheral breakdown of levodopa. So more levodopa is available for entry into brain.

Thus following advantages are expected with levodopa-carbidopa combination:

1. There is increased bioavailability of levodopa into brain and there is an increase in its half life.

2.  This reduces the dose requirement of levodopa.

3.  Its dose related adverse effects are minimized – Especially the effects due to peripheral dopamine, such as nausea, vomiting, and cardiac complications.

4. Thus lesser dose can be used since the beginning. So, when tolerance begins to show in, there is still comparatively a wider margin for increasing the doses; which means the tolerance to levodopa gets delayed due to addition of carbidopa.

5. The on-off phenomena are decreased.

6. Due to inhibition of peripheral dopa-decarboxylase, there is comparatively lesser effect of the drug interaction with vitamin B6 (Pyridoxine) [Note: The enzyme dopa decarboxylase in pyridoxine dependent]

7. In effect, there is better patient compliance. 

[Same advantages are shown in another format below for your revision]

——————————————————————-SAQ/Viva

Mention the problems that are not overcome even after using levodopa-carbidopa combination.

Even after using the levodopa-carbidopa combination, some of the problems (due to levodopa alone) are difficult to overcome. They are:

1. Involuntary movements
2. Behavioral abnormalities
3. Postural hypotension

——————————————————————-Drugs which are known to affect the dopaminergic transmission or block the dopaminergic receptors have a potential of producing Parkinson Like Symptoms. These are various types of involuntary movements also known as extrapyramidal reactions. This phenomenon is called Drug-induced Parkinson. One needs to be careful while prescribing these drugs.

Drugs causing Drug-induced Parkinson

-Anripsychotic Drugs (Neuroleptics): Chlorpromazine, Haloperidol

-Adrenergic Neurone Blocker: Guanethidine

-Catecholamine Depletors: Reserpine, Tetrabenazine

-Central Alpha-2 agonists: Methyl dopa, Clonidine

-Antiemetics (D2 blockers); Metoclopramide (Domperidone comparatively less likely)

-Tricyclic antidepressants

-Lithium

-Cinnarizine, Flunarizine

Drug induced Parkinson responds better to Anticholinergics (Atropine Substitutes) and Antihistamines. Hence they are preferred for treatment of Drug-induced Parkinson.