Antiparkinsonian Drugs or agents are used to treat Parkinson’s disease or Parkinsonism’s. Parkinsonism is a progressive neurodegenerative disorder that affecting mostly older peoples. In this post, we going to discuss Antiparkinosian agents, their classification, mechanism of action, and adverse effects of these agents. At the end of this post, there is a Download button from where you can also download the note you read.
What is Parkinsonism or Parkinson’s Disease ?
As we already told above that Parkinsonism is a progressive neurodegenerative disorder that mostly affects older peoples. It is an extrapyramidal motor disorder characterized by rigidity, tremor, and hypokinesia with secondary manifestations like defective posture, gait, and mask-like face.
Symptoms of Parkinson’s Disease
Symptoms of Parkinson’s disease are given below:
- Pill rolling tremors
- Akathesia: Inability to sit still
- Rigidity
- Kinesias (akinesia, bradykinesia)
- Unstable (stooped) posture
- No arm swinging in rhythm with legs
- Sialorrhea: profused salivary secretion
- Masked facial expression
Classification of Antiparkinsonian Drugs
Antiparkisonian drugs are classsified between two types Drugs affecting Brain dopaminergic System and Drugs Affecting Brain Cholinergic System. Detailed classification in given in the below list.
- Drugs Affecting Brain Dopaminergic System
- Dopamine Precursor: Levodopa
- Peripheral Decarboxylase Inhibitors: Carbidopa, Benserazide
- Dopaminergic Agonist: Bromocriptine, Ropinirole, Pergolide
- MAO B Inhibitors: Selegiline
- COMT Inhibitors: Entacapone, Tolcapone
- Dopamine Facilitator: Amantadine
- Drugs Affecting Brain Cholinergic System
- Central anticholinergics: Trihexyphenidyl, Procyclidine, Biperiden
- Antihistaminics: Orphenadrine, Promethazine
Dopamine Precursor- Levodopa
Levodopa is widely used for the treatment of all types of Parkinsonism, except the one
which is associated with antipsychotic therapy. All clinical manifestations respond to the
combination of Levodopa with Carbidopa. Rigidity, bradykinesia, abnormalities of posture, and locomotion respond well to the combination while tremors are less responsive. The
therapy started with a small dose of Carbidopa 25 mg + Levodopa 100 mg (1:4 ratio) three
times a day, 1 hour before meals. The dose of Levodopa is increased up to 250 mg (1:10
ratio) gradually. If necessary, a dopamine agonist like Bromocriptine may be added.
Mechanism of Action
Levodopa is an immediate precursor for transmitter DA which is stored and released as a transmitter.
Pharmacological Actions
Pharmacological actions of Levodopa on Parkinson’s disease are given below.
- Action on CNS
- Hypokinesia and Rigidity resolved
- Secondary Symptoms of Posture, Gait, Handwriting, Speech, Facial Expression, Mood, Selfcare and interest in life are generally normalized
- Action on CVS: Acts on β Receptors produces central action.
- Postural Hypotension
- CTZ: Triggers the center leading to nausea and Vomiting
- Endocrine:
- Mammotropes- Inhibit Prolactin Release
- Somatotropes- Increase GH Release
Adverse effects
Levodopa may cause mydriasis and may precipitate an attack of glaucoma in some
patients. Abnormalities in smell/taste, hot flushes, and precipitation of gout may occur. Mild
but transient increase in blood urea, serum transaminases, alkaline phosphatize and bilirubin
may also be observed.
Dose
2-3 gm/day (LEVOPA 0.5gm Tablet)
Peripheral Decarboxylase Inhibitors
Mechanism of Action
Administered along with levodopa and it increase its t½ in periphery and make more DA available to cross along with the BBB
Levodopa+ Carbidopa= Co-careldopa
Advantages
- Plasma t½ ↑, the dose is reduced
- Cardiac complications are minimized
- Pyridoxine reversal of Levodopa effect does not occur
- The ‘On-off ‘ effect is minimized since levels of DA sustained.
- The degree of improvement also higher
Dose
TIDOMET-LS : 10mg Carbidopa +100mg Levodopa
Dopaminergic Agonists
These drugs directly stimulate DA receptors and do not depend on the formation of DA from Levodopa. They have the following advantages:
- They do not require metabolic conversion to DA.
- They do not depend on the functional integrity of dopaminergic neurons.
- They have a longer duration of action and lesser on-off phenomenon as compared to Levodopa.
- They are more selective than Levodopa on DA receptors.
- They are less likely to generate damaging free radicals.
Mechanism of Action
Selective activation of DA receptors in dopaminergic tract particularly on D2 receptors.
Eg. Bromocriptine
Pharmacokinetics
A – Orally
D – in major organ brain and its capillaries
M – liver , t½= 6-10hrs.
E – in Urine
Side Effects
Side effects of these drugs contains Vomiting, Hallucinations, Hypotension, Nasal Stiffness,
Conjunctival infection, Fall in BP
Dose
5-10mg thrice daily smoothens ‘on-off’ Fluctuations
MAO B Inhibitor
Inhibitors of the enzyme MAO-B are useful to treat PD. Selegiline is an irreversible
inhibitor of MAO-B, an enzyme in dopaminergic neurons responsible for the metabolism of DA.
It makes more DA available for stimulation of its receptors. Initially, Selegiline may be used
alone. Later, it is used along with Levodopa + Carbidopa to minimize the problem of dyskinesia
associated with long-term use of Levodopa. Selegiline may cause insomnia. It should not be coadministered with TCAs and SSRIs for the risk of acute toxic reactions like hyperpyrexia, agitation, delirium, and coma.
Selegiline is available as 5 mg tablet: SELGIN, SALERIN, ELEGELIN
COMT Inhibitors
Mechanism of action: COMT plays a role in the degradation of DA in brain as well, COMT INHIBITORS could preserve DA formed in the striatum and supplement the peripheral effect eg: entacapone acts only in the periphery (due to short duration of action) , For tolcapone also the
central action is less important.
Pharmacokinetics:
A- Orally
D- By binding with plasma albumin
M- in the liver by cytochrome P450
E- in Faeces and Urine
Side effects: Nausea, Vomiting, Dyskinesia, Hallucination
Dose: Entacapone: 200mg with each dose of levedopa and carbidopa Tolcapone: 100-200mg BD or TDS
Dopamine Facilitator
Mechanism of action: It appears to act by promoting presynaptic synthesis and release of DA in the brain. Action on glutamate receptors through which the striatal dopaminergic system exerts its influence has also been suggested eg: AMANTADINE
Side effects: These are not generally serious: insomnia, dizziness, confusion, nightmares, rarely hallucination.
Dose: Fixed doses of 100mg BD is used
Central Acting Anticholinergics
Mechanism of action: They act by reducing the unbalanced cholinergic activity in the striatum of parkinsonian patients, similarly H1 antagonist act as central acting anticholinergics
Side effects: Impairment of memory and organic confusional states are more common in elders
Dose: Trihexyphenidyl : 2-10 mg/day
Procyclidine : 5-20mg/day
Promethazine : 25-75mg/day
Conclusion
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