CNS- DRUGS USED IN PARKINSONISM

1. Mrs. Mansi R. Hirlekar M.Sc. (N)
Antiparkinson’s D rugs
INTRODUCTION
• Parkinson’s disease is a chronic, progressive neurological disorder with rhythmic
tremors as its initial manifestation. These tremors lead to rigidity and weakness which
interfere with the ability to maintain posture.
• Other manifestations include bradykinesia (extremely slowed movements), shuffling
gait, drooling, and slow and slurred speech. Cranial nerve affectations lead to a mask-like
expression.
• It was described by James Parkinson in 1817
• 1% of population above 65 years of age
• Idiopathic in origin but can also be drug induced
• There is degeneration of nigrostriatal neurons in the basal ganglia resulting in dopamine
deficiency
• The balance between inhibitory dopaminergic neurons and excitatory cholinergic neurons
is disturbed

2. Mrs. Mansi R. Hirlekar M.Sc. (N)
ANTIPARKINSONS DRUGS:
Drugs used for management of signs and symptoms of Parkinson’s disease, a progressive,
chronic neurological disorder primarily characterized by lack of coordination.
The relative lack of dopamine combined with the relative excess of excitatory
acetylcholine causes the symptoms of Parkinson disease
The goal of therapy is to restore the balance between dopamine and acetylcholine
Drugs used to treat Parkinson disease increase dopamine levels, stimulate dopamine
receptors, extend the action of dopamine in the brain , or prevent the activation of
cholinergic receptors
Often combination of drugs is used to influence both functions. Protype for the
dopaminergic drug carbidopa-levodopa
CLASSIFICATION:
1. DRUGS THAT INCREASE DOPAMINE LEVELS
i. DA precursor: Levodopa
ii. Drugs that release dopamine: Amantadine
iii. Dopaminergic agonist: Bromocryptine, Pergolide, Lisuride, Ropinirole, Pramipexole
iv. Inhibit dopamine metabolism
• MAO inhibitors: Selegiline, Rasagiline
• COMT inhibitors: Tolcapone, Entacapone
2. DRUGS INFLUENCING CHOLINERGIC SYSTEM
i. Central anticholinergic : Benztropine, Benzhexol, Biperidine
ii. Antihistamines : Diphenhydramine, Orphenadrine, Promethazine

3. Mrs. Mansi R. Hirlekar M.Sc. (N)
DOPAMINE PRECURSOR
LEVODOPA:
• Main drug for idiopathic parkinsonism
• Immediate precursor L- Dopa ( a prodrug)
• Converted to dopamine in the peripheral tissues by peripheral decarboxylase enzyme
• A small amount (3-5%) of L-Dopa enters the brain
• Therefore, L-Dopa is always used in combination with carbidopa/ benserazide (peripheral
decarboxylase inhibitor) which does not cross the BBB
• Peripheral metabolism of L-Dopa is reduced
• Increasing the bioavailability of L-Dopa in the basal ganglia
• Improves all the clinical symptoms of parkinsonism but does not stop the progression of the
diseases
• Other actions: large amounts of L-Dopa are converted to dopamine in the periphery which brings
about other actions
• CTZ – dopamine stimulates the CTZ to induce vomiting
• CVS – it causes postural hypotension, tachycardia and arrhythmias. Dopamine is a catecholamine
• Endocrine – dopamine suppresses the prolactin secretion

4. Mrs. Mansi R. Hirlekar M.Sc. (N)
PHARMACOKINETICS
• Rapidly absorbed from the small intestine
• Presence of food delayed absorption ( some amino acids in the food compete with levodopa for
absorption and transport to brain
• Undergoes first pass metabolism in the gut and the liver
• Its t1/2 is 1-2hours
ADVERSE REACTION:
• 95% of L-Dopa is converted to Dopamine in the periphery
• Nausea , vomiting, anorexia, postural hypotension, palpitation and occasionally arrhythmias can
occur
• Behavioral effects like anxiety, depression, hallucinations and sometimes psychosis
• Abnormal involuntary movements like facial tics, grimacing, choreoatheoid movements of the
limbs
• Fluctuation in response to L-Dopa can occur after 2-5 years of use – known as on-off
phenomenon- where the patient swings alternately from periods of good response to severe
disabling disease
DRUG INTERACTION
• Pyridoxine enhances peripheral decarboxylation of levodopa and thus reduces its availability to
the CNS
• Phenothiazines and metoclopramide are DA antagonists they reverse the effects of levodopa
CARBIDOPA AND BENSERAZIDE:
• Peripheral Dopa decarboxylase inhibitors
• In combination with L-Dopa, prevent the formation of dopamine in the periphery
• Do not cross the BBB and hence allow levodopa to reach CNS
ADVANTAGES
• Dose of L-Dopa can be reduced by 75%
• Response to L-Dopa appears earlier
• Side effects like vomiting and tachycardia are largely reduced
• Pyridoxine does not interfere with treatment

5. Mrs. Mansi R. Hirlekar M.Sc. (N)
CARBIDOPA-LEVODOPA:
PHARMACTOTHERAPEUTICS:
• Combination drug used in treating Parkinson disease
PHARMACOKINETICS
• Administered : oral
• Metabolism: peripherally
• Onset: 1-2 months
• T ½ : 1 to 2 hours
PHARMACODYNAMICS
• Diffuses levodopa into the central nervous system (CNS), where it is converted to dopamine
• Carbidopa is administered in combination to prevent the conversion of levodopa to dopamine in
the periphery
CONTRAINDICATION AND PRECAUTION
• Hypersensitivity and undiagnosed pigment lesions
ADVERSE EFFECTS
• Nausea , vomiting, anorexia, orthostatic hypotension, abnormal movements, cardiac arrhythmias,
bruxim, and ballismus
DRUG INTRACTIONS
• Hydantoins, MAOIs, Phenothiazines, or tricyclic antidepressants
• Protein can interfere with absorption

6. Mrs. Mansi R. Hirlekar M.Sc. (N)
DRUGS THAT RELEASE DOPAMINE
AMANTADINE
• Antiviral drug
• Enhances the release of DA in the brain and diminishes the re-uptake of DA
• Response starts early and its adverse effects are minor
• Large dose produce insomnia, dizziness, vomiting, postural hypotension, hallucinations and ankle
edema
• Used in mild cases of parkinsonism in combination with L-Dopa as an adjunct
DOPAMINE RECEPTOR AGONISTS
BROMOCRIPTINE AND PERGOLIDE
• Ergot derivatives having dopamine agonistic activity at D2 receptors
• Bromocriptine is partial agonist while pergolide is an agonist at D1 receptors
ROPINIROLE AND PRAMIPEXOLE
• Selective D2 agonist are better tolerated
• Quickly attain therapeutic levels and adverse effects are milder except some sleep disorders
• Dopamine agonists are all longer acting because useful in the treatment of ‘on-off’ phenomenon
INDICATION
• In treatment of ‘on-off’ phenomenon
• As alternatives in the initial treatment of parkinsonism (particularly newer agents)
NOTE Lisuride is similar to Bromocriptine
ADVERSE EFFECTS
• Nausea, vomiting, hallucinations and skin eruptions
• Ergot derivatives can cause postural hypotension or hypertension initially
• First dose of phenomenon – sudden cardiovascular collapse

7. Mrs. Mansi R. Hirlekar M.Sc. (N)
DRUGS THAT INHIBIT DOPAMINE METABOLISM:
MONOAMINE OXIDASE INHIBITORS
SELEGILINE (DEPRENYL):
• Selective MAO- B inhibitors
• MAO- B in present in DA containing regions of the CNS
• Selegiline prolongs the action of L-Dopa by preventing its degradation
• May delay the progression of parkinsonism
USES
• Mild cases of parkinsonism,
• Also used as an adjunct to L-Dopa
ADVERSE EFFECTS:
• Nausea, postural hypotension, confusion and hallucinations
RASGILINE:
• More potent than selegiline
• Also slow the course and progression of disease by a neuroprotective effect like selegiline
DRUG INTRACTION
• The following are drug-drug interactions involved in the use of dopaminergic:
• MAOI: Increased therapeutic effects and risk of hypertensive crisis. MAOI should be stopped 14
days before beginning dopaminergic therapy.
• Vitamin B6, phenytoin: decreased levodopa efficacy
• Over-the-counter vitamins: decreased dopaminergic effectiveness
• The risk of drug interactions- serotonin syndrome if taken with TCA or SSRIs should be borne in
mild while using MAO inhibitors.
CATECHOL-O-METHYLTRANSFERASE (COMT) INHIBITORS
TOLCAPONE AND ENTACAPONE
• Inhibit the peripheral metabolism of L-Dopa thereby increasing its bioavailability
• Tolcapone crosses the BBB and enhances the availability of L-Dopa in the brain

8. Mrs. Mansi R. Hirlekar M.Sc. (N)
• Used as add-on drugs in parkinsonism
DRUGS THAT INFLUENCE CHOLINERGIC SYSTEM
ANTICHOLINERGIC:
• Cholinergic overactivity is overcome by anticholinergic
• Tremors, seborrhea and sialorrhea are reduced more than rigidity
• Atropine derivatives like Benzhexol and Benztropine are used
• Antihistamines owe their beneficial effects in parkinsonisms to their anticholinergic properties
USES
• Adjunct to L-Dopa
• Drugs of choice in drug induced parkinsonism
ADVERSE EFFECTS:
• Atropine like side effects such as dry mouth, constipation, urinary retention and blurred visions
may be encountered

9. Mrs. Mansi R. Hirlekar M.Sc. (N)
DRUG INDUCED PARKINSONISM
• Reserpine, metoclopramide sand Phenothiazines can induce parkinsonism
• Reserpine depletes catecholamine stores, while metoclopramide and Phenothiazines are dopamine
antagonist
TREATMENT
• Withdrawal of the drug usually reverses the symptoms
• When needed, one of the anticholinergic are effective
• L-Dopa or other dopamine agonists are not effective because DA receptors are blocked by drugs
like metoclopramide and Phenothiazines
NURSING RSPONSIBILITIES
• Asses Parkinson and extra pyramidal symptoms
• Caution patient to make position changes slowly
• Instruct patient about frequent rinsing of mouth
• Inform patient that this medication decreases perspiration, and over heating may occur during hot
weather
• Assess seizure activities
• Drug should be taken with food
• Teach patient to carry medicine, alert ID stating patients name, drug taken
• Teach patient not to stop medication without medical advice
Conclusion
• It is conducted that neuronal degeneration in SNPC leads to deficiency of dopamine in striatum is
a major cause of parkinsonism
• Levodopa and carbidopa are given in combination to give synergistic effect and make a balance
between dopaminergic and cholinergic system
• The use of Antiparkinson’s drugs is increasing continuously to overcome the symptoms
• The net result of all of these medications is the balancing out of the acetylcholine/ dopamine
balance and an improvement in movement