Drug Treatment Of Parkinson's Disease

Front 1

definition of Parkinson's disease

Back 1

progressive movement disorder found most commonly in the elderly.

Front 2

main motor symptoms

Back 2

tremor at rest
muscle rigidity
bradykinesia due to muscle rigidity
impaired postural balance leading to gait disturbances and falling

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pathophysiology

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loss of dopaminergic neurons in the substantia nigra.
these neurons supply the striatum with dopamine.
all these occur in the basal ganglia

Front 4

neurochemical changes in Parkinson's disease

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dopamine is an inhibitory neurotransmitter while acetylcholine Is an excitatory neurotransmitter in the CNS.
loss of dopaminergic neurons leads to an overwhelming action of excitation.

Front 5

classification of drugs used in treatment of Parkinson's disease

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anti cholinergic drugs
drugs that replace dopamine
dopamine agonists
drugs that cause release of dopamine
inhibitors of enzymes involved in dopamine metabolism.

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drugs that replace dopamine

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Levo-dopa

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pharmacodynamics of Levo-dopa

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provides dopaminergic neurons in the striatum with dopamine precursor.
the drug is converted to dopamine in the CNS thereby replacing lost dopamine.
dopamine cannot directly penetrate the CNS but levo-dopa can.

Front 8

pharmacokinetics of L-dopa

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L-dopa undergoes extensive first pass metabolism in the liver thereby reducing concentration getting to the brain.
this also increases the concentration of dopamine peripherally.
since dopamine is a cathecholamine, it causes severe cardiovascular effects

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to reduce peripheral dopamine......

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peripheral decarboxylation of L-dopa is inhibited by using a peripheral DOPA decarboxylase inhibitor (carbidopa).

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benefits of using carbidopa

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it increases amount of L-dopa penetrating the CNS
it also reduces peripheral concentration of dopamine and it's side effects

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dopamine agonists

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ERGOT DERIVATIVES
bromocriptine
pergoline
NON-ERGOT DERIVATIVES
ropinirole
pramipexole

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pharmacodynamics of dopamine agonists

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they target post synaptic dopaminergic receptors directly thereby enhancing dopamine neurotransmission.

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advantages of using dopamine agonists over others

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because they are non peptide molecules they do not require transporters to carry them into the CNS.
also, they do not require conversion by amimo acid decarboxylase.
they have long half lives.

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adverse effects of dopamine agonists

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occurs most commonly with the ergots
nausea,
peripheral edema,
hypotension,
excessive sedation,
hallucinations,
vivid dreams

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drugs that cause release of dopamine

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amantadine

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pharmacodynamics of amantadine

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stimulates release of dopamine from intact dopaminergic neurons

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anti cholinergic drugs used in management of Parkinson's disease

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atropine
scopolamine
benztropine
trihexyphenidyl

Front 18

phamacodynamics of anti cholinergics

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antagonize effect of acetylcholine thereby reducing its excitatory actions and restoring balance
inhibits uptake of dopamine

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atropine and scopolamine in Parkinson's management

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scopolamine is more used because it is 10x more potent than atropine because of easy penetration of the BBB.
used in treatment of mild symptoms
treatment of Parkinsonism syndrome
used in patient not responsive to L-dopa
used in patients on anti psychotics

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difference between Parkinsonism syndrome and Parkinson's disease

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the syndrome is just a symptom complex consisting of tremor are rest, bradykinesia, rigidity, postural imbalance. anything can cause this
the disease has the symptoms above but it is neurodegenerative.

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causes of Parkinson's disease

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idiopathic
drug induced
viral encephalitis
ischemia

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benztropine in management of Parkinson's disease

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abolishes tremor, rigidity and spasm
causes sedation
long duration of action

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trihexyphenidyl in Parkinson's management

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relieves tremor by abolishing cholinergic activity in the striatum

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side effects of anti cholinergics

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blurred vision
constipation
urinary retention
dry mouth
delirium
hallucinations

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drugs that inhibit metabolism of dopamine and L-dopa

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COMT inhibitors
tolcapone
entacapone
MAO inhibitors
selegiline

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pharmacodynamics of COMT inhibitors

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they act peripherally and centrally inhibiting COMT which catabolizes L-dopa.
this consequently increases the effective concentration of L-dopa.
tolcapone: central and peripheral actions, long duration of action
entacapone: peripheral actions, short DOA, given together with L-dopa/carbidopa

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MAO inhibitors

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inhibit MAO which catabolizes L-dopa.
MAOb is the predominant isozyme in the striatum.
selegiline is specific for MAOb
selegiline does not inhibit peripheral catabolism of cathecholamines

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selegiline

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inhibits breakdown of dopamine in the striatum