Anti-parkinsonism drugs

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ANTI-PARKINSONISM DRUGS by RAJIV (4th year Medical student)

anti-parkinsonism drugs 1

PARKINSON’S DISEASE
Parkinson’s Disease is a slowly progressive disorder that affects movement, muscle control & balance. Destroy certain part of cell in certain part of brain stem.

OBSERVATION
Diminished substantia nigra

FEATURES OF PARKINSONISM
1. Bradykinese
2. Muscular Rigidity
3. Resting Tremor
4. Impairment of Postural balance leading to Gait and Falling.

anti-parkinsonism drugs

MECHANISM OF PARKINSONISM
▫Dopamine neurons orginate in Substantia Nigra & Project to Neostriatum
▫They synapse on Stiatal Projection neurons that use neurotransmitter GABA
▫Striatal Interneuron use the excitatory neurotransmitter Ach and modulate activity of striatal output neurons
▫loss of striatal dopamine produce an imbalance in information processing in Neostriatum

PATHOLOGY
Loss of the pigmented, dopaminergic  neurons of substantia nigra

COMPLICATION
▫Death frequently
▫Complication of immobility
▫aspiration pneumonia
▫pulmonary embolism

COMMON ANTI-PARKINSONISM DRUGS
▫Sinemet
– Levadopa
– Carbidopa
▫Dopamine Agonist
▫Symmetrel
▫Eldepryl & Azilect
▫Anticholinergic
– Artane
– Cogentin
▫COMT Inhibitors
– Tasmar
– Comtan

SINEMET
▫Levodopa, Carbidopa
▫Is most commonly prescribed and most effective drug, especially for rigidity & Bradykinesia
▫Levadopa transported to nerve cells in the brain that produce dopamine
▫Sinemet is made up of Levadopa & Carbidopa
▫Levodopa enters brain & converted to dopamine
▫Carbidopa increases its effectiveness and prevent or lessens many of the side effects of Levadopa

DOPAMINE AGONIST
▫Requip, Mirapex, Neupro
▫Activate Dopamine receptor
▫Mimic or copy the function of dopamine in brain
▫Are first choice of drug
▫Do carry a risk of short-term side effect such as nausea, Vomiting, Dizziness, Light headedness, hallucination

SYMMETREL
▫For mild Parkinson’s Disease
▫cause side effects including confusion and memory problem
▫increases the amount of dopamine available for use in brain
▫reduce involuntary movement (dyskinesia) associated with Levadopa therapy

ELDEPRYL & AZILECT
▫Eldepryl may slow the progression of Parkinson’s Disease
▫Eldepryl- Common side effects include nausea, Dizziness/Fainting, Stomach pain
▫Azilect- Side effects include headache, Joint pain, Indigestion, Depression

COMT INHIBITORS
▫Tasmar, Comtan
▫When COMT is blocked, dopamine can retain .
▫Increase the effectiveness of Levadopa

ANTICHOLINERGIC
▫Artane, Cogentin
▫Used to restore the balance between two brain chemicals : Dopamine & Ach
▫Can impair memory and thinking

PHARMACOKINETICS
▫Only about 1-3% of administrated levodopa enters the brain unaltered. The remaining is metabolized extra-cerebrally, decarboxylation to dopamine.
▫Dopamine doesn’t enter Blood Brain Barrier
▫Plasma level of Levadopa are higher, Plasma half-life is longer and more dopa is available for entry into the brain

PHARMACOLOGICAL ACTION OF ANTI-PARKINSONISM DRUGS
(1) Levadopa as immediate precursor of dopamine

Increase dopamine production within the basal ganglia

(2) MAO-B Inhibitors (selegiline) block a major pathway in dopamine metabolism

Increase the duration of action of dopamine

(3) Dopamine receptor agonists (pramipexole, pergolide, bromocriptine) directly activate dopamine receptors on postsynaptic neurons
(4) Anti cholinergic drugs block the increased excitatory activity of cholinergic Interneuron on outflow pathway from basal ganglia

Is secondary to loss of inhibitor action of dopamine on these cholinergic Interneurons
(5) COMT Inhibitors (with central actions) block an alternate pathway in the metabolism of dopamine

ADVERSE EFFECT OF ANTI-PARKINSONISM DRUGS
▫Gastrointestinal Effects :: Anorexia, Vomiting
▫Cardiovascular Effects :: Cardiac Arrhythmia, Postural hypotension
▫Dyskinesia :: Choreoathetosis of face and distal extremities
▫Behavioural Effects :: Depression, Anxiety, Confusion, Insomnia, Euphoria etc.
▫Fluctuations in Response :: on-off phenomenon

CONTRAINDICATION
▫Psychotic patients
▫Active peptic ulcer (GI bleeding)
▫History of Melanoma
▫Angle closure glaucoma

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