Parkinson's Flashcards
What is Parkinson’s
slowly progressive degenerative CNS disorder
Characteristics of Pakinson’s
Tremor
Rigidity
Bradykinesia
Postural DIsturbances
Aetiology of primary Parkinson’s
Loss of Dopamine-producing neurons in substantia nigra= deficiency of DA in Basal Ganglia.
What is the neurotransmitter imbalance caused by Parkinson’s
Too little DA (low inhibitory) and too much ACh (high excitatory)
Cause of Tremors
due to involuntary skeletal muscle contractions
When is a tremor at its maximum
during rest
Is a tremor present during sleep
Nope
How does a tremor start
may start in Upper extremity, spread to ipsilateral LL and then to contralateral limb
Cause of rigidity
Due to continuous mucle contraction
What is Bradykinesia
slowness and poverty of movement
What is Hypokinesia
Muscular movements performed with decr. range of motion
Cause of Postural disturbance
there is loss of postural reflexes = tendency to fall forward (propulsion) or backward (retropulsion) when center of gravity is displaced
What other symptoms may be seen in Parkinson’s
Speech may be affected
Depression: common
Dementia: common
Which Dopaminergic agents are used?
DA precursors
DA R agonists
COMT inhibitors
MAO Type B inhibitors
Which are the DA precursor drugs
Levodopa
Which are the DA Receptor agonists
Bromocriptine
Ropinirole
Pergolide
Pramipexole
Apomorphine
Which are the COMTi drugs
Tolcapone
Entacapone
Which are MAO Type B inhibitors
Selegiline
Rasagiline
Which Anticholinergic agents are used
TBB
Trihexyphenidyl
Benzotrpine
Biperidin???
MOA of Levodopa
Is a DA precursor= facilitates synthesis of DA in brain
–> restores Dopaminergic neurotransmission in neostriatum by enhancing DA synthesis in surviving neurons of Substantia nigra
How is Levodopa therapy initiated (dosage)
With small doses and gradually increased
How effective is Levodopa therapy
not effective
Therapy loses its effectiveness after 2 years of use
Type of Parkinson Levodopa has no effect on
Drug-induced Parkinson
Where is Levodopa absorbed
in SI
What inactivates Levodopa
MAO in SI
Enzyme that converts Levodopa to DA
Dopa Decarboxylase.
Distribution of Levodopa
95% converted to DA in peripheral tissue; <1% enters brain
What interferes with Levodopa transport into CNS
ingestion of high protein meals
How should Levodopa be taken
On an empty stomach (at least 30mins before meals)
AE of Levodopa
Anorexia
Nausea
Psychiatric disturbances
Incr. HR
Mydriasis
Decr. BP
On-Off effect: rapud fluctuations in clinical state- hypokinesia and rigidity may suddenly worsen then improve
Development of involuntary choreiform movements- usually affecting face and limbs
Drugs that improve Levodopa efficacy
Carbidopa: peripheral Dopa-decarboxylase inhibitor
Selegiline: MAO-B inhibitor–> inhibits DA degradation in CNS
Rasagiline: irreversibly inhibits MAO-B
Domperidone: Peripheral dopamine antagonist
SE of Levodopa+Selegiline
HTN crisis
Insomnia
Potency of Rasagiline
5x more potent than Selegiline
SE of Levodopa+Rasagiline
Doesn’t cause insomnia
MOA of Entacapone
Selective reversible inhibitor of COMT
=prevents metabolism of Levodopa to 3-O-methyldopa–>
decr. palsma conc. of 3-O-methyldopa
Incr. central uptake of Levodopa
Incr. conc. of DA in brain
What is 3-O-methyldopa
A metabolite of Levodopa that competes with Levodopa for active transport into the CNS
SE of Entacapone
GI upsets
Postural Hypotension
Hallucinations
Sleep disorders
SE of Tolcapone
Associated with hepatic necrosis
MOA of Bromocriptine
Is a Dopamine Receptor Antagonist
Is a ergot derivative
Cons of Bromocriptine
it has many AEs
its very expensive
Caution when using Bromocriptine
MI or Peripheral Vascular disease
When is Bromocriptine used
Only for cases that cannot be effectively treated with Levodopa
AE of Bromocriptine that occur during first few months of use
Nausea
Dizziness
Drowsiness
Postural Hypotension
AE of Bromocriptine that occur at high doses over longer periods
Dyskinesia
Hallucinations
Confusion
Behavioural Abberations
What does Bromocriptine exacerbate
Peptic ulcers
Common AEs of Bromocriptine
Dementia
Depression
What is Amantadine
An anti-viral agent with moderate anti-Parkinson activity
When is Amantidine useful
useful as monotherapy for early, mild Parkinsonism
Can be used in combination with Levodopa
Effectiveness of Amantidine
It loses its effectiveness after several months
MOA of Amantidine
Releases DA from its stores and inhibits the re-uptake of DA from the synaptic cleft
AEs of Amantidine
Discolouration of the skin (esp. legs and oedema of ankles)
Pulmonary pleursis
Stops milk production (decr. prolactin)
Acute MI
CI of Amantadine
PVO
MI
Cardiac vascularity
AEs of Amantadine that may occur at high doses
Psychotic episodes
Convulsions
Nausea
MOA of Anticholinergics (antimuscarinics)
competitively antagonize ACh at MR.
They can cross BBB because they are lipphilic
Indications of Biperiden
Parkinsonism
When is an injection of Biperiden useful
it can be useful for rapid control of drug-induced acute dystonic reactions
AEs of Biperiden
Usual Anti-muscarinic effects
Pronounced drowsiness
Urinary retention
Visual disturbance
Aggrevation of glaucoma
Postural hypotension
Euphoria
Aberrations of co-ordination ???
What is Orphenadrine
Its an anti-histamine with anticholinergic effects
When is Orphenadrine used
for treatment of mild Parkinsonism
for elderly patients who cannot tolerate the potent parasympatholytic drugs
AEs of Orphenadrine
Drowsiness
Para-sympatholytic SEs: dry mouth, visual disturbance, urinary retention, constipation
Concurrent intake of alcohol or sedative may cause excessive sedation
Uses of Trihexyphenidyl/ Benztropin
its used for both idiopathic and drug-induced Parkinsonism.
What do Trihexyphenidyl/ Benztropin relieve
tremors due to Parkinsonism
What do large doses of Trihexyphenidyl/ Benztropin do
they induce a feeling of mental well-being and as such is abused for this feeling
AES of Trihexyphenidyl/ Benztropin
Parasympatholytic SEs: dry mouth, blurred vision, dizziness and nausea occur at beginning of therapy
Elderly: constipation and urinary retention
Tachycardia
Drowsiness
CI of Anticholinergics
Prostatic Hypertrophy: aggravate urinary retention associated with Prostatic Hypertrophy
Glaucoma: icr. IOR= exacerbate it
GI Obstruction
