Parkinson's Disease Flashcards
What is the mechanism of action of L-DOPA?
L-DOPA can cross the blood brain barrier where it is converted to dopamine by dopa decarboxylase
Why isn’t dopamine given directly to the patient?
Dopamine can’t cross the blood brain barrier to act directly
What is the pharmacokinetics of L-DOPA?
- Oral administration. Absorbed by active transport
- 90% inactivated in intestinal wall by monoamine oxidase & DOPA decarboxylase
- 9% is converted to dopamine in peripheral tissues by DOPA decarboxylase
- Less than 1% enters CNS -
- Half-life is 2 hours. Short dose interval and fluctuations in blood levels and symptoms as a result of this.
What are the side effects of L-DOPA?
- Dyskinesia + dystonia + “freezing”
- Psychosis (schizophrenia-like effects.Hallucination/delusion/paranoia)
- Nausea/vomiting/hypotension
- On and Off
- Wearing off
- Nausea/Anorexia
- Hypotension
- Tachycardia
What are some drug interactions demonstrated with L-DOPA?
- Pyridoxine increases peripheral breakdown of L-DOPA
- Many antipsychotic drugs block dopamine receptors and parkinsonism is a side effect
- MAOIs risk antihypertensive crisis
What is the mechanism of action of Dopamine receptor agonists?
-Dopamine receptor Agonist
What are examples of non-ergot derived dopamine receptor agonist?
- Ropinirole
- Pramipexole
- Rotigotine
- Apomorphine
What are advantages of dopamine receptor agonists?
- Direct acting
- Less dyskinesias/motor complication
- Possible neuroprotection
What are physical side effects of dopamine receptor agonists?
- Nausea
- Postural Hypotension
- Psychosis
- Confusion
- Sedation
What are disadvantages of dopamine receptor agonists?
- Less efficacy than L-DOPA
- Impulse control disorder
- More psychiatric
- Expensive
What are psychological side effects of dopamine receptor agonists? (impulse control disorders)
- Pathological gambling
- Hypersexuality, compulsive shopping
- Desire to increase dosage
- Punding
What are examples of Monoamine oxidase B inhibitors?
- Selegiline
- Rasagaline
What is the mechanism of action monoamine oxidase B inhibitors?
- MAOB metabolises dopamine
- Predominates in dopamine containing region
- MAOB inhibitors enhance dopamine by inhibiting MAOB
What are the advantages of Monoamine oxidase B inhibitors?
- Can be used along
- Prolong the action of L-DOPA
- Smooths out motor response
- May be neuroprotective
What are examples of anticholinergics?
- Trihexyphenidydyl
- Orphenadrine
- Procyclidine
What is the mechanism of action of anticholinergics in the treatment of Parkinson’s disease?
- Acetyl choline may have antagonistic effects to dopamine
- Minor role in treatment of Parkison’s Disease
What are the advantages of using anticholinergics in treatment of Parkinson’s disease?
- Treat tremor
- Not acting via dopamine systems
What are the disadvantages of using anticholinergics in treatment of Parkinson’s disease?
-No effect on bradykinesia
What are side effects of anticholinergics?
- Confusion
- Drowsiness
- Usual anticholinergic effects
What is the mechanism of action of Amantidine?
Unclear but possibly
- Enhanced dopamine release
- Anticholinergic NMDA inhibition
What are the advantages of Amantadine?
-Few side effects
What are the disadvantages of amantadine?
- Poorly efficacious
- Little effect on tremor
How is surgery used to treat Parkinson’s disease?
- Thalamus for tremor
- Globus Pallidus Interna for dyskinesias
- Deep brain stimulation of subthalamic nucleus
What are the uses of Surgery in Parkinson’s disease?
Of value in highly selected cases
- Dopamine response
- Significant side effect with L-DOPA
- No psychiatric illness
What are examples of Carbidopa?
- Co-careldopa (Sinemet)
- Co-beneldopa (Madopar
What is the mechanism of action of Carbidopa?
Peripheral decarboxylase inhibitor to prevent breadown of L-DOPA in peripheries
Why is carbidopa used with L-DOPA?
Used in combination with L-DOPA:
- Reduces dosage of L-DOPA required
- Decreases peripheral side effects
- Increased L-DOPA reaching the brain
What are examples of COMT inhibitors?
-Entacapone
What is the mechanism of action of COMT inhibitors?
- Prevents breakdown of L-dopa in the peripheries
- Also reduces peripheral breakdown of L-DOPa to 3-O-methyl dopa which competes with L-DOPA active transport into CNS
- Therefore, prolongs clinical effects of levodopa (motor response) and reduce wearing off)
What are the pharmacokinetics of COMT inhibitors?
- Doesn’t cross blood brain barrier
- No therapeutic effect alone
What are some physical manifestations of Parkinson’s disease?
- Tremor
- Rigiditiy
- Bradykinesia
- Postural Instability
What are some non-motor manifestations of Parkinson’s disease?
- Mood changes - depression and anxiety
- Pain
- Cognitive change
- Urinary symptoms
- Sleep disorder
- Sweating
- Constipation
How does Myasthenia Gravis present?
- Extraocular muscles - commonest presentation
- Bulbar involvement (dysphagia, dysphonia, dysarthria)
- Limb weakness (proximal symmetric)
- Respiratory muscle involvement
What are some drugs that exacerbate Myasthenia Gravis?
- Aminoglycoside
- Beta blocker, CCBs, Quinidine, Procainamide
- Chloroquine, Penicillamine
- Succinylcholine
- Magnesium
- ACE inhibitors
What are some complications associated with Myasthenia Gravis?
- Acute exacerbation (Myasthenia Crisis)
- Overtreatment (Cholinergic crisis)
Both have the same presentations with over and under-treatment
How is myasthenia graves treated?
-Acetylcholinesterase Inhibitors
What are some examples of acetylcholinesterase inhibitors?
Pyridostigmine (oral)
Neostigmine (oral and IV preparations)
What are some features of Neostigmine?
- Used in ITU
- Quicker action, duration up to 4 hours
- Significant anti-muscarininic side effects
Whats the mechanism of action of acetylcholinesterase inhibitors?
- Enhance neuromuscular transmission by preventing breakdown of Each in neuromuscular junction
- Skeletal and smooth mucle
- Excess dose cause depolarising block (cholinergic crisis)
- Muscarinic side effects with low dose
What is the mechanism of acton of pyridostigmine?
- Prevents breakdown of ACh in neuromuscular junction
- ACh is more likely to engage with remain receptors
What are some features of Pyridostimine therapy?
- Onset is 30 mins
- Peaks at 50-120 mins
- Duration of action is 3-6 hours
Give 30-40 mins before food
What are the anti muscurinic side effects of pyridostigmine?
Miosis and the SLUDGE syndrome
- Salivation
- Sweating
- Lacrimation
- Urinary incontinence
- Diarrhoea
- GI upset and Hyper motility
- Emesis
What are examples of ergot derived dopamine receptor agonist?
-Bromocriptine
Why are ergot derived dopamine receptor agonists no longer used?
-Too many side effects
