Parkinson's Disease Flashcards by Kofi Antwi

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

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Why isn’t dopamine given directly to the patient?

Dopamine can’t cross the blood brain barrier to act directly

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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.

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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

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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

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What is the mechanism of action of Dopamine receptor agonists?

-Dopamine receptor Agonist

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What are examples of non-ergot derived dopamine receptor agonist?

Ropinirole
Pramipexole
Rotigotine
Apomorphine

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What are advantages of dopamine receptor agonists?

Direct acting
Less dyskinesias/motor complication
Possible neuroprotection

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What are physical side effects of dopamine receptor agonists?

Nausea
Postural Hypotension
Psychosis
Confusion
Sedation

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What are disadvantages of dopamine receptor agonists?

Less efficacy than L-DOPA
Impulse control disorder
More psychiatric
Expensive

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What are psychological side effects of dopamine receptor agonists? (impulse control disorders)

Pathological gambling
Hypersexuality, compulsive shopping
Desire to increase dosage
Punding

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What are examples of Monoamine oxidase B inhibitors?

Selegiline

- Rasagaline

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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

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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

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What are examples of anticholinergics?

Trihexyphenidydyl
Orphenadrine
Procyclidine

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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

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What are the advantages of using anticholinergics in treatment of Parkinson’s disease?

Treat tremor

- Not acting via dopamine systems

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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