Lecture 23 - Neuropharmacology Flashcards by Callum Donoher

What is idiopathic Parkinson’s disease?

Neurodegenerative disorder where we lose dopaminergic neurones in the substantia Nigra so the basal ganglia (putamen) receive less dopamine

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What structures can form in Idiotpathic Parkinson’s disease?

Lewy bodies

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What occurs in the basal ganglia due to lack of dopamine in IPD?

Loss of dopaminergic neurones in substantia nigra pars compacts means neostriatum isn’t inhibited as much

More ACh is made which impairs mobility

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What are the 4 main clinical features of Parkinsonism?

Rest tremor
Lead pipe rigidity
Bradykinesia
Postural instability

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What is the rest tremor that is seen in Parkinson’s?

Its a low frequency pilll rolling tremor which disappears when you ask a patient to do a movement

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What is lead pipe rigidity that is seen with Parkinsonism?

Where you try and move the patients limb and there’s resisitance all the way

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What is bradykinesia?

Slow in intiating movements
Shuffling steps
Lack. Of arm swinging

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How do you diagnose Idiopathic Parkinson’s disease?

Clinical features of Parkinson’s (BRADYKINESIA is main one)

Must also respond to treatment of Levodopa

Structure neuro imaging is normal and other causes of parkinsonism has been ruled out

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What are some non motor manifestations of Parkinson’s?

Mood changes
Hallucinations
Cognitive change
REM sleep disorder

Restless leg
Fatigue
Pain
Urinary symptoms
Sweating
Low blood pressure

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What is the prognosis in Parkinson’s disease after 15years?

Most people get:
-dyskinesia (involuntary movements)
-falls
-cognitive decline (some hallucinations)
-somnolence (drowsiness and sleepiness)
-Swallowing difficulty
-hypophonia (quiet)

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Describe the process of dopamine release at a synaptic cleft:

Depolarisation of dopaminergic neurone leads to Ca2+ influx
Ca2+ binds to vesicles contacting dopamine
Vesicles bind to presynaptic membrane and release contents (dopamine) into synaptic cleft via exocytosis

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What is the gold standard drug for treating idiopathic Parkinson’s disease?

Levodopa

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Why dont we just use dopamine to treat Parkinson’s?

Dopamine cant cross BBB whereas levodopa does
Also dopamine would cause peripheral adverse effects

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Why does levodopa have a very limited effect in late stage Parkinson’s?

Levodopa works by the functioning dopaminergic neurones converting levodopa to dopamine
So in late stage Parkinson’s there are very few functioning dopaminergic neurones so little L-dopa is converted to dopamine

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How is levodopa administered?

Oral administration

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How is levodopa absorbed?

Active transport

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What enzymes inactivate levodopa in the gut wall?

Monoamine oxidase
Dopa decarboxylase

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Why does levodopa need regular dosing?

Short half life (2hrs)
This leads to fluctuations in blood levels and symptoms

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What is levodopa always prescribed with?
Why?

Peripheral dopa decarboxylase inhibitor

To prevent the conversion of levodopa into dopamine in the peripheries

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What is the drug given with levodopa which is a peripheral dopamine decarboxylase inhibitor?

Carbidopa

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What is the formulation called which contains levodopa and carbidopa?

Sinemet

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Why is the sinemet formulation better than just levodopa?

Reduces dose required and reduced side effects since more levodopa reaches brain

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What are the advantages of levodopa?

Highly efficious
Low side effects:
Nausea/anorexia (vomiting)
Hypotension
Psychosis (schizophrenia, hallucinations)
Tachycardia

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What drug do you not give as an antiemetic caused by giving levodopa and why?

Metoclopramide

Can cause extrapyradimal effects causing Parkinsonian symptoms

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What drug can be used as an anti-emetic caused by levodopa?

Domperidone

What are the disadvantages of levodopa?

Its a precursor so needs conversion Long term: -loss of efficacy -involuntary choreform movements -motor complications: May get rigid Wearing off Dyskinesias Dystopia (limb held in abnormal position) Freezing (will suddenly stop and become rigid)

What vitamin increases the peripheral breakdown of levodopa?

Vitamin B6 (pyridoxine)

What is the interaction of monoamine oxidase inhibitors with levodopa?

Can cause hypertensive crisis

What is the interaction of monoamine oxidase inhibitors with levodopa?

Can cause hypertensive crisis

What is the interaction of monoamine oxidase inhibitors with levodopa?

Can cause hypertensive crisis

What drugs can block dopamine receptors and cause Parkinsonism as a side effect?

Antipsychotic drugs

What is the point of giving levodopa with a Catechol-O-methyl Transferase (COMT) inhibitor?

Decreases breakdown of levodopa so prolongs the motor repsonse to levodopa

What are some COMT inhibitors given with levodopa? Can they cross the BBB?

Entacapone Opicapone Can’t cross BBB

What is the effect of giving COMT inhibitors by themselves? Why?

No therapeutic effect since doesn’t cross the blood brain barrier so is never given alone

What are some dopamine receptor agonists?

Ropinirole (tablet) Pramipexole (tablet) Rotigotine (patch) Apomorphine (subcutaneous)

When is apomorphine given? How is it given? What type of drug is this?

For patients with severe motor fluctuations Subcutaneously Dopamine receptor agonists

What are the advantages of dopamine receptor agonists?

Direct acting on receptors Less dyskinesias and motor complications Possible neuroprotection

What are the disadvantages of dopamine receptor agonists?

Less efficacy than levodopa Impulse control disorders More psychiatric s/e like hallucinations Expensive

What are some impulse count troll disorders that are caused by dopamine receptor agonists?

Can lose ability to control impulsiveness -pathological gambling -hypersexuality -compulsive shopping -desire to increase dose -punding

What is punding?

Compulsive sorting of things

What are the side effects of dopamine receptor agonists?

Sedation Hallucinations Confusion Nausea Hypotension

What drug do you give to a patient having severe motor fluctuations with Parkinson’s? How do you administer it?

Apomorphine Subcutaneously (dopamine receptor agonist)

What is the function of monoamine oxidase B? What effect do monoamine oxidase B inhbitors have?

Metabolises dopamine So inhibitors MAOB so dopamine is enchanced/stays around longer

What are some examples of monoamine oxidase B inhbitors?

Rasagaline Safinamide

What are some examples of anticholinergics to help treat Parkinson’s disease?

Trihexyphenidydyl Orphenadrine Procyclidine

What are the advantages of anticholinergics?

Treat tremor Not acting via dopamine systems

What are disadvantages of anticholinergics?

Doesnt help the bradykinesia Confusion Drowsiness

When is Amantadine rarely used for Parkinson’s?

When levodopa is inducing dyskinesia (choreiform movements)

What are the side effects of amantadine?

Hallucinations Confusion

When are Parkinson’s patients eligible for surgery?

Need good response to levodopa No psychiatric illness Significant side. Effects with levodopa so that’s not an eligible treatment

What are some consequences of not reveinving enough l-dopa?

L dopa withdrawal Severe akinnetic mutism Life threatening neuroleptic malignant syndrome (confusion, rigidity, fever, autonomic dysregulation)

What are some consequences of withdrawal from dopamine agonists?

Dopamine agonist withdrawal syndrome (DAWS) Neurophsyciatric symptoms (agitation, antic, anxiety, depression) autonomic symptoms

What is the pathophysiology of myasthenia Gravis?

Auto immune antibodies attatching to post synaptic ACh receptors blocking signals reaching muscle

What are some symptoms of myasthenia Gravis?

Flucatuating Fatiguable Weakness of skeletal muscle Extraocularmusucels Bulbar involvement (Dysphagia, dysphonia) Limb weakness Resp. Muscle involvement

What is meant by fatiguable in myasthenia gravis?

Muscles that are being used get weaker as you use it for seconds to minutes They will be back to full strength after rest for a couple mins

What are some drugs that can worsen myasthenia gravis?

Aminoglycosides B blockers Chloroquine Magnesium ACE inhibitors Syuccinylcholine

What are some complications of myasthenia gravis?

Acute exacerbation (myasthenic crisis) Overtreatment (cholinergic crisis)

What is the most commonly used drug to treat myasthenia?

Pyridostigmine

What is the mechanism of action of pyridostigmine?

Acetylcholinesterase inhibitors

What drugs except pyridostigmine can be used for myasthenia gravis?

Corticosteroids decrease immune response Steroid sparing drugs like azathioprine

What effects does pyridostigmine have?

Enhances neuromuscular transmission Skeletal and smooth muscle Excess does can cause depolarising block (paralysis) cholinergic crisis Muscarinic side effects (gut churning, diarrhoea, bradycardia)

When is neostigmine given? How is it given? Why is it only given here?

In the ITU Oral and IV Acts much quicker than neostigmine but causes SIGNIFICANT anti Muscarinic side effects

Why is the dosing interval for pyridostigmine crucial?

If not given on time can get Dysphagia, dysarthria and respiratory depression

What are the muscarinic side effects of pyridostigmine?

Miosis SLUDGE Salivation Sweating Lacrimation Urinary incontinence Diarrhoea GI upset and hypermotility Emesis

When do you dose patients withi pyridostigmine in relation to their meals and why?

40 to 60mins before meals to optimise swallowing Since it has peak actioon after 60 mins

Lecture 23 - Neuropharmacology Flashcards

(65 cards)