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Cpt > Neurologicall Pharmacology > Flashcards

Neurologicall Pharmacology Flashcards

1
Q

What is IPD?

A

Idiopathic PArkinsons disease:
• Neurodegenerative disorder - don’t know why the neurones degenerate
• Progressive clinical course - not symmetrical, one sided
• Motor symptoms improve with levodopa
• Non motor symptoms

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2
Q

What are the clinicl features of parkinsonism

A
  • Tremor* - Pill rolling tremour , very small amplitude
  • Rigidity* -
  • cog wheel rigidity - when patients move wrist through arc, can feel cog wheeling
  • lead pipe rigidity = same thoughout bend. Can have resistance, then give

• Bradykinesia** Caused by low dopamine state.
Degeration of opamine neurones
in substantia nigra low dopamine
in particular causes bradykinesia

• Postural instability

*low dopamine and disturbance
other neurotransmitter levels
**low dopamine

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3
Q

What are non-motor manifestations of parkinsonism

A
  • Mood changes
  • Pain
  • Cognitive change - dementia
  • Urinary symptoms
  • Sleep disorder - rem sleep behavious disorder
  • Sweating,e xcessive drooling
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4
Q

Describe the prognosis in PD

A

• 94% Dyskinesia - involuntary writhing movements caused by l-dopa
• 81% Falls - not a feature of early parkinsons
• 84% Cognitive decline (50%
hallucinations) - due to synuclein deposits which damage cells
• 80% Somnolence - exacerbated by drugs
• 50% Swallowing difficulty - a lot of drugs are oral
• 27% Severe speech problems - very very low volume

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5
Q

How can IPD be diagnosed

A
  • Clinical Features
  • Exclude other causes of Parkinsonism
  • Response to Treatment
  • Structural neuro imaging is normal
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6
Q

What are other causes of parkinsonism

A
  • Drug induced PArkinsonism
  • Vascular parkinsonism
  • Progressive supranuclear palsy
  • Multiple systems atrophy
  • Corticobasal degeneration
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7
Q

What is a DAT scan?

A
  • Labelled tracer
  • Presynaptic uptake
  • Abnormal in PD
  • Not diagnostic
  • Tremor
  • Neuroleptic
  • Vascular

Labelling ability to reuptake dopamine. Asymmetrical ii Parkinson’s . This isnt a scan
for Parkinson’s. Any conditions that damages the basal ganglia, will have abnormal
scan. These scans - if someone has a tremor - we do the scan - if it’s normal - a
tremor but for reasons that aren’t Parkinson’s if the skkan is normal. Euroleptic
drugs - tip someone to a tendency for Parkinson’s or might cause extrapyramidal
side effects. If your not sure in someone taking these drugs - ifi it’s normal, its the
drugs. If its not normal - combination of both

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8
Q

Describe the pathology of IPD

A 
• Neurodegeneration
• Lewy bodies 
– synucleinopathy
• Loss of pigment – 50% loss->symptoms
– Increased turnover
– Upregulate receptors
• Reduced dopamine
Cell bodied in substantiaa nigra -
dopamnergic cells.. n PID those
cells disappeared. Motor symptoms
dont manifest until 50% lost.
Already lost half the neurones.
Need to predict so they can be
treated before
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9
Q

Describe catecholamine synthesis

A

ss

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10
Q

Describe dopamine degradation

A

ss

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11
Q

What are drug classes used in IPD?

A
  • Levodopa (L-DOPA)
  • Dopamine receptor agonists
  • MAOI type B inhibitors
  • COMT inhibitors
  • Anticholinergics
  • Amantidine
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12
Q

Why is dopamine not used in IPD treatment?

A

does nto cross the bbb

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13
Q

What is L-dopa?

A

Levodopa must be taken up by dopaminergic cells in the substantia nigra
to be converted to dopamine. Fewer remaining cells - less reliable effect
of levodopa- motor fluctuations

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14
Q

Describe the PK of l-dopa

A
  • Oral administration
  • Absorbed by active transport • In competition with amino acids (NB high protein meals)
  • 90% inactivated in intestinal wall • monoamine oxidase & DOPA decarboxylase
  • T1/2 2 hours

• short dose interval
• fluctuations in blood levels and symptoms
• (physiologically dopamine is produced tonically)
• 9% converted to dopamine in peripheral tissues
• DOPA decarboxylase
• <1% enters CNS
• Again competes with amino acids for active transport across blood brain
barrier

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15
Q

What is l-dopa used in combination with and why

A 
L-DOPA is used in combination with a peripheral DOPA
decarboxylase inhibitor :
• Co-careldopa - Sinemet
• Co-beneldopa - Madopar
• Reduced dose required
• Reduced side effects
• Increased L-DOPA reaching brain
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16
Q

How do peripheral dopa decarbocylase inhibitors work?

A

Inhibit peripheral dopa decarboxylase, less l-dopa metabolised

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17
Q

What are the formulations of L-dopa?

A

Tablet formulations only
– Standard dosage – variable strengths
– Controlled release preparations (CR)
– Dispersible Madopar (not soluble)

18
Q

What are the advantages of L-DOPA

A 
Advantages
• Highly efficacious
• Low side effects
• Nausea/ anorexia
– Vomiting centres
• Hypotension
– central and peripheral
• Psychosis
– Schizophrenia-like
effects.
Hallucination/
delusion/ paranoia
• Tachycardia
Low ish side effects but may
be nauseous can give anti
emetic but avoid dopamine
blcokers like
metacloperamide. Give
domperidone which one
interfere.. need to get use to
feeling o dizziness when they
stand up can exacerbate
psychiatric effect and
increase hallucinations
19
Q

What are the disadvantages of L-dopa?

A

Disadvantages
• Precursor

• needs enzyme
conversion
• Long term

• Loss of efficacy (Only
effective in presence of
dopaminergic neurones)
• Involuntary movements
• Motor Complications
– On / off
– Wearing off
– Dyskinesias
– Dystonia
– Freezing

If interval is too long for
patient - if they eed bigger/
longer dose can feel need
before wearing of . Dystonia.

  • overuse and underuse of l-
    dopa not sure which. In
20
Q

What are DDIs of L-dopa?

A

• Pyridoxine (vitamin B6) increases peripheral
breakdown of L-DOPA

  • MAOIs risk hypertensive crisis
  • (not MOABIs at normal dose-lose specificity at high dose)

• Many antipsychotic drugs block dopamine receptors
and parkinsonism is a side effect (newer, ‘atypical’
antipsychotics less so)

21
Q

Wha are some examples of dopamine receptor agonists?

A

De Novo therapy
Add on therapy

• Non Ergot Ropinirole
Pramipexole

  • Patch Rotigotine
  • Subcutaneous Apomorphine - only for patients with severe motor fluctuations

No longer used:
• Ergot derived Bromocryptine
Pergolide
Cabergoline

22
Q

What are advantages of DRAs?

A 
Advantages
• Direct acting - doesnt need to be converted
• Less dyskinesias/
motor complications
• Possible
neuroprotection
23
Q

What are disadvantages of DRAs?

A 
Disadvantages
• Less efficacy than
L-DOPA
• Impulse control
disorders
• More psychiatric s/e
  • Dose limiting
  • Expensive
24
Q

What are examples of impulse control disorders?

A
  • Pathological Gambling
  • Hypersexuality
  • Compulsive Shopping
  • Desire to increase dosage
  • Punding - collecting and storing
25
Q

What are DRA side effects

A
  • Sedation
  • Hallucinations
  • Confusion
  • Nausea
  • Hypotension

Older the patient 0 more likely
to have pd. may have slight
dementia or confusion. Dont
want to onfoun

26
Q

What is monoamine oxidase B

A
  • Monoamine oxidase B
  • Metabolises dopamine
  • Predominates in dopamine containing regions in brain
  • MAOB inhibitors enhance dopamine
27
Q

What are examples of MAOI type B inhibitors

A

• Monoamine oxidase B inhibitors

  • Selegiline
  • Rasagaline
28
Q

What are the effects of MAOI-B inhibitors

A
  • Can be used alone
  • Prolong action of L-DOPA
  • Smooths out motor response
  • May be neuroprotective
29
Q

What are COMT inhibitors

A

• Catechol-O-methyl Transferase (COMT)
Inhibitors
• Entacapone – doesn’t cross BBB
reduce peripheral breakdown of l-dopa

No longer used:
• Tolcapone – crosses BBB but main effect peripheral

» Monitor liver function

30
Q

What are the effects of dCOMMT inhibitors

A

• Reduce peripheral breakdown of L-DOPA to 3-O-methyldopa
» 3-O-methyldopa competes with L-DOPA active transport into CNS

• No therapeutic effect alone

» Can use combination tablets COMT inhibitor and L-DOPA and
peripheral dopa decarboxylase inhibitor - Stalevo

• Have L-DOPA ‘sparing’ effect
• Prolongs motor response to L-DOPA
» Reduces symptoms of ‘wearing off’

31
Q

Describe the usage of Anticholinergics in pd

A

Acetyl Choline may have antagonistic effects to
dopamine

  • Trihexyphenidydyl
  • Orphenadrine
  • Procyclidine

• Minor role in treatment of PD

These do not affect
bradykinesia and rigidity bc
those are dopamine effects.
But t helps with tremor.but
it makes pl confused. Less
beneficial effects and too
many side effects to have a
major role. Tremor had less
impact then stiffness and
slowness.
32
Q

What are the advantages of anticholinergics

A

Advantages

• Treat tremor
• Not acting via
dopamine systems

33
Q

What are the disadvanteges of anticholinergics

A

Disadvantages

• No effect on
bradykinesia
• Side effects
• Confusion
• Drowsiness
• Usual anticholinergic s/e
34
Q

What is amantadine

A

• Mechanism action uncertain – possibly

  • enhanced dopamine release
  • Anticholinergic NMDA inhibition
  • Poorly effective
  • Few side effects
  • Little effect on tremor
35
Q

what are some surgery options for PD?

A
  • Carried out stereotactically
  • Of value in highly selected cases
  • Dopamine responsive
  • Significant side effects with L-DOPA
  • No psychiatric illness
  • Controlled trials
  • Lesion
  • Thalamus for tremor
  • Globus Pallidus Interna for dyskinesias
• Deep brain stimulation
• Subthalamic nucleus 
Dont destroy any brain
tissue. Put an electrode
into subthalamic nucleus.
Have to be dopamine
reposnisve but nto able to
take l dopa
36
Q

What is Myasthenia Gravis?

A

• Fluctuating, fatiguable, weakness skeletal
muscle
– Extraocular muscles – commonest presentation
– Bulbar involvement – dysphagia, dysphonia, dysarthria
– Limb weakness – proximal symmetric
– Respiratory muscle involvemeng

Double vision + ptosis and weakness common and possible slurring or speech/problem
swallowing - indicates MG

O sensory involvement - post
synaptic probelm. Extraoccula
muscles and bulbar muscles
(speech and swallowing) -
pharynx and larynx — limb Double vision + ptosis and weakness common and possible
37
Q

How do drugs which affect nmj affect MGtransmission

A 
Exacerbate it
• Aminoglycosides
• Beta-blockers, CCBs, quinidine,
procainamide
• Chloroquine, penicillamine
• Succinylcholine
• Magnesium
• ACE inhibitors
What drugs are we not
going to give them. Not
contraindicated but we
are not going to give
these. Safest thing - tell
them I theyre going to
start a thug tell the gp
that u have MG. doesnt
mean u cant abhvae it
but ight interfere
38
Q

What are complications of MG?

A

• Acute exacerbation
– Myasthenic crisis

• Overtreatment
– Cholinergic crisis

Muscles increasingly weak either secondary
to myasthenia crisis but can also be overtreatment - give ache inhibitor - ach is metabolise by esterase - leave ach there so. If oevrtert. Depolarising
block - caused by the treatment. Cant get cholinegic crisis if MG unless on a treatment
that would cause it

39
Q

What is the firts line management for MG

A

• Acetylcholinesterase inhibitors

40
Q

Describe the use of AChE inhibitors in MG

A 
• Acetylcholinesterase inhibitors
– Enhance neuromuscular transmission
– Skeletal and smooth muscle
– Excess dose can cause depolarising block – cholinergic crisis
– Muscarinic side effects

Pyridostigmine - oral
Neostigmine – oral and IV preparations (ITU)
• Quicker action, duration up to 4 hours
• Significant antimuscarinic side effect

41
Q

What is pyridostigmine

A 
• Prevents breakdown of ACh in NMJ
• ACh more likely to engage with remaining receptors
• Onset 30min; peak 60-120min; duration 3-6hr
• Dose interval and timing crucial
• Antimuscarinic side effect –
– miosis and the SSLUDGE syndrome:
» Salivation,
» Sweating,
» Lacrimation
» Urinary incontinence
» Diarrhea,
» GI upset and hypermotility
» Emesis)

Cpt (24 decks)

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