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Y2 LCRS - Pharm (additional) > Anti-PD drugs & Neuroleptics > Flashcards

Anti-PD drugs & Neuroleptics Flashcards

1
Q

What are the two dopamine removal mechanisms?

A

1) removal from synapse by transporters

2) enzymatic breakdown by dopamine

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2
Q

Outline the mechanism of removal of dopamine from the synapse

A

dopamine transporter/noradrenaline transporter

–> dopamine re-uptaken into neuronal glial cells

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3
Q

Which three enzymes break down dopamine in the synaptic cleft?

A

MAO-A
MAO-B (selective for dopamine)
COMT –> both intracellular + extracellular
acts both in the synaptic cleft + inside neuronal glial cells

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4
Q

How is dopamine produced?

A

L-tyrosine –> L-DOPA (enzyme = tyrosine hydroxylase)
L-DOPA –> Dopamine (enzyme = DOPA decarboxylase)
–> neuron activated –> dopamine released

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5
Q

What are the four main dopaminergic pathways and what pathologies are they involved in?

A 
Nigrostriatal pathway:
- SNc --> striatum (PD)
Mesolimbic pathway:
- VTA --> NAcc (schizophrenia)
Mesocortical pathway:
- VTA --> cerebellum (schizophrenia)
Tuberoinfundibular pathway:
- AN --> ME (inhibition = hyperprolactinaemia)
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6
Q

What genes are implicated in PD?

A

SNCA

LRK2

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7
Q

What is the pathophysiology of PD?

A

severe loss of dopaminergic projection cells in SNc
Lewy bodies + neurites
Abnormally phosphorylated neurofilaments, ubiquitin + a-synuclein

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8
Q

How does PD clinically present?

A

Motor symptoms –> resting tremor, bradykinesia, rigidity, postural instability
ANS effects –> olfactory deficits, hypotension, constipation
Neuropsychiatric effects –> sleep disorders, memory deficits, depression, iritability

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9
Q

What are the main ways PD is treated?

A

Dopamine replacement
Dopamine receptor agonists
MAO B inhibitors

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10
Q

How do you replace dopamine in PD?

A

give L-DOPA –> can cross BBB –> rapidly converted to DA (E= DOPA-Decarboxylase)
N.B. can’t give tyrosine as it won’t be converted, can’t give straight dopamine as it causes nausea + vomiting

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11
Q

What are the side effects of dopamine replacement therapy?

A

SE: dyskinesias + ON/OFF effects

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12
Q

How do you prevent nausea + vomiting in dopamine replacement therapy?

A

nause + vomiting caused by PERIPHERAL breakdown of L-DOPA –> give with adjuncts:
DOPA-Decarboxylase inhibitors –> Carbidopa + Benserazide
COMT inhibitors –> Entacapone + Tolacapone
can’t cross BBB, prevent peripheral breakdown of L-DOPA

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13
Q

What are the two types of dopamine receptor agonist? (+ examples of each)

A

Ergot derivatives –> Bromocriptidine + Pergotide

Non-ergot derivatives –> Ropinirole

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14
Q

Which type of dopamine receptor agonist is better + why?

A

non-ergots are better as they are not associated with cardiac fibrosis

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15
Q

Give an example of a MAO B inhibitor

A

Selegiline

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16
Q

What are the positive symptoms of schizophrenia?

A 
upregulates mesolimbic dopaminergic pathway
hallucinations
delusions
thought disorder (denial about oneself)
17
Q

What are the negative symptoms of schizophrenia?

A

decreased mesocortical dopaminergic activity
affective flattening –> lack of emotion
alogia –> lack of speech
avolition/apathy –> loss of motivation

18
Q

What is another name for an anti-psychotic?

A

neuroleptic
(1st gen AP = typical neuroleptic)
(2nd gen AP = atypical neuroleptic)

19
Q

Give some examples of first generation anti-psychotics

A

Chlorpromazine

Haloperidol

20
Q

How do first generation anti-psychotics work?

A

D2 receptor antagonists

21
Q

What are their side effects?

A

Chlorpromazine –> anti-cholinergic, esp sedation, + extrapyramidal (EP)
Haloperidol –> EP

22
Q

Give some examples of second generation anti-psychotics + their mechanisms of action

A

Clozapine –> 5HT2A receptor antagonist
Risperidone –> 5HT2A receptor antagonist
Quetiapine –> H1 agonist
Apipiprazole –> partial agonist of D2 + 5HT1A receptors

23
Q

Which is the only drug to treat both the positive and negative symptoms of schizophrenia?

A

Clozapine

24
Q

What are the side effects of the anti-psychotic drugs?

A

Chloropromazine –> anti-muscarinic side effects
Haloperidol –> EPS
Clozapine –> agranulocytosis
Risperidone –> weight gain + EPS
Quetiapine –> EPS (low)
Aripiprazole –> hyperprolactinaemia (low)

Y2 LCRS - Pharm (additional) (4 decks)

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