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Y2 LCRS Pharm HR > Anti-Parkinson's drugs and neuroleptics > Flashcards

Anti-Parkinson's drugs and neuroleptics Flashcards

1
Q

Why might Levodopa be an unsuitable drug to treat PD in some cases? What class of drugs are used in these cases?

A

PD may be so progressed as for DOPA-D to no longer be present for L-DOPA conversion to DA
Use DA receptor agonists in this case

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2
Q

Recall the MOA of clozapine

A

2nd generation neuroleptic - inhibits the 5HT2A receptor

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3
Q

Recall the MOA of risperidone

A

Very potent antagonist of DA and 5HT receptors

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4
Q

Recall the side effects of risperidone and where each of them originates

A

Extra-pyramidal: eg crooked neck - due to D2 antagonism

Hyperprolactinaemia: due to interference with tuberoinfundibular pathway

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5
Q

Recall the target of 1st generation neuroleptics

A

D2 receptors

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6
Q

What is avolition?

A

Lack of motivation

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7
Q

What is the main function of the mesolimbic pathway?

A

Reward

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8
Q

Recall the side effects of clozapine

A 
(SWAMP)
Side effects:
Weight gain
Agranulocytosis
Myocarditis
Potentially fatal neutropenia
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9
Q

What is the rationale behind using COMT inhibitors as an adjunctive therapy to L-DOPA?

A

Increase the amount of DA delivered to the brain by reducing peripheral breakdown

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10
Q

Recall the re-uptake transporters of DA

A

On pre-synaptic terminal: DAT and NET transporters

On glia: DAT

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11
Q

Recall the 4 major neuroanatomical sites of dopaminergic neurons and which regions they run between

A
  1. Nigrostriatal tract = Substantia nigra to striatum (most important in PD)
  2. Mesolimbic pathway = VTA to NA
  3. Mesocortical area = VTA to cerebrum
  4. Tubuloinfundibular (endocrine)
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12
Q

Recall the causes of the positive and negative symptoms of schizophrenia

A

Positive: increased activity in the mesolimbic dopaminergic pathway
Negative: decreased activity in the mesocortical dopaminergic pathway

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13
Q

What adjuncts can be given with L-DOPA to reduce peripheral metabolism and which of these is most common?

A

DOPA-D (most common)/ COMT/ MAO-A inhibitors

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14
Q

Inhibition of which dopaminergic pathway in the brain causes the motor symptoms of PD?

A

Nigrostriatal

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15
Q

Why is L-DOPA given in PD instead of tyrosine?

A

TH is a rate-limiting enzyme

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16
Q

Recall the cardinal symptoms of Parkinson’s disease

A 
Cardinal symptoms = motor symptoms
Resting tremor
Bradykinesia
Rigidity
Postural instability
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17
Q

Describe the efficacy of clozapine at treating schizophrenia

A

Good at treating positive symptoms, but 50 times less potent than haloperidol

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18
Q

What do Lewy bodies consist of?

A

Abnormally phosphoralated…:
neurofilaments
ubiquitin
alpha-synuclein

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19
Q

Recall the name of a MAO-B-inhibiting drug

A

selegiline

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20
Q

Recall 2 gene loci associated with Parkinson’s disease development

A

SNCA

LRRK2

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21
Q

Recall the synthesis pathway of DA

A

Occurs in synaptic bouton
Tyrosine –> L-DOPA (tyrosine hydroxylase, rate limiting enzyme)
L-DOPA –> DA (DOPA-decarboxylase)

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22
Q

Compare the high-incidence side effects of first generation neuroleptic drug options

A

Clozapine has anti-MUSCARINIC effects, especially causing sedation
Haloperidol has EXTRA-PYRAMIDAL side effects - especially a crooked neck and muscle disorders

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23
Q

Recall the indications for clozapine treatment

A

Must be treatment-resistant schizophrenia as side-effect profile is significant

24
Q

Recall the names of 2 COMT-inhibiting drugs

A

Entacapone

Tolecapone

25
Q

What is the rationale behind using MAO-B inhibitors as an adjunctive therapy to L-DOPA?

A

Reduce the dose required to produce the same effects by increasing the amount of L-DOPA delivered to the brain, therefore reducing the longterm effects

26
Q

Recall the histological changes that occur PD in the SNc

A

Lewy bodies and neurites will be present

27
Q

Recall thepossible sites of metabolism of DA, and the specificities of the enzymes involved

A

May be metabolised by:
MAO-A (specific for DA, NA and 5HT)
MAO-B (specific for DA only)
COMT (metabolises all catecholamines)

28
Q

What is the result of inhibition of the tubuloinfundibular dopaminergic pathway in the brain?

A

Hyperprolactinaemia

29
Q

Which of the non-motor symptoms of Parkinson’s disease are prodromal?

A

Sleep disturbance, anosmia, orthostatic hypotension, constipation

30
Q

Where is the most significant loss of dopaminergic neurons suffered in PD?

A

Substantia nigra compacta

31
Q

What is the main difference between ergot and non-ergot derivative dopamine receptor agonists

A

Ergot derivatives are associated with cardiac fibrosis

32
Q

What is affective flattening?

A

Lack of emotion

33
Q

What is the main difference between 1st and 2nd generation neuroleptics?

A

1st generation = DA receptor agonists

2nd generation = DA and 5HT receptor agonists

34
Q

Recall the MOA of quetiapine

A

5HT antagonist, D2R antagonist, Potent H1 receptor antagonist

35
Q

Recall where each of the enzymes involved in DA metabolism can be found

A

Pre-synaptic terminal: MAO-A+B
Glia: COMT and MAO-A
Post-synaptic terminal: COMT

36
Q

Describe the side effects of apiprazole use

A

Less significant weight gain and hyperprolactinaemia than other neuroleptics

37
Q

What is the other name for neuroleptic drugs?

A

Anti-psychotics

38
Q

Recall examples of 2nd generation neuroleptics

A

Clozapine
Risperidone
Aripiprazole
Quetiaprine

39
Q

What are the long-term side effects associated with L-DOPA administration?

A

Dyskinesias and on-off symptoms

40
Q

Recall the non-motor symptoms of Parkinson’s disease

A

ANS: anosmia, orthostatic hypotension, constipation
Neuropsychiatric: sleep disorders, amnesia, depression, irritability

41
Q

Describe the efficacy of haloperidol at treating schizophrenia

A

50 times more potent than clozapine at treating positive symptoms, but takes 6-8 weeks to become effective. Very little effect on negative symptoms

42
Q

Recall examples of 1st generation neuroleptics

A

Chlorpromazine

Haloperidol

43
Q

Describe the side effects of quetiapine

A

Lower incidence of EPS than other atypical neuroleptics

44
Q

What is the rationale behind using DOPA-D inhibitors as an adjunctive therapy to L-DOPA?

A

Prevents peripheral breakdown of L-DOPA to reduce nausea and vomiting, ensure more un-changed L-DOPA is delivered to the brain

45
Q

Recall the life expectancy reduction in schizophrenia and the reason for this

A

20-30 years

Due to use of drugs of abuse

46
Q

Recall the prevalence of schizophrenia in the UK

A

Around 1%

47
Q

What is alogia?

A

Lack of speech

48
Q

Recall the names of 2 DOPA-D inhibitors

A

Carbidopa

Benserazide

49
Q

Which of the dopaminergic pathways in the brain is most important in schizophrenia?

A

Mesolimbic

50
Q

Which of the neuroleptic drugs is the most effective, out of all the 1st and 2nd generation drugs, and why?

A

Clozapine

Treats both positive and negative symptoms

51
Q

What is the anatomical site of drug interference to produce a crooked neck as a side effect of drug use?

A

Extra-pyramidal

52
Q

What is the MOA of apiprazole?

A

Partial agonist of 5HT2A and D2 receptors, so should moderate these receptors to control both pos and neg symptoms of schizophrenia (but is in reality not that effective)

53
Q

Recall the coupling of D2 receptors and their immediate downstream signalling upon activation

A

Coupled to adenylate cyclase via a Gi protein

Adenylate cyclase linked to ATP–>cAMP, to increase [PKA]

54
Q

Recall the symptoms of schizophrenia

A

Positive: Hallucinations, paranoia, thought disorder
Negative: affective flattening, alogia and avolition

55
Q

What are the immediate side effects associated with L-DOPA metabolism peripherally

A

Activation of CTZ to produce nausea and vomiting

56
Q

Recall the 2 classes of dopamine receptor agonists used in PD treatment and give examples

A

Ergot derivatives: bromocriptine and pergolide

Non-ergot derivatives: ropinirole

Y2 LCRS Pharm HR (31 decks)

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