Anti-Parkinson's drugs and neuroleptics Flashcards
Why might Levodopa be an unsuitable drug to treat PD in some cases? What class of drugs are used in these cases?
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
Recall the MOA of clozapine
2nd generation neuroleptic - inhibits the 5HT2A receptor
Recall the MOA of risperidone
Very potent antagonist of DA and 5HT receptors
Recall the side effects of risperidone and where each of them originates
Extra-pyramidal: eg crooked neck - due to D2 antagonism
Hyperprolactinaemia: due to interference with tuberoinfundibular pathway
Recall the target of 1st generation neuroleptics
D2 receptors
What is avolition?
Lack of motivation
What is the main function of the mesolimbic pathway?
Reward
Recall the side effects of clozapine
(SWAMP) Side effects: Weight gain Agranulocytosis Myocarditis Potentially fatal neutropenia
What is the rationale behind using COMT inhibitors as an adjunctive therapy to L-DOPA?
Increase the amount of DA delivered to the brain by reducing peripheral breakdown
Recall the re-uptake transporters of DA
On pre-synaptic terminal: DAT and NET transporters
On glia: DAT
Recall the 4 major neuroanatomical sites of dopaminergic neurons and which regions they run between
- Nigrostriatal tract = Substantia nigra to striatum (most important in PD)
- Mesolimbic pathway = VTA to NA
- Mesocortical area = VTA to cerebrum
- Tubuloinfundibular (endocrine)
Recall the causes of the positive and negative symptoms of schizophrenia
Positive: increased activity in the mesolimbic dopaminergic pathway
Negative: decreased activity in the mesocortical dopaminergic pathway
What adjuncts can be given with L-DOPA to reduce peripheral metabolism and which of these is most common?
DOPA-D (most common)/ COMT/ MAO-A inhibitors
Inhibition of which dopaminergic pathway in the brain causes the motor symptoms of PD?
Nigrostriatal
Why is L-DOPA given in PD instead of tyrosine?
TH is a rate-limiting enzyme
Recall the cardinal symptoms of Parkinson’s disease
Cardinal symptoms = motor symptoms Resting tremor Bradykinesia Rigidity Postural instability
Describe the efficacy of clozapine at treating schizophrenia
Good at treating positive symptoms, but 50 times less potent than haloperidol
What do Lewy bodies consist of?
Abnormally phosphoralated…:
neurofilaments
ubiquitin
alpha-synuclein
Recall the name of a MAO-B-inhibiting drug
selegiline
Recall 2 gene loci associated with Parkinson’s disease development
SNCA
LRRK2
Recall the synthesis pathway of DA
Occurs in synaptic bouton
Tyrosine –> L-DOPA (tyrosine hydroxylase, rate limiting enzyme)
L-DOPA –> DA (DOPA-decarboxylase)
Compare the high-incidence side effects of first generation neuroleptic drug options
Clozapine has anti-MUSCARINIC effects, especially causing sedation
Haloperidol has EXTRA-PYRAMIDAL side effects - especially a crooked neck and muscle disorders
Recall the indications for clozapine treatment
Must be treatment-resistant schizophrenia as side-effect profile is significant
Recall the names of 2 COMT-inhibiting drugs
Entacapone
Tolecapone
