Anti-Parkinson's drugs and neuroleptics (B) Flashcards
What is the result of inhibition of the tubuloinfundibular dopaminergic pathway in the brain?
Hyperprolactinaemia
What are the non-motor clinical signs of PD?
Autonomic nervous system effects:
olfactory deficits, orthostatic hypotension, constipation
OCO
Neuropsychiatric:
sleep disorders, memory deficits, depression, irritability
DIMS
Where is the most significant loss of dopaminergic neurons suffered in PD?
Substantia nigra compacta (nigro-striatal)
What is the main difference between ergot and non-ergot derivative dopamine receptor agonists
Ergot derivatives are associated with cardiac fibrosis
What is affective flattening?
Lack of emotion
What is the main difference between 1st and 2nd generation neuroleptics?
1st generation = DA receptor antagonists
2nd generation = DA and 5HT receptor antagonists
Recall the MOA of quetiapine
Main function: potent H1 antagonist
Also: 5HT antagonist, D2R antagonist
Recall where each of the enzymes involved in DA metabolism can be found
Pre-synaptic terminal: MAO-A+B
Glia: COMT and MAO-A
Post-synaptic terminal: COMT
Describe the side effects of aripiprazole use
Less significant weight gain and hyperprolactinaemia than other neuroleptics
What is the other name for neuroleptic drugs?
Anti-psychotics
Recall examples of 2nd generation neuroleptics
Clozapine
Risperidone
Aripiprazole
Quetiapine
What are the long-term side effects associated with L-DOPA (levodopa) administration?
Dyskinesias and on-off symptoms
On off symptoms:
Long term Levodopa usage means that the periods of symptom control by the drug becomes shorter and shorter. Eventually, you will only have a short period of good symptom control right after you take the drug (on period) and this is followed by a return of symptoms (off) very quickly. So you end up being in this cycle of on and off
Describe the efficacy of haloperidol at treating schizophrenia
50 times more potent than clozapine at treating positive symptoms, but takes 6-8 weeks to become effective. Very little effect on negative symptoms
Recall examples of 1st generation neuroleptics
Chlorpromazine
Haloperidol
Describe the side effects of quetiapine
Lower incidence of EPS than other atypical neuroleptics
What is the rationale behind using DOPA-D inhibitors as an adjunctive therapy to L-DOPA?
Prevents peripheral breakdown of L-DOPA to reduce nausea and vomiting, ensure more un-changed L-DOPA is delivered to the brain
Recall the life expectancy reduction in schizophrenia and the reason for this
20-30 years
Due to use of drugs of abuse
Recall the prevalence of schizophrenia in the UK
Around 1%
What is alogia?
Lack of speech
Recall the names of 2 DOPA-D inhibitors
Carbidopa
Benserazide
Which of the dopaminergic pathways in the brain are involved schizophrenia?
Mesolimbic (increased activity- positive)
mesocortical (decreased activity- negative)
Which of the neuroleptic drugs is the most effective, out of all the 1st and 2nd generation drugs, and why?
Clozapine
Treats both positive and negative symptoms
What is the anatomical site of drug interference to produce a crooked neck as a side effect of drug use?
Extra-pyramidal
What is the MOA of aripiprazole?
PARTIAL AGONIST of 5HT2A and D2
Recall the coupling of D2 receptors and their immediate downstream signalling upon activation
Coupled to adenylate cyclase via a Gi protein
Gi inhibit AC & and lead to reduced cAMP & PKA
Recall the symptoms of schizophrenia
Positive: Hallucinations, paranoia, thought disorder
Negative: affective flattening, alogia and avolition
What are the immediate side effects associated with L-DOPA metabolism peripherally
Activation of CTZ to produce nausea and vomiting
Recall the 2 classes of dopamine receptor agonists used in PD treatment and give examples
Ergot derivatives: bromocriptine and pergolide
Non-ergot derivatives: ropinirole
