Anti-Parkinson's drugs and neuroleptics (B)

Question 1

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

Answer 1

Hyperprolactinaemia

Question 2

What are the non-motor clinical signs of PD?

Answer 2

Autonomic nervous system effects:
olfactory deficits, orthostatic hypotension, constipation
OCO
Neuropsychiatric:
sleep disorders, memory deficits, depression, irritability
DIMS

Question 3

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

Answer 3

Substantia nigra compacta (nigro-striatal)

Question 4

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

Answer 4

Ergot derivatives are associated with cardiac fibrosis

Question 5

What is affective flattening?

Answer 5

Lack of emotion

Question 6

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

Answer 6

1st generation = DA receptor antagonists

2nd generation = DA and 5HT receptor antagonists

Question 7

Recall the MOA of quetiapine

Answer 7

Main function: potent H1 antagonist

Also: 5HT antagonist, D2R antagonist

Question 8

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

Answer 8

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

Question 9

Describe the side effects of aripiprazole use

Answer 9

Less significant weight gain and hyperprolactinaemia than other neuroleptics

Question 10

What is the other name for neuroleptic drugs?

Answer 10

Anti-psychotics

Question 11

Recall examples of 2nd generation neuroleptics

Answer 11

Clozapine
Risperidone
Aripiprazole
Quetiapine

Question 12

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

Answer 12

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

Question 13

Describe the efficacy of haloperidol at treating schizophrenia

Answer 13

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

Question 14

Recall examples of 1st generation neuroleptics

Answer 14

Chlorpromazine

Haloperidol

Question 15

Describe the side effects of quetiapine

Answer 15

Lower incidence of EPS than other atypical neuroleptics

Question 16

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

Answer 16

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

Question 17

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

Answer 17

20-30 years

Due to use of drugs of abuse

Question 18

Recall the prevalence of schizophrenia in the UK

Answer 18

Around 1%

Question 19

What is alogia?

Answer 19

Lack of speech

Question 20

Recall the names of 2 DOPA-D inhibitors

Answer 20

Carbidopa

Benserazide

Question 21

Which of the dopaminergic pathways in the brain are involved schizophrenia?

Answer 21

Mesolimbic (increased activity- positive)

mesocortical (decreased activity- negative)

Question 22

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

Answer 22

Clozapine

Treats both positive and negative symptoms

Question 23

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

Answer 23

Extra-pyramidal

Question 24

What is the MOA of aripiprazole?

Answer 24

PARTIAL AGONIST of 5HT2A and D2

Question 25

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

Answer 25

Coupled to adenylate cyclase via a Gi protein

Gi inhibit AC & and lead to reduced cAMP & PKA

Question 26

Recall the symptoms of schizophrenia

Answer 26

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

Question 27

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

Answer 27

Activation of CTZ to produce nausea and vomiting

Question 28

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

Answer 28

Ergot derivatives: bromocriptine and pergolide

Non-ergot derivatives: ropinirole