PD and SCHIZOPHRENIA

Question 1

Dopamine synthesis pathway?

Answer 1

L-tyrosine to L-DOPA (tyrosine hydrolase)

L-DOPA to Dopamine (DOPA Decarboxylase)

Question 2

Dopamine removed by what?

Answer 2

Dopamine transporter (DAT)
& Noradrenaline transporter (NET)

Question 3

Which enzymes metabolise DA?

Answer 3

MAO-A (5HT/DA/NE)
MAO-B (DA)
COM-T (DA/NE)

COM-T also found on postsynaptic membrane

Question 4

Dopamine pathways?

Answer 4

Nigrostriatal pathway
SNc —> Striatum
Inhibition causes movement disorders

Mesolimbic pathway
VTA —> NAcc
Reward pathway

Mesocortical pathway
VTA to Cerebrum
Executive functions and complex behavioural functions

Tuberoinfundibular pathway
Arcuate nucleus to Median Eminence
Inhibition results in hyperprolactinaemia

Question 5

PD background?

Answer 5

1-2% of people over 60

5% of cases have genetic mutations in SNCA or LRRK2

Question 6

PD Pathophysiology?

Answer 6

1) severe loss of dopaminergic neurones in the SNc
2) Lewy bodies (cell body) and neurites (axons)
3) abnormally phosphorylated neurofilaments, ubiquitin and alpha synuclein

Question 7

3 types of clinical presentation of PD

Answer 7

Motor symptoms
ANS effects
Neuropsychiatric

Question 8

Motor symptoms PD

Answer 8

resting tremor
Bradykinesia
Postural instability
Rigidity

Question 9

ANS symptoms PD

Answer 9

Constipation
Orthostatic hypotension
Olfactory deficits

Question 10

Neuropsychiatric symptoms PD

Answer 10

Irritation
Memory problems
Sleep disorders

Question 11

Treatment PD

Answer 11

1)
L-DOPA
TH is rate limiting enzyme
L-DOPA rapid conversion to DA
Crosses BBB
Peripheral breakdown: n&v
LT S/E: Dyskinesias & on/off effects
(Abnormal limb/face movements and fluctuations in clinical state)
Adjuncts: Carbidopa and Benserazide
Do not cross BBB
Reduce dosage needed
Prevent peripheral breakdown

COMT inhibitors
Entacapone
Tolcapone
Increase amount of L-DOPA in brain

2) dopamine receptor agonists

Ergot derivatives 
Bromocriptine
Pergolide
Potent agonists of D2R
Assoc w/ cardiac fibrosis

Non-ergot derivatives
Ropinirole - also avail as ext formul
Rotigotine - also avail as patch

3) MAO-B Inhibitors
Selegiline
Rasagiline
Reduce dosage L-DOPA
Increase time before L-DOPA needed

Question 12

Types of D receptor

Answer 12

D1R/D5R = Gs

D2-4R = Gi

Question 13

Schizophrenia background

Answer 13

1% of population
15-35 yrs onset of symptoms
Higher incidence Ethnic minorities Eg afrocaribbean immigrants
20-30 year shorter life expectancy

Question 14

Types of Schizophrenia symptoms

Answer 14

Positive
Increased Mesolimbic

Negative
Decreased mesocortical

Question 15

Schizophrenia symptoms

Answer 15

Mesolimbic pos
Hallucinations (A&V)
Delusions (paranoia)
Thought disorder (denial about oneself)

Mesocortical neg
Affective flattening: lack of emotion
Alogia: lack of speech
Avolition/Apathy: lack of motivation

Question 16

Schizophrenia drug types

Answer 16

First and second generation anti psychotics

Question 17

First generation anti psychotics

Answer 17

Chlorpromazine
Possibly D2R Ant
High inc AntiACh esp sedation
Low inc EPS

Haloperidol
V. Potent D2R Ant (50x Chlorpromazine)
S/E: EPS

Question 18

Second generation anti psychotics

Answer 18

Clozapine
Most effective
V. potent antagonist 5HT 2A R
Only drug: trt-res Schizo and neg symp 
S/E: possibly fatal NP, AGRANULOCYTOSIS, myocardial failure, weight gain

Risperidone
V potent 5HT 2A R and D2R Ant
S/E: EPS & hyperprolactinaemia

Quetiapine
V potent H1R Ant
S/E: lower inc EPS

Aripiprazole
Partial agonist D2R & 5HTR
No more efficacious than typical AntiPsychotics
S/E: low inc hyperprolactinaemia and weight gain