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Parkinsons And Schizophrenia > PD and SCHIZOPHRENIA > Flashcards

Flashcards in PD and SCHIZOPHRENIA Deck (18)
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1

Dopamine synthesis pathway?

L-tyrosine to L-DOPA (tyrosine hydrolase)
L-DOPA to Dopamine (DOPA Decarboxylase)

2

Dopamine removed by what?

Dopamine transporter (DAT)
& Noradrenaline transporter (NET)

3

Which enzymes metabolise DA?

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

COM-T also found on postsynaptic membrane

4

Dopamine pathways?

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

5

PD background?

1-2% of people over 60
5% of cases have genetic mutations in SNCA or LRRK2

6

PD Pathophysiology?

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

7

3 types of clinical presentation of PD

Motor symptoms
ANS effects
Neuropsychiatric

8

Motor symptoms PD

resting tremor
Bradykinesia
Postural instability
Rigidity

9

ANS symptoms PD

Constipation
Orthostatic hypotension
Olfactory deficits

10

Neuropsychiatric symptoms PD

Irritation
Memory problems
Sleep disorders

11

Treatment PD

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

12

Types of D receptor

D1R/D5R = Gs

D2-4R = Gi

13

Schizophrenia background

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

14

Types of Schizophrenia symptoms

Positive
Increased Mesolimbic

Negative
Decreased mesocortical

15

Schizophrenia symptoms

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

16

Schizophrenia drug types

First and second generation anti psychotics

17

First generation anti psychotics

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

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

18

Second generation anti psychotics

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