Anti parkinsonian drugs

Question 1

what is dopmamine

Answer 1

monoamine neurotransmitter,

Question 2

describe dopamine metabolism

Answer 2

Tyrosine - L-DOPA - Dopamine

Question 3

what enzymes are involved in dopamine metabolism

Answer 3

Tyrosine Hydroxylase (TH)

DOPA Decarboxylase (DD)

Question 4

what trnasporters transport dopamine from the synapse and into
cells

Answer 4

Dopamine Transporter (DAT)

Noradrenaline/Norepinephrine Transporter (NET)

Question 5

where are these transporters found

Answer 5

dopaminergic neurones and glial cells

Question 6

what metabolises monamines

Answer 6

Monoamine Oxidases:
A - all monamines
B - specific for dopamine

Catechol-0-Methyltransferase
- catecholamines

Question 7

what are the dopaminergic pathways of the brain

Answer 7

Mesolimbic pathway
Mesocortical pathway
Nigrostriatal pathway
Tuberoinfundibular pathway

Question 8

describe the mesolimbic pathway

Answer 8

starts in VTA to NAcc - Euphoria

Question 9

In which conditions is the mesolimbic pathway disrupted in

Answer 9

addiction and schizophrenia

Question 10

describe the mesocortical pathway

Answer 10

starts in VTA - cerebral cortex (frontal lobe)

controls executive and behavioural functions

problem in schizoids

Question 11

describe the nigrostriatal pathway

Answer 11

starts in Substansia nigra pc - striatum

coordinates motor movement

Question 12

what part of the striatum is the NAcc in

Answer 12

ventral striatum

Question 13

describe the tuberoinfundibulnar pathway

Answer 13

from Arcuate nucleus - median eminence

(connects hypothalamus to pituitary

Question 14

what are some affects that having too much prolactin would cause

Answer 14

Galactorrhoea, Ammenorhoea, loss of libido

Question 15

describe the epidemiology of Parkinson’s

Answer 15

1-2% of individuals over 60

Question 16

5% of cases are due to what mutation in….

Answer 16

certain genes SNCA, LRRK2, Parkin

Question 17

categorise the symptomology of Parkinson’s

Answer 17

Motor
Autonomic
Neuropsychiatric

Question 18

what are the motor symptoms of Parkinson’s

Answer 18

Lead pipe rigidity
Bradykinesia
Resting tremor
postural instability
parkinsonian gait

Question 19

describe the parkinsonian gait

Answer 19

loss of arm swing, shuffling steps

Question 20

what are the autonomic symptoms of Parkinson’s

Answer 20

anosmia
postural hypotension
constipation

Question 21

neuropsychiatric symptoms of Parkinson’s

Answer 21

sleep disorders
Depression
Irritability

Question 22

describe the pathology of Parkinson’s

Answer 22

loss of dopaminergic neurones in substantia nigra pc

Question 23

what % loss of neurones do u need before motor symptoms appear

Answer 23

80%

Question 24

what do you see on the post mortem of a Parkinson’s patient

Answer 24

Lewy bodies (protein aggregates in cell bodies)

Lewy neurites (protein aggregates in cell axons)

Question 25

what are these protein aggregates made off

Answer 25

alpha-synuclein and ubiquitin

Question 26

categorise the treatment for Parkinson's

Answer 26

replace the dopamine - L-DOPA or agonist) reduce the breakdown on dopamine (MAO inhibitor)

Question 27

what is L-DOPA also known as

Answer 27

Levodopa

Question 28

why is L-DOPA the preferred choice of dopamine replacement

Answer 28

TH is rate limiting enzyme Rapidly converted to DA by DOPA-D can cross BBB

Question 29

what does peripheral breakdown of L-DOPA cause

Answer 29

Nausea and vomiting

Question 30

long term side effects of Levodopa

Answer 30

dyskinesias & ‘on-off’ effects. NOT disease-modifying

Question 31

what adjuncts are often given with levodopa therapy

Answer 31

DOPA decarboxylase inhibitors: Carbidopa & Benserazide COMT inhibitors: Entacapone & Tolcapone

Question 32

how do the DOPA-D inhibitors work

Answer 32

Do not cross BBB - prevent peripheral breakdown of levodopa Reduce required levodopa dosage

Question 33

how do the COMT inhibitors work

Answer 33

increase amount of levodopa in the brain

Question 34

which receptors does dopamine act on

Answer 34

D1,5(Gs linked) or | D2-4 (Gi-linked) receptors

Question 35

what are the dopamine agonists divided into

Answer 35

(potent D2 rc agonists): Ergot derivatives: Non-ergot derivatives:

Question 36

what problems are ergot derivatives associated with

Answer 36

Associated with cardiac fibrosis

Question 37

give examples of ergot derivative's

Answer 37

Bromocriptine, Carbergoline and Pergolide.

Question 38

give examples of non ergot derivative's

Answer 38

Ropinirole and Rotigatine

Question 39

Side-effects of Dopamine Agonists

Answer 39

Nausea Vomiting Hallucinations Impulse Control Disorders (e.g. pathological gambling) Psychosis Raynaud’s Phenomenon

Question 40

L-DOPA vs Dopamine Agonists which is better

Answer 40

L-DOPA = more effective, gold standard + less side effect

Question 41

how do MonoAmine Oxidase B Inhibitors help

Answer 41

Not as effective as L-DOPA useful in combination with L-DOPA to reduce doses used to delay the time which a patient starts L-DOPA

Question 42

give an example of MAO-B inhibitor

Answer 42

Selegiline

Question 43

give an example of Catechol-O-MethylTransferase Inhibitors are these a good treatment

Answer 43

Entacapone , Tolcapone NOT liscenced as monotherapy

Question 44

categorise Schizophrenia Symptomology

Answer 44

Positive symptoms: ↑ Mesolimbic dopaminergic activity Negative symptoms: ↓ Mesocortical dopaminergic activity

Question 45

+ve symptoms in schizophrenia

Answer 45

Hallucinations: Auditory & visual Delusions: Paranoia Thought disorder: Denial about oneself

Question 46

-ve symptoms in schizophrenia

Answer 46

Affective flattening: lack of emotion Alogia: lack of speech Avolition/ apathy: loss of motivation

Question 47

Schizophrenia – Who Gets It?

Answer 47

1% of population & has genetic influences Onset : 15-35 years (YOUNG) Higher incidence in ethnic minorities (eg Afro-Caribbean immigrants) - Second Generation Specifically

Question 48

what is the basis of schizophrenia pharmacology

Answer 48

The Anti-Psychotics are antagonists