Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHA333 > Parkinson's disease (PB) > Flashcards

Parkinson's disease (PB) Flashcards

1
Q

steps of conversion of tyrosine to adrenaline

A 
tyrosine
L-DOPA
dopamine
noradrenaline
adrenaline
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

DA receptor families and subtypes

A

D1 receptor family -> excitatory, inc cAMP and Ca

  • D1
  • D5

D2 receptor family -> inhibitory, dec cAMP and Ca

  • D2
  • D3
  • D4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What type of disorder is Parkinsons?

A

degenerative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What causes Parkinsons (basic)?

A

degeneration of dopamine secreting nerve cells

excess free radicals causes degeneration of neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are Lewy bodies?

A

cytoplasmic inclusions in surviving neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

mechanisms that cause neuron cell death

A

environmental toxins, aging, neuronal metabolism

  • > free radical formation, oxidative stress, excitotoxicity, vulnerable neurons
  • > DNA damage, lipid peroxidation, protein damage
  • > cell death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

symptoms of Parkinson’s

A

motor sympyoms (TRAP)

  • tremor
  • rigidity
  • akinesia
  • postural instability

non-motor symptoms

  • neuropsychiatric
  • sleep disturbances
  • autonomic disturbances
  • sensory disturbances
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

risk factors for Parkinson’s

A

non-smokers, low caffeine drinkers

genetic mutations in gene LRRK-2

mutations in parkin gene

neuroleptic drugs

antiemetics (prochloperazine, metoclopramide)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Where is DA produced?

A

substantia nigra within the basal ganglia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

role of basal ganglia

A

co-ordinate performance of well-learnt, voluntary, semi-automatic motor skills and movement sequences

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

roles of DA

A

cognitive tasks

  • maintaining attention
  • switching focus of attention
  • mood
  • problem solving
  • decision making
  • visual perception
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does progressive denegeration of DA producing neurons lead to formation of?

A

Lewy bodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

When are clinical signs of disease evident?

A

when 80% of DA producing neurons are lost

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

dopamine acetylcholine balance

A

DA neurons in substantia nigra and corpus striatum

striatum also rich in excitatory ACh neurons that counteract the action of DA

DA ergic system inhibits the ACh system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

UK Brain bank disgnostic criteria for PD

A

step 1: diagnosis
- bradykinesa and one of: rest tremor, rigidity, postural instability

step 2: exclusion criteria

  • Hx of repeated strokes, neuroleptic meds, head injury, definite encephalitis
  • presence of atypical features: early falls, supranuclear gaze palsy, ataxia and cerebellar features, early autonomic features, early cognitive decline, poor response to L-dopa

step 3: supportive slinical features (at least 3)
- unilateral onset, rest tremor, evidence of progression, persistent asymmetry, response to L-dopa, L-dopa induced dyskinesias, L-dopa response for 5+yrs, clinical course of 10+yrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

diagnosis of PD

A

based on TRAP (motor symptoms)

can get MRI/CT brain scans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

referral time if PD is suspected

A

not >6 weeks normal cases

not >2 weeks in severe/complex cases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

differential diagnosis for tremor disorders

A 
psychological tremor - anxiety, thyrotoxicosis, fine tremor
essential tremor
dystonic tremor
cerebellar disorders
vascular parkinsonism
drug induced parkinsonism
atypical parkinsonism disorders
dementia with Lewy bodies
functional (non organic)
normal pressure hydrocephalus
others
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

2 drug types for PD

A
  1. drugs that restore DA levels in nigro striatal DAergic tract
  2. drugs that restore the DA-ACh balance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

DA in nigro striatal tract drugs

A 
levodopa and carbidopa/benserazide
DA agonists
MAO-B inhibitors
COMT inhibitors
miscellaenous (amantadine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

drugs for DA/ACh balance

A

antimuscarinic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

2 brand/generics of L-dopa

A

Madopar - co-beneldopa

Sinemet - co-careldopa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

drugs in Madopar (co-beneldopa)

A

L-dopa + benserazide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

drugs in Sinemet (co-careldopa)

A

L-dopa + carbidopa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

formulations of Madopar

A

capsules
dispersible tabs
CR capsules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What drug has the highest conc in Madopar/Sinemet?

A

levodopa is the higher strength

eg. Madopar 62.5mg caps = levodopa 50mg and benserazide 12.5mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is duodopa?

A

intestinal gel with 20mg/ml levodopa and 5mg/ml carbidopa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

examples of dopamine agonists

A 
bromocriptine
carbergoline
pergolide
pramiprexole
ropinrole - Requip
rotigotine- Neupro
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

subcutaneous DA preparation

A

apomorphine - APO-go

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

MAO-B inhibitor

A

selegiline

resagiline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

COMT inhibitors

A

entacapone
tolcapone
L-dopa/carbidopa/entacapone - Stalevo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

antimuscarinics

A

trihexyphenidyl
orphenadrine
procyclodine- Kemadrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

miscellaneous

A

amantadine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

most effective med for Parkinsons

A

levodopa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

standard release preparations of levodopa

A

levodope/carbidopa - Sinemet

levodopa/benserazide - Madopar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

prolonged release preps of levodopa

A

levodopa/carbidope - Simemet CR

levodopa/benserazide - Madopar CR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

How are therapeutic/adverse effects got from levodopa?

A

from its decarboxylation to DA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What prevents peripheral breakdown of levodopa?

A

given with peripheral decarboxylase inhibitor to prevent peripheral break down

  • carbidopa
  • benserazide

smaller dose of levodopa needed to treat symptoms then

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What reduces N&V s/e of levodopa?

A

given with DOPA decarboxylase inhibitor

  • carbidopa, benserazide
40
Q

s/e of levodopa if given on own

A

N&V
cardiac arrhythmias
hypotension

41
Q

How do DOPA decarboxylase inhibitors work?

A

dec levodopa metabolism in peripheral tissues and metabolism in GIT

decarboxylation of levodopa doesn’t occur

more can cross BBB

-> fewer undesirable s/e

42
Q

Why does evodope have s/e when given alone?

A

it is metabolised in peripheral tissue and GIT to give s/e

43
Q

When are best results obtained from levodopa?

A

in 1st few years

44
Q

What impoevements are seen from using levodopa?

A

improvement in muscle rigidity and bradykinesia

normal motor functions

45
Q

Why does levodopa become less effective over time?

A

progressive loss of dopaminergic neurons

down regulation of D1/D2 R on post synaptic terminals

(some patients require reduced doses of levodopa to prevent s/e but inc frequency)

46
Q

dyskinesia

A

excessive and abnormal involuntary movements

47
Q

main s/e with levodopa especially on LT Tx

A

dyskinesia

dose related - higher dose = inc risk

48
Q

What Parkinson’s patients does dyskinesia occur more in?

A

younger patients

49
Q

'’on-off’’ effect with levodopa

A
  • fluctuations in clinical response
  • on = improved mobility but marked dyskinesia
  • off = marked akinesia, absense/loss of power of voluntary movement
  • reated to fluctuations in levodopa plasma concs
  • fluctuations smoothened out by adding DA R agonist
50
Q

s/e of levodopa

A
  • GI disturbances - anorexia, N&V
  • dry mouth
  • postural hypotension
  • drowsiness, sudden onset of sleep
  • dystonia (invol contraction of muscles)
  • dyskinesia
  • chorea (invol movements)
  • neuropsychiatric symptoms - hallucinations, confusion, abnormal dreams, insomnia
51
Q

amtiemetic for N&V from levodopa

A

domperidone

52
Q

what patients is levodopa c/i in

A

psychosis

53
Q

PK of levodopa

A

well absorbed on oral admin

54
Q

How to take levodopa

A

take on empty stomach 45mins before meal

foods inhibit absorption from gut and its transport into CNS

55
Q

interactions with levodopa

A
  • inc risk postural hypotension with antihypertensive drugs
  • risk of hypertensive crisus due to inc catecholamines with MAOIs
  • pyridoxine (vit B6) inc peripheral breakdown of L-dopa
56
Q

Uses of DA receptor agonists

A 
individual drugs
OR
in combination with levodopa/anticholinergic drugs
OR
patients who can't tolerate levodopa
57
Q

How does bromocriptine work?

A

selective D2 receptor agonist and partial agonist at D1 receptors

58
Q

Howdoes pergolide mesylate work?

A

directly stimulates both D1 and D2 receptors

59
Q

s/e with DA receprot agonists

A

associated with cardiac valve fibrosis

loses efficacy over time

60
Q

s/e of DA receptor agonists

A

GI disturbances - anorexia, N&V
cardiac arrhythmias
postural hypotension
drowsiness and sudden onset of sleep
dyskinesia
neuropsychoatric symptoms - hallucination, confusion, abnormal dreams, insomnia
pulmonary infiltrates and erythromelagia - Ergot related effects
impulse control disorder - pathological gambling

61
Q

2 classes of DA R agonists

A
  1. ergot alkaloids - bromocriptine, pergolide

2. non-ergot alkaloids - ropinirole, pramipexole, rotigotine

62
Q

Where fo ropinirole and pramipexole work (non-ergot alkaloid DA R agonists)?

A

affinity for D2 sub classes especially at D2 and D3 receptors

63
Q

advantage of pramipexole

A

neuroprotective - scavenges H2O2

64
Q

rotigotine (DA R agonist)

A
  • agonist at all 5 DA receptors
  • used to treat signs/symptoms of early PD
  • admin as once daily transdermal patch
  • gives even PK for 24 hrs
65
Q

advantages of Rotigotine

A

patch

  • good if compliance is an issue
  • oral route unavailable
66
Q

s/e of non-ergot alkaloid DA R agonists

A

GI - N&V
sleepiness and fatigue
marked hypotension
drowsiness, sudden onset of sleep, excessive daytime sleeping
dyskinesia
neuropsychiatric symptoms - hallucinations, confusion, abnormal dreams, insomnia

67
Q

Apomorphine

A

potent DA agonist

high affinity for D4 R

moderate affinity for D2, 3, 5 and some alpha R

low affinity for D1

via SC injection to give temp relief of ‘‘off’’ periods of akinesia, pre-filled pins

short effectiveness - 2hrs

for severe, advances PD, symptoms not controlled

68
Q

s/e with apomorphine

A
  • highly emetogenis, needs pre/post anti-emetics
  • same s/e as other DA agonists
  • prolongs QT interval
  • injection site reaction
  • abuse characteristics, inc dosing - hallucination, dyskineais, abnormal behaviour
69
Q

2 types of MAO

A

MAO-A - metabolises NA and 5-HT

MAO-B - metabolises DA

70
Q

examples of MAOIs

A

selegiline

rasagiline

71
Q

How do MAOIs work?

A

selective, irreversible inhibition of MAO-B

prevent breakdown of natural DA and DA from levodopa

-> inc DA levels in brain

doesn’t inhibit MAO-B

72
Q

What is seligeline metabolised to?

A

methamphetamine and amphetamine

73
Q

When are MAOIs effective?

A

in early PD

- monotherapy or in combination with levodopa

74
Q

How are MAOIs beneficial?

A

enables reduction in levodopa dose or smoothes the ‘‘on-off’’ fluctuations associated with levodopa

metabolite is neuroprotective - desmethylselegiline

75
Q

s/e of MAOIs

A
  • selectivity for brain MAO-B makes selegiline less likely to porcude ADRs involving peripheral tyramine (wine, cheese, chopped liver syndrome)
  • blocks MAO-A at high doses - hypertensive crisis due to peripheral accumulation of NA
  • fatal hyperthermia - can occur when given with meperidine/cocaine/fluoxetine
76
Q

What does COMT stand for?

A

catechol-O-methyltransferase

77
Q

examples of COMT inhibitors

A

tolcapone

entacapone

opicapone

78
Q

How do COMT inhibitors work?

A

inhibit peripheral metabolism of levodopa

may also reduce ‘‘on-off’’ fluctuations

79
Q

PK of COMT inhibitors

A

oral absorption not influenced by food

extensively bound to plasma albumin (98%)

extensively metabolised and eliminated in faeces/urine

80
Q

s/e with COMT inhibitors

A
  • related to inc plasma concs of levodopa
  • dyskinesia, nausea, confusion
  • diarrhoea, abdominal pain
  • orthostatic hypotension
  • sleep disorders
  • orange urine discolouration
  • tolcapine - potentially hepatotoxic
81
Q

dose of rasagiline and selegiline (COMT inhibitors)

A

rasagiline 1mg daily

selegiline 5mg daily

-> inc to 10mg after 2-4 weeks

82
Q

dose of entacapone

A

initially 200mg with each dose of levodopa with dopa-decarboxylase inhibitor

max 2g daily

83
Q

dose of tolcapone

A

tolcapone 100mg TDS (min gap 6hrs)

max dose 200mg TDS

first dose taken with levodopa and dopa-decarb inh

tolcapone only continued if substantial improvement seen after 3 weeks

84
Q

When are anticholinergics used?

A

before the introduction of levodopa

85
Q

MOA of anticholinergics

A

dec activity of Ach

86
Q

use of anticholinergics for PD

A

secondary adjuvant meds

help control tremors in early stages of disease

not used in idiopathic PD - less effective than DA drugs and could cause cognitive impairment

87
Q

s/e of anticholinergics

A 
constipation
blurred vision
dry mouth
urinary retention
neuropsychiatric symptoms - memory loss, confusion, hallucinations
88
Q

Can anticholinergics be used LT?

A

NO

because of their s/e

89
Q

What type of drug is Amantadine?

A

antiviral drug

used for Tx of influenza A

90
Q

MOA of amantadine

A

inc DA release in striatum

has anticholinergic activity

blocks NMDA glutamate R

91
Q

benefits/limitations of amantadine

A

less efficacy but less s/e than levodopa

little effect on tremor but more effective than anticholinergics against rigidity and bradykinesia

92
Q

s/e of amantadine

A 
difficulty concentrating
confusion
insomnia
nightmares
agitation
hallucinatons
leg swelling
dermatological rxns - Livedo reticularis (red/blue skin, worsens when cold)
93
Q

When is amantadine used

A

late stage PD

if pt has problems with dysinesia induced by levodopa

94
Q

Tx regimen for young PD pt

A

MAOI - rasagaline, selegiline
or
DA agonist (non-ergot)

THEN

L-dopa
COMT inhibitor

IF DYSKINESIA - reduce L-dopa and add amantadine

SEVERE MOTOR FLUCTUATIONS - SC apomorphine/duodopa

95
Q

Tx regimen for old/frial PD pt

A

L-dopa

THEN

MAOI
COMT inhibitor

IF DYSKINESIA - reduce L-dopa and add amantadine

SEVERE MOTOR FLUCTUATIONS - SC apomorphine/duodopa

PHA333 (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions