Applied neuropharmacology Flashcards

1
Q

summarise the sequence of events in synaptic transmission

A
  1. synthesise/packaging of NT in presynaptic terminal
  2. Na+ AP invades terminal
  3. VGCa2+ channels activated
  4. triggers Ca2+ dependent exocytosis of NT vesicles
  5. transmitter diffuses across cleft - binds to iono/metabotropic receptors to evoke presynaptic response
  6. presynaptic autoreceptors inhibit further NT release
  7. transmitter inactivated by uptake into glia/neurons or extracellular breakdown
  8. NT metabolised by cells
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2
Q

by what mechanisms can you reduce synaptic transmission

A
  • block VGNa+ channels
  • inhibit synthesis/packaging of NT
  • activate presynaptic inhibitory receptors
  • block postsynaptic receptors
  • block VGCa2+ channels
  • increase breakdown of NT
  • block release machinery
  • increase uptake of NT
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3
Q

by what mechanisms can you increase synaptic transmission

A
  • block uptake of NT
  • increase synthesis/packaging of NT
  • activate postsynaptic receptors
  • potentiate effects of NT on receptor
  • block breakdown of transmitter
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4
Q

list some neurotransmitters

A

acetylcholine

monoamines

  • noradrenaline
  • dopamine
  • seratonin

amino acids

  • glutamate
  • GABA
  • glycine

purines

  • ATP
  • adenosine

Neuropeptides

  • endorphins
  • CCK
  • substance P

Nitrous oxide

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5
Q

what characteristics do each individual neurotransmitter have

A

its own anatomical distribution

Its own range of receptors it acts on

Its own range of functions in different regions (some separated by the blood brain barrier)

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6
Q

what is the anatomical distribution of dopamine in the brain

A

brainstem
basal ganglia
limbic system+frontal cortex

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7
Q

what physiological functions are affected by dopamine

A

increases vomiting
voluntary movement
emotions/reward

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8
Q

what causes parkinsons

A

degeneration of dopamine cells in the substantial nigra

dopamine deficiency in the basal ganglia
can be because it it pharmacologically blocked as well

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9
Q

what type of receptor are dopamine receptors

A

metabotropic - g-protein coupled

5 subtypes - D1-D5

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10
Q

what determines the effect dopamine has in the body

A

depends what receptor (D1-D5) is expressed

means a selective agonist/antagonist can produce a specific therapeutic effect

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11
Q

what are the key enzymes in dopamine breakdown

A

MAO-B - monoamine oxidase B

COMT- catechol-O-methyltransferase

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12
Q

how does parkinsons present

A

stiffness
slow movements
change in posture
tremor - “pill-rolling”

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13
Q

what dopaminergic drugs can improve the symptoms of parkinsons

A

DA precursor - levodopa

DA agonists

  • ergots - cabergoline
  • non-ergots - ropinirole
  • apomorphine
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14
Q

what enzyme inhibitors are usually taken with levodopa

A

peripheral AAAD inhibitors
- carbidopa

MAOB inhibitors - safinamide

COMT inhibitors - entacapone

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15
Q

what do peripheral AAAD inhibitors do

A

decreases peripheral side effects of levodopa

allows greater proportion of oral dose to reach the CNS

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16
Q

what do MAOB and COMT inhibitors do

A

decrease metabolism of dopamine and so increase effectiveness of levodopa

17
Q

what features of parkinsons can dopaminergic drugs improve

A

Some motor features of Parkinson’s e.g. limb rigidity & bradykinesia, tremor

18
Q

what features of parkinsons can dopaminergic drugs worsen or cause

A

Nausea
Vomiting
Psychosis
Impulsivity / abnormal behaviours

19
Q

what are the effects of dopamine antagonists

A

improves

  • nausea
  • vomiting
  • psychosis

worsens/causes
- parkinsons

20
Q

what is domperidone and why is it safe to use in parkinsons

A

it is a dopamine antagonist AND anti-emetic

no anti-psychotic properties

BUT does not cross the BBB so can stop vomiting (vomiting centre outside the BBB) without worsening/causing parkinsons

21
Q

what is dyskinesia

A

abnormal involuntary movements

22
Q

what is the movement affect seen from dopaminergic drugs

A

dyskinesia

- “too much movement”

23
Q

what is the movement affect seen from dopamine antagonists

A

may cause parkinsonism

- “not enough movement”

24
Q

what other long term dopamine antagonists can cause parkinsonism

A

antipsychotics/anti-dizziness

- receptor blockade at basal ganglia

25
Q

what is the function of noradrenaline

A

reuptake blockers

tricyclic drugs - anti-depressants

MAO inhibitors - anti-depressants

26
Q

what is the function of serotonin and 5-HT

A

serotonin - antidepressants

triptans (5-HT) - migraine

27
Q

what is the function of GABA

A

GABA agonists - anti-epileptics, anti-anxiety