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Systems: Neurology AB > Applied Neuro-Pharmacology > Flashcards

Applied Neuro-Pharmacology Flashcards

1
Q

What is the sequence of evens in synaptic transmission?

A
  • Synthesis and packaging of neurotransmitter (usually) in presynaptic terminals
  • Na+ action potential invades terminal which activates voltage gated Ca2+-channels
  • Triggers Ca2+-dependent exocytosis of pre-packaged vesicles of transmitter
  • Transmitter diffuses across cleft and binds to ionotropic and/or metabotropic receptors to evoke postsynaptic response
  • Presynaptic autoreceptors inhibit further transmitter release
  • Transmitter is (usually) inactivated by uptake into glia or neurones or transmitter is (unusually) inactivated by extracellular breakdown
  • Transmitter is metabolised within cells
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2
Q

How can synaptic transmission be reduced by pharmacological manipulation?

A
  • Block voltage gated Na channels
  • Inhibit synthesis and packaging of NT
  • Activate presynaptic inhibitory receptors
  • Block postsynaptic receptors (eg. competitive antagonists, non competitive antagonists)
  • Block voltage gated Ca channels
  • Increase breakdown of transmitter
  • Block release machinery
  • Increase uptake of transmitter
  • Block voltage gated Na channels
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3
Q

How can synaptic transmission be increased by pharmacological manipulation?

A
  • Increase synthesis and packaging of NT (eg. by increasing availability of precursors)
  • Activate postsynaptic receptors with an agonist
  • Potentiate effects of transmitter on receptor (eg. increase channel open time)
  • Block breakdown of transmitter
  • Block uptake of transmitter
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4
Q

What types of neurotransmitters are there?

A
  • Acetylcholine
  • Monoamines
  • Amino acids
  • Purines
  • Neuropeptides
  • NO
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5
Q

Give examples of monoamine neurotransmitters

A
  • Noradrenaline
  • Dopamine
  • Serotonin (5-HT)
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6
Q

Give examples of amino acid neurotransmitters

A
  • Glutamate
  • GABA
  • Glycine
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7
Q

Give examples of purine neurotransmitters.

A
  • ATP

- Adenosine

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8
Q

Give examples of neuropeptide neurotransmitters

A
  • Endorphins
  • CCK
  • Substance P
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9
Q

Why is it no surprise that neurotransmitters have different functions in different regions?

A

There is a limited range of neurotransmitters

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10
Q

What does each 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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11
Q

What is the anatomical distribution of dopamine in the brain?

A
  • Brain stem
  • Basal ganglia
  • Limbic system an frontal cortex
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12
Q

What physiological functions are affected by dopamine?

A
  • Vomiting
  • Voluntary movement
  • Emotions/reward
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13
Q

What is Parkinson’s caused by?

A
  • Degeneration of DA cells in the substantia nigra (nigrostriatal)
  • DA deficiency in the basal ganglia
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14
Q

How is dopamine synthesised?

A
  • Glycine
  • Alanine
  • Phenylalanine
  • Tyrosine
  • DOPA
  • Dopamine
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15
Q

Why can dopamine not evoke fast EPSPs or IPSPs?

A

No inotropic receptors

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16
Q

What are the names of the dopamine receptors?

A

5 subtypes of metabotropic (ie. g-protein coupled) receptors names D1-D5

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17
Q

How does the effect of dopamine differ through the brain?

A

It can produce many effects and different effects in different brain regions depending on the receptors expressed

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18
Q

What are the key enzymes in dopamine metabolic breakdown?

A
  • MAO-B

- COMT

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19
Q

What does dopamine metabolic breakdown result in?

A

Homovanillic acid

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20
Q

How does Parkinson’s present?

A

Stiffness, slow movements, change in posture, tremor

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21
Q

What type of drugs can improve some symptoms of PD?

A

Dopaminergic drugs

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22
Q

What types of dopaminergic drugs are there?

A
  • DA precursors

- DA agonists

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23
Q

Give an example of a DA precursor

A

Levodopa

24
Q

Give examples of DA agonists ergots.

A
  • Bromocriptine
  • Pergolide
  • Cabergoline
25
Q

Give examples of DA agonist non-ergots

A
  • Ropnirole
  • Pramipexole
  • Rotigotine
26
Q

Why are DA agonist ergots no longer used?

A

5HT (2B) stimulation leads to fibrosis

27
Q

Give an example of a DA agonist

A

Apomorphine

28
Q

What enzyme inhibitors can be used in PD?

A
  • Peripheral AAAD inhibitors
  • MAOB inhibitors
  • COMT inhibitors
29
Q

Give examples of peripheral AAAD inhibitors

A
  • Carbidopa

- Benserazide

30
Q

Give examples of MAOB inhibitors

A
  • Selegiline
  • Rasagiline
  • Safinamide
31
Q

Give examples of COMT inhibitors

A
  • Entacapone

- Tolcapone

32
Q

What effect do enzyme inhibitors have in synthetic dopamine agonists?

A

No effect on synthetic dopamine agonists

33
Q

What effect do peripheral AAAD inhibitors have on levodopa?

A

Decrease peripheral side effects of levodopa and allows a greater proportion of the oral dose to reach the CNS

34
Q

What effect do COMT inhibitors have on levodopa?

A

Decrease metabolism of dopamine and so increase the effectiveness of levodopa

35
Q

What do dopaminergic drugs improve?

A

Some improve motor features of Parkinson’s

-e.g. limb rigidity and bradykinesia, tremor

36
Q

What do dopaminergic drugs worsen or cause?

A
  • Nausea
  • Vomiting
  • Psychosis
  • Impulsivity / abnormal behaviours
37
Q

What do dopaminergic drugs fail to help?

A

Midline features

  • Dysarthria
  • Balance
  • Cognition
38
Q

What do dopamine antagonists improve?

A
  • Nausea
  • Vomiting
  • Psychosis
39
Q

What do dopamine antagonists worsen or cause?

A

Parkinson’s

40
Q

What effect do DA antagonist antiemetic’s have on PD?

A

DA antagonist antiemetics will worsen PD and generally should not be used in people with PD

41
Q

Where is area postrema (vomiting centre) located?

A

Area postrema (vomiting centre) in the medulla is functionally OUTSIDE the BBB

42
Q

What feature would be required of a DA antagonist for it to not cause nausea?

A

A DA antagonist that didn’t cross the BBB

43
Q

What is domperidone?

A
  • DA antagonist that does not cross the BBB
  • Is an anti-emetic and does not have antipsychotic properties
  • Relatively safe in PD
44
Q

What does domperidone not do?

A

Cross the BBB

45
Q

What can be used with domperidone due to its anti-emetic property?

A

Apomoprhine

46
Q

Dyskinesias

A

AIMS: abnormal involuntary movements

47
Q

What type of drugs may cause dyskinesias?

A

Dopaminergic drugs

48
Q

What type of drugs may cause parkinsonism?

A

DA antagonists

49
Q

What type of dyskinesia is associated with long term DA antagonist use?

A

Tardive dyskineasias

50
Q

What is the function of noradrenaline?

A

Reuptake blockers

51
Q

What are tricyclic drugs used as?

A

Antidepressants

52
Q

What are MAO inhibitors used as?

A

Antidepressants

53
Q

What are selective serotonin reuptake inhibitors (SSRIs)?

A

Antidepressants

54
Q

What are triptans (selective 5HT agonists) used for?

A

Used in the treatment of migraines

55
Q

What are GABA agonists used for?

A
  • GABA agonists are anti-epilepsy drugs.

- They also have anti-anxiety properties

Systems: Neurology AB (51 decks)

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