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Neuro Pathology > Applied Neuropharmacology > Flashcards

Applied Neuropharmacology Flashcards

1
Q

What is the sequence of events in synaptic transmission? What is the exception?

A
  1. Synthesis and packaging of neurotransmitter (usually) in presynaptic terminals
  2. Na+ action potential invades terminal
  3. Activates voltage gated Ca2+ channels
  4. Triggers Ca2+ dependent exocytosis of pre packaged vesicles of transmitter
  5. Transmitter diffuses across cleft and binds to ionotropic and/or metabotropic receptors to evoke postsynaptic response
  6. Presynaptic autoreceptors inhibit further transmitter release
  7. Transmitter is (usually) inactivated by uptake into glia or neurones
  8. Or transmitter is (unusually) inactivated by extracellular breakdown
  9. Transmitter is metabolised within cells
    ACH IS THE EXCEPTION
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2
Q

How is Ach inactivated?

A

By enzymatic breakdown in the synaptic cleft

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3
Q

How are most transmitters inactivated?

A

By high affinity uptake into the neurons and glia

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4
Q

Examples of pharmacological manipulation to reduce synaptic transmission

A

Block the voltage gated Na+ channels e.g. local anaesthetics would block the APs
Block the voltage gated Ca2+ channels e.g. toxins from spiders
Block the release machinery e.g. botox - blocks all transmitter release
Block the post synaptic receptors e.g. receptor antagonists, competitive or non competitive
Activate those presynaptic inhibitor receptors
Increase breakdown of transmitter
Increase uptake of transmitter
Inhibit synthesis and packaging of transmitter

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5
Q

Examples of pharmacological manipulation to increase synaptic transmission

A

Increase synthesis by flooding the cells with the appropriate precursors
Use an agonist to activate the post synaptic receptors - not that useful cause activated all of the time
Allosteric drug which potentiates the effects of endogenous transmitters e.g. benzodiazepines and barbituates on GABA receptors
Block break down of transmitter e.g. Anticholinesterases on GABA
Block the uptake of transmitter

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6
Q

Examples of neurotransmitters

A 
Acetylcholine
Monoamines
- noradrenaline
- dopamine 
- serotonin (5-HT)
Amino acids
- Glutamate
- GABA
- Glycine
Purines
- ATP
- adenosine
Neuropeptides
- endorphins
- CCK
- Substance P 
NO
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7
Q

What is the brain and the PNS separated by?

A

BBB

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8
Q

What does BBB stand for?

A

Blood brain barrier

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9
Q

What does each neurotransmitter have?

A

Anatomical distribution
Own range of receptors it acts on
Own range of functions in different regions (some seperated by BBB)
Exploited by therapeutic uses

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10
Q

Where is dopamine found in the brain?

A

Brain stem
Basal ganglia
Limbic system and frontal cortex

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11
Q

What physiological functions are affected by dopamine?

A

Vomiting
Voluntary movement
Emotions/rewards

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12
Q

Where is the vomiting centre found?

A

Brainstem

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13
Q

What is the function of the basal ganglia?

A

Regulates movement

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14
Q

What is involved in the limbic system?

A

Behaviour

Reward

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15
Q

Pathology of Parkinson’s disease

A

Degeneration of DA cells in the SN
DA deficiency in the basal ganglia
Fairly selective degeneration of a certain type of neurones

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16
Q

Does dopamine cross the BBB?

A

No

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17
Q

What are tyrosine and DOPA and can these get into the BBB?

A

Precursors of dopamine - these can get through the BBB

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18
Q

Where is DOPA broken down into dopamine?

A

In the liver

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19
Q

What are the dopamine receptors? What types of receptors are these?

A 
D1
D2
D3
D4
D5
These are all metabotropic
20
Q

Does dopamine have ionotropic receptors? What does this mean?

A

No

Dopamine cannot evoke fast EPSPs or IPSPs

21
Q

What is the only neurodegenerative disorder that can be manipulated?

A

Parkinson’s disease

22
Q

What TYPES of drugs can be used to treat parkinsons disease?

A

DA precursor
DA agonists
Enzyme inhibitors

23
Q

Example of a DA precursor

A

Levodopa

24
Q

Examples of DA agonists

A 
Ergots
- bromocriptine 
- pergolife
- cabergoline
Non-ergots
- Ropinirole
- Pramipexole 
- Rotigotine 
Apomorphine
25
Q

Examples of enzyme inhibitors

A 
Peripheral AAAD inhibitors 
- carbidopa
- benserazide 
MOAB inhibitors
- selegiline
- rasagiline
- sanfinamide
COMT inhibitors
- entacapone
- tolcapone
26
Q

What do dopaminergic drugs improve?

A

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

27
Q

What do dopaminergic drugs worsen or cause?

A

Nausea
Vomiting
Pyschosis
Impulsivity/abnormal behaviours

28
Q

How do dopaminergic drugs cause vomiting?

A

More dopamine working on the brainstem working areas which promotes vomiting

29
Q

Examples of impulsivity / abnormal behaviours that dopaminergic drugs can cause

A 
Impulsivity
- gambling
- hypersexuality
Emotion 
- hallucinations etc
30
Q

What do dopaminergic drugs fail to help?

A

“Midline” features

  • dysarthria
  • balance
  • cognition
31
Q

What do dopamine antagonists do? What would this induce?

A

Block the dopamine system

This would induce parkinsonian syndrome

32
Q

What do dopamine antagonists improve?

A

Nausea
Vomiting
Psychosis

33
Q

What do dopamine antagonists worsen or cause?

A

Parkinson’s

34
Q

What is another name for the vomiting centre?

A

Area postrema

35
Q

Where is the vomiting centre found in respect to the BBB?

A

Outside of the BBB

36
Q

Features of doperidone

A

Does not go into the BBB
Reduces the nausea feeling
Does not make parkinsons worse

37
Q

What type of drug is doperidone?

A

DA antagonist

Anti emetic

38
Q

What type of drug is apomorphine?

A

A powerful emetic

39
Q

What does AIM stand for?

A

Abnormal involuntary movements

40
Q

Features of long term DA Antagonist use

A

Often cause parkinsonism
Sometimes cause dyskinesias
- tardive dyskinesiasis

41
Q

Who needs to be on lifelong DA antagonists?

A

Antipsychotics and schizophrenia patients

42
Q

What type of drug are MAO inhibitors?

A

Antidepressants

43
Q

What type of drugs are SSRIs?

A

Antidepressants

44
Q

What are triptans (selective 5HT agonists) used to treat?

A

Migraine

45
Q

What type of drug are GABA agonists?

A

Anti epilepsy drugs

also have anti anxiety properties

Neuro Pathology (21 decks)

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