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Pharmacology & Physiology 1 > Drugs & Synaptic Transmission > Flashcards

Drugs & Synaptic Transmission Flashcards

1
Q

Where is Nor Adrenaline stored in the body?

A

In vesicles

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2
Q

Name 3 examples of cholinesterase inhibitors

A

Short acting - Edrophonium
Medium term - Neostigmine or Physotigmine
Irreversible - Parathion, ecothiophate or dyflos

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3
Q

What are the 2 ways reuptake of NA occurs?

A

Uptake 1 - via (NET) neuronal transporter of
unmetabolised NA - high affinity

Uptake 2 - via (ENT) extraneuronal monoamine
transporter - low affinity

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4
Q

What is the effect of cholinesterase inhibitors?

A

Raise Ach levels as Ach not degraded

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5
Q

Which toxins affect SNARE proteins on cholinergic nerves?

A 
Tetanus virus 
Botulinim toxin (peptidase)
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6
Q

How is Nor Adrenaline produced from its precursor tyrosine?

A
  1. Tyrosine -> DOPA (dihydroxyphenylalanine) via Tyrosine
    Hydroxylase
  2. DOPA -> Dopamine via DOPA Decarboxylase
  3. Dopamine -> Nor Adrenaline via Dopamine β hydrolase

(4.) NA -> Adrenaline via Phenylethanamide N-
methyltransferase

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7
Q

What is the effect of toxins on the cholinergic synapse?

A

Inhibit vesicular fusion process

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8
Q

Where is adrenaline stored?

A

In β glands in the liver

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9
Q

Which drugs are used to stimulate adrenergic synapses?

A
  • Amphetamine
  • Tyramine
  • Ephedrine

Taken up instead of NA which can’t compete

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10
Q

How is the cholinergic synapse regulated?

A

Via Na+ channel blockers (e.g. lignocaine)

Via neuronal Ca2+ channel blockers (e.g. conotoxin analogue zicnotide)

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11
Q

How is adrenergic synapse activity regulated?

A

By clinically used and research based drugs

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12
Q

What is the function of the drug Hemicholinium ?

A

Inhibits the uptake of precursor Choline

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13
Q

How do vesicles release their contents?

A

Using SNARE proteins to fuse with the membrane to release their contents

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14
Q

What is the precursosr of Nor adrenaline?

A

Tyrosine

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15
Q

How do MOA inhibitors work to regulate adrenergic synapses?

A

e.g. Tranylcypromine Isocarboxazid
blocks MOA enzymes
Tyramine taken up - displacing NA
NA spills out uncontrollably of vesicles

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16
Q

What is the role of the drug Vesamicol?

A

Prevents choline storage in vesicles by displacing it

17
Q

What is the effect of toxins on SNARE proteins?

A

Toxins eat away at SNARE proteins on cholinergic nerves

18
Q

What are the functions of the 2 parts of the botulinim toxin?

A

1 - binds to choline transporter enables 2nd part

2 - Degradative part to get into cell

19
Q

Which part of the autonomic system do adrenergic synapses work with?

A

Sympathetic nervous system

20
Q

Name clinical drugs used to regulate adrenergic synapses

A
  • Desipramine
  • Imipramine
  • Cocaine
21
Q

What induces the production of the precursor choline?

A

Uptake of Choline driven by the depolarisation of the cell by Na+

22
Q

Outline the events at an adrenergic synapse leading to a response

A
  1. Nor Adrenaline synthesised
  2. Storage of NA in vesicles
  3. Depolaristaion in nerve terminal due to influx of Na+
  4. Causes Ca2+ channels to open
  5. [Ca2+] increases
  6. Ca2+ binds to synpatotagmin stabilising snare pin
  7. Creates kink in membrane causing vesicle pore ot open
  8. Release of NA neurotransmitter across synapse to
    interact with receptors on postsynaptic membrane
  9. Re uptake of unmetabolised NA by Neuronal
    transporter
23
Q

How does Botulinim toxin degrade SNARE proteins?

A

By heating to >85℃ for >5mins

24
Q

How is Ach inactivated at a cholinergic synapse?

A

Ach degraded into Choline + Acetate by cholinesterase enzyme

  • inactivates receptor
  • choline can be used again via re uptake
25
Q

Outline how the SNARE proteins cause vesicular fusion

A
  1. VAMP interacts with Syntaxin-1 or SNAP25 when
    synaptotagmin binds to Ca2+
  2. tSNARE-vSNARE complex forms –> snare pin
  3. Snare pin pulled closer to membrane
  4. Ca2+ bound synaptotagmin stabilises snare pin
  5. Creates kink in membrane enabling vesicle pore to
    open
  6. Vesicular contents released
26
Q

What is the effect of neurotoxins?

A

Inhibit neurotransmitter release from vesicles

27
Q

Outline the events that take place at a cholinergic synapse

A
  1. Precursor Choline synthesised
  2. Choline –> AcetylCholine via choline acetyltransferase
  3. Ach stored in vesicles
  4. Voltage gated Na+ channels open creating influx of
    Na+
  5. Causes Ca2+ channels to open
  6. Ca2+ binds to synpatotagmin, stabilising snare pin
  7. Creates kink in membrane causing veiscle pore to open
  8. Release of Ach across synapse
  9. Ach Inactivated after interaction with postsynaptic
    membrane
28
Q

What is the effect of drugs used clinically to regulate adrenergic synpases?

A

Block uptake mechanism of NA back into nerves
NA receptors are therefore always activated
=> [NA] high

29
Q

What are the 2 types of SNARE proteins?

A

VSNAREs - in vesicles (synaptobrevin & VAMP)

TSNAREs - on membrane (syntaxin-1 & SNAP25)

30
Q

Name the drugs used in research to regulate Adrenergic synapse activity

A

Reserpine - stops NA uptake into vesicles

Guanethidine - displaces NA in vesicles

31
Q

Which part of the autonomic nervous system do cholinergic synapses operate on?

A

Parasympathetic nervous system

Pharmacology & Physiology 1 (9 decks)

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