Lecture 42 Applied Neurological-Pharmacology Flashcards Preview

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Flashcards in Lecture 42 Applied Neurological-Pharmacology Deck (26)
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1
Q

Describe the sequence of events in synaptic transmission

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
2
Q

Pharmacological manipulation to reduce synaptic transmission

A
  • Block the voltage gated Na+ channels – eg local anaesthetics, would block all action potentials, not too useful.
  • Block the voltage gated Ca2+ channels – eg those clever spider toxins, would block all transmitter release, not too useful.
  • Block the release machinery, eg botox, would block all transmitter release, not too useful.
  • Block the postsynaptic receptors, eg receptor antagonists, competitive or non-competitive. Selectivity helps. Lots of examples of that.
  • Activate those presynaptic inhibitory receptors.
  • Increase breakdown of transmitter (though I can’t think of an example of that).
  • Increase uptake of transmitter (though I can’t think of an example of that).
  • Inhibit synthesis and packaging of transmitter.
3
Q

Pharmacological manipulation to increase synaptic transmission

A
  • Increase synthesis by flooding the cells with the appropriate precursors.
  • Use an agonist to activate the postsynaptic receptors - though that is not so useful because they get activated all the time – most of which is inappropriate.
  • Better to use an allosteric drug that does activate the receptor on its own, but potentiates the effects of the endogenous transmitter, eg benzodiazepines and barbiturates on GABA receptors.
  • Block break down of transmitter – eg anticholinesterases on Ach.
  • Or block the uptake of transmitter.
4
Q

Describe Pharmacological Manipulation to Increase Synaptic Transmission

A
  • Increase synthesis by flooding the cells with the appropriate precursors.
  • Use an agonist to activate the postsynaptic receptors - though that is not so useful because they get activated all the time – most of which is inappropriate.
  • Better to use an allosteric drug that does activate the receptor on its own, but potentiates the effects of the endogenous transmitter, eg benzodiazepines and barbiturates on GABA receptors.
  • Block break down of transmitter – eg anticholinesterases on Ach.
  • Or block the uptake of transmitter.
5
Q

Each neurotransmitter has

A
  • Its own anatomical distribution
  • Its own rage of receptors it acts on
  • Its own range of functions in different regions
6
Q

What is the anatomical distribution in the brain of dopamine

A
  • Brain stem
  • Basal ganglia
  • Limbic system and frontal cortex
7
Q

What physiological functions are affected by dopamine

A
  • Voluntary movement
  • Emotions/reward
  • Vomiting
8
Q

Describe Parkinson’s disease

A
  • Degeneration of DA cells in the substantia nigra (nigrostriatal)
  • DA deficiency in the basal ganglia
  • Stiffness, slow movements, change in posture, tremor
9
Q

Describe Dopamine synthesis

A

Glycine–> Alanine–>Phenylalanine–>Tyrosine–>DOPA—>Dopamine

10
Q

What enzymes are involved in the synthesis of dopamine

A

Tyrosine
Hydroxylase
Aromatic aa
Decarboxylase

11
Q

How many subtypes are there of dopamine receptors

A
5 Metabotropic (protein coupled)
Dopamine cannot evoke fast EPSPs or IPSPs
12
Q

Name enzymes involved in Dopamine Metabolic Breakdown

A

MOAD

COMT

13
Q

What is dopamine breakdown product

A

Homovanillic acid

14
Q

Name a precursor that is a Dopaminergic drugs

A

Levodopa

15
Q

Name DA agonists

A

Ergots- Bromocriptine
Non-ergots- Ropinirole
Apomorphine
Improve symptoms of PD

16
Q

Name enzyme inhibitor drugs

A

Carbidopa
MOA inhibitors
COMT inhibitors

17
Q

What do Dopaminergic drugs improve

A

• Some motor features of Parkinson’s

e.g. limb rigidity & bradykinesia, tremor

18
Q

What fo dopaminergic drugs cause or worsen

A
  • Nausea
  • Vomiting
  • Psychosis
  • Impulsivity / abnormal behaviours
  • Fail to help midline features such as dysarthria, balance, cognition
19
Q

Dopamine antagonists improve

A
  • Nausea
  • Vomiting
  • Psychosis
20
Q

Dopamine antagonist worsen

A

Parkinsonism

21
Q

Why do Dopamine antagonists worsen Parkinsons

A
Area postrema (vomiting centre) in the medulla is functionally OUTSIDE the BBB.
If there was a DA antagonist that didn’t cross the BBB that would be ok
22
Q

Name a DA antagonist that doesn’t cross the blood brain barruer

A

Domperidone

23
Q

Dopaminergic may cause what type of abnormal movement

A

Dyskinesias: Abnormal Involuntary Movements- too much movement

24
Q

DA antagonist may cause

A

Parkinsonism- not enough movement

25
Q

What are the consequences of long term DA antagonist uses

A

Often cause Parkinsonism (receptor blockade in basal ganglia), • Tardive dyskinesias (orofaciolingual

26
Q

Name anti-depressants in relation to their neurotransmitter functions

A

Noradrenaline reuptake blockers- antidepressants
MOA inhibitors- antidepressants
Selective serotonin reuptake inhibitors- antidepressants

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