52 lines
2.2 KiB
Plaintext
52 lines
2.2 KiB
Plaintext
Caffeine has four identifiable actions in vitro, but the relationship
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between these actions and the drugs effects in vivo are not well
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established. In ascending order of dose response (i.e. from most
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sensitive to least sensitive) these are:
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1. Adenosine receptor blockade, as you have already mentioned
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2. Phosphodiesterase inhibition - this enzyme is responsible for the
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breakdown of cAMP and therefore this action of the methylxanthines leads
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to increased cAMP 2nd messenger functions.
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3. Action at Ca++ channels to increase entry of Ca++ into cells and to
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decrease sarcolemma sequestration of Ca++. This may be related to the
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weak positive inotropic effect of the se drug at high dose rates
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(together with increased cAMP dep protein kinase activity due to number
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2?)
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4. Binding to GABA receptors at the benzodiazepine site (query clinical
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relevance because of high KD).
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Ted Whittem (whittem@massey.ac.nz)
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===========================================================================
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>Caffeine has four identifiable actions in vitro, but the relationship
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>between these actions and the drugs effects in vivo are not well
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>established. In ascending order of dose response (i.e. from most
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>sensitive to least sensitive) these are:
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>1. Adenosine receptor blockade, as you have already mentioned
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This is the important one. Tolerance to caffeine is associated
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with increased adenosine receptor activity and a shifting of
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A1 receptors to the high affinity state (and a decrease of beta-adrenergic
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activity).
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>2. Phosphodiesterase inhibition - this enzyme is responsible for the
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>breakdown of cAMP and therefore this action of the methylxanthines leads
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>to increased cAMP 2nd messenger functions.
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From what I understand, caffeine doesn't reach high enough serum
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levels to significantly inhibit phosphodiesterase in people.
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>3. Action at Ca++ channels to increase entry of Ca++ into cells and to
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>decrease sarcolemma sequestration of Ca++. This may be related to the
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>weak positive inotropic effect of the se drug at high dose rates
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>(together with increased cAMP dep protein kinase activity due to number
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>2?)
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>4. Binding to GABA receptors at the benzodiazepine site (query clinical
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>relevance because of high KD).
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Don't think this is clinically relevant.
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>Ted Whittem
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--M@
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