Xanthines Chemische Eigenschaften,Einsatz,Produktion Methoden
Chemische Eigenschaften
Three xanthines are pharmacologically important: caffeine,
theophylline, and theobromine. All three alkaloids,
which occur naturally in certain plants, are widely
consumed in the form of beverages (infusions or decoctions)
derived from these plants. Coffee primarily contains
caffeine (about 100–150 mg per average cup); tea
contains caffeine (30–40 mg per cup) and theophylline;
and cocoa contains caffeine (15–18 mg per cup) and
theobromine. Cola drinks also contain significant
amounts of caffeine (about 40 mg/12 oz). The CNS
stimulation associated with these beverages is predominantly
due to the caffeine.
The xanthines are readily absorbed by the oral and
rectal routes. Although these agents can be administered
by injection (aminophylline is a soluble salt of
theophylline), intravascular administration is indicated
only in status asthmaticus and apnea in premature infants.
Intramuscular injection generally produces considerable
pain at the injection site.
The compounds are extensively metabolized, primarily
to uric acid derivatives. There is, however, no indication
that methylxanthines aggravate gout.
Biologische Funktion
The compounds known as xanthines, methylxanthines,
or xanthine derivatives constitute a particularly interesting
class of drugs. Since they possess diverse pharmacological pharmacological
properties, there is always a question of
where most appropriately to discuss them in a pharmacology
text. The xanthines are clearly CNS stimulants,
although not all have this characteristic equally.While
the xanthines have legitimate therapeutic uses, by far
the greatest public exposure to them is in xanthinecontaining
beverages, including coffee, tea, cocoa, and
cola drinks. The popularity of xanthine-containing
drinks appears to be related to its subtle CNS stimulant
effect. It is primarily for this reason that xanthines are
listed as CNS stimulants in this text.
Mechanism of action
The mechanism of action of methylxanthine-induced
stimulation of the CNS has been the subject of much investigation,
and at least two other possible mechanisms
of action of the methylxanthines have been suggested.
The first derives from the ability of the methylxanthines
to act as antagonists of the naturally occurring compound
adenosine, a substance that can inhibit both neuronal
activity and behavior through direct postsynaptic
action on neurons and through indirect action involving
presynaptic inhibition of neurotransmitter release. The
A1 subtype of the purine receptors mediates these actions
of adenosine. Thus, as an equilibrium-competitive
antagonist of adenosine, the methylxanthines may produce
excitation either by direct blockade of inhibitory
effects of adenosine at the neuron or by an antagonism
of the presynaptic inhibitory effect of adenosine on the
release of an excitatory substance (e.g., acetylcholine).
Another suggested mechanism of action involves
the chloride channel. As discussed previously, the chloride
channel is intimately associated with neuronal inhibition,
and its activity appears to be modulated at many
different sites. Caffeine can compete for binding at the
benzodiazepine site and would therefore be expected to
reduce chloride conductance. Thus, caffeine may act
functionally like the analeptic stimulants that limit chloride
channel activation.
Nebenwirkungen
Toxicity associated with the methylxanthines usually
takes the form of nervousness, insomnia, and in severe
cases, delirium. Cardiovascular stimulation is seen as
tachycardia and extrasystoles. Excessive respiratory
stimulation may occur, and diuresis may be prominent.
The intravenous administration of aminophylline
(or theophylline) may present some problems if the
drug is given too rapidly. In such cases, severe headache,
hypotension, and palpitation accompany drug administration.
Subsequently the patient may show signs of excessive
CNS stimulation, shock, and even death.
Children appear to be especially prone to this toxicity.
Arzneimittelwechselwirkung
An interaction of potential clinical significance involves
the xanthines and the coumarin anticoagulants. Xanthines
by themselves shorten clotting time by increasing tissue
prothrombin and factor V and in this regard may be expected
to antagonize the effectiveness of oral anticoagulants.
However, the usual therapeutic doses of xanthines
cause no significant effect on the patient’s response to
oral anticoagulants.
Xanthines Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
