The Contribution of cocoa additive to cigarette smoking addiction

Page 76 of 207 RIVM report 650270002
Histamine
histamine-releasing drugs. Histamine receptors are widely distributed in the CNS.
The central histamine receptors may regulate the cardiovascular system, diuresis and
food intake. Histamine also induces gastric secretion.
Histamine provokes bronchoconstriction, but some conflicting results were found
about the breathing frequency and the tidal volume. It seems that different
mechanisms with opposite effects are acting simultaneously.
The histamine inhalation dose causing a 20% fall in forced expiratory volume in one
second (PD20) was shown to be between 0.73 mg -1.20 mg in young normal adults. In
astmatics the histamine dose for PD20 was significantly lower (about 0.23 mg). The
estimated daily histamine intake through cigarette smoking is about 2000 times less
than the PD20 in normal adults. Therefore it is expected that the histamine dose in
cigarette will not evoke any bronchoconstrictory effects.
Conclusion
It seems that the histamine dose of cigarette smoking is not high enough to evoke any
bronchoconstrictory effects. However, the (longterm) effects of histamine and/or its
pyrolysis/combustion products on the pulmonary system are unknown and need
further study.
PHARMACOKINETICS
Absorption
In four Ascaris-sensitive rhesus monkeys, the fractional absorption of 3 H-histamine
( 3 HH) and airway response, as pulmonary resistance (R1), was measured of standard
histamine aerosols containing trace amounts of 3 HH for control runs (Run 1) and of
runs after Ascaris antigen challenge (Run 2). The mean rate of accumulation of
radioactivity in the plasma volume as a function of delivered dose during histamine
exposure (2 min) was fivefold greater for Run 2 (0.047% delivered dose/min) as
compared with Run 1 (0.009% delivered dose/min). These data are consistent with
the hypothesis that airway mucosal hyperpermeability induced by an allergic reaction
is one of the factors contributing to airway hyperreactivity by increasing flows of
inhaled bronchoactive agents to effector sites in the airway wall (35).
In a double blind oral test histamine-rich (22.8 mg/l) and histamine free wine to eight
healthy subjects were given. Blood samples were taken at 0, 10, 30 and 45 minutes
after ingestion of the wine for measurement of plasma histamine and
methylhistamine. Urine was collected 5 hours before and 5 hours after ingestion for
measurement of urinary methylhistamine. No change in plasma histamine and plasma
and urinary methylhistamine was seen. This study shows that the amount of
histamine in wine has no clinical or biological effect in healthy subjects, and this
emphasised the efficiency in man of the systems for degradation of histamine that is
absorbed by the alimentary tract (36).
Bioavailability
The bioavailability through the pulmonary system seems to be high. In a study, 14 Chistamine
was administered intrabronchially to asthmatic patients and controls. The
urinary excretion of total radioactivity, 14 C-histamine and its radioactive metabolites
was measured. It was found that the excretion of total radioactivity was complete
within 24 h. The excretion rate was equal to that observed after intravenous injection