Asthma, Drugs and Supplements
| Asthma, Drugs and Supplements |
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Some currently used pharmaceutical formulations for bronchodilation, such as theophylline, have a narrow therapeutic margin because adverse effects often occur at concentrations high enough to be effective.
Other products do not provide
sufficient plasma drug concentrations for therapeutic efficacy over a 12-hour period,
particularly in patients with high clearance rates, such as children and patients who
smoke. 125
In addition, prednisone, the most common antiinflammatory drug used to treat asthma, is also associated with a variety of adverse side effects.
Such limited effectiveness of presently
available treatments has recently sparked research into less toxic, immune-enhancing
nutritional approaches to treating asthma.
DS Pearlman noted that antihistamines are a diverse group of drugs that act principally to prevent histamine-receptor interaction through competition with histamine for histamine receptors.
Consequently, they are helpful therapeutically in preventing, rather than reversing, histaminic actions.
Individual antihistaminic drugs act to inhibit histaminic action at one or another histamine receptor (H1 or H2-receptor), but not at both receptors.
Antihistamines in general exert a wide
variety of pharmacological activities. Their use is frequently accompanied by undesirable
side-effects, notably CNS depression, dryness of mucous membranes, and gastrointestinal
effects.126
Serum gastrin concentrations are affected by corticosteroid administration. As noted elsewhere in this hypothesis, asthma symptoms are linked to excess gastric acid.
In a study of patients suffering from bronchial asthma serum gastrin concentrations were measured before and after the feeding of a standard meal.
All subjects studied were divided into 2 main groups: I. Those not receiving corticosteroids and II. Those undergoing long-term treatment with corticosteroids.
Results obtained from these two groups were compared to those found in 32 healthy persons.
In group I, a statistically significant increase in serum gastrin concentrations was seen in subjects with the atopic form of bronchial asthma, before test meal ingestion and 15, 30 and 60 min after, where as in subjects with non atopic form of bronchial asthma an increase in serum gastrin concentration was found before the feeding of test meal and 15, 60, 90 and 120 min after.
In all subjects suffering from both forms of bronchial asthma and belonging to group II, serum gastrin concentrations were significantly elevated in comparison with healthy persons.
This increase in serum gastrin level was greater in subjects with non atopic form of bronchial asthma.
Patients having contracted complications associated with corticosteroids administration presented serum gastrin levels higher than those without complications. The researchers concluded that oral administration of corticosteroids resulted in more intensive stimulation of gastrin release than parenteral administration.127
Pyroxidine Deficiency and Depressed
Immunity
Pyroxidine deficiency results in depressed immunity, noted by a reduction in the quantity and quality of antibodies produced, shrinkage of lymphatic tissues (including the thymus gland), decreased thymic hormone activity, and a reduction in the number and activity of lymphocytes.128
Asthma, Vitamin B6 and Tryptophan Metabolism
In general, asthmatics have a defect in tryptophan metabolism and reduced platelet transportation of serotonin possibly as a result of low vitamin B6 levels.
Double-blind clinical studies show that some patients benefit from vitamin B6 supplementation to correct the blocked tryptophan mechanism. As the body converts tryptophan to create niacin, patients with impaired tryptophan metabolism may also benefit from supplementation with niacin.129
Vitamin B6 Decreases Asthmatic Attacks (Deficiency of Magnesium or Riboflavin?)
In one study, oral supplementation with 50 mg of vitamin B6 twice daily resulted in a dramatic decrease in frequency and severity of wheezing and asthmatic attacks.
Although all patients reported benefit, in seven of the patients supplementation failed to produce a substantial elevation of the pyridoxal-5-phosphate. This suggests that some patients may need even more vitamin B6, or they may be deficient in magnesium or riboflavin.
As magnesium deficiency has been reported extensively in asthmatic patients, supplementation with magnesium appears to be indicated.130A
Theophylline and Vitamin B6 Reduction
The asthma drug theophylline has been linked with a reduction of plasma pyridoxal-5'-phosphate concentrations in asthmatic patients.
R Delport, and colleagues noted that plasma pyridoxal-5'-phosphate concentrations were significantly lower in a group of 28 asthmatic women when compared to 33 controls.
Plasma pyridoxal levels in the two groups were not different. Theophylline was administered to a group of 17 volunteers and resulted in large reductions in plasma pyridoxal-5'-phosphate levels, while plasma pyridoxal levels and urinary 4-pyridoxic acid excretion were unaffected by theophylline therapy.
An in vitro study showed that theophylline did not interfere with the high performance liquid chromatography assay for pyridoxal-5'-phosphate, indicating that theophylline could affect liver metabolism of vitamin B6.131
Theophylline and Depression of Vitamin B1 and B6
T Shimizu, et al. studied the relation between theophylline and circulating vitamin levels in children with asthma.
Twenty-three asthmatic children, ranging in age from 7 to 15 with a mean of 10.8 years and including 16 patients who were treated with slow-release theophylline and 7 patients not receiving any type of theophylline preparation, were enrolled in this study.
They all were inpatients who had been hospitalized for the control of asthma.
Steady-state serum theophylline and vitamin A, B1, B2, B6, B12 and C levels were evaluated in these patients.
Circulating vitamin B1 and B6 levels were depressed in asthmatic children treated with theophylline compared to those not receiving the agent (38.4 +/- 1.6 (mean +/- SEM) vs. 46.4 +/- 3.5 ng/ml and 7.1 +/- 0.5 vs. 11.8 +/- 2.1 ng/ml, respectively, p < 0.05).
A significant negative correlation between theophylline and circulating levels of vitamin B6 was demonstrated in the subjects of this study (rs = -0.657, p < 0.001). In contrast, no relationship was noted between theophylline and circulating vitamin B1 levels.
They concluded that theophylline induces depression of circulating vitamin B1 and B6 levels in asthmatic children, although a dose-dependent interaction between theophylline and vitamin B1 would be unlikely. Similar results were found in a previous study by Shimizu, et al.132,133
Asthma, Vitamin B6 and Quercitin
II Balabolkin and associates studied the therapeutic efficacy of vitamins B6, P and E in children with allergic diseases. Bronchial asthma and atopic dermatitis were treated more effectively if maximal doses of vitamin B6 were used.
Quercetin was found to be useful for treatment of children with pollinosis in order to correct impairments in metabolism of lymphocyte membrane lipids.134
Theophylline, B6 and Vascular Disease
Theophylline/vitamin B6 interaction has also been reported to be a risk factor in premature vascular disease.
JB Ubbink and colleagues noted that homocysteine, an atherogenic amino acid, is either remethylated to methionine or metabolized to cysteine by the transsulfuration pathway.
The biochemical conversion of homocysteine to cysteine is dependent upon two consecutive, vitamin B-6-dependent reactions.
To study the effect of a selective vitamin B-6 deficiency on transsulfuration, researchers performed oral methionine load tests on 22 vitamin B-6-deficient asthma patients treated with theophylline (a vitamin B-6 antagonist) and 24 age- and sex-matched controls with a normal vitamin B-6 status.
Both groups had normal circulating vitamin B-12 and folate concentrations. Methionine loading resulted in significantly higher increases in circulating total homocysteine and cystathionine concentrations in vitamin B-6-deficient patients compared with controls. 6 wk of vitamin B-6 supplementation (20 mg/d) significantly reduced post-methionine load increases in circulating total homocysteine concentrations in deficient subjects, but had no significant effect on the increase in total homocysteine concentrations in controls.
The increases in post-methionine load circulating cystathionine concentrations were significantly reduced in both groups after vitamin supplementation.
It is concluded that a vitamin B-6
deficiency may contribute to impaired transsulfuration and an abnormal methionine load
test, which is associated with premature vascular disease.135
Therefore, the use of folic acid to decrease homocysteine levels in asthma patients is also suggested, as folic acid has been shown in numerous recent studies to reduce homocysteine. Folic acid is necessary to convert homocysteine into methionine via remethylation.
Theophylline Seizures and Vitamin
B6
In animal studies, a beneficial effect of pyroxidine (vitamin B6) has been reported. Theophylline-induced seizures have significant morbidity and mortality and are difficult to treat.
Theophylline therapy for asthma has been observed to depress plasma pyridoxal 5'-phosphate (PLP) levels which may decrease gamma-aminobutyric acid (GABA) synthesis and thereby contribute to seizures.
The researchers hypothesized that treatment with pyridoxine might prove beneficial in theophylline-induced seizures.
One hundred thirty-nine mice were injected with 250 mg theophylline/kg ip and 89 mice were injected with 250-750 mg pyridoxine/kg ip as treatment.
Decreased rates of seizure (42 vs 70%) and death (29 vs 56%) were observed.
Six New Zealand White rabbits were given 115 mg theophylline/kg iv over 50 min followed by treatment with an iv bolus of 115 mg pyridoxine/kg, with subsequent continuous drip infusion of 230 mg/kg over 50 min.
Serum theophylline levels and plasma PLP levels showed significant negative correlation prior to pyridoxine infusion with a mean peak theophylline level of 182 micrograms/ml and a mean low PLP level of 64 nM/L. Electroencephalogram (EEG) tracings were obtained before infusions, during theophylline infusion and during pyridoxine infusion.
All 6 rabbits developed abnormal EEGs during theophylline infusion and all 6 rabbit EEG patterns returned to baseline during treatment with pyridoxine.
These findings suggest that pyridoxine may partially reverse theophylline-induced central nervous system toxicity.136
Asthma Deaths and Tranquilizer Use
Interactions with other drugs can produce fatal occurences.
Asthma sufferers are more than three times as likely to die from an attack if they have taken a major tranquilizer in the previous 12 months.
Doctors have been warned about prescribing tranquillizers to their asthma patients as a result of these findings.
Researchers from McGill University in
Montreal, Canada made the discovery after analyzing 131 cases of death or near-death
following an asthma attack.137