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PubMed1981

[Non allergic skin reactions of drugs (author's transl)].

Non allergic skin reactions are differentiated in the following way: overdose, idiosyncrasy, intolerance and side effects. An intoxication caused by an overdose of a drug may be initiated by an increased resorption through the skin (e. g. salicylic acid or the obsolete boric acid). An overdose of a drug often leads to coma and in many cases, if the patients are lying unattended (e. g. at home). ischemic skin reactions, such as blisters or necrosis occur at pressure areas. Intolerance is an undesirable reaction, produced by a normal therapeutic dose of the drug. Reactions of special interest are those imitating an anaphylactic reaction (type I), such as histamine liberation, complement activation or intolerance to analgetics, dyes or preserving agents. Idiosyncrasy summarizes reactions, which differs both qualitatively and quantitatively from the normal response to therapeutic dose of a drug. Additionaly these reactions are characterized by an underlying biochemical disturbance: drug-induced porphyric crisis in porphyria acuta intermittens, INH induced pellagra or drug-induced lupus erythematosus are discussed in this context in greater detail. Side effects of a drug is a misnomen, but this term cannot be done without. These undesired effects can be differentiated into obligatory effects as seen after cytostatic treatment in the form of alopecia; and possible reactions such as chloasmas after treatment with oral hormonal contraceptives. We assume that some of these side effects would belong to the category of idiosyncrasy or intolerance, if their pathogenesis were known.

Anaphylaxis↗
PubMed1983

[Haemaccel 35: adverse reactions in a multicentric, prospective study].

Polygeline (haemaccel 35 Behringwerke) was tested in 1147 patients in a prospective and multicentre study facing systemic anaphylactoid or cutaneous anaphylactoid side effects. 8 patients showed mainly cutaneous reactions (redness and itchy swelling) and only one an increase of ventilating pressure during anaesthesia (0.78%). Polygeline showed according to an improved preparation unexpected reactions only of the cutaneous anaphylactoid type (no severe systemic life threatening reaction, histamine liberation 1 ng/ml or less according to Lorenz).

Adolescent↗
PubMed1980

Effect of the new theophylline derivatives on degranulation of mast cells and phosphodiesterase activity in smooth muscles.

Effect of the new theophylline derivative (beta-hydroxy-benzylopiperazinopropyl-theophylline), designed as R6 on degranulation of the mast cells from rat mesenteries, was tested in vitro and in vivo. In vitro it was found that R6 significantly inhibited mast cell degranulation induced both by the histamine liberator C 48/80 and by rabbit globulin directed against rat serum proteins. The effect was comparable to that revealed by mepyramine, but much stronger than the effects of DSCG and aminophylline. The influence of R6 on mast cells degranulation was less pronounced in the in vivo systems. It was demonstrated by histochemical methods that R6 did not change activity of lactic and succinic dehydrogenases, neither activity of lysosomal hydrolases. In separate system including small intestine from rat it was shown that R6 inhibited activity of the phosphodeisterase in smooth muscles. It was suggested that the effect of R6 on mast cells degranulation is mediated by an increase in cAMP as well as by indirect influence on Ca++ influx.

Animals↗
PubMed1980

[Basic peptides from bee venom, IV. Synthesis of the mast cell-degranulating peptide by liquid-phase fragment condensation (author's transl)].

The synthesis of the mast cell-degranulating peptide by liquid-phase fragment condensation is described. After the carboxyterminal of the peptide is condensated with polyethylene-glycol (Mr 10000) the following fragments are coupled stepwise on the polymer, a soluble carrier in dichloromethane by the dicyclohexylcarbodiimide/hydroxybenzotriazole-method. Pos. 17-21 Boc-Lys(Z)-Ile-Cys(SiPr)-Gly-Lys(Z) (I) Pos. 12-16 Boc-Pro-His(Trt)-Ile-Cys(Trt)-Arg(Tos) (II) Pos. 8-11 Boc-His(Trt)-Val-Ile-Lys(Z) (III) Pos. 5-7 Boc-Cys(SiPr)-Lys(Z)-Arg(Tos) (IV) Pos. 1-4 Boc-Ile-Lys(Z)-Cys(Trt)-Asn(Mbh) (V) It is practical to crystallize the polyethyleneglycol peptide-coupling products from ethanol after each step. Most of the protecting groups can be removed by treatment of the complete polyethylene-glycol-peptide in trifluoroacetic acid/HBr. In methanol, saturated with ammonia, the peptide is removed in the amid-form from the carrier. The guanidyl-blocking group disappears by solving the peptide in liquid HF. The crude peptide is converted into the tetra-S-sulfonate derivate by oxidative sulfitolysis and purified by ion-exchange and gel chromatography. After reduction by mercaptoethanol a cautious air-reoxidation of the SH- to the SS-peptide followed. Rechromatography on ion-exchange and dextran gels yields a peptide with good biological activity in rat cell histamin-liberation and inflammation inhibition compared with the natural recombinated product.

Amino Acid Sequence↗
PubMed1994

[The risk of anesthesia in bronchopulmonary diseases].

Surgery and anaesthesia, including positioning and mechanical ventilation, encompass alterations in respiratory mechanics and gas exchange persisting through the postoperative period and may cause respiratory complications. The closer the anatomical ties between the surgical site and the respiratory system, the higher the pulmonary risks. Pre-existing respiratory and pulmonary diseases further increase the patient's risk. In addition to the numerous patients suffering from chronic obstructive pulmonary disease, patients with restrictive disorders, e.g. obesity, are concerned as well. Arterial oxygen saturation tracked by pulse oximetry is recommended for screening the respiratory system. Patients at an increased risk of respiratory complications should be scheduled individually for preoperative preparation, anaesthesia requirements, and postoperative management. When anaesthetizing patients with coexisting pulmonary disease, regional anaesthesia is preferred unless limited by the surgical procedure or for obvious technical reasons. Pasch provides recommendations for the management of anesthesia: Acute respiratory obstruction should be prevented by personal attention and pharmacological protection. Anaesthetics and relaxants with parasympathomimetic and histamine liberating effects should be avoided. Attention should be paid to hazardous pharmacological interactions with existing respiratory therapy. Bronchospasm should be avoided by deep anaesthesia and by smooth intubation and extubation. Pain therapy is an essential requirement for respiratory therapy in the postoperative period to maintain or to restore pulmonary function with improved performance.

Anesthesia, Conduction↗
PubMed1995

[Efficacy and tolerance of allergenic extracts Allergovit and Novo-Helisen depot in immunotherapy of allergic diseases].

The aim of this study was to evaluate the efficacy, tolerance and immunogenity of allergenic extracts: Allergovit and Novo-Hellisen depot (produced by Allergopharma--Germany), used for sIT in pollinosis and house dust mite allergy. The treatment was carried out on 40 patients for three years. The evaluation included the results of a physical examination, the score of symptoms from self-observations and the consumption of antiallergic medicines. In addition to the serum IgE and IgG4 the percentage of histamine, liberated by a-IgE and specific allergens, from peripheral blood basophils was determined. In some of patients treated with Novo-Helisen depot the specific and nonspecific bronchial challenge tests were made. It was shown that the allergenic extracts Allergovit and Novo-Helisen depot are effective in treatment of pollinosis and house dust mite allergy, and are well tolerated by the patients. The changes in humoral response during sIT manifest their immunogenity. The sIT with Allergovit decreases the sensitivity of the peripheral blood basophils, whereas the treatment with Novo-Helisen depot causes a diminution of bronchial specific and nonspecific reactivity and a negativisation of late allergic reaction.

Adolescent↗
PubMed1996

[Iatrogenic drug-induced bronchospasm, cough, and bronchiolitis. Etiologic and physiopathologic aspects].

Iatrogenic respiratory disorders include bronchic manifestations (asthma, bronchospasm, cough) and bronchiolar manifestations (constrictive or proliferative bronchiolitis). Many pharmacologic agents can induce a bronchospasm. The bronchospasm induced by acetylsalicylic acid and nonsteroidal anti-inflammatory agents, often severe, is mediated by the inhibition of the cyclooxygenase enzyme; it can be prevented by eviction of the drug or desensitization. Leukotriene receptor antagonists and 5-lipoxygenase inhibitors may also be useful. Beta-blockers including cardioselective beta-blockers, cholinergic agonists, inhaled agents, angiotensin-converting enzyme inhibitors (ACE), vindesine, histamine liberators, etc..., can also induce a bronchospasm. Most of the same agents can also induce an isolated cough, particularly beta-blockers, inhaled agents, and ACE, which cause 75% of the reported cases of iatrogenic cough. ACE-induced cough usually disappears within 1 to 4 days after withdrawal of the treatment, confirming the diagnosis; ACE-induced cough may be prevented by sodium cromoglycate. The risk of obliterans bronchiolitis with expiratory airflow impairment during rheumatoid arthritis is increased by D-penicillamine. Many drugs can be involved in the pathogenesis of bronchiolitis obliterans organizing pneumonia, which presents with various clinical and radiological aspects. The physician has to keep in mind that bronchospasm, cough, or bronchiolitis of unknown origin, may have a iatrogenic cause.

Bronchial Spasm↗
PubMed1983

[Histamine and prolactin liberation in the rhesus monkey].

The effect of intra venous (i.v.) or intra cerebroventriculaire (i.c.v.) administration of histamine (HA) on plasma prolactin (PRL) levels was investigated in ovariectomized Rhesus Monkeys. Intra venous injection of 50 micrograms/kg HA increased the plasma PRL concentration but icv administration of 10 and 50 micrograms decreased PRL plasma levels. Intra venous injection of 2-thiazolyl-éthylamine, a H1 receptor agonist, rapidly stimulated PRL release (peak PRL concentration at 5 min) suggesting a direct effect on the pituitary. In contrast intra venous administration of the H2 receptor agonist, impromidine, inhibited PRL release at low doses. High doses of impromidine increased PRL concentrations but this effect was delayed (PRL peak values were reached at 20 minutes). Our results show that HA may influence PRL release in the primate via H1 and H2 receptors located at both pituitary and central levels.

Animals↗
PubMed1977

[Histamine and serotonin liberation and vascular permeability in a focus of acute aseptic inflammation].

Degranulation of mast cells of albino rat peritoneal fluid and mesentery of the small intestine and the release of histamine and serotonin in acute aseptic peritonitis began the first minute after the damage and reached their maximum by the 5-th minute; by the 15-th minute the level of free amines did not differ significantly from the initial one. The dynamics of the immediate phase of increased vascular permeability corresponded to the dynamics of the free amines. The greatest increase of vascular permeability was noted on the 10th--15-th minute; it decreased considerably by the 20th minute. It was concluded that histamine and serotonin caused an increase of vascular permeability in acute aseptic peritonitis mainly within 15 minutes after the damage.

Acute Disease↗
PubMed1985

Analysis of the factor(s) involved in pathogenesis of zymosan-induced inflammation in rats.

The role of mast cell degranulation in increased vascular permeability in zymosan-air-pouch inflammation, an experimental model of inflammation induced by zymosan in rats, was investigated. The complement in the inflammatory pouch fluid was exhausted, and mast cells in the pouch wall subcutaneous tissues were degranulated. The histamine level in the pouch fluid was elevated immediately after application of zymosan in the preformed air-pouch and then quickly declined. Plasma exudation into the pouch fluid changed in close parallel with the change of histamine level. Application of compound 48/80 in the air-pouch also brought about liberation of histamine from mast cells, accompanied with elevation of vascular permeability similar to that observed in the zymosan-air-pouch inflammation. However, the amount of the plasma exudation in the zymosan-air-pouch inflammation was about twice as high as that induced by compound 48/80, though the quantity of histamine liberated in the two cases was almost equal. Rats depleted of histamine and serotonin were incapable of responding to compound 48/80, but zymosan still induced increased vascular permeability. A combination treatment with pyrilamine and methysergide did not abolish plasma exudation caused by zymosan, but brought about complete blockade of the vascular permeability response to compound 48/80. These results suggest that some mechanisms independent of degranulation of mast cells are responsible in part for the initial sudden elevation of vascular permeability in zymosan-induced inflammation.

Animals↗