piperidines and Drug-Hypersensitivity

Topics: Acute Disease; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Chlorpromazine; Clinical Trials as Topic; Drug Hypersensitivity; Female; Humans; Male; Methotrimeprazine; Middle Aged; Palmitic Acids; Paranoid Disorders; Piperidines; Psychiatric Status Rating Scales; Schizophrenia; Sulfonamides; Time Factors

Although up to half of patients receiving chemotherapeutic agents develop hypersensitivity reactions to the same, desensitization protocols can induce temporary tolerance to allow patients to continue to receive first-line treatment. Approximately 25% of patients develop cutaneous hypersensitivity reactions to ibrutinib, but there are no published management guidelines.. We describe the case of a 71-year-old woman with chronic lymphocytic leukemia who developed a delayed maculopapular rash with lip tingling and swelling following ibrutinib therapy.. We performed a novel 11-step desensitization procedure to ibrutinib allowing us to successfully induce tolerance against IgE-mediated symptoms in this patient.. As indications for ibrutinib use expand and more patients present with IgE-mediated symptoms, we expect that this protocol will provide benefit for many such patients.

Topics: Adenine; Aged; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Piperidines; Pyrimidines

Alectinib is an oral tyrosine kinase inhibitor currently recommended by the National Comprehensive Cancer Network (NCCN) as the preferred first-line treatment option for the treatment of metastatic anaplastic lymphoma kinase (ALK) gene rearrangement-positive non-small cell lung cancer (NSCLC). Skin toxicity is a known adverse effect of this medication, yet current recommendations are unclear regarding how to best manage patients who develop severe skin toxicity while taking alectinib.. Here, we describe a case of successful rechallenge with alectinib by utilizing a desensitization procedure in a patient who had developed severe alectinib-induced skin toxicity about two weeks into treatment.. Alectinib is currently recommended as the preferred first-line treatment option for the treatment of metastatic anaplastic lymphoma kinase gene rearrangement-positive NSCLC due to improved progression-free survival when compared to crizotinib. The development of skin toxicity can lead to early discontinuation of alectinib treatment, forcing providers and patients to select alternative, potentially less effective options. This case report provides evidence that patients who have experienced severe skin toxicity due to alectinib may be able to continue this first-line treatment option by rechallenging them using a desensitization procedure.

Topics: Adenocarcinoma of Lung; Aged; Anaplastic Lymphoma Kinase; Carbazoles; Desensitization, Immunologic; Drug Hypersensitivity; Exanthema; Female; Humans; Lung Neoplasms; Piperidines; Protein Kinase Inhibitors

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Hypersensitivity; Drug Substitution; Humans; Idiopathic Pulmonary Fibrosis; Lung Neoplasms; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Quinazolines; Spirometry; Vascular Endothelial Growth Factor Receptor-2

Allergic reactions during anaesthesia are rare and the cause is seldom immediately obvious. Incorrect guesses for the offending substance can lead to suboptimal management. Furthermore there is a risk of a serious reaction on subsequent exposure to the real allergen. We present a case of suspected allergy to fentanyl investigated at the Danish Anaesthesia Allergy Centre. Allergy to this drug could not be demonstrated by skin tests or challenge. The reaction was due to unspecific histamine release induced by several opioids given at the same time. Future pretreatment with antihistamine was recommended.

Topics: Analgesics, Opioid; Anesthetics, Intravenous; Drug Hypersensitivity; Female; Fentanyl; Histamine Release; Humans; Piperidines; Propofol; Remifentanil; Skin Tests; Young Adult

Topics: Adult; Angioedema; Antipsychotic Agents; Drug Hypersensitivity; Haloperidol; Humans; Isoxazoles; Male; Piperidines

H1-antihistamines are probably the most frequently used drugs in allergic diseases, with widely established efficacy, tolerance, and safety. We report a patient with urticaria due to ingestion of ebastine and fexofenadine. Skin prick tests, patch tests, and basophil activation tests with the implicated drugs and antihistamines from other families were negative. The oral challenges with the implicated antihistamines and other antihistamines tested were positive, but the patient tolerated an oral challenge with cetirizine. We present a patient with urticaria induced by different antihistamines in whom the diagnosis was established by oral challenge. The mechanism of sensitization remains unclear.

Topics: Administration, Oral; Butyrophenones; Diagnosis, Differential; Drug Hypersensitivity; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Middle Aged; Piperidines; Terfenadine; Urticaria

Meglitinides (repaglinide and nateglinide) are insulin secretagogues used to treat diabetes mellitus. We present a case of hypersensitivity reaction to repaglinide in a 61-year-old man who developed a maculopapular rash 5 days after treatment. Skin prick tests including repaglinide (0.5 g/mL) and patch tests (0.05% in pet and saline) were performed, and the results were negative. A blind oral challenge test with repaglinide was performed and the therapeutic dose was subsequently taken at home every 24 hours for 7 days. The result was positive with a delayed reaction at day 3. A punch biopsy of the skin lesions revealed drug-induced exanthema. The clinical manifestations, the latency period, the reappearance of cutaneous lesions after rechallenge, and the histopathology report of the skin biopsy suggest a type IV mechanism.

Topics: Carbamates; Cyclohexanes; Diabetes Mellitus, Type 2; Drug Hypersensitivity; Erythema; Exanthema; Humans; Hypoglycemic Agents; Male; Middle Aged; Nateglinide; Patch Tests; Phenylalanine; Piperidines

Allergies to iron salts are seldom reported. We studied a patient with iron-deficiency anemia who had suffered anaphylactic reactions caused by oral iron salts. An allergy study was performed using single-blind, placebo-controlled oral challenge and skin tests with various iron salts as well as excipients in commercial formulations. Oral challenges were positive for 2 of the commercial formulations of iron salts. Intradermal tests with ferrous sulphate and ferrous lactate also showed positive results. All of the cutaneous tests using the excipients were negative. A desensitization protocol was designed which enabled us to readminister ferrous sulphate, although antihistamines were necessary to guarantee good tolerance to iron salts. We report a patient with allergy to iron salts, positive skin tests, and positive controlled challenge. We highlight the desensitization protocol designed to complete the therapeutic management of the anemia.

Topics: Aged; Anaphylaxis; Butyrophenones; Chlorpheniramine; Desensitization, Immunologic; Drug Hypersensitivity; Female; Ferrous Compounds; Histamine H1 Antagonists; Humans; Lactates; Piperidines

H1-antihistamines are commonly used drugs, and probably the most frequently used for allergic diseases. They are pharmacologic inverse agonists of histamine at H1 receptor sites and try to shift the equilibrium of this receptor toward the inactive state, preventing H1 response. A wide variety of adverse effects have been attributed to antihistamines, and they can exceptionally induce skin reactions. We report the case of a patient with several episodes of urticaria induced by different families of antihistamines - piperazines and piperidines. We performed skin prick tests (SPT), patch tests and oral challenges to different antihistamines. We found positive SPT to some antihistamines, and positive oral challenge in others with negative SPT. The route of sensitization remained unclear, and our patient could not finally tolerate any antihistamine after the oral challenges we performed. We support the hypothesis that antihistamines may shift the H1 histamine receptor to the active conformation instead of the inactive conformation, prompting adverse reactions after dosing. This is the first report of urticaria induced by different antihistamines in the same patient with positive SPT to several others.

Topics: Adult; Conjunctivitis; Drug Hypersensitivity; Female; Histamine H1 Antagonists; Humans; Piperazines; Piperidines; Rhinitis; Urticaria

The pharmacological mechanisms of allergic cough in the guinea pig were studied. Actively sensitized guinea pigs were exposed to aerosols of antigen to elicit coughing. In separate experiments, naive guinea pigs were exposed to aerosols of capsaicin to elicit coughing. Both allergic and capsaicin-induced cough were inhibited by loratadine (0.3-10 mg kg-1 p.o.) and chlorpheniramine (0.1-3.0 mg kg-1 p.o.). Neither cimetidine (10 mg kg-1 s.c.), nor thioperamide (3-10 mg kg-1 s.c.), inhibited allergic or capsaicin-induced cough. Codeine (3-30 mg kg-1 p.o.), salbutamol (0.003-3.0 mg kg-1 s.c.) and ipratropium (0.03-1.0 mg kg-1 s.c.) inhibited both allergic and capsaicin-induced cough. Hexamethonium (10 and 30 mg kg-1 s.c.) inhibited allergic, but not capsaicin-induced cough. Allergic and capsaicin-induced cough were unaffected by phenidone (5.0 and 10.0 mg kg-1 s.c.). Indomethacin (5.0 and 10.0 mg kg-1 s.c.) had no effect on allergic cough but slightly inhibited capsaicin-induced cough. We conclude that allergic and capsaicin-induced cough are modulated by histamine H1 receptor and cholinergic mechanisms. Histamine H2 or histamine H3 receptor mechanisms, and lipoxygenase and cyclooxygenase products of arachidonic acid metabolism do not influence allergic and capsaicin-induced cough. Ganglionic mechanisms play a minor role in the production of allergic cough and no role in capsaicin-induced cough.

Topics: Administration, Oral; Aerosols; Albuterol; Analysis of Variance; Animals; Antitussive Agents; Capsaicin; Chlorpheniramine; Cimetidine; Codeine; Cough; Drug Hypersensitivity; Guinea Pigs; Hexamethonium; Histamine Antagonists; Indomethacin; Injections, Subcutaneous; Ipratropium; Loratadine; Male; Ovalbumin; Piperidines; Receptors, Histamine H1; Receptors, Histamine H2

Five patients who reacted with the hypersensitive syndrome to zimeldine showed no reaction to one of two other selective 5-HT reuptake inhibitors, citalopram or paroxetine. This further strengthens the impression that the mechanism for the hypersensitivity syndrome induced by zimeldine does not seem to be related primarily to the 5-HT reuptake inhibition as such.

Topics: Aged; Aged, 80 and over; Antidepressive Agents; Citalopram; Combined Modality Therapy; Depressive Disorder; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Liver Function Tests; Male; Paroxetine; Piperidines; Serotonin Antagonists; Zimeldine

AHR-14310C(5-[2-[4-[bis(4-fluorophenyl)hydroxymethyl- 1-piperidinyl]ethyl]-3-methyl]-2-oxazolidinone ethanedioate, hydrochloride salt) displays potent and long-acting antihistaminic activity in guinea pigs and in dog and guinea pig models of immediate hypersensitivity. Given orally 1, 5 or 24 hr before an i.v. histamine challenge, AHR-14310C produced ED50 values of 0.76, 0.22 and 0.58 mg/kg, respectively, in protecting naive guinea pigs from the lethal effects of the histamine challenge. AHR-14310C was also effective when the histamine was administered as an aerosol (1-, 5- and 24-hr ED50 values = 0.69, 0.38 and 1.08 mg/kg, respectively). AHR-14310C also attenuated the anaphylactic responses to aerosolized antigen in sensitive guinea pigs and the skin response to antigen in naturally sensitive dogs. AHR-14310C, at doses in vastly excess of those required to block histamine-induced hypotension, did not alter the electroencephalogram of cats, as did the sedating antihistamine, diphenhydramine. AHR-14310C did not affect the autonomic responses to acetylcholine, isoproterenol, epinephrine or 1,1-dimethyl-4-phenylpiperazinium chloride in dogs. At low doses (0.316-1.0 mg/kg p.o.), AHR-14310C blocked antigen-induced tracheal mucous changes in sensitive rats. AHR-14310C has therapeutic potential in allergic individuals, particularly in asthmatics, where bronchorrhea or mucus plugging is a problem.

Topics: Acetylcholine; Animals; Cats; Dogs; Drug Hypersensitivity; Female; Guinea Pigs; Histamine Antagonists; Histamine H1 Antagonists; Male; Muscle, Smooth; Oxazoles; Oxazolidinones; Piperidines; Rats; Rats, Inbred Strains; Skin Tests; Sleep

Topics: Acute Disease; Adult; Aminopyrine; Benzophenones; Dipyrone; Drug Combinations; Drug Hypersensitivity; Humans; Male; Myocarditis; Piperidines; Pulmonary Edema

Ketotifen administered prior to aspirin offered protection against bronchoconstriction in 13 of 14 patients with aspirin-sensitive asthma. In four other subjects, suffering from urticaria/angioedema following ingestion of aspirin-like drugs, pretreatment with ketotifen resulted in total prevention of the adverse reactions. These results support the suggestion of a common pathogenetic mechanism operating in two distinct clinical patterns of idiosyncrasy to aspirin and other cyclo-oxygenase inhibitors. They also indicate that ketotifen might find application in treatment of adverse reactions to aspirin.

Topics: Adult; Aspirin; Asthma; Bronchi; Bronchial Spasm; Drug Hypersensitivity; Female; Histamine H1 Antagonists; Humans; Ketotifen; Male; Middle Aged; Piperidines; Placebos; Thiophenes

Topics: Adult; Aspirin; Asthma; Bronchial Spasm; Drug Hypersensitivity; Humans; Ketotifen; Piperidines; Thiophenes

A 72 years old man treated with perhexiline maleate (400 mg during 15 months) complained of skin rash, sensitive neuropathy, liver damage and mild renal insufficiency. Clinical status improved when the treatment was stopped, but liver size and renal status remained inchanged. Liver biopsy were performed at 0,6 and 15 months after the end of treatment. Inflammation and hepatocyte necrosis, seen on the first specimen, disappeared latter. Steatosis and voluminous, swollen, foamy liver seen were present in the three biopsies. Sclerosis had increased in the last one in spite of treatment arrest. Histochemical study exhibited liver storage of triglycerides, fatty acids, phospholipids, and gangliosides. Cytoplasmic glycogen was increased and some nuclei were glycogenated. Enzymatic pattern suggests a minor form of type I glycogen storage or increased neoglycogenesis. Perhexiline relation to this complex liver storage is discussed.

Topics: Aged; Drug Hypersensitivity; Gangliosides; Humans; Liver; Male; Perhexiline; Piperidines

Topics: Drug Hypersensitivity; Female; Humans; Hungary; Middle Aged; Muscle Relaxants, Central; Piperidines; Propiophenones; Vasodilator Agents

Topics: Adult; Aged; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Piperidines

Topics: Adult; Age Factors; Aged; Androstanes; Body Weight; Drug Hypersensitivity; Female; Galantamine; Gallamine Triethiodide; Heart Rate; Humans; Injections, Intradermal; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Piperidines; Salivation; Steroids; Tubocurarine; Vertigo

Topics: Adult; Analgesics; Anaphylaxis; Drug Hypersensitivity; Female; Humans; Piperidines; Resuscitation

Topics: Antiemetics; Cerebral Angiography; Cerebral Ventriculography; Dihydroxyphenylalanine; Drug Hypersensitivity; Humans; Myelography; Phenothiazines; Piperidines; Vomiting