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Drug Allergy
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
On re-exposure to the drug, cross-linking of the drug-specific IgE occurs leading to activation of mast cells and subsequent release of mediators including histamine, tryptase and arachidonic acid metabolites leading to symptoms. Symptoms can consist of pruritus, flushing, urticaria, GI symptoms (pain, emesis or diarrhea), angioedema, wheezing, laryngeal edema and hypotension possibly leading to anaphylactic shock. Type I reactions usually occur within minutes to hours after exposure and therefore are referred to as immediate type hypersensitivity reactions. The most common causative agents include beta-lactam antibiotics, platinum-based chemotherapeutics and perioperative agents. Type I reactions that are not IgE mediated are believed to be caused by direct mast cell activation by a drug. This type of reaction is referred to as a ‘pseudoallergic’ reaction. Examples include reactions to opiates, vancomycin or iodinated radiocontrast media. The MRGPRX2 receptor is located on mast cells and has been implicated in pseudoallergic reactions (Subramnaian et al. 2016).
Hypersensitivity and Urticaria
Published in Gabriella Fabbrocini, Mario E. Lacouture, Antonella Tosti, Dermatologic Reactions to Cancer Therapies, 2019
Cataldo Patruno, Maria Ferrillo, Maria Vastarella
However, reactions also may arise as a result of nonimmunologic mechanisms and caused by drug intolerance (idiosyncratic or pseudoallergic). Symptoms of a drug-induced pseudoallergic or anaphylactoid reaction resulting from the direct release of histamine and producing flushing, rash, pruritus, urticaria, hypotension, and mucous secretion can sometimes make it difficult to distinguish it from a true DHR. Symptoms are generally more severe in anaphylactic than in anaphylactoid reactions with cardiovascular collapse and bronchospasm occurring more frequently in the former and cutaneous manifestations seen more often in the latter (4).
Development of palliative medicine in the United Kingdom and Ireland
Published in Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita, Textbook of Palliative Medicine and Supportive Care, 2015
Hypersensitivity reactions to opioids are rare. Patients may report being "allergic" to opioids, and it is important to distinguish between "true" immune-mediated reactions (rare) and reactions that mimic an immune allergic response (nonallergic or pseudoallergy). Patients often consider side effects (e.g., nausea, sedation) to be an allergy; hence, it is important to check what problems a specific opioid has caused for an individual patient.
Lipoplexes and polyplexes as nucleic acids delivery nanosystems: The current state and future considerations
Published in Expert Opinion on Drug Delivery, 2022
Bruno Costa, Beatriz Boueri, Claudia Oliveira, Isabel Silveira, Antonio J. Ribeiro
Ideally, preclinical studies would allow anticipating any unwanted in vivo responses and fine-tuning non-viral vectors at earlier stages to avoid them. Even though it is possible to conduct most assessments in vitro, the grouping of those and in vivo methods to identify relevant biomarkers that allow us to establish the safety and efficacy profiles is needed to address the complex biological environments [14,15]. Failure to do so can lead not only to blood incompatibilities, as evidenced by hemolysis and thrombogenicity, but also to complement activation (e.g. complement activation-related pseudoallergy or CARPA), cytokine induction (e.g. cytokine storm), and even undesirable immunosuppression [16]. Even with good in vitro–in vivo correlations observed for hemolysis, complement-mediated responses, and cytokine-mediated ones [17], the immune system comprises several types of immune cells and other organism’s cells. Because of that, it is difficult to assess the immunological reactions in vitro. Besides, current synthetic-material-based nanosystems are relatively bulky (>100 nm), causing them to accumulate preferably in the liver and tumors [18], as opposed to smaller particles that distribute systemically. Consequently, in vivo models are needed to determine their biodistribution patterns. Hence, it is not possible yet to discard animal studies.
Nanoliposomes as drug delivery systems: safety concerns
Published in Journal of Drug Targeting, 2022
Yu. A. Tereshkina, T. I. Torkhovskaya, E. G. Tikhonova, L. V. Kostryukova, M. A. Sanzhakov, E. I. Korotkevich, Yu. Yu. Khudoklinova, N. A. Orlova, E. F. Kolesanova
High risk is possible for patients with hypersensitivity. Hypersensitivity reactions of varying severity, up to anaphylactic shock, associated with the activation of the complement system, were observed in some patients after intravenous administrations of liposomal drug Doxil® and particularly (>10%) Ambisome® (liposomes with antifungal drug amphotericin B,) [111]. Sometimes a special reaction is observed, called CARPA (complement-activation-related pseudoallergy) [97,111]. It turns out to be mild and rapidly transient in most patients. However, there are cases of its sharp severity, and even sometimes (although extremely rare, ≤0.01%) fatal outcomes [97]. The main manifestation of CARPA is cardio-pulmonary stress, so the safety problem applies primarily to patients with heart diseases. Several such manifestations were observed under the action of the antitumor liposomal drug Doxil [111].
A multistage oral delivery system of PTX for improving oral bioavailability and enhancing anticancer efficacy
Published in Drug Development and Industrial Pharmacy, 2021
Ting Zhao, Hongli Zhou, Wanyan Wu, Xu Song, Tao Gong
As breast cancer has a high incidence in women worldwide, it is urgently in need of efficient treatment [1,2]. Chemotherapy is still the primary choice in clinical treatment [3,4]. Paclitaxel (PTX), which binds to the β-subunit of tubulin and inhibits the proliferation of cells, is regarded as one of the most effective and broad spectrum anticancer agents for clinical chemotherapy [5,6]. However, the clinical application of PTX is greatly restricted by its poor water solubility, low intestinal uptake, and low therapeutic index [7,8]. To improve the poor water solubility, Cremophor EL (CEL), and ethanol (50:50 (v/v)) were applied as solubilizers in Taxol® (commercial injection of PTX) [9]. But these excipients cause poor compliance and complement activation-related pseudoallergy (CARPA) [10–12]. The mechanism of CARPA is that CEL forms abnormal micelles and crystals in blood after Taxol® injection intravenously [13]. However, CARPA could be reduced by oral administration [14,15].