Characteristics and Theories Related to Acute and Chronic Tolerance Development
S.J. Mulé, Henry Brill in Chemical and Biological Aspects of Drug Dependence, 2019
Drug refers to any chemical or substance used to produce an alteration or response (a pharmacologic effect) in a biological system (whole organism or an isolated component of the organism). Drug tolerance (or simply tolerance for the purposes of this chapter) is a state of decreased responsiveness of the system to a pharmacologic action of the drug, resulting from prior exposure of the system to that drug. It is defined in reference to the magnitude of response to the first dose of the drug, and it is expressed quantitatively as a reduction in the response to a subsequent dose of the same size, or, in some cases, as the increment of dosage required to produce a subsequent response equal in magnitude to the initial response. The definition declares that the state is acquired only by prior exposure to the drug (or a congener, see cross tolerance below), and thereby excludes a variety of other factors (genetic, environmental, developmental, pharmacologic, etc.) which may influence the responsiveness of the system to the drug. Obviously, it is essential to control experiments on tolerance for changes in responsiveness due to these other factors or arising spontaneously.
Drug Allergy
Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial in Textbook of Allergy for the Clinician, 2021
Drug tolerance is defined as a state in which a patient with a drug allergy will tolerate a drug without experiencing an adverse reaction. Induction of tolerance modifies a patient’s response to a drug temporarily which permits it to be given when it is needed. A procedure for inducing drug tolerance is also referred to as drug desensitization. It is done in situations where an alternate non–cross-reacting medication cannot be used and has been used to treat reactions that are IgE-mediated, non-IgE mediated, pharmacologic and undefined (Caimmi et al. 2019) (Der Groot and Mulder 2010). The procedure has proven to be markedly effective, allowing for successful drug administration in almost any patient with drug hypersensitivity when supervised by experienced clinicians.
The parathyroid glands
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie in Bailey & Love's Short Practice of Surgery, 2018
The extracellular calcium sensing receptor (CaR) on the parathyroid cell surface negatively regulates secretion of PTH. Activation of the receptor decreases secretion of PTH, thereby decreasing bone turnover. Calcimimetics, such as cinacalcet, amplify the sensitivity of the CaR to extracellular calcium, altering the set point and thereby decreasing PTH production. The use of calcimimetics has gained widespread acceptance in secondary hyperparathyroidism, but use in PHTP is largely limited to patients unfit for surgery. Despite this, a number of small studies have shown normalisation of PTH levels and a reduction in bone remodelling, with durable results at 2 years, with the use of cinacalcet. Drug tolerance, especially gastrointestinal side effects, can be problematic and may limit the duration of usage.
10th European immunogenicity platform open symposium on immunogenicity of biopharmaceuticals
Published in mAbs, 2020
S. Tourdot, A. Abdolzade-Bavil, J. Bessa, P. Broët, A. Fogdell-Hahn, M. Giorgi, V. Jawa, K. Kuranda, N. Legrand, S. Pattijn, J. A. Pedras-Vasconcelos, A. Rudy, P. Salmikangas, D. W. Scott, V. Snoeck, N. Smith, S. Spindeldreher, D. Kramer
It was recommended that drug tolerance be reported separately for screening and confirmatory assays. The drug tolerance is defined as the highest drug concentration that can still enable a reactive result to be detected in a screening assay and a positive result in a confirmatory assay. Multiple validation runs should be performed and median tolerated drug concentration at each ADA level assessed. The drug tolerance in other populations should be recommended only if population-specific cut points are implemented. Regulatory considerations expect a sufficient drug tolerance to enable detection of ADA in the presence of serum drug at the time of sample collection. However, if no clinical consequences are observed in patients with low-level ADA responses, assay drug tolerance may be acceptable even if the expected drug level is tolerated only at ADA concentrations higher than 100 ng/mL. For selectivity, both screening and confirmatory tiers should be tested to ensure that matrix does not interfere with the confirmatory state. The use of one LPC set at a level that robustly screens and confirms should be considered. Other factors to be considered during selectivity assessments include hemolytic/lipemia samples, diseased state and preexisting antibodies. There is no recommendation for assessing selectivity during co-medications.
Improved effectiveness from individualized dosing of self-administered biologics for the treatment of moderate-to-severe psoriasis: a 5-year retrospective chart review from a Spanish University Hospital
Published in Journal of Dermatological Treatment, 2020
Roser Sanz-Gil, Antonio Pellicer, M. Carmen Montesinos, Francisca Valcuende-Cavero
In addition, there are differences between doses often prescribed in clinical practice and the doses specified in the approved European Medicines Agency (EMA) product information, which result in discrepancies between the real cost of these therapies in clinical practice versus their theoretical cost (5). The causes for these variations are diverse. In a significant proportion of patients with good initial clinical response, a gradual loss of effectiveness is observed over time, which is often attributed to the production of antibodies against the drug (4). Previous studies have shown that starting treatment with drugs whose effectiveness may decrease over time may increase the total cost over time (6). In other patients, the response is so satisfactory that the dose intervals may be lengthened without losing effectiveness. Other reasons for increasing dose intervals also include tight schedules, surgical interventions, or the desire to become pregnant. Therefore, evaluation of the performance of these therapies over time is crucial for the understanding of drug tolerance and possible therapeutic failure.
Sexual satisfaction and body image in outpatient male opioids users receiving harm reduction services
Published in Journal of Substance Use, 2021
Mojtaba Habibi, Mohammad Darharaj, Mohammad Arghabaei, Shirin Khalili
In line with previous research indicating that patients with substance use disorder have a negative body image (e.g., Pomerleau & Saules, 2007; Spring et al., 1992), current results also revealed that opioids users receiving harm reduction services had a more negative body image than non-users. Taking substance use-related physical harms into account may explain this finding. In fact, besides unpleasant psychological consequences of substance use disorder, drug use is also associated with many negative physical consequences including loss of appetite, anorexia, severe weight loss, skin problems, etc. (Romanelli & Smith, 2006), which, in turn, may cause patients with substance use disorder to be perceived as unattractive and experience more negative body image. This can be particularly the case if patients are using drugs for a long period of time. In this case, substance use will destroy the brain’s reward system and as a result, drug tolerance occurs. Thus, substance users need to use higher doses of drugs, which causes them to experience more physical harm and more negative body image. However, more research is needed to determine trajectories leading patients with opioids user disorder to a negative body image.
Related Knowledge Centers
- ADDiction
- Allergen
- Allergen Immunotherapy
- Drug Holiday
- Physiology
- Allergy
- Pharmacology
- Substance Dependence
- Psychology
- Side Effect