Definition of a Paradoxical Effect

Therefore, some researchers suggest that paradoxical drug reactions occur when the typical dosage of a drug is above the personal threshold for a positive response. While this theory may explain some types of paradoxical effects, there is not enough evidence based on human clinical trials, so this currently remains an unfounded theory. After the success of the specific treatment and after the effects of the «paradoxical reaction» have subsided, longer periods of uncomplicated wound treatment follow (Box 42.3). Small wounds close with a stable scar; Large wounds or wounds located at critical sites often require a skin graft (Figure 42.10). Guidelines for wound management should be followed carefully. In environments where health services are well established and functional, this is routine. In resource-poor environments where most cases need to be treated, this phase is critical and the initial success of the specific treatment phase is often compromised by an intermediate secondary bacterial infection. An evidence base shows that some paradoxical drug reactions are common, while others appear in case-by-case reports. More research is needed to definitively determine the cause of paradoxical reactions and how to prevent them. Fortunately, paradoxical reactions are not common and do not pose a great risk to most people.

While researchers once assumed that stimulants only produce paradoxical calming effects in ADHD patients, the consensus has now changed. Recent studies show that low doses of stimulants help improve executive function and focus attention in patients with and without ADHD. Paradoxical stimulating reactions are therefore dose-dependent. The most important aspect in treating paradoxical reactions to benzodiazepines is to detect or identify that the reaction occurs, and then stop the drug. This can be difficult in people who have paradoxical reactions and are also physically dependent on benzodiazepines, as it is often a matter of determining what causes what between withdrawal syndrome and paradoxical reaction, and then determining how to stop the offending agent (benzodiazepine) and treat severe withdrawal syndrome at the same time. Sometimes those who have tolerated benzodiazepine in the past may experience a start after being sensitized to the drug. You may experience a paradoxical response to dose correction to correct or stabilize excessive dose reduction. Or sometimes, those who have already tolerated benzodiazepines are quickly stopped and have severe symptoms. You can reinsert benzodiazepine to get relief from withdrawal syndrome, only to have a paradoxical reaction when it is recovered.

However, there are several indications that paradoxical reactions to benzodiazepines, barbiturates, inhalation anesthetics, propofol, neurosteroids and alcohol, for example, are associated with structural deviations of GABAA receptors. The combination of the five subunits of the receptor (see image) can be modified so that, for example, the reaction of the receptor to GABA remains unchanged, but the reaction to one of the substances mentioned differs significantly from normal. It may seem paradoxical that Nebraskans, especially in rural areas, identify and vote for Republicans, despite opposition from GOP officials on some popular issues. When lesions are cut without antifungal therapy, recurrent infection with M. Ulcerans occurs between 7% and 16%, but recurrence after antibiotic therapy alone is now known to be rare, only 0-2.5% (Sarfo et al., 2010; Chauty et al., 2007; Phillips et al., 2014b) and many so-called repetitions in the past may have been paradoxical reactions. The reasons for the recurrence are not known, but lack of adherence to the antibiotic regimen may play a role. The development of antimicrobial resistance has not been reported in humans. Clinical or radiological worsening of tuberculosis is thought to occur in 2-23% of HIV-negative people after initiation of effective tb treatment.52 These paradoxical responses can easily manifest as an exacerbation of systemic symptoms or symptoms greater than respiratory failure or neurological deterioration. Extrapulmonary tuberculosis, particularly CNS involvement, is an important risk factor for paradoxical reactions.52 Paradoxical reactions after initiation of effective chemotherapy have been associated with the conversion of the skin response into purified protein derivative of anergy into a positive response,53 and an increase in serum TNF-α concentration, which may result from the release of antigens from the mycobacterial wall, 54 In the case of a paradoxical-reacting benzodiazepine, symptoms include: A case of vertebral tuberculosis as a paradoxical response to anti-tuberculosis therapy in an immunocompromised patient has been described (Volpe-Chaves et al., 2020) [A].

Typical benzos-induced effects are as follows: Although the mechanism underlying the paradoxical effects of benzos remains uncertain, these events appear to be associated with dosage, with higher doses increasing the likelihood of adverse and paradoxical reactions of benzos, according to this review of studies. Stimulant drugs such as Ritalin and Adderall have a paradoxical effect on children and adults with ADHD. For most people, taking stimulants induces hyperactivity. However, for those with ADHD, the opposite effects are triggered. Some children who have prescribed stimulants for attention deficit hyperactivity disorder find problems with the sleep manifesto, although hyperactivity decreases and the ability to concentrate is improved. The exact cause of paradoxical reactions to drugs is not known. However, some researchers believe that this happens when the dose of a particular drug is too high or too low for a particular person. Genetics, drug tolerance and current infections may also play a role. Children and the elderly may be more susceptible to paradoxical reactions to medications than other age groups. Chlorpromazine, an antipsychotic and antiemetic classified as an «important» sedative, can cause paradoxical effects such as restlessness, excitement, insomnia, bizarre dreams, exacerbation of psychotic symptoms, and toxic states of confusion. [6] If the patient is not diagnosed with this reaction, this may lead to a gradual increase in the dose of benzodiazepine in order to «control» the misdiagnosed emerging symptoms of the paradoxical reaction, which leads to an increase or worsening of the symptoms of paradoxical reaction, as opposed to their improvement, while having to spend the time that the patient may have to devote to benzodiazepine rejuvenation, is considerably extensive.

Ionizing radiation is a practical example of hormesis in action. Although they are lethal in large quantities due to the way they damage DNA and trigger mutations, lower doses of ionizing radiation can be used as an effective cancer treatment. The exact mechanism of paradoxical reactions is still poorly understood. It is thought that paradoxical reactions may be the same phenomenon associated with an increased risk of suicidal thoughts from the use of antidepressants in children. The paradoxical reaction (or paradoxical effect) is an effect of a chemical substance such as a drug that is opposite to what is normally expected. An example of a paradoxical reaction is pain caused by an analgesic. A paradoxical reaction to the drug represents an opposite result to the result that could be expected from the known effects of the drug. There are three types: 1. A paradoxical reaction in a condition for which the drug is explicitly prescribed. 2. Paradoxical precipitation of a disease for which the drug is indicated when the drug is used for an alternative indication. 3.

Paradoxical effects in relation to any aspect of the pharmacology of the medicinal product, but which are not related to the usual indication. In two-way drug reactions, a drug can produce opposite effects, either in the same person or in different people, with effects usually different from the expected positive effect. The paradoxical and bidirectional effects of drugs can sometimes be used for benefit; Some can be detrimental. Such reactions occur in a variety of classes of drugs. Some are common; others are reported in individual case reports. Paradoxical effects are often detrimental because they are opposite to the direction of the expected effect. They can make it difficult to assess adverse drug reactions, pharmacovigilance and clinical management. Bidirectional effects can be clinically helpful or detrimental. From a clinical-toxicological point of view, an alteration in pharmacokinetics or pharmacodynamics in case of overdose can exacerbate paradoxical and bidirectional effects. Some antidotes have paradoxical properties that complicate management. Seemingly clinically paradoxical or bidirectional effects and reactions occur when conflicts occur at different levels in self-regulated biological systems, as complexity increases from subcellular components such as receptors to cells, tissues, organs, and the individual as a whole.

These can be understood incompletely. The mechanisms of these effects include different effects on the same receptor, due to changes over time and downstream effects; stereochemical effects; multiple receptor targets with or without associated temporal effects; antibody-mediated reactions; three-dimensional architectural boundaries; pharmacokinetic effects of the competing compartment; Disturbance and nonlinear effects in oscillating systems, systemic overcompensation and other higher-level feedback mechanisms, and multi-level feedback response loops.