190:, a nuclear receptor involved in the production of metabolic enzymes, which increases the metabolism of other drugs. This could either cause reactive intermediates/drug activity to persist for longer than necessary, or the drug will be cleared quicker than normal and prevent any therapeutic actions from occurring. Ethanol induces CYP2E1 enzymes in the liver, which can lead to increased NAPQI formation in addition to that formed by acetaminophen.
88:. In some people, administration of penicillin can induce production of specific antibodies and initiate an immune response. Activation of this response when unwarranted can cause severe health concerns and prevent proper immune system functioning. Immune responses to pharmaceutical exposure can be very common in accidental contamination events.
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There are many mechanisms by which pharmaceutical drugs can have toxic implications. A very common mechanism is covalent binding of either the drug or its metabolites to specific enzymes or receptor in tissue-specific pathways that then will elicit toxic responses. Covalent binding can occur during
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is a crucial step in the activity of certain pharmaceuticals. Often, the parent form of the drug is not the active form and it needs to be metabolized in order to produce its therapeutic effects. In other cases, bioactivation is not necessarily needed for drugs to be active and can instead produce
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is a very effective anti-cancer drug that causes congestive heart failure while treating tumors. Doxorubicin is an uncoupling agent in that it inhibits proper functioning of complex I of the electron transport chain in mitochondria. It then leads to the production of ROS and the inhibition of ATP
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On-target toxicity is also referred to as mechanism-based toxicity. This type of adverse effect that results from pharmaceutical drug exposure is commonly due to interactions of the drug with its intended target. In this case, both the therapeutic and toxic targets are the same. To avoid toxicity
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Drug-drug interactions can occur when certain drugs are administered at the same time. Effects of this can be additive (outcome is greater than those of one individual drug), less than additive (therapeutic effects are less than those of one individual drug), or functional alterations (one drug
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Adverse effects at targets other than those desired for pharmaceutical treatments often occur with drugs that are nonspecific. If a drug can bind to unexpected proteins, receptors, or enzymes that can alter different pathways other than those desired for treatment, severe downstream effects can
223:. Many of these drugs, especially the SSRIs, function by blocking the metabolism or reuptake of neurotransmitters to treat depression and anxiety. Chronic exposure or overdose of these pharmaceuticals can lead to serotonin and CNS hyperexcitation, weight changes, and, in severe cases, suicide.
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used to treat inflammation and pain. Overdoses or treatments in conjunction with other NSAIDs can produce additive effects, which can lead to increased oxidative stress and ROS activity. Chronic exposure to aspirin can lead to CNS toxicity and eventually affect respiratory function.
586:- 'Psychiatric Polypharmacy: A Word of Caution', Leslie Morrison, MS, RN, Esq, Paul B. Duryea, Charis Moore, Alexandra Nathanson-Shinn, Stephen E. Hall, MD, James Meeker, PhD, DABFT, Charles A. Reynolds, PharmD, BCPP, Protection & Advocacy, Inc.
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There are many different pharmaceutical drugs that can produce adverse effects after biotransformation, interaction with alternate targets, or through drug-drug interactions. All pharmaceuticals can be toxic, depending on the dose.
96:, has been shown to alter the humoral adaptive immune response in gilthead seabream. In this case, pharmaceuticals can produce adverse effects not only in humans, but also in organisms that are unintentionally exposed.
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Rodenas, M.C.; Cabas, I.; Abellán, E.; Meseguer, J.; Mulero, V.; García-Ayala, A. (December 2015). "Tamoxifen persistently disrupts the humoral adaptive immune response of gilthead seabream (Sparus aurata L.)".
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changes how another is absorbed, distributed, and metabolized). Drug-drug interactions can be of serious concern for patients who are undergoing multi-drug therapies. Coadministration of
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Anti-depressants have been prescribed since the 1950s, and their prevalence has significantly increased since then. There are many classes of anti-depressant pharmaceuticals, such as
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production. Doxorubicin has been shown to be selectively toxic to cardiac tissue, although some toxicity has been seen in other tissues as well. Other anti-cancer drugs, such as
413:"Downregulation of organic anion transporting polypeptide (OATP) 1B1 transport function by lysosomotropic drug chloroquine: implication of OATP-mediated drug-drug interactions"
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reactive intermediates that initiate stronger adverse effects than the original form of the drug. Bioactivation can occur through the action Phase I metabolic enzymes, such as
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Rosa, Gian Marco; Gigli, Lorenzo; Tagliasacchi, Maria
Isabella; Di Iorio, Cecilia; Carbone, Federico; Nencioni, Alessio; Montecucco, Fabrizio; Brunelli, Claudio (March 2016).
182:(ROS). ROS can cause cellular damage in a multitude of ways, a few of which being DNA and mitochondrial damage and depletion of antioxidant enzymes such as
243:, are extremely effective at treating and reducing tumor proliferation, but have high incidences of cardiac arrhythmias and myocardial infarctions.
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109:(aldosterone receptor antagonist), which should increase aldosterone levels, but has shown to produce atrophy of the prostate.
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Alam, Khondoker; Pahwa, Sonia; Wang, Xueying; Zhang, Pengyue; Ding, Kai; Abuznait, Alaa H.; Li, Lang; Yue, Wei (2016).
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146:, an anti-malaria drug, and statins for treatment of cardiovascular diseases has been shown to cause inhibition of
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during treatment, many times the drug needs to be changed to target a different aspect of the illness or symptoms.
129:. Reactive intermediates can cause a loss of function in some enzymatic pathways or can promote the production of
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after being biotransformed to produce reactive intermediates. Acetaminophen is metabolized by CYP2E1 to produce
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field. The field of pharmacotoxicology also involves the treatment and prevention of pharmaceutically induced
170:(APAP) is a very common drug used to treat pain. High doses of acetaminophen has been shown to produce severe
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38:. Pharmacotoxicology can be separated into two different categories:
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Casarett and Doull's toxicology : the basic science of poisons
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186:. In terms of drug-drug interactions, acetaminophen activates
541:"Update on cardiotoxicity of anti-cancer treatments"
350:"On-target and off-target-based toxicologic effects"
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150:(OATPs) and lead to systemic statin exposure.
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42:(the effects of a drug on an organism), and
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460:Klaassen, Curtis D., ed. (2013).
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496:. London: Taylor & Francis.
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263:Guengerich, F. Peter (2011).
522:"Toxicity of Selected Drugs"
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348:Rudmann, Daniel G. (2013).
281:10.2133/dmpk.DMPK-10-RV-062
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221:tricyclic anti-depressants
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131:reactive oxygen species
137:Drug-drug interactions
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391:"Drug Interactions"
100:Off-target toxicity
63:On-target toxicity.
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30:and agents in the
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