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Questions and Answers
What is a symptom of salicylate overdose?
Which treatment is specifically indicated for benzodiazepine overdose?
What condition is associated with sedative-hypnotic overdose?
Which of the following describes a potential effect of stimulant overdose?
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What is a severe symptom of serotonin syndrome caused by SSRIs?
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In cases of tricyclic antidepressant overdose, which of the following is part of the treatment plan?
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What is a common gastrointestinal symptom of sedative-hypnotic overdose?
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Which condition is characterized by warm, sweaty skin during overdose?
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What is a considered key intervention for managing antimuscarinic drug toxicity?
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Which of the following is a common clinical feature of cholinomimetic drug toxicity?
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In the management of opioid overdose, what is the primary critical support required?
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Which of the following poison management strategies focuses on reducing the amount of poison in a consumer product?
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What is indicated for decontamination of cholinomimetic drug poisoning?
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What type of packaging is utilized to prevent access to poisonous substances in consumer products?
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What is a crucial step in managing a poisoned patient before administering antidotes?
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Which of the following is NOT a feature of antimuscarinic drug toxicity?
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Which heavy metal exposure route primarily affects the central nervous system?
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Which chelator is used as an antidote for lead poisoning?
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What is the primary target organ for inorganic arsenic exposure?
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Which of the following metals has the gastrointestinal tract as its primary route of absorption?
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Which chelator is specifically mentioned for treating mercury poisoning?
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What is the first requirement in the management of heavy metal toxicity?
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Which type of mercury exposure causes damage primarily to the kidneys?
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What class of substances do chelators belong to in the context of heavy metal poisoning?
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Which HLA gene variant is associated with abacavir-induced skin toxicity?
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What is the likely adverse effect associated with the HLA-B*15:02 variant?
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What adverse effect is linked to the HLA polymorphisms of DRB1 *15:01, DRB5 *01:01, and DQB1 *06:02 haplotype?
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Which SNP is associated with statin-induced myopathy?
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Which HLA variant is linked to increased ALT levels and is associated with ximelagatran?
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What type of study analyzes the complete genomes of individuals to find associations with specific phenotypes?
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HLA-B*57:01 is also associated with which other adverse effect besides abacavir-induced skin toxicity?
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Which of the following accurately describes the role of SNPs in modern pharmacogenetics?
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What characterizes an off-target effect of a drug?
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Which of the following describes an idiosyncratic drug response?
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What type of drug interaction does ketoconazole exemplify?
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Which scenario best describes a hypersensitivity response to medication?
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How does the mechanism of action differ in toxic drug responses compared to allergic responses?
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Which of the following would most likely lead to drug-induced hepatotoxicity?
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Which response is characteristically associated with apoptotic cell death?
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What is a common effect of off-target drug interactions with β2-selective agonists?
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What is a potential outcome of immunotoxicity?
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What is the importance of contextual factors in understanding drug toxicity?
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What distinguishes a toxic drug response from an idiosyncratic response?
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What is a critical step when treating an allergic drug reaction?
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Which drug's off-target effect is associated with cardiotoxicity?
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What defines necrosis compared to apoptosis?
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What is a common symptom of systemic immunotoxicity?
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Study Notes
On-Target and Off-Target Effects
- On-target effects refer to exaggerated pharmacologic actions due to overdose or increased drug sensitivity at the correct receptor in the right tissue.
- Diphenhydramine (Benadryl) exemplifies on-target effects by causing drowsiness as H1-antihistamine enters the central nervous system.
- Cholinesterase inhibitors can cause peripheral cholinergic effects, leading to SLUDGE (Salivation, Lacrimation, Urination, Diarrhea, Gastrointestinal distress, Emesis).
- Off-target effects occur when drugs unintentionally affect unintended targets, such as terfenadine's cardiotoxicity through potassium channel blockage.
- β2-selective agonists, used for asthma treatment, can inadvertently stimulate β1 receptors at high doses, resulting in tachycardia.
Harmful Immune Responses and Immunotoxicity
- Some drugs may be perceived as foreign by the immune system, typically associated with larger drugs.
- Activation of the immune system can lead to hypersensitivity or autoimmune responses, often resulting in skin rashes.
- Immunotoxicity denotes immune system damage either as a drug effect or a therapeutic goal, raising infection risks.
- Examples include cytotoxic cancer chemotherapy, inhaled corticosteroids for chronic obstructive pulmonary disease, and immunotherapies like Rituximab targeting CD20+ B cells.
Hypersensitivity Responses
- Toxic responses occur in all subjects given high enough doses; idiosyncratic responses are limited to certain genetically predisposed individuals.
- Allergic drug reactions can vary widely with incidence rates from a few percent to nearly 100%, depending on the drug.
- Toxic and idiosyncratic reactions depend on drug dose, while allergic responses are independent of the dose.
- Mechanisms differ: toxic effects via drug-receptor interactions and allergic reactions are mediated by antigen-antibody responses.
Contexts of Drug Toxicity
- Drug toxicity can stem from overdose, drug-drug interactions (pharmacokinetic and pharmacodynamic), and drug-herb interactions.
- Cellular mechanisms of toxicity include apoptosis (programmed cell death) and necrosis (uncontrolled cell death), which can damage surrounding tissues.
Drug-Drug Interactions
- Ketoconazole, an antifungal, inhibits CYP 3A4, potentially causing toxic accumulation of concurrently used drugs metabolized by this pathway.
- Sildenafil increases cGMP, and when combined with nitroglycerin, may lead to severe hypotension due to cumulative effects on vascular smooth muscle.
Drug-Herb Interactions
- Ginkgo biloba can inhibit platelet aggregation, raising bleeding risks when taken with nonsteroidal anti-inflammatory drugs (NSAIDs).
Drug-Induced Hepatotoxicity
- Liver metabolism of some drugs can lead to toxicity; acetaminophen metabolism can produce a harmful metabolite, especially in cases of overdose or other liver strain.
Genetic Factors and Modern Pharmacogenetics
- HLA gene variants can associate with drug-induced toxicities, highlighting the importance of genetic testing in predicting adverse reactions.
- Genome-wide association studies (GWAS) help identify genetic polymorphisms affecting drug metabolism, such as in statin-induced myopathy.
Management of Poisoned Patients
- Vital function maintenance, poison identification, decontamination, enhanced elimination, and antidote administration are crucial steps in managing poisoning.
Toxic Syndromes from Drug Groups
- Antimuscarinic drugs present with delirium and tachycardia; cholinomimetics can lead to hyperactive bowel and bradycardia.
- Opioids typically manifest through sedation; salicylates may cause metabolic acidosis and dehydration.
- Stimulants may induce agitation and hyperthermia; SSRIs can lead to mild to severe serotonin syndrome symptoms.
- Intervention for tricyclic antidepressant overdose requires a focus on controlling seizures.
Heavy Metals and Chelation Therapy
- Metals like lead, arsenic, and mercury can have toxic effects due to interaction with enzyme sulfhydryl groups.
- Chelators (e.g., dimercaprol, succimer) treat heavy metal poisoning by forming stable, non-toxic complexes with metal ions for excretion.
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