DABT flashcards
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32 cards. Read the term and the definition here. The deck at the top of this page is optional.
- LD50
- The median lethal dose: the amount of a substance that kills 50% of a test population under defined conditions. Lower values indicate greater acute lethality.
- Therapeutic index
- Ratio of the median toxic dose to the median effective dose (TD50/ED50). A larger index generally indicates a wider margin between therapeutic and toxic exposures.
- NOAEL
- No-observed-adverse-effect level: the highest tested dose producing no statistically or biologically significant increase in adverse effects compared with controls.
- Hormesis
- A biphasic dose-response in which low doses produce a stimulatory or protective effect while high doses produce inhibition or toxicity. It challenges simple linear low-dose assumptions.
- Threshold dose
- The dose below which a non-genotoxic effect is not expected to occur because protective and repair mechanisms handle the exposure. Genotoxic carcinogens are often modeled without a threshold.
- Volume of distribution
- Apparent volume calculated as amount of drug in the body divided by plasma concentration. Large values suggest extensive tissue binding or distribution outside plasma.
- Clearance
- Volume of plasma cleared of a substance per unit time. For intravenous dosing, clearance equals dose divided by total area under the concentration-time curve.
- Half-life
- Time required for plasma concentration to fall by half. For first-order kinetics, half-life equals 0.693 times volume of distribution divided by clearance.
- First-pass metabolism
- Hepatic and intestinal metabolism that reduces the fraction of an orally administered dose reaching systemic circulation. It lowers oral bioavailability and can create active or toxic metabolites.
- Bioactivation
- Metabolic conversion of a relatively inert parent compound into a reactive toxic metabolite. Acetaminophen conversion to NAPQI by cytochrome P450 is a classic example.
- Centrilobular hepatic injury
- Liver damage concentrated in zone 3 around central veins, where cytochrome P450 activity is high and glutathione may be depleted. Acetaminophen and carbon tetrachloride show this pattern.
- Proximal tubular toxicity
- Kidney injury in proximal tubules due to active uptake, high metabolic activity, and concentration of filtered toxins. Heavy metals and aminoglycosides commonly target this segment.
- Cholinergic crisis
- Excess acetylcholine from acetylcholinesterase inhibition causes salivation, lacrimation, urination, diarrhea, bronchoconstriction, bradycardia, and muscle fasciculations. Organophosphates and carbamates produce this syndrome.
- hERG blockade
- Blockade of the cardiac potassium channel encoded by hERG delays ventricular repolarization, prolonging the QT interval and increasing risk of torsades de pointes.
- Bleomycin pulmonary fibrosis
- The anticancer drug bleomycin can cause DNA damage and oxidative injury in lung tissue, leading to pneumonitis and progressive pulmonary fibrosis, especially at cumulative doses.
- Organophosphate antidotes
- Atropine blocks muscarinic effects, while pralidoxime reactivates acetylcholinesterase if given before enzyme aging. Both are used together in significant organophosphate poisoning.
- Methanol poisoning
- Methanol is metabolized by alcohol dehydrogenase to formaldehyde and then formic acid, causing metabolic acidosis and retinal injury. Fomepizole or ethanol blocks this metabolism.
- Warfarin mechanism
- Warfarin inhibits vitamin K epoxide reductase, reducing regeneration of active vitamin K and synthesis of clotting factors II, VII, IX, and X. Vitamin K reverses its anticoagulant effect.
- Tetrodotoxin
- A potent natural neurotoxin that blocks voltage-gated sodium channels, preventing nerve and muscle action potentials. It causes paralysis and respiratory failure and is found in pufferfish.
- Aflatoxin B1
- A mycotoxin produced by Aspergillus species that is bioactivated to an epoxide forming DNA adducts. It is a potent hepatocarcinogen associated with contaminated grains and nuts.
- Reference dose
- An estimate of a daily oral exposure likely to be without appreciable lifetime risk. It is derived by dividing a no-observed-adverse-effect level by uncertainty factors.
- Margin of exposure
- Ratio of a point of departure, such as a benchmark dose or NOAEL, to estimated human exposure. Larger values indicate greater distance between exposure and hazardous doses.
- Cancer slope factor
- An upper-bound estimate of cancer risk per unit dose, used with exposure to estimate excess lifetime cancer risk. Risk equals dose multiplied by the slope factor.
- Bradford Hill criteria
- Guidelines for judging causality in epidemiology, including strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy. Temporality is essential.
- Relative risk
- Risk in an exposed group divided by risk in an unexposed group. It is estimated in cohort studies and indicates how many times more likely an outcome is after exposure.
- Odds ratio
- Odds of exposure among cases divided by odds of exposure among controls. It approximates relative risk for rare outcomes and is commonly used in case-control studies.
- Randomization
- Assignment of study subjects to groups by chance, which balances known and unknown confounders across groups and supports causal interpretation of differences in outcomes.
- Cohort study
- A study that follows exposed and unexposed groups over time and compares incidence of outcomes. It can estimate relative risk directly but may be costly and susceptible to loss to follow-up.
- Case-control study
- A study that compares past exposures among people with a disease and similar people without it. It is efficient for rare outcomes but estimates odds ratios and is vulnerable to recall bias.
- Negative control
- A study group receiving vehicle or no active treatment, used to establish baseline response and distinguish treatment effects from background variability or procedural effects.
- Good Laboratory Practice
- A quality system covering organization, personnel, facilities, equipment, protocols, records, and reporting for nonclinical safety studies. It ensures data integrity and regulatory acceptability.
- Benchmark dose
- A modeled dose associated with a specified small increase in response, often using a lower confidence limit. It is an alternative point of departure to NOAEL.