115 Questions
What type of dose-response relationship is used to examine the mechanism of interaction between a toxicant and a biological system?
Graded or individual
Which type of dose-response graph represents the cumulative sum of responses from lower to higher doses?
Cumulative / Accumulated
What does the vertical axis in a dose-response graph represent?
In vivo or in vitro response
Which type of pharmaceutical graph is used when the responses of test organisms follow a normal distribution?
Probit
In which type of dose-response relationship are different doses administered to observe the population response characterized by 'all or none'?
Quantic or population-based
What does the horizontal axis in a dose-response graph represent?
Dose in mg/kg
What is the primary focus of descriptive toxicology?
Quantitative toxicity testing of chemicals
Which subdiscipline of modern toxicology delves into the underlying molecular basis of toxicants' impact on organisms?
Mechanistic toxicology
What characterizes hazardous waste according to the text?
Potential for causing disease and death
What is the main goal of regulatory toxicology?
Determining legal uses of specific chemicals
Which discipline contributes to an understanding of toxicology by focusing on the effects of toxins on embryos and fetuses?
Developmental Toxicology
What is the main concern addressed by environmental toxicology as mentioned in the text?
Predicting effects on populations and ecosystems
What is the branch of science that deals with the study of poisons or toxicants?
Toxicology
Which of the following is NOT one of the time-dependent processes related to toxicants according to the text?
Metabolism
Toxicodynamics examines the mechanisms by which toxicants produce unique cellular effects within the organism. What are some components of these mechanisms?
Changes to the cell's plasma membrane
Which component is NOT typically considered in toxicity testing according to the text?
Age of the test organism
What is lipid peroxidation, as mentioned in the text as a component of toxicity testing?
Oxidation of fatty acids leading to cell death
In toxicity testing, what advantage do logarithmic doses have over linear doses?
They maximize the range of doses tested while minimizing the possibility of missing small doses that could represent the response threshold.
What are the most important factors affecting the likelihood of a xenobiotic being absorbed?
Route of exposure, concentration of the substance, and chemical and physical properties
Which factor is NOT considered important in determining xenobiotic absorption?
Intensity of the toxic effect
What is the role of cell membranes in xenobiotic absorption?
They form formidable barriers to prevent entry of xenobiotics into body tissues
Which route of exposure/absorption is considered an important route for many pharmaceuticals?
Gastrointestinal (GI) tract
What type of tail do lipid molecules in cell membranes possess?
Lipophilic
Which statement best describes the movement of xenobiotics through cell membranes?
Xenobiotics must cross several cell membranes to move within and between different areas of the body
What is the primary function of cell membranes in the body?
To act as a major defense that prevents foreign substances from entering body tissues
Lipinski's rule of five indicates poor absorption if which criteria are violated?
MW > 500 Da
Lipid solubility plays a key role in xenobiotic absorption due to its attraction to:
Non-polar substances
Chemical and physical properties are important factors affecting xenobiotic absorption; which property directly affects absorption by being attracted to lipid-soluble substances?
Lipid solubility
Which type of toxic responses include CNS damage, carcinogenesis, mutagenesis, and teratogenesis?
Irreversible toxic responses
What determines the reversibility of toxicity damage?
The length of exposure
Which type of cell membrane contains many pores and is found in kidney cells and liver cells?
Type 3
What type of toxicity occurs when adverse effects take years to appear following exposure to a toxicant?
Delayed toxicity
Which component of the cell membrane is very low in mitochondria?
Cholesterol
In what type of tissue might rapidly regenerating tissue only suffer from reversible toxic responses?
Liver tissue
Which type of exposure results in local toxicity?
Exposure to ingested toxicants
Which type of toxicity is restricted only at the initial site of exposure to the toxicant?
Localized toxicity
What affects the absorption of toxicants across cell membranes?
The protein-to-lipid ratio
Which type of toxicant undergoes biotransformation in the liver if taken orally?
Organophosphates
Which system is responsible for draining excess fluid from the tissues in the body?
Lymphatic system
What is the primary determinant of a toxicant's rate of distribution to organs or tissues?
Blood flow and diffusion rate
If a toxicant accumulates at a site other than the target organ, it may be viewed as a protective process because?
The plasma levels of the toxicant decrease
Which factor influences the distribution of toxicants by determining the volume in which the amount of drug would need to be uniformly dissolved?
Volume of distribution (Vd)
How does a chemical with distribution only to the plasma compartment affect its volume of distribution (Vd)?
High plasma concentration and low Vd
What facilitates the distribution of xenobiotics that are protein-bound across cell membranes?
Specialized transport across the plasma membrane
What determines the final distribution of a xenobiotic in various tissues of the body?
"Barriers" slowing down toxicant entrance
Why may some toxicants selectively accumulate in certain parts of the body?
Due to their inability to cross cell membranes easily
Which mechanism allows for toxicants to be released into circulation as they are eliminated?
Storage depots equilibrium with free toxicant fraction in plasma
What facilitates the distribution of xenobiotics that are protein-bound across cell membranes?
Specialized transport across the plasma membrane
What does it mean when a toxicant is considered more potent?
It produces a response at a lower dose compared to another toxicant
What does a higher efficacy of a toxicant indicate?
The dose-response relationship continues over a greater range of doses
What is the margin of safety (TI) used to express?
The range of doses between non-effective dose and lethal dose
Which type of toxicity involves irreversible cellular changes that lead to long-lasting symptoms?
Chronic toxicity
What is the significance of a large LD01/ED99 ratio for pharmaceuticals?
It shows the drug can be therapeutic at low doses compared to lethal doses
What type of curve suggests a toxicant of high potency?
A steep curve at a smaller dose
Which type of channels can permit the entry of cations such as lead, barium, or strontium?
Voltage-gated calcium channels
What type of interactions primarily occur during protein-ligand interactions in plasma proteins?
Hydrophobic forces, hydrogen bonding, and van der Waals forces
What does it mean when dose–response curves exhibit nontraditional shapes?
'Hormetic effects' are observed
What is implied by intersecting or crossed sigmoidal lines on cumulative dose-response graphs?
'Mixed or reversed toxicity relationship'
Which organ likely concentrates more toxicants than all other organs combined?
Liver
What does chronic toxicity result from?
Repeated exposures of less than a lifetime
Why is the first-pass effect important in toxicology?
To allow immediate detoxification by the liver
What is the purpose of determining the margin of safety from two toxicity studies like an ED and LD study?
To determine the range between effective and lethal doses
Which type of storage depot lowers the concentration of a toxicant in the target organ?
Adipose tissue
What is the major protein in plasma responsible for binding many different compounds?
Albumin
Which type of channels mediate the influx of arsenide?
Aquaporins
What type of barrier do brain capillaries lack and are joined by tight junctions?
Tight junctions
What phenomenon takes place between the bone surface and extracellular fluid in contact with it for toxicant deposition and reversible storage?
Surface chemistry phenomenon
What is the most common way that xenobiotics cross cell membranes?
Passive diffusion
Which mechanism involves the movement of molecules down a concentration gradient without requiring metabolic energy?
Facilitated diffusion
What type of transport can be inhibited by a metabolic poison and may be saturated at high substrate concentrations?
Active transport
In which mechanism do water-soluble molecules pass through small aqueous pores, allowing the movement of molecules of 50-60k MW?
Passive diffusion
Which process requires ATP, produces vesicles, and may fuse with lysosomes?
Endocytosis
What is the function of a sodium-potassium pump in terms of ion movement?
3Na+ out of the cell, 2K+ into the cell
What is the statistic used to represent the distance of test organisms' responses from the mean?
Standard deviation
If a toxicant has a small standard deviation compared to another toxicant, what does this indicate about the dose-response relationship?
The toxicant with the small SD has a narrower range of doses yielding responses.
What is the term used to describe the dose at which the first test organism responds on a cumulative dose-response graph?
Threshold dose
Which term refers to doses on the left side of the threshold dose where no responses are observed?
Subthreshold doses
At what percentage level does the mean response occur on a cumulative dose-response graph?
50%
What is observed on the right side of a cumulative dose-response graph when doses increase beyond a certain point?
Ceiling effect
Which term represents the dose resulting in the death of test organisms?
Lethal dose (LD)
What is the primary factor that determines the toxicity manifested by a xenobiotic in the body?
The concentration in plasma proteins
Why might a highly lipophilic toxicant concentrated in body fat be less severe in toxicity in an obese person than a lean individual?
Its concentration is lower in the target organ due to storage in fat
Which organ is mentioned as having a high capacity for binding various chemicals, potentially concentrating more toxicants than all other organs combined?
Liver
What characterizes the skeletal uptake of xenobiotics, particularly with regard to deposition and storage in bone?
It can be dynamic and may not always be detrimental
What is the primary driving force behind protein-ligand interactions that bind toxicants to plasma proteins?
Hydrophobic forces
How do plasma proteins bound to toxicants interact with capillary walls?
The proteins and bound toxicants cannot cross capillary walls
What is a major anatomical reason why some toxicants do not readily enter the CNS?
High protein concentration in the interstitial fluid of the CNS
How do glial cell processes (astrocytes) affect toxicant entry into the CNS?
Act as barriers to toxicants entering the CNS
In what way is the placental barrier similar to the blood-brain barrier?
Both lack pores between cell layers
What role do lipids in the plasma membranes play in the placental barrier?
Limit the entry of water-soluble toxicants
How does the protein concentration in the interstitial fluid of the CNS differ from other body fluids?
It prevents diffusion of polar compounds
What is the primary function of glial cell processes (astrocytes) surrounding capillaries in the CNS?
Prevent diffusion of water-soluble toxicants
What is the primary function of the loop of Henle in the kidney?
To reabsorb water from the filtrate
Which of the following toxicants undergo reabsorption by renal tubules into the peritubular capillaries?
Acetaminophen
What characterizes the proximal convoluted tubule in the kidney in terms of toxicant reabsorption?
Reabsorption of sodium and sulfate ions
Which component of the nephron is responsible for being the charge/size selective site of filtration?
Glomerulus
What is the main function of the descending tubule in the kidney nephron?
Reabsorption of water from the filtrate
In kidney toxicity, which of the following chemicals is known to be filtered through renal corpuscles and secreted across tubular epithelium?
MTBE (gasoline additive)
Which enzyme is primarily found in the ER, cytoplasm, and mitochondria?
Microsomal Flavin-Containing Monooxygenase
What is the primary role of Cytochrome P-450?
Oxidation of drugs and xenobiotics
Which enzyme is responsible for oxidizing tertiary amines to N oxides?
Mixed Function Oxidase 3
What is the major function of Microsomal Flavin-Containing Monooxygenase?
Detoxify xenobiotics via oxidation
Which enzyme is localized in the soluble fraction of the liver, kidney, and lungs?
Alcohol dehydrogenase
What is the primary product of the first detoxification stage of benzene?
Epoxide
What is the primary role of NADPH Cytochrome P-450 reductase?
Transfer electrons to Cytochrome P-450
What property do biotransformed metabolites usually acquire compared to the original toxicant?
They become more hydrophilic
Which enzyme type is primarily associated with phase II reactions in the metabolism of xenobiotics?
Cytosolic enzymes
Which organs have a medium capacity for biotransformation processes?
Intestines, kidneys, and lungs
In phase I of xenobiotic metabolism, what is the primary effect of introducing a polar group into the molecule?
Increasing water solubility
Which cells possess a limited ability for biotransformation processes?
Hepatocytes and skin cells
What can occur in some cases during xenobiotic metabolism that leads to a sequence termed an activation mechanism?
'Activation' mechanism producing more toxic intermediates or products
'Microsomal enzymes are associated with which phase of xenobiotic metabolism?'
'Phase I reactions'
'Which bacterial population has a significant impact on biotransformation in the body?'
'More than 400 bacterial species'
'Which factor can impair an individual's capacity to biotransform xenobiotics?'
'Nutritional status'
'Where do most biotransformation reactions occur at the subcellular level?'
'Endoplasmic reticulum'
Test your knowledge on the process of biotransformation, where both endogenous and exogenous substances are converted into hydrophilic molecules for elimination from the body. Understand the four changes that occur to facilitate the elimination of toxicants through this process.
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