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ABP Med Toxicology practice questions

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Question 1General principles of toxicology and risk assessment

Which term describes the absorption, distribution, metabolism, and excretion of a toxicant within the body?

  1. Toxicogenomics
  2. Toxicovigilance
  3. Toxicokinetics Correct answer.
  4. Toxicodynamics

Explanation

Toxicokinetics describes how a chemical is absorbed, distributed, metabolized, and excreted, and it determines the concentration reaching the target site over time. Toxicodynamics describes the resulting effects on the organism. The two terms are often summarized as what the body does to the chemical versus what the chemical does to the body.

Question 2General principles of toxicology and risk assessment

An LD50 value represents the dose of a substance that...

  1. kills half of an exposed test population Correct answer.
  2. kills every member of a test population
  3. is lethal to half of humans after one exposure
  4. produces no observable effect in half of the animals

Explanation

The LD50 is a median lethal dose estimated in a defined test population under specified conditions. It is used to compare acute lethality across chemicals but is not a human safe exposure level. Values depend on species, route, and study conditions.

Question 3General principles of toxicology and risk assessment

Which exposure route generally produces the most rapid systemic absorption of a volatile organic solvent?

  1. Dermal contact
  2. Inhalation Correct answer.
  3. Oral ingestion
  4. Subcutaneous injection

Explanation

The lungs provide a large surface area and a thin alveolar membrane, and volatile solvents readily partition from alveolar air into blood. Inhaled chemicals also bypass first-pass hepatic metabolism, which favors rapid systemic availability. Oral and dermal absorption are generally slower and more variable.

Question 4General principles of toxicology and risk assessment

The therapeutic index of a drug is most commonly expressed as which ratio?

  1. LD50 divided by ED50 Correct answer.
  2. ED50 divided by LD50
  3. Cmax divided by AUC
  4. NOAEL divided by LOAEL

Explanation

The therapeutic index compares the dose producing a therapeutic effect with the dose producing toxicity, commonly as LD50 divided by ED50. A larger ratio indicates a wider margin of safety. It is a population-based index and does not guarantee safety in every individual.

Question 5General principles of toxicology and risk assessment

Glucuronidation of a xenobiotic is classified as which type of biotransformation reaction?

  1. Renal tubular secretion
  2. Passive diffusion
  3. Phase II conjugation Correct answer.
  4. Phase I oxidation

Explanation

Phase II conjugation attaches endogenous groups such as glucuronic acid, sulfate, or glutathione to a xenobiotic or its metabolite, generally increasing water solubility for excretion. Glucuronidation is catalyzed by UDP-glucuronosyltransferases. Phase I reactions instead introduce or expose functional groups through oxidation, reduction, or hydrolysis.

Question 6General principles of toxicology and risk assessment

The no-observed-adverse-effect level (NOAEL) is best defined as the...

  1. dose at which exposure first becomes measurable in blood
  2. highest tested dose without a significant adverse effect Correct answer.
  3. dose that produces toxicity in half of the test animals
  4. lowest dose that causes any measurable biological change

Explanation

The NOAEL is the highest dose tested that does not produce a statistically or biologically significant adverse effect compared with controls. The LOAEL is the lowest dose that does produce such an effect. NOAELs are study-specific and are not regulatory safe exposure limits by themselves.

Question 7General principles of toxicology and risk assessment

For many non-cancer toxic endpoints, a threshold is assumed to exist because...

  1. repair and homeostatic mechanisms must be overwhelmed Correct answer.
  2. all synthetic chemicals are assumed to be genotoxic at low doses
  3. individual susceptibility is assumed not to vary between people
  4. the toxic effect increases linearly from zero dose

Explanation

At low exposures, detoxification, DNA repair, and compensatory physiological processes can prevent injury, so an adverse effect appears only after these defenses are overwhelmed. This threshold concept supports the use of NOAELs and uncertainty factors for many non-cancer endpoints. Genotoxic carcinogens are frequently evaluated with non-threshold assumptions instead.

Question 8General principles of toxicology and risk assessment

Which step of the risk assessment paradigm combines hazard identification, dose-response assessment, and exposure assessment?

  1. Exposure assessment
  2. Hazard identification
  3. Dose-response assessment
  4. Risk characterization Correct answer.

Explanation

Risk characterization integrates hazard identification, dose-response assessment, and exposure assessment to estimate the likelihood and severity of adverse effects in a defined population. It also communicates assumptions, uncertainties, and the confidence in the estimate. The other steps provide the individual inputs to this final synthesis.

Question 9General principles of toxicology and risk assessment

A chronic rat study identifies a NOAEL of 5 mg/kg/day. Applying a 10-fold interspecies factor and a 10-fold intraspecies factor, what reference dose is derived?

  1. 0.05 mg/kg/day Correct answer.
  2. 0.005 mg/kg/day
  3. 50 mg/kg/day
  4. 0.5 mg/kg/day

Explanation

The composite uncertainty factor is 10 for interspecies differences times 10 for intraspecies variability, or 100. Dividing the NOAEL of 5 mg/kg/day by 100 gives 0.05 mg/kg/day. Additional factors may be applied when data are incomplete.

Question 10General principles of toxicology and risk assessment

Repeated exposure to a cytochrome P450 inducer can alter the toxicity of a co-administered chemical by...

  1. preventing its distribution into peripheral tissues
  2. reducing its clearance and prolonging its half-life
  3. blocking its absorption from the gastrointestinal tract
  4. increasing metabolic clearance of the parent chemical Correct answer.

Explanation

Enzyme induction increases the amount of cytochrome P450 available to metabolize a co-administered chemical, raising its clearance. This generally lowers parent-drug exposure, although toxicity may increase if a reactive metabolite is formed. The net effect therefore depends on whether the parent or a metabolite causes harm.

Question 11General principles of toxicology and risk assessment

Why can oral administration produce lower systemic exposure than intravenous administration of the same dose?

  1. First-pass metabolism in gut wall and liver Correct answer.
  2. Renal excretion is absent after intravenous dosing
  3. Oral absorption is always slower than renal clearance
  4. The drug is completely bound to plasma proteins

Explanation

After oral absorption, portal venous blood carries the chemical to the liver before it reaches the systemic circulation, and enterocytes and hepatocytes may metabolize it. This presystemic elimination is called the first-pass effect and reduces oral bioavailability. Intravenous dosing bypasses this step.

Question 12General principles of toxicology and risk assessment

Functional antagonism between two chemicals is best illustrated when one chemical...

  1. alters the other chemical's distribution or excretion
  2. opposes its effect through a different receptor pathway Correct answer.
  3. binds the other chemical and forms an inactive complex
  4. competes for the same receptor binding site

Explanation

Functional antagonism occurs when two chemicals produce opposite physiological effects through different receptors or pathways, such as opposing actions on heart rate or vascular tone. Chemical antagonism involves direct binding, and competitive antagonism involves the same receptor. Dispositional antagonism changes absorption, distribution, metabolism, or excretion.

Question 13General principles of toxicology and risk assessment

A chemical has a plasma half-life of 8 hours and is given at a constant rate. Approximately when will steady-state concentration be reached?

  1. 24 hours
  2. 32 to 40 hours Correct answer.
  3. 80 hours
  4. 8 hours

Explanation

With constant dosing, plasma concentration approaches steady state after about four to five elimination half-lives. For an 8-hour half-life, this is approximately 32 to 40 hours. At steady state, the rate of input equals the rate of elimination and further accumulation is minimal.

Question 14General principles of toxicology and risk assessment

A large apparent volume of distribution (Vd) for a toxicant indicates that the substance...

  1. distributes extensively into tissues Correct answer.
  2. has essentially zero oral bioavailability
  3. has no protein binding in the blood
  4. is eliminated very rapidly by the kidneys

Explanation

Volume of distribution relates the amount of chemical in the body to its plasma concentration. A large value means that most of the chemical has partitioned into tissues, leaving little in plasma, and it does not represent a real anatomical space. This parameter helps interpret distribution and guide elimination strategies.

Question 15General principles of toxicology and risk assessment

Which statement describes the purpose of exposure assessment in risk assessment?

  1. It determines the slope of the dose-response curve.
  2. It identifies whether an agent can cause harm.
  3. It estimates the amount, frequency, and routes of contact. Correct answer.
  4. It combines all evidence into a final risk estimate.

Explanation

Exposure assessment estimates how much of an agent reaches a population, by which routes, and over what duration and frequency. It supplies the exposure information needed for risk characterization. Hazard identification and dose-response assessment address the intrinsic toxicity of the agent.

Question 16General principles of toxicology and risk assessment

In carcinogen risk assessment, linear low-dose extrapolation is most appropriate for...

  1. genotoxic carcinogens assumed to lack a threshold Correct answer.
  2. non-genotoxic carcinogens with a demonstrated threshold
  3. essential nutrients with a homeostatic range
  4. reversible irritants that cause no DNA damage

Explanation

Genotoxic carcinogens are often assumed to have some probability of causing DNA damage even at very low doses, so linear low-dose extrapolation is used as a default. Non-genotoxic carcinogens may justify a threshold or nonlinear approach when their mode of action supports it. The choice should be based on mechanistic evidence.

Question 17General principles of toxicology and risk assessment

A physiologically based pharmacokinetic (PBPK) model differs from a classical compartmental model mainly by...

  1. describing only acute, single-dose exposures
  2. requiring no information about the route of exposure
  3. using anatomical compartments, blood flows, and partition coefficients Correct answer.
  4. assuming that all tissues have identical blood flow

Explanation

PBPK models represent organs and tissues with realistic blood flows and volumes, linked by partition coefficients, so they can support route, dose, and species extrapolation. Classical compartmental models are data-driven and lump the body into abstract compartments. The physiological structure of PBPK models improves mechanistic interpretation.

Question 18General principles of toxicology and risk assessment

The benchmark dose (BMD) approach is often preferred over the NOAEL approach because it...

  1. eliminates the need for any uncertainty factors
  2. requires no information about the shape of the dose-response relationship
  3. uses the full dose-response curve and is less dose-spacing dependent Correct answer.
  4. always produces a more conservative value than the NOAEL

Explanation

Benchmark dose modeling fits a curve to all dose-response data and estimates the dose associated with a specified benchmark response, together with confidence limits. This makes it less dependent on the particular doses selected and on dose spacing than the NOAEL. It does not eliminate the need for uncertainty factors.

Question 19General principles of toxicology and risk assessment

Mode-of-action (MOA) analysis in risk assessment primarily serves to...

  1. identify key events linking exposure to toxicity Correct answer.
  2. establish the commercial use category and regulatory status of a chemical
  3. calculate the oral bioavailability of the chemical in humans
  4. measure the chemical's elimination half-life in laboratory animals

Explanation

Mode-of-action analysis describes the sequence of key events from exposure to the adverse outcome and evaluates whether those events are plausible in humans. It helps decide whether a threshold or non-threshold approach is appropriate and how species differences should be handled. It complements, rather than replaces, exposure assessment.

Question 20General principles of toxicology and risk assessment

Two solvents both depress the central nervous system by the same membrane mechanism. The default approach for assessing their combined effect is...

  1. synergism
  2. dose addition Correct answer.
  3. response addition
  4. potentiation

Explanation

Chemicals that act by the same mode of action are assumed to behave as if they were dilutions of one another, so dose addition is the default mixture approach. Response addition is used when agents act independently through different mechanisms. Synergism and potentiation describe greater-than-additive interactions.

Question 21Toxicokinetics, toxicodynamics, and laboratory testing

Which pharmacokinetic parameter is defined as the theoretical volume that would contain the total body burden of a drug at the same concentration measured in plasma?

  1. Bioavailability
  2. Volume of distribution Correct answer.
  3. Elimination half-life
  4. Clearance

Explanation

Volume of distribution (Vd) relates the amount of drug in the body to its plasma concentration (Vd = amount/Cp). It is a theoretical volume rather than an anatomic space, and a large value implies extensive tissue uptake. Clearance, bioavailability, and half-life describe different pharmacokinetic processes.

Question 22Toxicokinetics, toxicodynamics, and laboratory testing

A drug given orally is extensively metabolized by the intestinal wall and liver before reaching the systemic circulation. Which term describes this effect?

  1. Zero-order elimination
  2. Enterohepatic recirculation
  3. Plasma protein binding
  4. First-pass metabolism Correct answer.

Explanation

An orally absorbed drug passes through enterocytes and the portal circulation before reaching the systemic circulation, so gut-wall and hepatic metabolism can reduce its bioavailability. This presystemic loss is called first-pass metabolism. Enterohepatic recirculation involves biliary excretion followed by reabsorption, not initial presystemic extraction.

Question 23Toxicokinetics, toxicodynamics, and laboratory testing

For a drug following first-order elimination, approximately what fraction of the drug remains after four half-lives?

  1. One thirty-second
  2. One-quarter
  3. One-sixteenth Correct answer.
  4. One-half

Explanation

In first-order elimination a constant fraction is removed per unit time, so each half-life halves the remaining amount. After four half-lives the fraction remaining is (1/2)^4 = 1/16, about 6% of the original amount. One-half corresponds to one half-life and one-quarter to two half-lives.

Question 24Toxicokinetics, toxicodynamics, and laboratory testing

Inhibition of cytochrome P450 enzymes by a co-ingested drug most typically produces which change in the victim drug?

  1. Increased renal clearance
  2. Shortened elimination half-life
  3. Reduced oral bioavailability
  4. Increased plasma concentration Correct answer.

Explanation

Competitive or mechanism-based inhibition of CYP enzymes reduces metabolic clearance of the victim drug, so plasma concentrations rise and the elimination half-life lengthens. Bioavailability may increase rather than decrease when first-pass metabolism is inhibited. Renal clearance is usually unaffected because these are metabolic interactions.

Question 25Toxicokinetics, toxicodynamics, and laboratory testing

Which formula is used to calculate the serum anion gap?

  1. Na + K − bicarbonate
  2. Chloride + bicarbonate − Na
  3. Na − (chloride + bicarbonate) Correct answer.
  4. Na − Cl

Explanation

The anion gap is calculated as sodium minus the sum of chloride and bicarbonate, normally about 8–12 mmol/L. It estimates unmeasured anions such as lactate, ketones, and toxins. Adding potassium is a nonstandard variant that shifts the reference range.

Question 26Toxicokinetics, toxicodynamics, and laboratory testing

Which analyzer measures carboxyhemoglobin and methemoglobin directly by multi-wavelength spectrophotometry?

  1. Flame atomic absorption spectrometer
  2. Co-oximeter Correct answer.
  3. Standard blood gas analyzer
  4. High-performance liquid chromatography

Explanation

A co-oximeter uses multiple wavelengths to measure carboxyhemoglobin, methemoglobin, and other hemoglobin species directly. Standard blood gas analyzers measure pH and blood gases and may calculate saturation from PO2, which is misleading when dyshemoglobins are present. Chromatography and atomic absorption are reference methods rather than routine direct co-oximetry.

Question 27Toxicokinetics, toxicodynamics, and laboratory testing

Measured serum osmolality is 320 mOsm/kg and calculated osmolality is 285 mOsm/kg. What does the osmolal gap most suggest?

  1. Unmeasured osmoles Correct answer.
  2. Reduced serum albumin level
  3. Severe hypernatremia alone
  4. A pure laboratory error

Explanation

The osmolal gap is measured minus calculated osmolality, and a value above about 10 mOsm/kg suggests unmeasured osmoles such as methanol, ethylene glycol, isopropanol, or acetone. Hypernatremia is included in the calculated osmolality and does not by itself widen the gap. Albumin contributes little to osmolality.

Question 28Toxicokinetics, toxicodynamics, and laboratory testing

For a highly protein-bound drug, which change in the overdose setting can increase the free (active) fraction?

  1. Increased renal tubular secretion
  2. Increased albumin concentration
  3. Displacement by a bound drug Correct answer.
  4. Alkalization of urine

Explanation

Only unbound drug is pharmacologically active and available for elimination. Displacement from albumin by a competing drug raises the free fraction, at least transiently. Higher albumin lowers the free fraction, and urine pH or tubular secretion affects elimination rather than binding.

Question 29Toxicokinetics, toxicodynamics, and laboratory testing

Total body clearance of a drug is best described by which relationship?

  1. Half-life divided by volume of distribution
  2. Amount in body divided by plasma concentration
  3. Volume of distribution multiplied by half-life
  4. Infusion rate divided by steady-state level Correct answer.

Explanation

Clearance is the volume of plasma cleared of drug per unit time, calculated as the rate of elimination divided by plasma concentration; at steady state this equals infusion rate divided by steady-state concentration. Volume of distribution multiplied by half-life is not clearance, and amount divided by concentration defines volume of distribution.

Question 30Toxicokinetics, toxicodynamics, and laboratory testing

Ethanol at high concentrations is eliminated at a constant rate regardless of concentration. This pattern is termed:

  1. Second-order kinetics
  2. First-order kinetics
  3. Zero-order kinetics Correct answer.
  4. Michaelis-Menten independent

Explanation

Zero-order elimination removes a constant amount per unit time because the eliminating enzyme is saturated, so concentration falls linearly. First-order elimination removes a constant fraction and produces an exponential decline. Ethanol shows zero-order behavior at high concentrations and first-order behavior at low concentrations.

Question 31Toxicokinetics, toxicodynamics, and laboratory testing

Which property most favors removal of a toxin by hemodialysis?

  1. High molecular weight
  2. Large volume of distribution
  3. Low protein binding Correct answer.
  4. Extensive tissue binding

Explanation

Hemodialysis removes solutes that are small, water-soluble, poorly protein-bound, and distributed in a small volume. A large volume of distribution or extensive tissue binding means little toxin is present in plasma to be dialyzed. High molecular weight limits diffusion across the dialysis membrane.

Question 32Toxicokinetics, toxicodynamics, and laboratory testing

Alkalinization of urine enhances elimination of which weak acid?

  1. Salicylate Correct answer.
  2. Phencyclidine
  3. Amphetamine
  4. Lidocaine

Explanation

Salicylate is a weak acid; alkalinizing urine converts it to the charged salicylate ion, which is poorly reabsorbed, a process called ion trapping. Amphetamine, phencyclidine, and lidocaine are weak bases whose elimination is enhanced by acidifying urine.

Question 33Toxicokinetics, toxicodynamics, and laboratory testing

Which finding is most characteristic of symptomatic methemoglobinemia?

  1. High carboxyhemoglobin with normal methemoglobin
  2. Low arterial PO2 with normal saturation
  3. Low co-oximetry saturation with normal PO2 Correct answer.
  4. Metabolic alkalosis with hypoventilation

Explanation

In methemoglobinemia, ferric heme cannot bind oxygen and shifts the dissociation curve, so co-oximetry shows low saturation while dissolved oxygen (PO2) is normal. Arterial PO2 is typically normal because oxygen tension is unaffected. Carboxyhemoglobin and methemoglobin are distinct dyshemoglobins measured separately.

Question 34Toxicokinetics, toxicodynamics, and laboratory testing

Which laboratory finding supports organophosphate poisoning?

  1. Depressed red cell cholinesterase activity Correct answer.
  2. Elevated serum lactate dehydrogenase
  3. Increased carboxyhemoglobin
  4. Elevated plasma pseudocholinesterase activity

Explanation

Organophosphates inhibit acetylcholinesterase, so both erythrocyte (true) and plasma (pseudo) cholinesterase activities fall. Red cell activity reflects the synaptic enzyme more closely and may remain depressed for weeks. Elevated LDH or carboxyhemoglobin is unrelated to this mechanism.

Question 35Toxicokinetics, toxicodynamics, and laboratory testing

For a drug with a short half-life given on a fixed schedule, a trough concentration should be obtained:

  1. At any random time
  2. At the midpoint of the dosing interval
  3. Immediately after the dose
  4. Just before the next dose Correct answer.

Explanation

Trough levels are drawn just before the next dose, when distribution is complete and concentration is lowest, allowing comparison with reference ranges. Sampling immediately after a dose reflects the peak and distribution phase. Mid-interval sampling is used only for specific drugs with defined protocols.

Question 36Toxicokinetics, toxicodynamics, and laboratory testing

Which drug is a well-recognized cause of a false-positive amphetamine immunoassay?

  1. Digoxin
  2. Acetaminophen
  3. Metformin
  4. Pseudoephedrine Correct answer.

Explanation

Immunoassays use antibodies that can cross-react with structurally similar compounds; pseudoephedrine and ephedrine are common causes of false-positive amphetamine results. Acetaminophen, metformin, and digoxin are not typical amphetamine cross-reactants. Confirmatory testing such as GC-MS or LC-MS/MS is required.

Question 37Toxicokinetics, toxicodynamics, and laboratory testing

A drug follows Michaelis-Menten kinetics. As the dose rate approaches Vmax, what happens to steady-state concentration?

  1. A fall caused by induced clearance
  2. A steep, disproportionate rise Correct answer.
  3. A proportional rise matching the dose
  4. No change once Vmax is reached

Explanation

In Michaelis-Menten elimination, clearance falls as concentration approaches Vmax because enzymes are saturated. Steady-state concentration then rises steeply with small increases in dose rate, so toxicity can appear after modest dose adjustments. Proportionality applies only when concentrations are well below Km.

Question 38Toxicokinetics, toxicodynamics, and laboratory testing

Immediately after a massive tricyclic antidepressant overdose, which factor best explains why plasma concentrations correlate poorly with clinical severity?

  1. Rapid renal excretion of unchanged parent drug
  2. Complete absence of plasma protein binding
  3. Tissue distribution and active metabolites Correct answer.
  4. Saturation of hepatic zero-order metabolism

Explanation

Tricyclic antidepressants are highly lipophilic, have large volumes of distribution, and are extensively tissue-bound; plasma levels therefore reflect only a small fraction of the body burden early after overdose. Active metabolites and sodium-channel blockade contribute to toxicity. Renal excretion of parent drug is minimal, and protein binding is substantial.

Question 39Toxicokinetics, toxicodynamics, and laboratory testing

Which statement best describes a competitive antagonist at a receptor?

  1. It shifts the agonist curve rightward Correct answer.
  2. It lowers the maximal agonist response
  3. It permanently inactivates the receptor
  4. It raises agonist receptor affinity

Explanation

A competitive antagonist binds reversibly at the same site as the agonist and can be overcome by more agonist, shifting the dose-response curve rightward without lowering the maximum. Noncompetitive antagonists reduce the maximal response. Irreversible antagonists persist until new receptors are synthesized.

Question 40Toxicokinetics, toxicodynamics, and laboratory testing

A single acute acetaminophen ingestion occurred at a known time. When is the Rumack-Matthew nomogram valid for risk assessment?

  1. Only after 24 hours have passed
  2. Only if the patient is symptomatic
  3. At 4 hours or more after ingestion Correct answer.
  4. At any time after the ingestion

Explanation

The Rumack-Matthew nomogram is validated for single acute ingestions with a known time and is applied at 4 hours or more after ingestion, when absorption is largely complete. Earlier levels may not reflect peak concentration. The nomogram is not validated for chronic or repeated supratherapeutic ingestions.

Question 41Analgesics, sedative-hypnotics, and cardiovascular drugs

In a large acetaminophen overdose, hepatic injury is caused mainly by accumulation of which species?

  1. NAPQI Correct answer.
  2. Cysteine conjugate of acetaminophen
  3. Acetaminophen sulfate conjugate
  4. Acetaminophen glucuronide conjugate

Explanation

At therapeutic doses most acetaminophen is glucuronidated or sulfated, but these pathways saturate in overdose and CYP2E1 oxidation generates NAPQI. NAPQI depletes hepatic glutathione and covalently binds cellular proteins, producing centrilobular necrosis. N-acetylcysteine restores glutathione and also conjugates NAPQI directly.

Question 42Analgesics, sedative-hypnotics, and cardiovascular drugs

A healthy 22-year-old ingests about 30 ibuprofen tablets and is brought to the emergency department an hour later. Which clinical course is most typical of a moderate ibuprofen overdose?

  1. Severe metabolic acidosis with seizures
  2. Acute hepatic failure within 24 hours
  3. Status epilepticus requiring intubation
  4. Nausea and abdominal pain Correct answer.

Explanation

Most nonsteroidal anti-inflammatory drug overdoses produce only nausea, vomiting, epigastric pain, and mild drowsiness, with complete recovery after supportive care. Serious effects such as metabolic acidosis, seizures, and acute kidney injury are rare and reported mainly with massive ingestions. Hepatotoxicity is characteristic of acetaminophen, not ibuprofen.

Question 43Analgesics, sedative-hypnotics, and cardiovascular drugs

A comatose patient with pinpoint pupils has a respiratory rate of four per minute and receives naloxone. Titration should continue until which endpoint is reached?

  1. Heart rate exceeds 100 beats per minute
  2. Adequate spontaneous ventilation Correct answer.
  3. Complete return of consciousness
  4. Pupils become fully dilated

Explanation

Naloxone is titrated to restore adequate spontaneous ventilation rather than full arousal. Abrupt complete reversal can precipitate agitation, vomiting, acute withdrawal, and pulmonary edema. Because naloxone is shorter acting than many opioids, the patient must be observed for recurrent sedation.

Question 44Analgesics, sedative-hypnotics, and cardiovascular drugs

Which antidote is used for symptomatic bradycardia and hypotension caused by beta-blocker overdose?

  1. Glucagon Correct answer.
  2. Naloxone
  3. Octreotide
  4. Flumazenil

Explanation

Glucagon activates adenylyl cyclase through receptors that are separate from the beta-adrenergic receptor, so it bypasses the blockade and raises intracellular cyclic AMP. High-dose insulin with glucose, calcium, vasopressors, and pacing are additional options. Octreotide is used for sulfonylurea-induced hypoglycemia, not beta-blocker toxicity.

Question 45Analgesics, sedative-hypnotics, and cardiovascular drugs

A 45-year-old swallows 40 tablets of lisinopril and arrives asymptomatic two hours later. Which finding is most expected as the ingestion evolves?

  1. Wide QRS from sodium channel block
  2. Torsades de pointes requiring magnesium
  3. Hypotension as the main finding Correct answer.
  4. Immediate hepatic failure

Explanation

Angiotensin-converting enzyme inhibitor overdose produces vasodilation and hypotension, which may appear after an asymptomatic interval of several hours. Bradycardia is uncommon and hyperkalemia is rarely severe in acute overdose with normal renal function. Treatment is intravenous fluids, vasopressors, and prolonged observation.

Question 46Analgesics, sedative-hypnotics, and cardiovascular drugs

Which statement best explains why supportive care alone is usually sufficient in an isolated benzodiazepine overdose?

  1. Benzodiazepine receptors have no antagonist
  2. Tolerance develops within minutes
  3. Respiratory depression is usually mild Correct answer.
  4. Renal clearance is extremely rapid

Explanation

Benzodiazepines have a plateau in their dose-response curve for ventilatory depression, so isolated overdose rarely causes clinically important respiratory compromise. Significant apnea usually requires a co-ingestant such as ethanol or an opioid, or underlying pulmonary disease. Flumazenil is therefore reserved for selected cases because of its seizure risk.

Question 47Analgesics, sedative-hypnotics, and cardiovascular drugs

A patient presents six hours after a single intentional acetaminophen ingestion. Which statement about the Rumack-Matthew nomogram is correct?

  1. Charcoal given before the level invalidates it
  2. A level drawn before 4 hours can be plotted directly
  3. A level on or above the line warrants NAC Correct answer.
  4. The nomogram applies to repeated ingestions

Explanation

The nomogram is valid for a single acute ingestion with a known time, using a serum level drawn at least four hours afterward, when absorption is complete. A level at or above the treatment line is an indication for N-acetylcysteine. When the time of ingestion is unknown or ingestions are repeated, treatment is started empirically without the nomogram.

Question 48Analgesics, sedative-hypnotics, and cardiovascular drugs

Why is sodium bicarbonate given to alkalinize the urine in salicylate poisoning?

  1. It converts salicylate to salicyluric acid
  2. It traps ionized drug in the tubule Correct answer.
  3. It increases hepatic glucuronidation
  4. It prevents plasma protein binding

Explanation

Salicylate is a weak acid, and an alkaline tubular fluid increases the fraction that is ionized and therefore unable to diffuse back across the tubular epithelium. This ion trapping enhances renal elimination and is most effective when urine pH is kept above about 7.5. Systemic alkalinization also limits salicylate entry into the central nervous system.

Question 49Analgesics, sedative-hypnotics, and cardiovascular drugs

Which opioid is most strongly associated with QT prolongation and torsades de pointes at high doses?

  1. Morphine
  2. Methadone Correct answer.
  3. Oxycodone
  4. Hydromorphone

Explanation

Methadone inhibits the hERG potassium channel and can prolong the QT interval in a dose-dependent manner. Risk is increased by high doses, CYP3A4 inhibitors, hypokalemia, and underlying cardiac disease. Patients on high-dose methadone warrant periodic electrocardiographic monitoring.

Question 50Analgesics, sedative-hypnotics, and cardiovascular drugs

A patient taking an SSRI becomes agitated and diaphoretic and has clonus and a seizure after ingesting tramadol. Which mechanism best explains these findings?

  1. GABA-A receptor blockade
  2. Monoamine reuptake inhibition Correct answer.
  3. NMDA receptor antagonism
  4. Pure mu-opioid receptor agonism

Explanation

Tramadol both agonizes mu receptors and inhibits serotonin and norepinephrine reuptake, so combining it with an SSRI can precipitate serotonin toxicity and lowers the seizure threshold. Naloxone does not reverse these monoaminergic effects. Seizures can also occur with therapeutic tramadol use.