- In a zero‐order elimination process, which of the following is true?
- The rate of drug removal is independent of drug concentration
- \(Cl = \tfrac{\text{rate of elimination}}{Cp}\)
- \(t_{\tfrac{1}{2}} = 0.7 \times \tfrac{Vd}{Cl}\)
- All are true
By definition, zero‐order elimination means the same amount of drug is removed per unit time, regardless of its plasma concentration. Clearance (\(Cl\)) is always defined as \(\tfrac{\text{rate}}{Cp}\), but in zero‐order kinetics, \(Cl\) varies with concentration and the half‐life formula in \(C\) only applies to first‐order processes.
- For highly polar drugs (e.g., mannitol) that undergo minimal metabolism, which factor primarily determines their elimination?
- Renal excretion rate
- Metabolic clearance
- Absorption rate
- Distribution rate
- All of the above
Highly polar drugs are filtered by the kidney and excreted unchanged. Their elimination (clearance) is therefore driven by renal excretion rate (glomerular filtration and tubular secretion), not by metabolism, absorption, or distribution.
- Systemic bioavailability (\(F\)) is related to hepatic extraction ratio (\(E\)) by \(F=1-E\). What does \(E\) represent?
- Fraction excreted unchanged in urine
- Overall elimination fraction
- Hepatic extraction ratio
- Extent of enterohepatic recycling
\(E\) is the hepatic extraction ratio, the fraction of drug removed by the liver on a single pass.
- For most drugs exhibiting first‐order kinetics, which equation correctly defines clearance?
- \(Cl = \tfrac{\text{rate of elimination}}{Cp}\)
- \(Cl = Q \times E\)
- \(Cl = 0.7 \times \tfrac{V_d}{t_{\frac{1}{2}}}\)
- All are correct
Clearance can be defined three equivalent ways under first‐order kinetics:
\(\dfrac{\text{rate}}{Cp}\)
\(\text{organ blood flow } \times \text{ extraction ratio}\)
\(t_{\tfrac{1}{2}} = 0.7\: \dfrac{V_d}{Cl} ⇒ Cl = 0.7\: \dfrac{V_d}{t\tfrac{1}{2}}\)
- If morphine has an oral bioavailability (\(F\)) of 0.24, how much of a 10 mg dose reaches systemic circulation?
- 24 mg
- 0.24 mg
- 2.4 mg
- 4.1 mg
\(\text{Systemic dose} = F \times \text{administered dose}\) \(= 0.24 \times 10 \text{ mg} = 2.4 \text{ mg}\)
- Given that \(V_d = \tfrac{230 \text{ L}}{70 \text{ kg}}\) and \(Cl = \tfrac{60 \text{ L/hr}}{70 \text{ kg}}\) for morphine, approximately how much of a 10 mg IV dose remains after 8 hours in a 70 kg patient?
- 5 mg
- 2.5 mg
- 1.25 mg
- 0.625 mg
Morphine follows first-order kinetics:
\(C(t)=C_0\,e^{-kt}\)
\(\quad k=\dfrac{Cl}{V_d}=\dfrac{60}{230}\approx0.261\:\mathrm{hr}^{-1}\)
After 8 hours:
\(C(8)=10\times e^{-0.261\times8}\approx1.25\:\mathrm{mg}\)
- What is the overall hepatic clearance of morphine if hepatic blood flow is reduced by \(\tfrac{1}{2}\)? (Assume the given clearance of \(Cl = \tfrac{60\:\mathrm{L/hr}}{70\:\mathrm{kg}}\) is entirely hepatic.)
- \(\tfrac{30 \text{ L/hr}}{70 \text{ kg}}\)
- \(\tfrac{60 \text{ L/hr}}{70 \text{ kg}}\)
- \(\tfrac{120 \text{ L/hr}}{70 \text{ kg}}\)
- \(\tfrac{250 \text{ L/hr}}{70 \text{ kg}}\)
Hepatic clearance (\(Cl_H\)) equals liver blood flow (\(Q_H\)) multiplied by extraction ratio. Halving \(Q_H\) halves clearance:
\(Cl_{H,\text{new}} = \tfrac{1}{2}\times 60 = 30\:\mathrm{L/hr}\)
- Which of the following Phase II enzymes can directly act on codeine?
- Glucuronyl transferase
- Sulfotransferase
- Glutathione transferase
- Choices A and B
- All of the above
Codeine is conjugated by UDP‐glucuronyl transferases (O- and N-glucuronidation) and by sulfotransferases. Glutathione transferases act on reactive electrophiles, not directly on codeine itself.
- Which cytochrome P450 isozyme does not participate appreciably in drug metabolism?
- CYP1A2
- CYP2C9
- CYP3A4
- CYP51
- All are drug-metabolizing isoforms
CYP1A2, CYP2C9, and CYP3A4 are major drug-metabolizing enzymes. CYP51 (lanosterol 14α-demethylase) is involved in cholesterol biosynthesis and does not significantly metabolize xenobiotics.
- Which cytochrome P450 isozyme is responsible for the bulk of Phase I drug metabolism?
- CYP1A2
- CYP2C9
- CYP2D6
- CYP3A4
- CYP51
CYP3A4 metabolizes roughly half of all marketed drugs, making it the predominant Phase I enzyme in the human liver and intestine.
- Which of the following enzymes could metabolize ethanol?
- Cytochrome P450
- Alcohol dehydrogenase
- Glucuronyl transferase
- Sulfotransferase
- All of the above
Ethanol is primarily oxidized to acetaldehyde by alcohol dehydrogenase and by the microsomal ethanol‐oxidizing system (CYP2E1). Minor pathways generate ethyl glucuronide (via UDP‐glucuronyl transferase) and ethyl sulfate (via sulfotransferases).
- Which of the following are similarities between cytochrome P450 and monoamine oxidase (MAO)?
- Both add oxygen from O2 to substrates and also form water
- Both carry out direct heteroatom oxidations
- Both carry out oxidative deaminations
- Both carry out N-dealkylations
- All of the above
Both cytochrome P450 enzymes and MAO catalyze oxidative deamination of amine substrates. Other reactions are characteristic of P450 but not MAO.
- What would be the preferred route of metabolism of succinylcholine?
- Ester hydrolysis
- N-oxidation
- Glucuronide conjugation
- Choices A and B
- All of the above
Succinylcholine is rapidly inactivated by plasma pseudocholinesterase (butyrylcholinesterase) via ester hydrolysis; oxidative and conjugative pathways are negligible.
- Which of the following causes the smallest change in water solubility?
- Hydroxylation
- Glucuronidation
- Sulfation
- Glutathione conjugation
Hydroxylation (Phase I) adds a single polar –OH group, only modestly increasing solubility. Phase II conjugations introduce large polar moieties, dramatically enhancing water solubility.
- Cigarette smoke induces CYP1A isozymes. Theophylline is primarily metabolized by CYP1A. What happens to theophylline clearance in an asthmatic patient hospitalized and unable to smoke?
- No change
- Increase
- Decrease
Smoking induction of CYP1A2 increases theophylline clearance. When smoking stops, enzyme induction wanes and clearance decreases, raising theophylline plasma levels unless dose is adjusted.