Introduction: Ionization and biological action MCQs With Answer are essential for B. Pharm students mastering how a drug’s ionization state influences absorption, distribution, excretion, and receptor interactions. This topic covers pKa, pH partition theory, Henderson-Hasselbalch calculations, ion trapping, weak acids and bases, zwitterions, and clinical manipulations like urine pH alteration to modify renal elimination. Understanding ionization helps predict drug permeability across membranes, protein binding effects, blood–brain barrier penetration, and pharmacokinetic behavior. These focused MCQs emphasize both conceptual depth and applied calculations to prepare you for exams and practical pharmacology. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which principle explains why non-ionized drugs cross lipid membranes more readily?
- Lipophilicity and pH partition theory
- Active transport by P-glycoprotein
- First-pass metabolism
- Renal clearance
Correct Answer: Lipophilicity and pH partition theory
Q2. Henderson-Hasselbalch equation for a weak acid is written as:
- pH = pKa + log([HA]/[A-])
- pH = pKa + log([A-]/[HA])
- pKa = pH + log([HA]/[A-])
- pH = log([HA]/[A-])
Correct Answer: pH = pKa + log([A-]/[HA])
Q3. A weak acid (pKa 4.0) is placed in stomach (pH 1.5). The predominant form at this pH is:
- Mostly ionized (A-)
- Mostly unionized (HA)
- Equal ionized and unionized
- Completely dissociated
Correct Answer: Mostly unionized (HA)
Q4. For a weak base with pKa 9.0 at physiological pH 7.4, the predominant species in plasma is:
- Unionized base (B)
- Ionized cation (BH+)
- Neutral zwitterion
- Undissociated acid form
Correct Answer: Ionized cation (BH+)
Q5. Which statement about ion trapping is correct?
- Unionized drugs get trapped in compartments of similar pH
- Ionized drugs cross membranes easily and then become trapped
- Drugs become trapped in compartments where they are ionized and cannot cross back
- Ion trapping applies only to large protein-bound drugs
Correct Answer: Drugs become trapped in compartments where they are ionized and cannot cross back
Q6. Which factor does NOT directly affect the ionization state of a drug?
- pKa of the drug
- pH of the environment
- Lipid solubility (log P) of the drug
- Temperature of the environment (physiological range)
Correct Answer: Lipid solubility (log P) of the drug
Q7. Percent ionization of a weak acid at pH = pKa is approximately:
- 0%
- 25%
- 50%
- 100%
Correct Answer: 50%
Q8. Which drug example is a weak acid commonly used in B. Pharm teaching?
- Propranolol
- Aspirin
- Diazepam
- Codeine
Correct Answer: Aspirin
Q9. Which equation yields the ratio of ionized to unionized forms for a weak base?
- [BH+]/[B] = 10^(pH – pKa)
- [B]/[BH+] = 10^(pH – pKa)
- [BH+]/[B] = 10^(pKa – pH)
- [B]/[BH+] = 10^(pKa + pH)
Correct Answer: [BH+]/[B] = 10^(pKa – pH)
Q10. A weak base with pKa 8.4 is taken orally. Which region favors its absorption due to higher unionized fraction?
- Stomach (pH 2)
- Small intestine (pH 6-7.5)
- Urine (variable pH)
- Blood (pH 7.4)
Correct Answer: Small intestine (pH 6-7.5)
Q11. Which is a correct implication of the pH partition hypothesis for drug absorption?
- Only ionized drugs are absorbed across membranes
- Unionized form is more lipid soluble and better absorbed
- Protein binding determines absorption, not ionization
- All charged molecules are rapidly absorbed
Correct Answer: Unionized form is more lipid soluble and better absorbed
Q12. Which clinical manipulation increases excretion of a weak base?
- Alkalinize the urine
- Acidify the urine
- Increase plasma protein binding
- Administer a P-gp inhibitor
Correct Answer: Acidify the urine
Q13. Plasma pH is approximately 7.4. For a weak acid with pKa 7.4, the fraction ionized is:
- ~10%
- ~25%
- ~50%
- ~75%
Correct Answer: ~50%
Q14. Which class of drugs commonly exists as zwitterions at physiological pH?
- Benzodiazepines
- Amino acid–derived drugs (e.g., cephalosporins)
- Simple weak acids like aspirin
- Alkaloids without acidic groups
Correct Answer: Amino acid–derived drugs (e.g., cephalosporins)
Q15. In Henderson-Hasselbalch for a weak base, pH = pKa + log([B]/[BH+]). If pH >> pKa, which form predominates?
- Ionized BH+
- Unionized B
- Equal amounts
- Degraded drug
Correct Answer: Unionized B
Q16. Which statement best describes how protein binding interacts with ionization?
- Ionized drugs always bind more strongly to plasma proteins
- Unionized hydrophobic drugs often have higher protein binding
- Protein binding is independent of lipophilicity and ionization
- Protein binding converts drugs to ionized forms
Correct Answer: Unionized hydrophobic drugs often have higher protein binding
Q17. If a weak acid drug (pKa 5.0) enters urine with pH 8.0, what happens to its ionization and excretion?
- Becomes more unionized and reabsorbed
- Becomes more ionized and excreted (ion trapping)
- No change in ionization
- Undergoes metabolism in urine
Correct Answer: Becomes more ionized and excreted (ion trapping)
Q18. Which of these factors increases a drug’s ability to cross the blood–brain barrier?
- High ionized fraction at pH 7.4
- Low lipid solubility
- High unionized fraction at pH 7.4 and small molecular size
- High plasma protein binding
Correct Answer: High unionized fraction at pH 7.4 and small molecular size
Q19. Which drug property is LEAST affected by ionization state?
- Membrane permeability
- Intrinsic receptor affinity (for charged receptors)
- Renal tubular reabsorption
- Number of chiral centers
Correct Answer: Number of chiral centers
Q20. A drug with pKa 6.0 is in plasma pH 7.4. For a weak acid, is it mostly ionized or unionized?
- Mostly unionized
- Mostly ionized
- Exactly 50% ionized
- Completely unionized
Correct Answer: Mostly ionized
Q21. Which clinical example uses urine alkalinization to enhance excretion?
- Phenobarbital overdose
- Amphetamine overdose
- Methadone poisoning
- Iron overdose
Correct Answer: Phenobarbital overdose
Q22. Which of the following is true about weak acids in the gastrointestinal tract?
- They are better absorbed in the stomach when unionized
- They are best absorbed in alkaline environments
- They are always ionized in all GI regions
- They are not affected by pH at all
Correct Answer: They are better absorbed in the stomach when unionized
Q23. A weak base has pKa 8.0 and is in a compartment at pH 6.0. Which form predominates?
- Unionized base (B)
- Ionized form (BH+)
- Zwitterion
- Neutral acid (HA)
Correct Answer: Ionized form (BH+)
Q24. Which lab value is most relevant when calculating ionization-dependent renal clearance?
- Serum creatinine
- Urine pH
- Blood glucose
- Liver enzymes
Correct Answer: Urine pH
Q25. Which of the following pairs correctly matches drug and its general ionization at physiological pH?
- Lidocaine — mostly ionized (weak base)
- Aspirin — mostly unionized (weak base)
- Doxycycline — non-ionizable
- Propranolol — mostly ionized (weak acid)
Correct Answer: Lidocaine — mostly ionized (weak base)
Q26. Henderson-Hasselbalch predicts that a weak acid will be 99% ionized when pH is how many units above pKa?
- 1 unit above pKa
- 2 units above pKa
- 3 units above pKa
- 5 units above pKa
Correct Answer: 3 units above pKa
Q27. Which describes a zwitterion?
- A molecule carrying both positive and negative charges but overall neutral
- A permanently positively charged ion only
- A permanently negatively charged ion only
- An uncharged lipophilic molecule
Correct Answer: A molecule carrying both positive and negative charges but overall neutral
Q28. A drug’s pKa is 3.5. At intestinal pH 6.5, what is true for a weak acid?
- Mostly unionized and well absorbed
- Mostly ionized and less absorbed
- Unchanged ionization compared to pH 3.5
- Converted into a base
Correct Answer: Mostly ionized and less absorbed
Q29. Why are local anesthetics often formulated with vasoconstrictors when injected?
- To increase ionization and immediate systemic absorption
- To reduce local blood flow, prolonging local high unionized concentration and effect
- To alkalinize tissue and prevent action
- To promote metabolism in the tissue
Correct Answer: To reduce local blood flow, prolonging local high unionized concentration and effect
Q30. Which of these is a practical application of ionization knowledge in forensic or clinical toxicology?
- Using activated charcoal to change ionization
- Manipulating urine pH to enhance elimination of overdosed drugs
- Changing blood pH to increase hepatic metabolism
- Converting drugs to prodrugs to increase ionization
Correct Answer: Manipulating urine pH to enhance elimination of overdosed drugs
Q31. Which is TRUE about lipophilicity (log P) and ionization?
- Log P applies only to ionized species
- Ionized species usually have lower lipophilicity than unionized species
- Ionization always increases log P
- Unionized forms are always hydrophilic
Correct Answer: Ionized species usually have lower lipophilicity than unionized species
Q32. For a weak base drug, which scenario promotes renal reabsorption?
- Acidic urine making the drug ionized
- Alkaline urine making the drug unionized
- High urine flow only
- Presence of urinary enzymes
Correct Answer: Alkaline urine making the drug unionized
Q33. At pH equal to pKa + 1 for a weak acid, what fraction is ionized roughly?
- ~9%
- ~50%
- ~91%
- ~99%
Correct Answer: ~91%
Q34. Which type of receptor interaction may favor an ionized drug?
- Hydrophobic binding pocket with no charged residues
- Electrostatic interactions with opposite charges at receptor site
- Passive diffusion through lipids
- Non-specific protein adsorption
Correct Answer: Electrostatic interactions with opposite charges at receptor site
Q35. A drug is poorly absorbed orally because it is highly ionized in the gut. Which strategy could improve its absorption?
- Co-administer with a pH modifier to favor unionized form locally
- Administer with activated charcoal
- Decrease gastric emptying time
- Increase urine pH
Correct Answer: Co-administer with a pH modifier to favor unionized form locally
Q36. Which best describes amphoteric drugs?
- Drugs that are strictly acidic
- Drugs that cannot ionize
- Drugs that can act as either acid or base (contain both functional groups)
- Drugs that are permanently charged
Correct Answer: Drugs that can act as either acid or base (contain both functional groups)
Q37. Which process is MOST likely to change a drug’s pKa?
- Co-administration with other drugs
- Chemical modification such as esterification (prodrug formation)
- Changing urine pH
- Altering body temperature within physiological range
Correct Answer: Chemical modification such as esterification (prodrug formation)
Q38. Given a weak acid with pKa 4.0, calculate qualitatively how much more ionized it will be at pH 7.0 compared to pH 4.0?
- No change
- Approximately 1000-fold more ionized
- Approximately 3-fold more ionized
- Less ionized at pH 7.0
Correct Answer: Approximately 1000-fold more ionized
Q39. Which pharmacokinetic parameter is directly affected by ionization and unionized fraction?
- Volume of distribution (Vd)
- Renal clearance via tubular reabsorption
- Intrinsic hepatic clearance only
- Rate of enthalpy change
Correct Answer: Renal clearance via tubular reabsorption
Q40. A drug with pKa 7.4 is given intravenously. Which compartment will provide roughly equal ionized and unionized concentrations?
- Gastric lumen (pH 1.5)
- Plasma (pH 7.4)
- Small intestine (pH 6.5)
- Saliva (pH 6.8)
Correct Answer: Plasma (pH 7.4)
Q41. Which laboratory technique can determine pKa experimentally for a drug candidate?
- Mass spectrometry only
- Titration curve (potentiometric titration)
- IR spectroscopy without reference
- Thin-layer chromatography exclusively
Correct Answer: Titration curve (potentiometric titration)
Q42. Which statement about ionization and topical absorption is TRUE?
- Ionized forms penetrate intact stratum corneum better than unionized forms
- Unionized, lipophilic forms penetrate skin more readily
- Ionization has no effect on dermal absorption
- Only proteins determine topical penetration
Correct Answer: Unionized, lipophilic forms penetrate skin more readily
Q43. In overdose management, which is a correct pairing of manipulation and targeted drug type?
- Urine alkalinization for salicylate (weak acid) overdose
- Urine alkalinization for amphetamine (weak base) overdose
- Urine acidification for phenobarbital (weak acid) overdose
- Urine acidification for aspirin (weak acid) overdose
Correct Answer: Urine alkalinization for salicylate (weak acid) overdose
Q44. Which effect does increased ionization have on passive diffusion across membranes?
- Increases passive diffusion
- Decreases passive diffusion
- No effect on diffusion
- Converts diffusion to active transport
Correct Answer: Decreases passive diffusion
Q45. Which forensic principle uses ion trapping to explain drug accumulation in fetal blood?
- Fetal blood is more acidic than maternal blood, trapping weak bases in fetal circulation
- Fetal blood is more alkaline than maternal blood, trapping weak acids in fetal circulation
- Placenta prevents any ionized drug transfer
- Only unionized drugs are actively transported into fetal blood
Correct Answer: Fetal blood is more acidic than maternal blood, trapping weak bases in fetal circulation
Q46. A basic drug has pKa 7.0. At pH 5.0, the ratio [BH+]/[B] is approximately:
- 0.01
- 1
- 100
- 1000
Correct Answer: 100
Q47. In designing a prodrug to improve oral absorption, one aim regarding ionization is to:
- Increase permanent ionization
- Mask ionizable groups to increase unionized lipophilic form during absorption
- Create a charged metabolite for slower absorption
- Remove all polar groups to prevent metabolism
Correct Answer: Mask ionizable groups to increase unionized lipophilic form during absorption
Q48. Which is a direct consequence of ionization on drug–receptor interaction?
- Ionization only affects absorption, not receptor binding
- Charged groups may form ionic bonds with opposite charges on receptors, altering affinity
- Ionization always reduces receptor affinity
- Receptor binding depends solely on molecular weight
Correct Answer: Charged groups may form ionic bonds with opposite charges on receptors, altering affinity
Q49. A weak acid with pKa 5.0 is 99% ionized at what pH relative to pKa?
- pH 5.0
- pH 6.0
- pH 8.0 (3 units above pKa)
- pH 4.0 (1 unit below pKa)
Correct Answer: pH 8.0 (3 units above pKa)
Q50. Which educational takeaway best summarizes ionization and biological action for B. Pharm students?
- Ionization only matters for pharmacology exams and not for clinical practice
- Understanding pKa, pH, ion trapping, and Henderson-Hasselbalch is crucial to predict drug absorption, distribution, elimination, and action
- Ionization can be ignored if a drug is highly potent
- All drugs become unionized in the body regardless of pH
Correct Answer: Understanding pKa, pH, ion trapping, and Henderson-Hasselbalch is crucial to predict drug absorption, distribution, elimination, and action
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