Local anesthetics are drugs that reversibly block nerve conduction to produce loss of sensation in a defined area. This introduction reviews structure–activity relationships (SAR), mechanism of action (voltage-gated sodium channel blockade), classification into ester and amide types, and key physicochemical determinants such as pKa, lipid solubility and protein binding. It also covers pharmacokinetics (absorption, metabolism by plasma esterases or hepatic CYPs), clinical properties (onset, potency, duration) and toxicity (CNS and cardiovascular effects, allergic reactions, methemoglobinemia). Understanding SAR helps predict activity and safety, aiding formulation and clinical choice. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which molecular feature primarily distinguishes ester-type from amide-type local anesthetics?
- Presence of an ester linkage between aromatic and intermediate chain
- Presence of a tertiary amine in the molecule
- Degree of lipid solubility
- Ability to cross the blood-brain barrier
Correct Answer: Presence of an ester linkage between aromatic and intermediate chain
Q2. The primary mechanism of action of most local anesthetics is:
- Blockade of voltage-gated sodium channels in the neuronal membrane
- Antagonism of GABA receptors
- Inhibition of acetylcholinesterase
- Activation of opioid receptors
Correct Answer: Blockade of voltage-gated sodium channels in the neuronal membrane
Q3. A lower pKa of a local anesthetic results in which clinical effect?
- Faster onset of action due to more nonionized drug at physiological pH
- Greater protein binding and longer duration
- Increased systemic toxicity
- Reduced lipid solubility
Correct Answer: Faster onset of action due to more nonionized drug at physiological pH
Q4. Which property most strongly correlates with potency of local anesthetics?
- Lipid solubility of the molecule
- Aqueous solubility
- pKa value
- Molecular weight
Correct Answer: Lipid solubility of the molecule
Q5. Which metabolic pathway mainly inactivates amide local anesthetics?
- Hepatic microsomal cytochrome P450 metabolism
- Plasma pseudocholinesterase hydrolysis
- Renal excretion as unchanged drug
- Metabolism by bacterial esterases
Correct Answer: Hepatic microsomal cytochrome P450 metabolism
Q6. Which adverse effect is characteristic of local anesthetic systemic toxicity (LAST)?
- CNS excitation followed by depression, seizures, and cardiovascular collapse
- Bronchospasm and immediate anaphylaxis only
- Renal failure with oliguria
- Pancreatitis
Correct Answer: CNS excitation followed by depression, seizures, and cardiovascular collapse
Q7. Which local anesthetic is well known to cause methemoglobinemia in susceptible patients?
- Prilocaine
- Lidocaine
- Bupivacaine
- Tetracaine
Correct Answer: Prilocaine
Q8. Which statement about protein binding of local anesthetics is true?
- Higher protein binding generally prolongs duration of action
- Higher protein binding speeds onset of action
- Protein binding determines pKa of the drug
- All ester anesthetics have higher protein binding than amides
Correct Answer: Higher protein binding generally prolongs duration of action
Q9. Which nerve fibers are blocked first by local anesthetics?
- Small myelinated fibers (e.g., pain) are blocked before large myelinated fibers
- Large myelinated fibers (e.g., motor) are blocked before small fibers
- Unmyelinated fibers are always resistant
- All fibers are blocked simultaneously regardless of size
Correct Answer: Small myelinated fibers (e.g., pain) are blocked before large myelinated fibers
Q10. Which modification in SAR generally increases duration of action?
- Increasing lipid solubility and protein binding
- Lowering molecular weight
- Increasing water solubility
- Removing the tertiary amine
Correct Answer: Increasing lipid solubility and protein binding
Q11. The typical site of action on the sodium channel for local anesthetics is:
- Within the inner pore of the voltage-gated sodium channel accessible from the intracellular side
- Extracellular ligand-binding site on the channel
- At the selectivity filter preventing K+ flow
- At the channel’s beta subunit interface only
Correct Answer: Within the inner pore of the voltage-gated sodium channel accessible from the intracellular side
Q12. Which local anesthetic is an amide and commonly used for infiltration and nerve block with intermediate duration?
- Lidocaine
- Tetracaine
- Chloroprocaine
- Procaine
Correct Answer: Lidocaine
Q13. Allergic reactions to local anesthetics are most frequently associated with which class?
- Ester-type local anesthetics due to PABA derivatives
- Amide-type local anesthetics due to hepatic metabolites
- All classes equally cause true IgE-mediated allergy
- Only topical anesthetics cause allergies
Correct Answer: Ester-type local anesthetics due to PABA derivatives
Q14. Which parameter is most important in predicting onset time of a local anesthetic?
- pKa relative to physiological pH
- Lipid solubility
- Protein binding
- Pka of sodium channels
Correct Answer: pKa relative to physiological pH
Q15. Which local anesthetic has a long duration and high cardiotoxicity risk and is commonly used for epidural and regional anesthesia?
- Bupivacaine
- Lidocaine
- Procaine
- Chloroprocaine
Correct Answer: Bupivacaine
Q16. Addition of epinephrine to a local anesthetic primarily:
- Causes vasoconstriction, reducing systemic absorption and prolonging duration
- Increases metabolic clearance by liver enzymes
- Directly increases blockade potency at sodium channels
- Neutralizes acidity to speed onset
Correct Answer: Causes vasoconstriction, reducing systemic absorption and prolonging duration
Q17. Which structural element is essential for local anesthetic activity (common pharmacophore)?
- Aromatic ring linked by an intermediate chain to a tertiary amine
- Two aromatic rings separated by a sulfonamide
- A free carboxylic acid and secondary amine
- A quaternary ammonium permanently charged
Correct Answer: Aromatic ring linked by an intermediate chain to a tertiary amine
Q18. Which clinical scenario increases risk of systemic toxicity from local anesthetics?
- Rapid IV injection of high dose during nerve block
- Use of low concentration for topical anesthesia
- Administration in highly vascular area with epinephrine
- Subcutaneous infiltration at low doses
Correct Answer: Rapid IV injection of high dose during nerve block
Q19. Which factor decreases the effectiveness of local anesthetics in infected tissues?
- Acidic pH converting drug to ionized form, reducing membrane penetration
- Increased lipid solubility of the drug
- Enhanced protein binding at infection site
- Increased vascular resistance
Correct Answer: Acidic pH converting drug to ionized form, reducing membrane penetration
Q20. Which of the following is a short-acting ester local anesthetic often used for short procedures?
- Chloroprocaine
- Bupivacaine
- Ropivacaine
- Lidocaine
Correct Answer: Chloroprocaine
Q21. The ‘use-dependent’ block of sodium channels by local anesthetics means:
- Block is more effective on frequently firing (active) neurons
- Block is only effective when channels are closed
- Block requires coadministration of opioids
- Block is independent of membrane potential
Correct Answer: Block is more effective on frequently firing (active) neurons
Q22. Which metabolite of ester local anesthetics is implicated in allergic reactions?
- Para-aminobenzoic acid (PABA)
- N-desethyl metabolite
- Glucuronide conjugate
- Nitroso derivative
Correct Answer: Para-aminobenzoic acid (PABA)
Q23. Ropivacaine differs from bupivacaine in that it:
- Has reduced cardiotoxicity and is a pure S-enantiomer
- Is an ester and more rapidly hydrolyzed
- Has much faster onset due to lower pKa
- Causes methemoglobinemia commonly
Correct Answer: Has reduced cardiotoxicity and is a pure S-enantiomer
Q24. In terms of blockade recovery, which sequence is correct for loss of function?
- Pain → Temperature → Touch → Motor
- Motor → Touch → Temperature → Pain
- Touch → Pain → Motor → Temperature
- Temperature → Motor → Pain → Touch
Correct Answer: Pain → Temperature → Touch → Motor
Q25. Which clinical measure is recommended as immediate treatment for severe cardiovascular collapse due to local anesthetic toxicity?
- Intralipid (lipid emulsion) therapy
- High-dose benzodiazepines alone
- Immediate renal dialysis
- Intravenous naloxone
Correct Answer: Intralipid (lipid emulsion) therapy
Q26. Which of the following local anesthetics is most likely to be hydrolyzed by plasma cholinesterase?
- Procaine
- Lidocaine
- Bupivacaine
- Ropivacaine
Correct Answer: Procaine
Q27. A high degree of ionization at physiological pH will:
- Reduce membrane permeation and slow onset
- Increase membrane permeation and accelerate onset
- Increase lipid solubility
- Enhance protein binding immediately
Correct Answer: Reduce membrane permeation and slow onset
Q28. Which local anesthetic is commonly used topically and has potent long-acting properties suitable for spinal anesthesia?
- Tetracaine
- Procaine
- Chloroprocaine
- Lidocaine
Correct Answer: Tetracaine
Q29. During development of SAR, substitution on the aromatic ring of local anesthetics primarily affects:
- Lipid solubility and potency
- pKa of the tertiary amine
- Plasma protein binding exclusively
- Ability to be hydrolyzed by esterases
Correct Answer: Lipid solubility and potency
Q30. Which factor would most likely prolong systemic half-life of an amide local anesthetic?
- Hepatic impairment reducing metabolism
- Presence of plasma cholinesterase deficiency
- Coadministration of epinephrine causing hepatic hyperperfusion
- High plasma albumin increasing clearance
Correct Answer: Hepatic impairment reducing metabolism
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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