What is the most toxic β-blocker?

• A. Metoprolol
• B. Propranolol
• C. Bisoprolol
• D. Nadolol

Answer: (B)

Understanding why a beta-blocker is more toxic in overdose hinges on two factors: receptor selectivity and how well the drug enters the brain. Non-selective blockers that are highly lipophilic tend to cause the most trouble because they block both beta-1 and beta-2 receptors throughout the body and readily cross the blood–brain barrier. Propranolol fits this profile: it blocks both_beta receptors and is highly lipid-soluble, so it can reach the heart, lungs, vasculature, and the central nervous system. In overdose, this leads to severe bradycardia and hypotension from cardiac depression, bronchospasm if beta-2 is blocked in the lungs, and potentially CNS effects like confusion or seizures due to brain penetration. It can also have membrane-stabilizing (sodium channel-blocking) effects at high doses, adding to toxicity.

Nadolol is also non-selective but is more hydrophilic, so it penetrates the CNS less and tends to have fewer CNS toxic effects than propranolol. Metoprolol and bisoprolol are cardioselective, mainly blocking beta-1 receptors, which reduces the risk of bronchospasm and some CNS effects, making them less toxic overall in overdose compared with propranolol.

So, the most toxic among these is propranolol because its non-selective beta-blockade combined with high lipophilicity leads to greater systemic and central nervous system toxicity in overdose.