Final answer:
The second barrier a drug encounters on its way to a target organ is plasma protein binding. High affinity to plasma proteins can restrict the drug's availability to tissues. Subsequent barriers, like the blood-brain barrier (BBB), can further challenge the drug's delivery to targeted organs like the CNS.
Step-by-step explanation:
The second barrier a drug must pass to reach its target organ after entering the bloodstream is the binding to plasma proteins, which can prevent the drug from penetrating into the tissues and the target organ. This is crucial because only the unbound, or "free", drug can exert pharmacological effects within the tissues. Should a drug possess a high affinity for plasma proteins, its effective tissue concentration could be low, thereby hindering its therapeutic efficacy. Subsequent barriers may include the blood-brain barrier (BBB) for drugs targeting the central nervous system, which is specifically designed to restrict the passage of most substances into the CNS, thus posing a challenge for pharmaceutical companies in drug delivery to this organ.