Why don't some people respond to local anesthesia or novocaine?

Local : Anesthesia has to come into contact with nerves to work. Any barrier to contact will impede function. Ph changes can impact effect. So can local anesthesia concentration and proximity to the stimulation.

Expiration: All people respond to local anesthetics, if properly administered and if the local anesthetic used has not expired. All drugs have an expiration date, after which they may not longer be effective. There are two main types of local anesthetics based on their chemical structure, amino amide (lidocaine) and amino ester (novocaine).

Genetics: There seem to be a very small percentage of people who are resistant or immune to local anesthetics. The mechanism is not clear at this time.

Several reasons: With regard to dental anesthesia, anatomical differences between patients may affect whether or not the local is effective. An acute infection/abscess produces a difference in ph which can make it more difficult to achieve profound anesthesia. Certain medical conditions also may make it more difficult for the local anesthetics to be metabolized, and more difficult for the patient.