Pharmacological antagonists may be physical, chemical and physiological depending on the mechanism. Surely drugs that precipitate local anesthetics or unfavourable millieu (such as unfavourable pH) affects ionization of the drug, e.g. lidocaine in acidic environment. 

If you would be so kind to upload certain papers backing up your claims for local anesthetic resistance, maybe a more precise answer could be given. It would surely bring benefit for the discussion.

Reagrds!

Dear Essam A. Al- Moraissi

Great question, I lean towards a failure of action rather a resistance.   

The main cause that comes to my mind is inflammation at the site, which,  has previously been related to the pH shift to acidic, however,   experimental proof for  the role of pH is lacking.   

Other possible causes of LA failure can include nerve supply from multiple nerves simultaneously,  areas with very thick bony plates and last but not the least patient anxiety., which causes an apparent failure rather than a real failure of the LA.   

Dear Mandana Donoghue ,

Thanks for your answer, but, I am talking here about those patients without inflammation and with a proper injection tech. and with talking of anatomical variation in mind. They have a history of failed anesthesia for all types of injections and teeth and since long time.

Some humans have a variance in their sodium channel that make them less perceptible for local anesthetic. The drug can not connect properly on the channel, and is therefore unable to block it.

I read once that up to 5%(?) of the populations are slow responder to local anesthetic. Delaying the time for full effect for a couple of minutes.

However, I have no paper readily avaliable to show you right now.

Here a paper on local anesthetic physiology that also touches the resistance of local anaesthetics (point mutations and fiber resistance). Maybe this is a basis from where more literature can be found.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541190/

Dear Ib Jammer,

Too much, I want to thank you for this paper

Here is an article that I wrote more than 10 years ago regarding local anesthetic resistance

Patients suffering from Ehlers - Danlos syndrome type III do not respond to local anaesthetic

Dear Andrea M Trescot,

Thanks very much for your helpful and guidance paper. You have concluded that Mepivacaine is the best local anesthetic for those patients who have had a history of resistant to local anesthesia .

Do you think, for those patients who have a resistant to lidocaine, could anesthetizing 

them using mepivacaine ?

It was the most common, but there have been many that were most numb to bupivicaine, so I prefer to skin test to be sure. But if I am in the middle of a case, and the patient does not seem to be getting numb to lidocaine, I reach for mepivicaine next.

Dear  Andrea M Trescot,

Thank you very much for your answer and your paper

Sure one may try Mepivacaine in such cases. However, the effect can not always be as expected due to the genetic polymorphism of the sodium channel receptor protein. 

One may also, time and resources permitting, try out what is described here.

Scand J Rheumatol. 1991;20(3):190-5.

The response to local anaesthetics (EMLA-cream) as a clinical test to diagnose

between hypermobility and Ehlers Danlos type III syndrome.

Arendt-Nielsen L(1), Kaalund S, Høgsaa B, Bjerring P, Grevy C.  Aalborg University, Denmark.

To make a differential diagnosis of Ehlers Danlos (EDS) Type III syndrome and

Hypermobile patients has been difficult. In genetic advising and prognosis of the

EDS patients there are need for new tools to separate them from hypermobile

patients. Topical analgesics (EMLA cream) was applied to seven EDS patients, ten

hypermobile patients, and to fifteen controls. The analgesic efficacy of

cutaneous analgesia was evaluated by sensory and pain thresholds to brief argon

laser stimuli, and the depth of the cutaneous analgesia was measured by sensory

and pain threshold depth to controlled needle insertions. Controls and

hypermobiles did not differ in their response to cutaneous analgesia. The

thresholds to cutaneous laser stimulation and the depth of analgesia increased

significantly less in the Ehlers Danlos patients compared to the other two

groups. In clinical practice a needle insertion test can easily be applied to

investigate if patients are responders or non-responders to local analgesics.

Dear Essam A. Al- Moraissi

There seems to be some cross tolerance between local anesthetics and opioids and in the patients with chronic pain who overuse or abuse opioids,there is some resistance to local anesthetics;possibly through Na channels in the spinal cord and peripheral receptors of pain; you might find these articles useful:

http://www.ncbi.nlm.nih.gov/pubmed/17604467

http://www.ncbi.nlm.nih.gov/pubmed/17646519

http://www.ncbi.nlm.nih.gov/pubmed/22973332

Warm regards

Ali

Dear Ali Dabbagh ,

Thank you for your answer and your hepful links

Most welcome

 There are  reports that some persons exposed to scorpion sting developed resistance

resistance to local anesthetics.