|Year : 2015 | Volume
| Issue : 4 | Page : 265-268
Phentolamine mesylate: It's role as a reversal agent for unwarranted prolonged local analgesia
Harpreet Singh Grover1, Anil Gupta2, Neha Saksena1, Neha Saini1
1 Department of Periodontology, Faculty of Dental Sciences, SGT University, Budhera, Gurgaon, Haryana, India
2 Department of Pedodontics and Preventive Dentistry, Faculty of Dental Sciences, SGT University, Budhera, Gurgaon, Haryana, India
|Date of Web Publication||18-Sep-2015|
Dr. Neha Saksena
Department of Periodontology, Faculty of Dental Sciences, SGT University, Budhera, Gurgaon, Haryana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Administration of local anesthesia is an integral procedure prior to dental treatments to minimize the associated pain. It is learned that its effect stays more than the time required for the dental procedure to be completed. This prolonged soft tissue anesthesia (STA) can be detrimental, inconvenient, and unnecessary. Phentolamine mesylate, a Food and Drug Administration-approved drug essentially serves the purpose of faster recovery from numbness at the site of local anesthesia. This article reviews the development of the drug phentolamine mesylate and its indication as a local anesthetic reversal agent. A literature search for phentolamine mesylate as a STA reversal agent was conducted in PubMed using the terms "dental local anesthesia reversal, phentolamine mesylate" up to March 2014. The search was limited to articles published in English. The search revealed 13 PubMed indexed articles stating the development and application of phentolamine mesylate. Phentolamine mesylate is an important step in the progress of developing patient care as well as an aid to the dental clinician.
Keywords: Dental local anesthesia, local anesthesia reversal, phentolamine mesylate
|How to cite this article:|
Grover HS, Gupta A, Saksena N, Saini N. Phentolamine mesylate: It's role as a reversal agent for unwarranted prolonged local analgesia. J Indian Soc Pedod Prev Dent 2015;33:265-8
|How to cite this URL:|
Grover HS, Gupta A, Saksena N, Saini N. Phentolamine mesylate: It's role as a reversal agent for unwarranted prolonged local analgesia. J Indian Soc Pedod Prev Dent [serial online] 2015 [cited 2022 Aug 10];33:265-8. Available from: http://www.jisppd.com/text.asp?2015/33/4/265/165646
| Introduction|| |
Administration of local anesthetic drugs is responsible for prevention of pain that arise during dental procedures. This elimination of pain has been effective in performing the necessary dental procedures successfully. The advent of local anesthesia has benefitted the patients, the health care providers and the horizon of dental therapeutics have grown by leaps and bounds. With the indispensable use of local anesthetic agents, it is learned that its effect stays more than the time required for the dental procedure to be completed. This prolonged soft tissue anesthesia (STA) can be detrimental, inconvenient and unnecessary. Local anesthesia reversal is the action of choice in cases where prolonged anesthesia after a dental procedure is not needed. Phentolamine mesylate, a Food and Drug Administration (FDA) approved drug essentially serves the purpose of faster recovery from numbness at the site of local anesthesia. This article reviews the development of the drug phentolamine mesylate and its indication as a local anesthetic reversal agent.
| Methods|| |
We conducted a search in the PubMed using the terms "dental local anesthesia reversal, phentolamine mesylate" up to March 2014. The search was limited to articles published in English.
| Findings|| |
The search revealed 13 articles which are listed in [Table 1].
|Table 1: List of PubMed indexed studies published on phentolamine mesylate|
Click here to view
| Local Anesthetic Drugs|| |
Local anesthetic drugs are the safest and most effective drugs for the management of pain in dental procedures. A local anesthetic agent prevents the generation and conduction of a nerve's impulse. Local anesthetic agents can be classified on the basis of its chemical structure (esters or amides) and on the duration of action (short, intermediate, or long-acting)  [Table 2].
| Duration of Anesthesia|| |
A local anesthetic should be compatible with the tissues (not irritating) with temporary and completely reversible action. It should have a rapid onset of action with duration of action sufficient to complete the dental procedure comfortably. The length of time for which pain control is necessary is the first consideration in the selection of an appropriate local anesthetic.  The approximate duration of action for several common anesthetics is as follows  [Table 3].
| Residual Soft Tissue Anesthesia|| |
An average dental appointment length is of 44 min. Thus agent with an intermediate duration of action is most often used.  Anesthesia of the supporting tissues - both bone and soft tissue (lip, tongue, chin, nose, and cheek) - usually persists for several hours after pulpal anesthesia has been lost.  The residual STA may result in injury, either self-inflicted (e.g., biting) or secondary to thermal or chemical burns. It adds to the inconvenience or annoyance of the patient and the doctor. Prolonged STA interferes with the patients' normal daily activities in three aspects: Perceptual (perception of altered physical appearance), sensory (lack of sensation), and functional (diminished ability to speak, smile, drink, and control drooling). This elicits moderate to extreme emotions of dislike among the adult and adolescent patients.  A prospective study by College et al. on 320 children revealed 18% of children younger than 4 years, 16% of children between 4 and 7 years, and 13% of children between 8 and 11 years displayed postdental treatment soft tissue trauma after receiving mandibular nerve block injection.  Unintentional biting and injury of the lips, tongue, and cheeks has been reported in pediatric patients due to prolonged STA.  A misdiagnosed case of lip biting injuries as bacterial infections may result in unnecessary administration of antibiotics. 
| Reversal of Residual Soft Tissue Anesthesia|| |
Transcutaneous electrical nerve stimulation
To reduce the prolonged STA, transcutaneous electrical nerve stimulation (TENS) - a procedure used in the field of medicine to provide relief from chronic pain and edema with the delivery of a low-frequency electrical stimulus to an area, was employed.  TENS increases tissue perfusion produced by capillary and arteriolar dilation while stimulating the contraction of skeletal muscles to the area applied. Thus, the local anesthetic drug would undergo a more rapid redistribution into the capillaries and venules in that area thereby reducing the duration of residual STA.  The application of intraoral TENS was not very well accepted because of its cumbersome apparatus and difficulty in placing and stabilizing the electrodes intraorally resulting in achievement of limited success. 
| Phentolamine Mesylate|| |
The search for means to minimize the prolonged postoperative anesthesia and reduce the inadvertent injuries arising from it was led to the introduction of phentolamine mesylate. Phentolamine is a nonselective α-adrenergic receptor antagonist that competitively inhibits the ability of sympathomimetic amines like norepinephrine and epinephrine to stimulate vascular contraction. The smooth muscles of vascular beds, including those beneath the oral mucosa, contain α-receptors (predominantly α1), and the ultimate effect of α-receptor blockade is vasodilation.  The administration of phentolamine mesylate causes vasodilation at the site where the anesthetic agent is injected which leads to enhanced absorption of local anesthetic and thus shortens the duration of anesthesia.  Originally, phentolamine has been in use for the diagnosis and treatment of patients with pheochromocytoma and for the treatment and the prevention of dermal necrosis following intravenous administration or extravasation of norepinephrine in the USA since 1952.  Other indications of its use is given in [Table 4]. ,
Phentolamine mesylate, marketed under the proprietary name OraVerse, was granted FDA approval on May 12, 2008 with an indication for the reversal of STA (lip and tongue numbness) and the associated functional deficits resulting from a local dental anesthetic containing a vasoconstrictor.  The dose of oral submucosal injections of phentolamine approved by the FDA is 0.2-0.8 mg. No significant cardiovascular changes, most notably hypotension or tachycardia has been associated with the approved dose of phentolamine. The use of phentolamine may be indicated in the management of pediatric, geriatric patients along with the medically compromised and differently-abled patients. It can be administered when performing conservative dental procedures and nonsurgical periodontics. The FDA has not yet approved the use of phentolamine reversal for children below 6 years of age, and safety data only extend down to children 4 years of age and 15 kg in weight.  It can be used in patients with special needs that are prone to self-inflected injury while tissues remain numb, fragile diabetic or elderly patient for whom adequate nutritional intake at fixed intervals is required and patients who must return to work and communicate effectively. A study sought to identify and quantify complications with the local anesthetic administration, and its reversal concluded that safe administration of dental care is achievable with or without phentolamine mesylate.  In asymptomatic patients undergoing endodontic treatment, phentolamine is recommended to be administered in patients who wish to speedily return to normal soft tissue sensation as pulpal anesthesia also reverses rapidly. ,
| Conclusion|| |
Numbness after the completion of the dental procedure is often unnecessary. Phentolamine mesylate helps in the reversal of this unwanted prolonged STA. It is responsible for rapid recovery from local anesthesia and thus helps the patient restores its routine abilities to eat, drink, and function. Phentolamine mesylate is an important step in the progress of developing patient care by suggesting significant benefits and an aid to the dental clinician to shorten the posttreatment duration and accelerate a safe return to normal oral soft tissue function.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Boynes SG, Riley AE, Milbee S, Bastin MR, Price ME, Ladson A. Evaluating complications of local anesthesia administration and reversal with phentolamine mesylate in a portable pediatric dental clinic. Gen Dent 2013;61:70-6.
Elmore S, Nusstein J, Drum M, Reader A, Beck M, Fowler S. Reversal of pulpal and soft tissue anesthesia by using phentolamine: A prospective randomized, single-blind study. J Endod 2013;39:429-34.
Becker DE, Reed KL. Local anesthetics: Review of pharmacological considerations. Anesth Prog 2012;59:90-101.
Fowler S, Nusstein J, Drum M, Reader A, Beck M. Reversal of soft-tissue anesthesia in asymptomatic endodontic patients: A preliminary, prospective, randomized, single-blind study. J Endod 2011;37:1353-8.
Yagiela JA. What′s new with phentolamine mesylate: A reversal agent for local anaesthesia? SAAD Dig 2011;27:3-7.
Hersh EV, Lindemeyer RG. Phentolamine mesylate for accelerating recovery from lip and tongue anesthesia. Dent Clin North Am 2010;54:631-42.
Tavares M, Goodson JM, Studen-Pavlovich D, Yagiela JA, Navalta LA, Rogy S, et al.
Reversal of soft-tissue local anesthesia with phentolamine mesylate in pediatric patients. J Am Dent Assoc 2008;139:1095-104.
Laviola M, McGavin SK, Freer GA, Plancich G, Woodbury SC, Marinkovich S, et al.
Randomized study of phentolamine mesylate for reversal of local anesthesia. J Dent Res 2008;87:635-9.
Moore PA, Hersh EV, Papas AS, Goodson JM, Yagiela JA, Rutherford B, et al.
Pharmacokinetics of lidocaine with epinephrine following local anesthesia reversal with phentolamine mesylate. Anesth Prog 2008;55:40-8.
Chi D, Kanellis M, Himadi E, Asselin ME. Lip biting in a pediatric dental patient after dental local anesthesia: A case report. J Pediatr Nurs 2008;23:490-3.
Malamed SF. Local anesthetics: Dentistry′s most important drugs, clinical update 2006. J Calif Dent Assoc 2006;34:971-6.
Malamed SF. Handbook of Local Anesthesia. 5 th
ed. St. Louis, Mo: Mosby; 2004.
American Dental Association. 2002 Survey of Dental Practice - Characteristics of Dentists in Private Practice and their Patients. Chicago, IL: American Dental Association; 2004.
Rafique S, Fiske J, Banerjee A. Clinical trial of an air-abrasion/chemomechanical operative procedure for the restorative treatment of dental patients. Caries Res 2003;37:360-4.
College C, Feigal R, Wandera A, Strange M. Bilateral versus unilateral mandibular block anesthesia in a pediatric population. Pediatr Dent 2000;22:453-7.
Bertoti DB. Electrical stimulation: A reflection on current clinical practices. Assist Technol 2000;12:21-32.
Munshi AK, Hegde AM, Girdhar D. Clinical evaluation of electronic dental anesthesia for various procedures in pediatric dentistry. J Clin Pediatr Dent 2000;24:199-204.
Meechan JG, Gowans AJ, Welbury RR. The use of patient-controlled transcutaneous electronic nerve stimulation (TENS) to decrease the discomfort of regional anaesthesia in dentistry: A randomised controlled clinical trial. J Dent 1998;26:417-20.
Zentgraf M, Ludwig G, Ziegler M. How safe is the treatment of impotence with intracavernous autoinjection? Eur Urol 1989;16:165-71.
Loggie JM. Hypertension in children and adolescents. II. Drug therapy. J Pediatr 1969;74:640-54.
[Table 1], [Table 2], [Table 3], [Table 4]
|This article has been cited by|
||Novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury
| ||Zarin Zainul, Bo Ma, Mert Koka, Jenny L. Wilkerson, Yuma T. Ortiz, Laura Kerosuo, Vijayendran Chandran |
| ||Scientific Reports. 2022; 12(1) |
|[Pubmed] | [DOI]|
||Efficacy of phentolamine mesylate in reducing the duration of various local anesthetics
| ||Alejandro Gago-García, Cayetana Barrilero-Martin, Miguel Ángel Alobera-Gracia, Mariano del Canto-Pingarrón, Jesús Seco-Calvo |
| ||Journal of Dental Anesthesia and Pain Medicine. 2021; 21(1): 49 |
|[Pubmed] | [DOI]|
||Local anesthesia reversal— A review
| ||Avineet Kaur, Reshma Dodwad, Raghu K N, Mithunj Kaslekar, Vikram Shetty, Alwin Antony, Ummey Salma |
| ||International Journal of Oral Health Dentistry. 2021; 7(2): 89 |
|[Pubmed] | [DOI]|
||Use of Phentolamine Mesylate in Implant Surgery: Analysis of Adverse Effects and Haemodynamic Changes
| ||Clara Vintanel-Moreno, José María Martínez-González, Natalia Martínez-Rodríguez, Cristina Meniz-García, Isabel Leco-Berrocal |
| ||Journal of Clinical Medicine. 2021; 10(17): 3875 |
|[Pubmed] | [DOI]|
||Local Anesthesia in Pediatric Dentistry: A Literature Review on Current Alternative Techniques and Approaches
| ||Sivakumar Nuvvula, Kanamarlapudi V Saikiran, Sainath R Elicherla, Varada Sahithi, Mahesh Nunna, Ramasubba R Challa |
| ||Journal of South Asian Association of Pediatric Dentistry. 2021; 4(2): 148 |
|[Pubmed] | [DOI]|
||Effect of phentolamine mesylate on regression of lidocaine–epinephrine epidural anaesthesia in sheep
| ||Hadi Imani Rastabi, Javad Jamshidian, Ali Baniadam, Fereshteh Alipour |
| ||Veterinary Anaesthesia and Analgesia. 2020; 47(2): 267 |
|[Pubmed] | [DOI]|