The mechanisms of action and use of botulinum neurotoxin type A in aesthetics: Key Clinical Postulates II

Abstract

Background The literature on botulinum neurotoxin type A (BoNT‐A) is extensive, often contradictory, and confounded by a competitive market of products and research attempting to distinguish brand individuality. Methods A comprehensive review of literature on the principles of BoNT‐A in aesthetics as well as clinical examples. Results In 2017, the Eight Key Clinical Postulates were formulated as a guide for the aesthetic practitioner in understanding BoNT‐A pharmacodynamics and to compare different toxins. These are now updated to include (a) All type A toxins act identically; (b) The mathematical relationship between toxin and receptor is the basis of efficacy, and clinical efficacy is influenced by molecular potency and patient attributes including muscle mass, gender, age, and ethnicity; (c) Efficacy, onset, and duration are functions of “molecular potency” defined as the number of active 150 kDa molecules available for binding; (d) “Molecular potency” is difficult to objectively quantify for commercially available toxins; (e) Up to a point, increased molecular potency decreases time to onset and increases duration of effect, and the “Molecular Potency Quotient” is a construct for comparing molecular potency commercial cost; (f) The area of effect of a toxin injection is dependent upon molecular potency, diffusion (passive), and spread (active); (g) Differing reconstitution volumes; and (h) Increased number of injection sites can affect spread, onset, and duration of effect. Conclusions The principles of BoNT‐A use in aesthetics are complex yet understandable as outlined in the framework of the updated Eight Key Clinical Postulates and serves as a useful tool for providing the most effective treatment and interpreting research on present and future toxin formulations.

Botulinum Toxin Type A for Glabellar Frown Lines: What Impact of Higher Doses on Outcomes?

“…Even though somewhat confounded by different study designs, current data point to a potential BoNT-A ceiling dose for glabellar lines. However, it is likely that the ceiling dose is influenced by factors such as sex, muscle mass and age, since these are known to impact clinical efficacy [ 11 , 22 , 37 , 38 , 39 , 40 ].…”

Botulinum toxin–induced blepharoptosis: Anatomy, etiology, prevention, and therapeutic options

“…5 The lower the spread of toxin, the higher the accuracy in treating intended targets and the lower the chance of eliciting side effects such as ptosis. 5 3). 8,47 Medical-dependent risk factors include prior facial surgical procedures, neurological conditions such as multiple sclerosis or myasthenia gravis, and prior history of Bell's palsy or other induced eyelid ptosis.…”

“…Unfortunately, there are no means to ensure that BoNT‐A will bind only to the muscles that an administrator intends to target. The degree to which injected toxin may overflow from a targeted region to an unintended targeted region is largely determined by the active physical distribution of toxin suspension or spread 5 . This is dependent on factors such as site of injection (muscle mass), reconstitution volume, injection volume, depth, speed of injection, and needle gauge, which comprise injection technique 5 .…”

“…The degree to which injected toxin may overflow from a targeted region to an unintended targeted region is largely determined by the active physical distribution of toxin suspension or spread 5 . This is dependent on factors such as site of injection (muscle mass), reconstitution volume, injection volume, depth, speed of injection, and needle gauge, which comprise injection technique 5 . The lower the spread of toxin, the higher the accuracy in treating intended targets and the lower the chance of eliciting side effects such as ptosis 5 …”

“…While Dysport, Xeomin, and Jeuveau are approved for the treatment of glabellar lines, Botox is approved for the additional management of lateral canthal lines (LCL) and forehead frontalis lines (Figure 1). 5 Off-label BoNT-A cosmetic indications include treatment of bunny lines, perioral lines, mental crease and dimpled chin, mouth frown, platysmal bands, and horizontal neck lines. 6 Possible side effects of BoNT-A at the injection sites include bleeding, bruising, swelling, erythema, and pain which can be minimized by using thinner needles and diluting BoNT-A with saline.…”