1. Botox Amir Hooshang Vahedi MD - Physiatrist

2. OnabotulinumtoxinA Botox | Botox® | Botox® Cosmetic Classification: Musculoskeletal Agents Skeletal Muscle Relaxants

3. Structures of botulinum toxins

4. normal fusion and release of acetylcholine from nerve terminals through interaction of vesicle and membrane-bound (SNARE) proteins. Parasympathetic nerves innervate the urinary bladder with (A)nerve terminal in an unactivated state displaying numerous vesicles containing the neurotransmitter acetylcholine (B) after nerve activation, assembly of the SNARE protein complex (C) release of acetylcholine and activation of post junctional muscarinic receptors

5. Diagram of parasympathetic nerve terminal demonstrating (A)binding of the toxin heavy chain to an as yet unidentified receptor and internalization of the toxin within the nerve terminal (B) translocation of the light chain into the cytosol (C) inhibition of neurotransmitter release by cleavage of specific SNARE proteins. A to G represent different botulinum toxin serotypes.

6. Mechanism of action of botulinum toxins on soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins. SNAP-25 is affected by botulinum toxin type A, preventing vesicular fusion and acetylcholine release

7.  Botox is an inhibitor of the release of acetylcholine and other transmitters at the neuromuscular junction of somatic nerves in striated muscle and of autonomic nerves in smooth muscle.  Two of the serotypes are available type A and type B.  Type A toxins are more potent and longer-acting than type B.  7.5—10 units of type A is roughly equivalent in degree of muscle paralysis to 320—480 units of type B.

8. Indications...Dosage  Achalasia† Achalasia  blepharospasmblepharospasm  cervical dystoniacervical dystonia  hyperhidrosis hyperhidrosis  neurogenic bladder†neurogenic bladder  sialorrhea†sialorrhea  spasticity†spasticity  strabismusstrabismus †non-FDA-approved indication

9. For the treatment of spasticity†:  for the chronic management of focal spasticity† in pediatric patients with cerebral palsy with concurrent equinus gait (tiptoeing): Children 2—18 years: total dose of 4 Units/kg IM (maximum dose 200 Units per treatment) was administered every 3 months.  for the treatment of spasticity† following a stroke: Adults: Botox was administered as 50 Units IM in each of wrist and four finger muscles (50 Units per muscle); optional injections were given in one or two thumb muscles (20 Units per muscle). (total dose 200—240 Units)

10.  For second-line treatment of neurogenic bladder†:  Adults: Commonly reported dose range is 200—300 Units injected into the detrusor muscle using 20—30 injections, sparing the trigone. In some studies, effects lasted up to 9 months.  Children: A dose of 12 Units/kg (maximum 300 Units) was injected into the detrusor muscle using 30—50 injections, sparing the trigone. improvements were noted up to 6 months after treatment.

11. Contraindications/Precautions  Infection Infection  albumin hypersensitivityalbumin hypersensitivity  amyotrophic lateral sclerosis (ALS)amyotrophic lateral sclerosis (ALS)  autonomic neuropathyautonomic neuropathy  botulismbotulism  breast-feedingbreast-feeding  cardiac diseasecardiac disease  cerebral palsycerebral palsy  childrenchildren  dysphagiadysphagia  elderly elderly  hyperthyroidism hyperthyroidism  inflammationinflammation  myasthenia gravis myasthenia gravis  myopathymyopathy  neuromuscular diseaseneuromuscular disease  ocular diseaseocular disease  pregnancypregnancy  thyroid diseasethyroid disease  visual disturbancevisual disturbance

12.  Patients with cervical dystonia should be informed of the possibility of experiencing dysphagia.  Rare consequences of severe dysphagia include aspiration, dyspnea, pneumonia, and the need to reestablish an airway.  patients with smaller neck muscle mass and patients who require bilateral injections into the sternocleidomastoid muscle have been reported to be at greater risk for dysphagia.  Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia.  Injections into the levator scapulae may be associated with an increased risk of upper respiratory infection and dysphagia.

13.  Botulinum toxin is classified in FDA pregnancy risk category C.  in patients with myopathy associated with neuromuscular disease amyotrophic lateral sclerosis (ALS), motor neuropathy (autonomic neuropathy) myasthenia gravis Lambert-Eaton syndrome  These patients may be at increased risk of clinically significant systemic effects including severe dysphagia and respiratory compromise from typical doses of onabotulinumtoxinA.

14.  Patients should be evaluated for potential causes of secondary hyperhidrosis (e.g., thyroid disease like hyperthyroidism) to avoid symptomatic treatment of hyperhidrosis without the diagnosis and/or treatment of the underlying disease.  The safe and effective use of onabotulinumtoxinA for hyperhidrosis in other body areas have not been established.

15.  dose selection for elderly patients (aged 65 and over) should be cautious, usually starting at the low end of the dosing range.  OnabotulinumtoxinA should be used cautiously in patients with cardiac disease. There have been rare reports of adverse reactions involving the cardiovascular system, including arrhythmia and myocardial infarction.

16. Interactions  AbobotulinumtoxinAAbobotulinumtoxinA  Aminoglycosides Aminoglycosides  ChloroquineChloroquine  HydroxychloroquineHydroxychloroquine  Neuromuscular blockers Neuromuscular blockers  RimabotulinumtoxinBRimabotulinumtoxinB

17.  The effects of the botulinum toxin can be potentiated by aminoglycosides, neuromuscular blockers, or other drugs that interfere with neuromuscular transmission.  The effect of administering another botulinum neurotoxin serotype (e.g., rimabotulinumtoxinB, abobotulinumtoxinA) at the same time or within several months of each other is unknown.  chloroquine antagonized the actions of onabotulinumtoxinA and rimabotulinumtoxinB.  Hydroxychloroquine may also interfere with the actions of botulinum toxin types A and B.