Botox Jersey City

Botulinum neurotoxin A

Ribbon diagram of tertiary structure of BotA (P0DPI1). PDB entry 3BTA.
Clinical data
Trade names	Botox, Myobloc, Jeuveau, Dysport, Letybo, and others
Other names	BoNT, botox
Biosimilars	abobotulinumtoxinA, daxibotulinumtoxinA, daxibotulinumtoxinA-lanm, evabotulinumtoxinA, incobotulinumtoxinA, letibotulinumtoxinA, letibotulinumtoxinA-wlbg,[1] onabotulinumtoxinA, prabotulinumtoxinA, relabotulinumtoxinA, rimabotulinumtoxinB
AHFS/Drugs.com	abobotulinumtoxinA Monograph daxibotulinumtoxinA Monograph incobotulinumtoxinA Monograph onabotulinumtoxinA Monograph prabotulinumtoxinA Monograph rimabotulinumtoxinB Monograph
MedlinePlus	a619021
License data
Pregnancy category
Routes of administration	Intramuscular, subcutaneous, intradermal
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
UNII
KEGG
Chemical and physical data
Formula	C6760H10447N1743O2010S32
Molar mass	149323.05 g·mol−1
NY (what is this?)		(verify)

Botulinum toxin, or botulinum neurotoxin (commonly called botox), is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species.^[23] It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction, thus causing flaccid paralysis.^[24] The toxin causes the disease botulism.^[25] The toxin is also used commercially for medical and cosmetic purposes.^[26][27] Botulinum toxin is an acetylcholine release inhibitor and a neuromuscular blocking agent.^[1][22]

The seven main types of botulinum toxin are named types A to G (A, B, C1, C2, D, E, F and G).^[26][28] New types are occasionally found.^[29][30][31] Types A and B are capable of causing disease in humans, and are also used commercially and medically.^[32][33][34] Types C–G are less common; types E and F can cause disease in humans, while the other types cause disease in other animals.^[35]

In 2025 the structure of the complete 14 subunit botulinum neurotoxin complex (L-PTC) was solved.^[36]

Botulinum toxins are among the most potent toxins recorded in scientific literature.^[37][38] Intoxication can occur naturally as a result of either wound or intestinal infection or by ingesting formed toxin in food. The estimated human median lethal dose of type A toxin is 1.3–2.1 ng/kg intravenously or intramuscularly, 10–13 ng/kg when inhaled, or 1 μg/kg when taken by mouth.^[39]

Botulinum toxin is used to treat a number of therapeutic indications, many of which are not part of the approved drug label.^[27]

Botulinum toxin is used to treat a number of disorders characterized by overactive muscle movement, including cerebral palsy,^[40][41] post-stroke spasticity,^[42] post-spinal cord injury spasticity,^[43] spasms of the head and neck,^[44] eyelid,^[25] vagina,^[45] limbs, jaw, and vocal cords.^[46] Similarly, botulinum toxin is used to relax the clenching of muscles, including those of the esophagus,^[47] jaw,^[48] lower urinary tract and bladder,^[49] or clenching of the anus which can exacerbate anal fissure.^[50] Botulinum toxin appears to be effective for refractory overactive bladder.^[51]

Strabismus, otherwise known as improper eye alignment, is caused by imbalances in the actions of muscles that rotate the eyes. This condition can sometimes be relieved by weakening a muscle that pulls too strongly, or pulls against one that has been weakened by disease or trauma. Muscles weakened by toxin injection recover from paralysis after several months, so injection might seem to need to be repeated, but muscles adapt to the lengths at which they are chronically held,^[52] so that if a paralyzed muscle is stretched by its antagonist, it grows longer, while the antagonist shortens, yielding a permanent effect.^[53]

In January 2014, botulinum toxin was approved by UK's Medicines and Healthcare products Regulatory Agency for treatment of restricted ankle motion due to lower-limb spasticity associated with stroke in adults.^[54][55]

In July 2016, the US Food and Drug Administration (FDA) approved abobotulinumtoxinA (Dysport) for injection for the treatment of lower-limb spasticity in pediatric patients two years of age and older.^[56][57] AbobotulinumtoxinA is the first and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity.^[58] In the US, the FDA approves the text of the labels of prescription medicines and for which medical conditions the drug manufacturer may sell the drug. However, prescribers may freely prescribe them for any condition they wish, also known as off-label use.^[59] Botulinum toxins have been used off-label for several pediatric conditions, including infantile esotropia.^[60]

Botulinum toxin (BTO) injections are a modern clinical trend to treat hyperhidrosis, of which palmar hyperhidrosis is a frequent symptom.^[61] For example, AbobotulinumtoxinA has been approved for the treatment of axillary hyperhidrosis, which cannot be managed by topical agents.^{[46][62][63][64]}

In 2010, the FDA approved intramuscular botulinum toxin injections for prophylactic treatment of chronic migraine headache.^[65] However, the use of botulinum toxin injections for episodic migraine has not been approved by the FDA.^[66][67]

In cosmetic applications, botulinum toxin is considered relatively safe and effective^[68] for reduction of facial wrinkles, especially in the uppermost third of the face.^[69] Commercial forms are marketed under the brand names Botox Cosmetic/Vistabel from Allergan, Dysport/Azzalure from Galderma and Ipsen, Xeomin/Bocouture from Merz, Jeuveau/Nuceiva from Evolus, manufactured by Daewoong in South Korea.^[70] The effects of botulinum toxin injections for glabellar lines ("11's lines" between the eyes) typically last two to four months and in some cases, product-dependent, with some patients experiencing a longer duration of effect of up to six months or longer.^[69] Injection of botulinum toxin into the muscles under facial wrinkles causes relaxation of those muscles, resulting in the smoothing of the overlying skin.^[69] Smoothing of wrinkles is usually visible three to five days after injection, with maximum effect typically a week following injection.^[69] Muscles can be treated repeatedly to maintain the smoothed appearance.^[69]

DaxibotulinumtoxinA (Daxxify) was approved for medical use in the United States in September 2022.^[22][71] It is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines (wrinkles between the eyebrows).^[22][71][72] DaxibotulinumtoxinA is an acetylcholine release inhibitor and neuromuscular blocking agent.^[22] The FDA approved daxibotulinumtoxinA based on evidence from two clinical trials (Studies GL-1 and GL-2), of 609 adults with moderate to severe glabellar lines.^[71] The trials were conducted at 30 sites in the United States and Canada.^[71] Both trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines.^[71] Participants received a single intramuscular injection of daxibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows.^[71] The most common side effects of daxibotulinumtoxinA are headache, drooping eyelids, and weakness of facial muscles.^[71]

LetibotulinumtoxinA (Letybo) was approved for medical use in the United States in February 2024.^[1][73][74] It is indicated to temporarily improve the appearance of moderate-to-severe glabellar lines.^[1][75] The FDA approved letibotulinumtoxinA based on evidence from three clinical trials (BLESS I [NCT02677298], BLESS II [NCT02677805], and BLESS III [NCT03985982]) of 1,271 participants with moderate to severe wrinkles between the eyebrows for efficacy and safety assessment.^[73] These trials were conducted at 31 sites in the United States and the European Union.^[73] All three trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines (wrinkles between the eyebrows).^[73] Participants received a single intramuscular injection of letibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows.^[73] The most common side effects of letibotulinumtoxinA are headache, drooping of eyelid and brow, and twitching of eyelid.^[73]

Botulinum toxin is also used to treat disorders of hyperactive nerves including excessive sweating,^[62] neuropathic pain,^[76] and some allergy symptoms.^[46] In addition to these uses, botulinum toxin is being evaluated for use in treating chronic pain.^[77] Studies show that botulinum toxin may be injected into arthritic shoulder joints to reduce chronic pain and improve range of motion.^[78] The use of botulinum toxin A in children with cerebral palsy is safe in the upper and lower limb muscles.^[40][41]

While botulinum toxin is generally considered safe in a clinical setting, serious side effects from its use can occur. Most commonly, botulinum toxin can be injected into the wrong muscle group or with time spread from the injection site, causing temporary paralysis of unintended muscles.^[79] In at least three cases temporary diplopia was reported due to subcutenious injections for cosmetic purposes.^[80]

Side effects from cosmetic use generally result from unintended paralysis of facial muscles. These include partial facial paralysis, muscle weakness, and trouble swallowing. Side effects are not limited to direct paralysis, however, and can also include headaches, flu-like symptoms, and allergic reactions.^[81] Just as cosmetic treatments only last a number of months, paralysis side effects can have the same durations.^[82] At least in some cases, these effects are reported to dissipate in the weeks after treatment.^[83] Bruising at the site of injection is not a side effect of the toxin, but rather of the mode of administration, and is reported as preventable if the clinician applies pressure to the injection site; when it occurs, it is reported in specific cases to last 7–11 days.^[84] When injecting the masseter muscle of the jaw, loss of muscle function can result in a loss or reduction of power to chew solid foods.^[81] With continued high doses, the muscles can atrophy or lose strength; research has shown that those muscles rebuild after a break from Botox.^[85]

Side effects from therapeutic use can be much more varied depending on the location of injection and the dose of toxin injected. In general, side effects from therapeutic use can be more serious than those that arise during cosmetic use. These can arise from paralysis of critical muscle groups and can include arrhythmia, heart attack, and in some cases, seizures, respiratory arrest, and death.^[81] Additionally, side effects common in cosmetic use are also common in therapeutic use, including trouble swallowing, muscle weakness, allergic reactions, and flu-like syndromes.^[81]

In response to the occurrence of these side effects, in 2008, the US Food and Drug Administration (FDA) notified the public of the potential dangers of the botulinum toxin as a therapeutic. Namely, the toxin can spread to areas distant from the site of injection and paralyze unintended muscle groups, especially when used for treating muscle spasticity in children treated for cerebral palsy.^[86] In 2009, the FDA announced that boxed warnings would be added to available botulinum toxin products, warning of their ability to spread from the injection site.^{[87][88][89][90]} However, the clinical use of botulinum toxin A in children with cerebral palsy has been proven to be safe with minimal side effects.^[40][41] Additionally, the FDA announced name changes to several botulinum toxin products, to emphasize that the products are not interchangeable and require different doses for proper use. Botox and Botox Cosmetic were given the generic name of onabotulinumtoxinA, Myobloc as rimabotulinumtoxinB, and Dysport retained its generic name of abobotulinumtoxinA.^[91][87] In conjunction with this, the FDA issued a communication to health care professionals reiterating the new drug names and the approved uses for each.^[92] A similar warning was issued by Health Canada in 2009, warning that botulinum toxin products can spread to other parts of the body.^[93]

Botulinum toxin produced by Clostridium botulinum (an anaerobic, gram-positive bacterium) is the cause of botulism.^[25][94][95] Humans most commonly ingest the toxin from eating improperly canned foods in which C. botulinum has grown. However, the toxin can also be introduced through an infected wound. In infants, the bacteria can sometimes grow in the intestines and produce botulinum toxin within the intestine and can cause a condition known as floppy baby syndrome.^[96] In all cases, the toxin can then spread, blocking nerves and muscle function. In severe cases, the toxin can block nerves controlling the respiratory system or heart, resulting in death.^[23]

Botulism can be difficult to diagnose, as it may appear similar to diseases such as Guillain–Barré syndrome, myasthenia gravis, and stroke. Other tests, such as brain scan and spinal fluid examination, may help to rule out other causes. If the symptoms of botulism are diagnosed early, various treatments can be administered. In an effort to remove contaminated food that remains in the gut, enemas or induced vomiting may be used.^[97] For wound infections, infected material may be removed surgically.^[97] Botulinum antitoxin is available and may be used to prevent the worsening of symptoms, though it will not reverse existing nerve damage. In severe cases, mechanical respiration may be used to support people with respiratory failure.^[97] The nerve damage heals over time, generally over weeks to months.^[98] With proper treatment, the case fatality rate for botulinum poisoning can be greatly reduced.^[97]

Two preparations of botulinum antitoxins are available for treatment of botulism. Trivalent (serotypes A, B, E) botulinum antitoxin is derived from equine sources using whole antibodies. The second antitoxin is heptavalent botulinum antitoxin (serotypes A, B, C, D, E, F, G), which is derived from equine antibodies that have been altered to make them less immunogenic. This antitoxin is effective against all main strains of botulism.^[99][31]

Botulinum toxin exerts its effect by cleaving key proteins required for nerve activation. First, the toxin binds specifically to presynaptic surface of neurons that use the neurotransmitter acetylcholine. Once bound to the nerve terminal, the neuron takes up the toxin into a vesicle by receptor-mediated endocytosis.^[101] As the vesicle moves farther into the cell, it acidifies, activating a portion of the toxin that triggers it to push across the vesicle membrane and into the cell cytoplasm.^[23] Botulinum neurotoxins recognize distinct classes of receptors simultaneously (gangliosides, synaptotagmin and SV2).^[102] Once inside the cytoplasm, the toxin cleaves SNARE proteins (proteins that mediate vesicle fusion, with their target membrane bound compartments) meaning that the acetylcholine vesicles cannot bind to the intracellular cell membrane,^[101] preventing the cell from releasing vesicles of neurotransmitter. This stops nerve signaling, leading to flaccid paralysis.^[23][102]

The toxin itself is released from the bacterium as a single chain, then becomes activated when cleaved by its own proteases.^[46] The active form consists of a two-chain protein composed of a 100-kDa heavy chain polypeptide joined via disulfide bond to a 50-kDa light chain polypeptide.^[103] The heavy chain contains domains with several functions; it has the domain responsible for binding specifically to presynaptic nerve terminals, as well as the domain responsible for mediating translocation of the light chain into the cell cytoplasm as the vacuole acidifies.^[23][103] The light chain is a M27-family zinc metalloprotease and is the active part of the toxin. It is translocated into the host cell cytoplasm where it cleaves the host protein SNAP-25, a member of the SNARE protein family, which is responsible for fusion. The cleaved SNAP-25 cannot mediate fusion of vesicles with the host cell membrane, thus preventing the release of the neurotransmitter acetylcholine from axon endings.^[23] This blockage is slowly reversed as the toxin loses activity and the SNARE proteins are slowly regenerated by the affected cell.^[23]

The seven toxin serotypes (A–G) are traditionally separated by their antigenicity. They have different tertiary structures and sequence differences.^[103][104] While the different toxin types all target members of the SNARE family, different toxin types target different SNARE family members.^[100] The A, B, and E serotypes cause human botulism, with the activities of types A and B enduring longest in vivo (from several weeks to months).^[103] Existing toxin types can recombine to create "hybrid" (mosaic, chimeric) types. Examples include BoNT/CD, BoNT/DC, and BoNT/FA, with the first letter indicating the light chain type and the latter indicating the heavy chain type.^[105] BoNT/FA received considerable attention under the name "BoNT/H", as it was mistakenly thought it could not be neutralized by any existing antitoxin.^[31]

Botulinum toxins are closely related to tetanus toxin. The two are collectively known as Clostridium neurotoxins and the light chain is classified by MEROPS as family M27.^[106] Clostridium neurotoxins belong in the wider family of AB toxins, which also includes Anthrax toxin and Diphtheria toxin. Nonclassical types include BoNT/X (P0DPK1), which is toxic in mice and possibly in humans;^[29][30] a BoNT/J (A0A242DI27) found in cow Enterococcus;^[107] and a BoNT/Wo (A0A069CUU9) found in the rice-colonizing Weissella oryzae.^[105]

One of the earliest recorded outbreaks of foodborne botulism occurred in 1793 in the village of Wildbad in what is now Baden-Württemberg, Germany. Thirteen people became sick and six died after eating pork stomach filled with blood sausage, a local delicacy. Additional cases of fatal food poisoning in Württemberg led the authorities to issue a public warning against consuming smoked blood sausages in 1802 and to collect case reports of "sausage poisoning".^[108] Between 1817 and 1822, the German physician Justinus Kerner published the first complete description of the symptoms of botulism, based on extensive clinical observations and animal experiments. He concluded that the toxin develops in bad sausages under anaerobic conditions, is a biological substance, acts on the nervous system, and is lethal even in small amounts.^[108] Kerner hypothesized that this "sausage toxin" could be used to treat a variety of diseases caused by an overactive nervous system, making him the first to suggest that it could be used therapeutically.^[109] In 1870, the German physician Müller coined the term botulism to describe the disease caused by sausage poisoning, from the Latin word botulus, meaning 'sausage'.^[109]

In 1895, Émile van Ermengem, a Belgian microbiologist, discovered what is now known as Clostridium botulinum and confirmed that a toxin produced by the bacteria causes botulism.^[110] On 14 December 1895, there was a large outbreak of botulism in the Belgian village of Ellezelles that occurred at a funeral where people ate pickled and smoked ham; three of them died. By examining the contaminated ham and performing autopsies on the people who died after eating it, van Ermengem isolated an anaerobic microorganism that he called Bacillus botulinus.^[108] He also performed experiments on animals with ham extracts, isolated bacterial cultures, and toxins extracts from the bacteria. From these he concluded that the bacteria themselves do not cause foodborne botulism, but rather produce a toxin that causes the disease when ingested.^[111] As a result of Kerner's and van Ermengem's research, it was thought that only contaminated meat or fish could cause botulism. This idea was refuted in 1904 when a botulism outbreak occurred in Darmstadt, Germany, because of canned white beans. In 1910, the German microbiologist J. Leuchs published a paper showing that different strains of Bacillus botulinus caused the outbreaks in Ellezelles and Darmstad and that the toxins were serologically distinct.^[108] In 1917, Bacillus botulinus was renamed Clostridium botulinum, as it was decided that the term Bacillus should refer to a group of aerobic microorganisms, while Clostridium would be used only to describe a group of anaerobic microorganisms.^[110] In 1919, Georgina Burke used toxin-antitoxin reactions to identify two strains of Clostridium botulinum, which she designated A and B.^[110]

This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources in this section. Unsourced material may be challenged and removed. (August 2018) (Learn how and when to remove this message)

Over the next three decades, 1895–1925, as food canning was approaching a billion-dollar-a-year industry, botulism was becoming a public health hazard. Karl Friedrich Meyer, a Swiss-American veterinary scientist, created a center at the Hooper Foundation in San Francisco, where he developed techniques for growing the organism and extracting the toxin, and conversely, for preventing organism growth and toxin production, and inactivating the toxin by heating. The California canning industry was thereby preserved.^[112]

With the outbreak of World War II, weaponization of botulinum toxin was investigated at Fort Detrick in Maryland. Carl Lamanna and James Duff^[113] developed the concentration and crystallization techniques that Edward J. Schantz used to create the first clinical product. When the Army's Chemical Corps was disbanded, Schantz moved to the Food Research Institute in Wisconsin, where he manufactured toxin for experimental use and provided it to the academic community.

The mechanism of botulinum toxin action – blocking the release of the neurotransmitter acetylcholine from nerve endings – was elucidated in the mid-20th century,^[114] and remains an important research topic. Nearly all toxin treatments are based on this effect in various body tissues.

Ophthalmologists specializing in eye muscle disorders (strabismus) had developed the method of EMG-guided injection (using the electromyogram, the electrical signal from an activated muscle, to guide injection) of local anesthetics as a diagnostic technique for evaluating an individual muscle's contribution to an eye movement.^[115] Because strabismus surgery frequently needed repeating, a search was undertaken for non-surgical, injection treatments using various anesthetics, alcohols, enzymes, enzyme blockers, and snake neurotoxins. Finally, inspired by Daniel B. Drachman's work with chicks at Johns Hopkins,^[116] Alan B. Scott and colleagues injected botulinum toxin into monkey extraocular muscles.^[117] The result was remarkable; a few picograms induced paralysis that was confined to the target muscle, long in duration, and without side effects.

After working out techniques for freeze-drying, buffering with albumin, and assuring sterility, potency, and safety, Scott applied to the FDA for investigational drug use, and began manufacturing botulinum type A neurotoxin in his San Francisco lab. He injected the first strabismus patients in 1977, reported its clinical utility in 1980,^[118] and had soon trained hundreds of ophthalmologists in EMG-guided injection of the drug he named Oculinum ("eye aligner").

In 1986, Oculinum Inc, Scott's micromanufacturer and distributor of botulinum toxin, was unable to obtain product liability insurance, and could no longer supply the drug. As supplies became exhausted, people who had come to rely on periodic injections became desperate. For four months, as liability issues were resolved, American blepharospasm patients traveled to Canadian eye centers for their injections.^[119]

Based on data from thousands of people collected by 240 investigators, Oculinum Inc (which was soon acquired by Allergan) received FDA approval in 1989 to market Oculinum for clinical use in the United States to treat adult strabismus (crossed eyes) and blepharospasm (uncontrollable blinking).^[120] Allergan then began using the trademark Botox.^[121] This original approval was granted under the 1983 US Orphan Drug Act.^[122]

The effect of botulinum toxin type-A on reducing and eliminating forehead wrinkles was first described and published by Richard Clark, MD, a plastic surgeon from Sacramento, California. In 1987 Clark was challenged with eliminating the disfigurement caused by only the right side of the forehead muscles functioning after the left side of the forehead was paralyzed during a facelift procedure. This patient had desired to look better from her facelift, but was experiencing bizarre unilateral right forehead eyebrow elevation while the left eyebrow drooped, and she constantly demonstrated deep expressive right forehead wrinkles while the left side was perfectly smooth due to the paralysis. Clark was aware that Botulinum toxin was safely being used to treat babies with strabismus and he requested and was granted FDA approval to experiment with Botulinum toxin to paralyze the moving and wrinkling normal functioning right forehead muscles to make both sides of the forehead appear the same. This study and case report of the cosmetic use of Botulinum toxin to treat a cosmetic complication of a cosmetic surgery was the first report on the specific treatment of wrinkles and was published in the journal Plastic and Reconstructive Surgery in 1989.^[123] Editors of the journal of the American Society of Plastic Surgeons have clearly stated "the first described use of the toxin in aesthetic circumstances was by Clark and Berris in 1989."^[124]

J. D. and J. A. Carruthers also studied and reported in 1992 the use of botulinum toxin type-A as a cosmetic treatment.[78] They conducted a study of participants whose only concern was their glabellar forehead wrinkle or furrow. Study participants were otherwise normal. Sixteen of seventeen participants available for follow-up demonstrated a cosmetic improvement. This study was reported at a meeting in 1991. The study for the treatment of glabellar frown lines was published in 1992.^[125] This result was subsequently confirmed by other groups (Brin, and the Columbia University group under Monte Keen^[126]). The FDA announced regulatory approval of botulinum toxin type A (Botox Cosmetic) to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines) in 2002 after extensive clinical trials.^[127] Well before this, the cosmetic use of botulinum toxin type A became widespread.^[128] The results of Botox Cosmetic can last up to four months and may vary with each patient.^[129] The US Food and Drug Administration (FDA) approved an alternative product-safety testing method in response to increasing public concern that LD50 testing was required for each batch sold in the market.^[130][131]

Botulinum toxin type-A has also been used in the treatment of gummy smiles;^[132] the material is injected into the hyperactive muscles of upper lip, which causes a reduction in the upward movement of lip thus resulting in a smile with a less exposure of gingiva.^[133] Botox is usually injected in the three lip elevator muscles that converge on the lateral side of the ala of the nose; the levator labii superioris (LLS), the levator labii superioris alaeque nasi muscle (LLSAN), and the zygomaticus minor (ZMi).^[134][135]

William J. Binder reported in 2000 that people who had cosmetic injections around the face reported relief from chronic headaches.^[136] This was initially thought to be an indirect effect of reduced muscle tension; however, the toxin is now known to inhibit the release of peripheral nociceptive neurotransmitters, thereby suppressing the central pain processing systems responsible for migraine headaches.^[137][138]

This article needs to be updated. Please help update this article to reflect recent events or newly available information. (October 2017)

As of 2018^[update], botulinum toxin injections are the most common cosmetic operation, with 7.4 million procedures in the United States, according to the American Society of Plastic Surgeons.^[139]

The global market for botulinum toxin products, driven by their cosmetic applications, was forecast to reach $2.9 billion by 2018. The facial aesthetics market, of which they are a component, was forecast to reach $4.7 billion ($2 billion in the US) in the same timeframe.^[140]

In 2020, 4,401,536 botulinum toxin Type A procedures were administered.^[141] In 2019 the botulinum toxin market made US$3.19 billion.^[142]

Botox cost is generally determined by the number of units administered (avg. $10–30 per unit) or by the area ($200–1000) and depends on the physician's expertise, clinic location, number of units, and treatment complexity.^[143]

In the US, Botox for medical purposes is usually covered by insurance if deemed medically necessary by a doctor and covers a plethora of medical problems including overactive bladder (OAB), urinary incontinence due to neurologic conditions, headaches and migraines, TMJ, spasticity in adults, cervical dystonia in adults, severe axillary hyperhidrosis (or other areas of the body), blepharospasm, upper or lower limb spasticity.^[144][145]

Botox's potential to reduce facial wrinkles was discovered in the 1990s, leading to its FDA approval for cosmetic use in 2002. Standard areas for aesthetics Botox injections include areas on the face or neck that can form fine lines and wrinkles due to every day muscle contractions and/or facial expressions such as smiling, frowning, squinting, and raising eyebrows. These areas include the glabellar region between the eyebrows, horizontal lines on the forehead, crow's feet around the eyes, and even circular bands that form around the neck secondary to platysmal hyperactivity.^[146]

Botox for excessive sweating is FDA approved.^[79]

Botulinum toxin has been recognized as a potential agent for use in bioterrorism.^[147] It can be absorbed through the eyes, mucous membranes, respiratory tract, and non-intact skin.^[148] The effects of botulinum toxin are different from those of nerve agents involved insofar in that botulism symptoms develop relatively slowly (over several days), while nerve agent effects are generally much more rapid. Evidence suggests that nerve exposure (simulated by injection of atropine and pralidoxime) will increase mortality by enhancing botulinum toxin's mechanism of toxicity.^[149] With regard to detection, protocols using NBC detection equipment (such as M-8 paper or the ICAM) will not indicate a "positive" when samples containing botulinum toxin are tested.^[150] To confirm a diagnosis of botulinum toxin poisoning, therapeutically or to provide evidence in death investigations, botulinum toxin may be quantitated by immunoassay of human biological fluids; serum levels of 12–24 mouse LD₅₀ units per milliliter have been detected in poisoned people.^[151]

During the early 1980s, German and French newspapers reported that the police had raided a Baader-Meinhof gang safe house in Paris and had found a makeshift laboratory that contained flasks full of Clostridium botulinum, which makes botulinum toxin. Their reports were later found to be incorrect; no such lab was ever found.^[152]

The examples and perspective in this section deal primarily with the United States and do not represent a worldwide view of the subject. You may improve this section, discuss the issue on the talk page, or create a new section, as appropriate. (April 2017) (Learn how and when to remove this message)

Commercial forms are marketed under the brand names Botox (onabotulinumtoxinA),^{[18][91][153]} Dysport/Azzalure (abobotulinumtoxinA),^[91][154] Letybo (letibotulinumtoxinA),^[1][2][155] Myobloc (rimabotulinumtoxinB),^[20][91] Xeomin/Bocouture (incobotulinumtoxinA),^{[156][157][158]} and Jeuveau (prabotulinumtoxinA).^[159][70]

Botulinum toxin A is sold under the brand names Jeuveau, Botox, and Xeomin. Botulinum toxin B is sold under the brand name Myobloc.^[20]

In the United States, botulinum toxin products are manufactured by a variety of companies, for both therapeutic and cosmetic use. A US supplier reported in its company materials in 2011 that it could "supply the world's requirements for 25 indications approved by Government agencies around the world" with less than one gram of raw botulinum toxin.^[160] Myobloc or Neurobloc, a botulinum toxin type B product, is produced by Solstice Neurosciences, a subsidiary of US WorldMeds. AbobotulinumtoxinA), a therapeutic formulation of the type A toxin manufactured by Galderma in the United Kingdom, is licensed for the treatment of focal dystonias and certain cosmetic uses in the US and other countries.^[92] LetibotulinumtoxinA (Letybo) was approved for medical use in the United States in February 2024.^[1]

Besides the three primary US manufacturers, numerous other botulinum toxin producers are known. Xeomin, manufactured in Germany by Merz, is also available for both therapeutic and cosmetic use in the US.^[161] Lanzhou Institute of Biological Products in China manufactures a botulinum toxin type-A product; as of 2014, it was the only botulinum toxin type-A approved in China.^[161] Botulinum toxin type-A is also sold as Lantox and Prosigne on the global market.^[162] Neuronox, a botulinum toxin type-A product, was introduced by Medy-Tox of South Korea in 2009.^[163]

Botulism toxins are produced by bacteria of the genus Clostridium, namely C. botulinum, C. butyricum, C. baratii and C. argentinense,^[164] which are widely distributed, including in soil and dust. Also, the bacteria can be found inside homes on floors, carpet, and countertops even after cleaning.^[165] Complicating the problem is that the taxonomy for C. botulinum remains chaotic. The toxin has likely been horizontally transferred across lineages, contributing to the multi-species pattern seen today.^[166][167]

Food-borne botulism results, indirectly, from ingestion of food contaminated with Clostridium spores, where exposure to an anaerobic environment allows the spores to germinate, after which the bacteria can multiply and produce toxin.^[165] Critically, ingestion of toxin rather than spores or vegetative bacteria causes botulism.^[165] Botulism is nevertheless known to be transmitted through canned foods not cooked correctly before canning or after can opening, so is preventable.^[165] Infant botulism arising from consumption of honey or any other food that can carry these spores can be prevented by eliminating these foods from diets of children less than 12 months old.^[168]

This section needs expansion with: modern content and referencing on antibiotic susceptibilities. You can help by adding to it. (February 2015)

Proper refrigeration at temperatures below 4.4 °C (39.9 °F) slows the growth of C. botulinum.^[169] The organism is also susceptible to high salt, high oxygen, and low pH levels.^{[35][failed verification]} The toxin itself is rapidly destroyed by heat, such as in thorough cooking.^[170] The spores that produce the toxin are heat-tolerant and will survive boiling water for an extended period of time.^[171]

The botulinum toxin is denatured and thus deactivated at temperatures greater than 85 °C (185 °F) for five minutes.^[35] As a zinc metalloprotease (see below), the toxin's activity is also susceptible, post-exposure, to inhibition by protease inhibitors, e.g., zinc-coordinating hydroxamates.^[103][172]

University-based ophthalmologists in the US and Canada further refined the use of botulinum toxin as a therapeutic agent. By 1985, a scientific protocol of injection sites and dosage had been empirically determined for treatment of blepharospasm and strabismus.^[173] Side effects in treatment of this condition were deemed to be rare, mild and treatable.^[174] The beneficial effects of the injection lasted only four to six months. Thus, blepharospasm patients required re-injection two or three times a year.^[175]

In 1986, Scott's micromanufacturer and distributor of Botox was no longer able to supply the drug because of an inability to obtain product liability insurance. People became desperate, as supplies of Botox were gradually consumed, forcing him to abandon people who would have been due for their next injection. For a period of four months, American blepharospasm patients had to arrange to have their injections performed by participating doctors at Canadian eye centers until the liability issues could be resolved.^[119]

In December 1989, Botox was approved by the US FDA for the treatment of strabismus, blepharospasm, and hemifacial spasm in people over 12 years old.^[121]

In the case of treatment of infantile esotropia in people younger than 12 years of age, several studies have yielded differing results.^[60][176]

Botulinum toxin type-A is now a common treatment for muscles affected by the upper motor neuron syndrome (UMNS), such as cerebral palsy,^[40] for muscles with an impaired ability to effectively lengthen. Muscles affected by UMNS frequently are limited by weakness, loss of reciprocal inhibition, decreased movement control, and hypertonicity (including spasticity). In January 2014, Botulinum toxin was approved by UK's Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of ankle disability due to lower limb spasticity associated with stroke in adults.^[54] Joint motion may be restricted by severe muscle imbalance related to the syndrome, when some muscles are markedly hypertonic, and lack effective active lengthening. Injecting an overactive muscle to decrease its level of contraction can allow improved reciprocal motion, so improved ability to move and exercise.^[40]

Sialorrhea is a condition where oral secretions are unable to be eliminated, causing pooling of saliva in the mouth. This condition can be caused by various neurological syndromes such as Bell's palsy, intellectual disability, and cerebral palsy. Injection of botulinum toxin type-A into salivary glands is useful in reducing the secretions.^[177]

Botulinum toxin type-A is used to treat cervical dystonia, but it can become ineffective after a time. Botulinum toxin type B received FDA approval for treatment of cervical dystonia in December 2000. Brand names for botulinum toxin type-B include Myobloc in the United States and Neurobloc in the European Union.^[161]

Onabotulinumtoxin A (trade name: Botox) received FDA approval for treatment of chronic migraines on 15 October 2010. The toxin is injected into the head and neck to treat these chronic headaches. Approval followed evidence presented to the agency from two studies funded by Allergan showing a very slight improvement in incidence of chronic migraines for those with migraines undergoing the Botox treatment.^[134][178]

Since then, several randomized control trials have shown botulinum toxin type A to improve headache symptoms and quality of life when used prophylactically for participants with chronic migraine^[179] who exhibit headache characteristics consistent with: pressure perceived from outside source, shorter total duration of chronic migraines (<30 years), "detoxification" of participants with coexisting chronic daily headache due to medication overuse, and no current history of other preventive headache medications.^[180]

A few small trials have found benefits in people with depression.^{[181][182][183]} A 2021 meta-analysis supports the usefulness of botox in unipolar depression, but finds significant heterogenity among the findings.^[184] The main hypothesis for its action is based on the facial feedback hypothesis.^[185] Another hypothesis involves a connection between the facial muscle and specific brain regions in animals, but additional evidence is required to support or disprove this theory.^[183]

The drug for the treatment of premature ejaculation has been under development since August 2013, and is in Phase II trials.^[182][186]

• Carruthers JD, Fagien S, Joseph JH, Humphrey SD, Biesman BS, Gallagher CJ, et al. (January 2020). "DaxibotulinumtoxinA for Injection for the Treatment of Glabellar Lines: Results from Each of Two Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Studies (SAKURA 1 and SAKURA 2)". Plastic and Reconstructive Surgery. 145 (1): 45–58. doi:10.1097/PRS.0000000000006327. PMC 6940025. PMID 31609882.
• Solish N, Carruthers J, Kaufman J, Rubio RG, Gross TM, Gallagher CJ (December 2021). "Overview of DaxibotulinumtoxinA for Injection: A Novel Formulation of Botulinum Toxin Type A". Drugs. 81 (18): 2091–2101. doi:10.1007/s40265-021-01631-w. PMC 8648634. PMID 34787840.

• Overview of all the structural information available in the PDB for UniProt: P0DPI1 (Botulinum neurotoxin type A) at the PDBe-KB.
• Overview of all the structural information available in the PDB for UniProt: P10844 (Botulinum neurotoxin type B) at the PDBe-KB.
• Overview of all the structural information available in the PDB for UniProt: A0A0X1KH89 (Bontoxilysin A) at the PDBe-KB.
• "AbobotulinumtoxinA Injection". MedlinePlus.
• "IncobotulinumtoxinA Injection". MedlinePlus.
• "OnabotulinumtoxinA Injection". MedlinePlus.
• "PrabotulinumtoxinA-xvfs Injection". MedlinePlus.
• "RimabotulinumtoxinB Injection". MedlinePlus.

Method of medication administration

This article is about the medical procedure. For other uses, see Injection.

An injection (often and usually referred to as a "shot" in US English, a "jab" in UK English, or a "jag" in Scottish English and Scots) is the act of administering a liquid, especially a drug, into a person's body using a needle (usually a hypodermic needle) and a syringe.^[1] An injection is considered a form of parenteral drug administration; it does not involve absorption in the digestive tract. This allows the medication to be absorbed more rapidly and avoid the first pass effect. There are many types of injection, which are generally named after the body tissue the injection is administered into. This includes common injections such as subcutaneous, intramuscular, and intravenous injections, as well as less common injections such as epidural, intraperitoneal, intraosseous, intracardiac, intraarticular, and intracavernous injections.

Injections are among the most common health care procedures, with at least 16 billion administered in developing and transitional countries each year.^[2] Of these, 95% are used in curative care or as treatment for a condition, 3% are to provide immunizations/vaccinations, and the rest are used for other purposes, including blood transfusions.^[2] The term injection is sometimes used synonymously with inoculation, but injection does not only refer to the act of inoculation. Injections generally administer a medication as a bolus (or one-time) dose, but can also be used for continuous drug administration.^[3] After injection, a medication may be designed to be released slowly, called a depot injection, which can produce long-lasting effects.

An injection necessarily causes a small puncture wound to the body, and thus may cause localized pain or infection. The occurrence of these side effects varies based on injection location, the substance injected, needle gauge, procedure, and individual sensitivity. Rarely, more serious side effects including gangrene, sepsis, and nerve damage may occur. Fear of needles, also called needle phobia, is also common and may result in anxiety and fainting before, during, or after an injection. To prevent the localized pain that occurs with injections the injection site may be numbed or cooled before injection and the person receiving the injection may be distracted by a conversation or similar means. To reduce the risk of infection from injections, proper aseptic technique should be followed to clean the injection site before administration. If needles or syringes are reused between people, or if an accidental needlestick occurs, there is a risk of transmission of bloodborne diseases such as HIV and hepatitis.

Unsafe injection practices contribute to the spread of bloodborne diseases, especially in less-developed countries. To combat this, safety syringes exist which contain features to prevent accidental needlestick injury and reuse of the syringe after it is used once. Furthermore, recreational drug users who use injections to administer the drugs commonly share or reuse needles after an injection. This has led to the development of needle exchange programs and safe injection sites as a public health measure, which may provide new, sterile syringes and needles to discourage the reuse of syringes and needles. Used needles should ideally be placed in a purpose-made sharps container which is safe and resistant to puncture. Some locations provide free disposal programs for such containers for their citizens.

Types

[edit]

Injections are classified in multiple ways, including the type of tissue being injected into, the location in the body the injection is designed to produce effects, and the duration of the effects. Regardless of classification, injections require a puncture to be made, thus requiring sterile environments and procedures to minimize the risk of introducing pathogens into the body. All injections are considered forms of parenteral administration, which avoids the first pass metabolism which would potentially affect a medication absorbed through the gastrointestinal tract.

Systemic

[edit]

Many injections are designed to administer a medication which has an effect throughout the body. Systemic injections may be used when a person cannot take medicine by mouth, or when the medication itself would not be absorbed into circulation from the gastrointestinal tract. Medications administered via a systemic injection will enter into blood circulation, either directly or indirectly, and thus will have an effect on the entire body.

Intravenous

[edit]

Intravenous injections, abbreviated as IV, involve inserting a needle into a vein, allowing a substance to be delivered directly into the bloodstream.^[4] An intravenous injection provides the quickest onset of the desired effects because the substance immediately enters the blood, and is quickly circulated to the rest of the body.^[5] Because the substance is administered directly into the bloodstream, there is no delay in the onset of effects due to the absorption of the substance into the bloodstream. This type of injection is the most common and is used frequently for administration of medications in an inpatient setting.

Another use for intravenous injections includes for the administration of nutrition to people who cannot get nutrition through the digestive tract. This is termed parenteral nutrition and may provide all or only part of a person's nutritional requirements. Parenteral nutrition may be pre-mixed or customized for a person's specific needs.^[6] Intravenous injections may also be used for recreational drugs when a rapid onset of effects is desired.^[7][8]

Intramuscular injections, abbreviated as IM, deliver a substance deep into a muscle, where they are quickly absorbed by the blood vessels into systemic circulation. Common injection sites include the deltoid, vastus lateralis, and ventrogluteal muscles.^[9] Medical professionals are trained to give IM injections, but people who are not medical professionals can also be trained to administer medications like epinephrine using an autoinjector in an emergency.^[10] Some depot injections are also administered intramuscularly, including medroxyprogesterone acetate among others.^[11] In addition to medications, most inactivated vaccines, including the influenza vaccine, are given as an IM injection.^[12]

Subcutaneous injections, abbreviated as SC or sub-Q, consist of injecting a substance via a needle under the skin.^[13] Absorption of the medicine from this tissue is slower than in an intramuscular injection. Since the needle does not need to penetrate to the level of the muscle, a thinner and shorter needle can be used. Subcutaneous injections may be administered in the fatty tissue behind the upper arm, in the abdomen, or in the thigh. Certain medications, including epinephrine, may be used either intramuscularly or subcutaneously.^[14] Others, such as insulin, are almost exclusively injected subcutaneously. Live or attenuated vaccines, including the MMR vaccine (measles, mumps, rubella), varicella vaccine (chickenpox), and zoster vaccine (shingles) are also injected subcutaneously.^[15]

Intradermal injections, abbreviated as ID, consist of a substance delivered into the dermis, the layer of skin above the subcutaneous fat layer, but below the epidermis or top layer. An intradermal injection is administered with the needle placed almost flat against the skin, at a 5 to 15 degree angle.^[16] Absorption from an intradermal injection takes longer than when the injection is given intravenously, intramuscularly, or subcutaneously. For this reason, few medications are administered intradermally. Intradermal injections are most commonly used for sensitivity tests, including tuberculin skin tests and allergy tests, as well as sensitivity tests to medications a person has never had before. The reactions caused by tests which use intradermal injection are more easily seen due to the location of the injection, and when positive will present as a red or swollen area. Common sites of intradermal injections include the forearm and lower back.^[16]

An intraosseous injection or infusion is the act of administering medication through a needle inserted into the bone marrow of a large bone. This method of administration is only used when it is not possible to maintain access through a less invasive method such as an intravenous line, either due to frequent loss of access due to a collapsed vessel, or due to the difficulty of finding a suitable vein to use in the first place.^[17] Intraosseous access is commonly obtained by inserting a needle into the bone marrow of the humerus or tibia, and is generally only considered once multiple attempts at intravenous access have failed, as it is a more invasive method of administration than an IV.^[17] With the exception of occasional differences in the accuracy of blood tests when drawn from an intraosseous line, it is considered to be equivalent in efficacy to IV access. It is most commonly used in emergency situations where there is not ample time to repeatedly attempt to obtain IV access, or in younger people for whom obtaining IV access is more difficult.^[17][18]

Injections may be performed into specific parts of the body when the medication's effects are desired to be limited to a specific location, or where systemic administration would produce undesirable side effects which may be avoided by a more directed injection.

Injections to the corpus cavernosum of the penis, termed intracavernous injections, may be used to treat conditions which are localized to the penis. They can be self-administered for erectile dysfunction prior to intercourse or used in a healthcare setting for emergency treatment for a prolonged erection with an injection to either remove blood from the penis or to administer a sympathomimetic medication to reduce the erection.^[19] Intracavernosal injections of alprostadil may be used by people for whom other treatments such as PDE5 inhibitors are ineffective or contraindicated. Other medications may also be administered in this way, including papaverine, phentolamine, and aviptadil.^[20] The most common adverse effects of intercavernosal injections include fibrosis and pain, as well as hematomas or bruising around the injection site.^[20]

Medications may also be administered by injecting them directly into the vitreous humor of the eye. This is termed an intravitreal injection, and may be used to treat endophthalmitis (an infection of the inner eye), macular degeneration, and macular edema.^[21] An intravitreal injection is performed by injecting a medication through the pupil into the vitreous humor core of the eye after applying a local anesthetic drop to numb the eye and a mydriatic drop to dilate the pupil. They are commonly used in lieu of systemic administration to both increase the concentrations present in the eye, as well as avoid systemic side effects of medications.^[21]

When an effect is only required in one joint, a joint injection (or intra-articular injection) may be administered into the articular space surrounding the joint. These injections can range from a one-time dose of a steroid to help with pain and inflammation to complete replacement of the synovial fluid with a compound such as hyaluronic acid.^[22] The injection of a steroid into a joint is used to reduce inflammation associated with conditions such as osteoarthritis, and the effects may last for up to 6 months following a single injection.^[22] Hyaluronic acid injection is used to supplement the body's natural synovial fluid and decrease the friction and stiffness of the joint.^[22] Administering a joint injection^[23] generally involves the use of an ultrasound or other live imaging technique to ensure the injection is administered in the desired location, as well as to reduce the risk of damaging surrounding tissues.^[24]

Long-acting injectable (LAI) formulations of medications are not intended to have a rapid effect, but instead release a medication at a predictable rate continuously over a period of time. Both depot injections and solid injectable implants are used to increase adherence to therapy by reducing the frequency at which a person must take a medication.^{[25]: 3â€Å} 

A depot injection is an injection, usually subcutaneous, intradermal, or intramuscular, that deposits a drug in a localized mass, called a depot, from which it is gradually absorbed by surrounding tissue. Such injection allows the active compound to be released in a consistent way over a long period.^[26] Depot injections are usually either oil-based or an aqueous suspension. Depot injections may be available as certain salt forms of a drug, such as decanoate salts or esters. Examples of depot injections include haloperidol decanoate, medroxyprogesterone acetate,^[26] and naltrexone.^[27]

Injections may also be used to insert a solid or semi-solid into the body which releases a medication slowly over time. These implants are generally designed to be temporary, replaceable, and ultimately removed at the end of their use or when replaced. There are multiple contraceptive implants marketed for different active ingredients, as well as differing duration of action - most of these are injected under the skin.^[28] A form of buprenorphine for the treatment of opioid dependence is also available as an injectable implant.^[29] Various materials can be used to manufacture implants including biodegradable polymers, osmotic release systems, and small spheres which dissolve in the body.^{[25]: 4, 185, 335â€Å} 

The act of piercing the skin with a needle, while necessary for an injection, also may cause localized pain. The most common technique to reduce the pain of an injection is simply to distract the person receiving the injection. Pain may be dampened by prior application of ice or topical anesthetic, or pinching of the skin while giving the injection. Some studies also suggest that forced coughing during an injection stimulates a transient rise in blood pressure which inhibits the perception of pain.^[30] For some injections, especially deeper injections, a local anesthetic is given.^[30] When giving an injection to young children or infants, they may be distracted by giving them a small amount of sweet liquid, such as sugar solution,^[31] or be comforted by breastfeeding^[32] during the injection, which reduces crying.

A needle tract infection, also called a needlestick infection, is an infection that occurs when pathogens are inadvertently introduced into the tissues of the body during an injection. Contamination of the needle used for injection, or reuse of needles for injections in multiple people, can lead to transmission of hepatitis B and C, HIV, and other bloodstream infections.^[33][34][35] Injection drug users have high rates of unsafe needle use including sharing needles between people.^[36] The spread of HIV, Hepatitis B, and Hepatitis C from injection drug use is a common health problem,^[37] in particular contributing to over half of new HIV cases in North America in 1994.^[7]

Other infections may occur when pathogens enter the body through the injection site, most commonly due to improper cleaning of the site before injection. Infections occurring in this way are mainly localized infections, including skin infections, skin structure infections, abscesses, or gangrene.^[38] An intravenous injection may also result in a bloodstream infection (termed sepsis) if the injection site is not cleaned properly prior to insertion. Sepsis is a life-threatening condition which requires immediate treatment.^{[16]: 358, 373â€Å} 

Injections into the skin and soft tissue generally do not cause any permanent damage, and the puncture heals within a few days. However, in some cases, injections can cause long-term adverse effects. Intravenous and intramuscular injections may cause damage to a nerve, leading to palsy or paralysis. Intramuscular injections may cause fibrosis or contracture.^[39] Injections also cause localized bleeding, which may lead to a hematoma. Intravenous injections may also cause phlebitis, especially when multiple injections are given in a vein over a short period of time.^[40] Infiltration and extravasation may also occur when a medication intended to be injected into a vein is inadvertently injected into surrounding tissues.^[41] Those who are afraid of needles may also experience fainting at the sight of a needle, or before or after an injection.^[42]

Proper needle use is important to perform injections safely,^[43] which includes the use of a new, sterile needle for each injection. This is partly because needles get duller with each use and partly because reusing needles increases risk of infection. Needles should not be shared between people, as this increases risk of transmitting blood-borne pathogens. The practice of using the same needle for multiple people increases the risk of disease transmission between people sharing the same medication.^[43] In addition, it is not recommended to reuse a used needle to pierce a medication bag, bottle, or ampule designed to provide multiple doses of a medication, instead a new needle should be used each time the container must be pierced. Aseptic technique should always be practiced when administering injections. This includes the use of barriers including gloves, gowns, and masks for health care providers. It also requires the use of a new, sterile needle, syringe and other equipment for each injection, as well as proper training to avoid touching non-sterile surfaces with sterile items.^[13]

To help prevent accidental needlestick injury to the person administering the injection, and prevent reuse of the syringe for another injection, a safety syringe and needle may be used.^[44] The most basic reuse prevention device is an "auto-disable" plunger, which once pressed past a certain point will no longer retract. Another common safety feature is an auto-retractable needle, where the needle is spring-loaded and either retracts into the syringe after injection, or into a plastic sheath on the side of the syringe. Other safety syringes have an attached sheath which may be moved to cover the end of the needle after the injection is given.^[44] The World Health Organization recommends the use of single-use syringes with both reuse prevention devices and a needlestick injury prevention mechanism for all injections to prevent accidental injury and disease transmission.^[44]

Novel injection techniques include drug diffusion within the skin using needle-free micro-jet injection (NFI) technology.^[45][46]

Used needles should be disposed of in specifically designed sharps containers to reduce the risk of accidental needle sticks and exposure to other people.^[47] In addition, a new sharps container should be begun once it is 3⁄4 full. A sharps container which is

3⁄4 filled should be sealed properly to prevent re-opening or accidental opening during transportation.^[48] Some locations offer publicly accessible "sharps take-back" programs where a sharps container may be dropped off to a public location for safe disposal at no fee to the person. In addition, some pharmaceutical and independent companies provide mail-back sharps programs, sometimes for an additional fee.^[48] In the United States, there are 39 states that offer programs to provide needle or syringe exchange.^[49]

Over half of non-industrialized countries report open burning of disposed or used syringes. This practice is considered unsafe by the World Health Organization.^[2]

The aspiration is the technique of pulling back on the plunger of a syringe prior to the actual injection. If blood flows into the syringe it signals that a blood vessel has been hit.^[50]

Due to the prevalence of unsafe injection practices, especially among injection drug users, many locations have begun offering supervised injection sites and needle exchange programs, which may be offered separately or colocated. These programs may provide new sterile needles upon request to mitigate infection risk, and some also provide access to on-site clinicians and emergency medical care if it becomes required. In the event of an overdose, a site may also provide medications such as naloxone, used as an antidote in opioid overdose situations, or other antidotes or emergency care. Safe injection site have been associated with lower rates of death from overdose, less ambulance calls, and lower rates of new HIV infections from unsafe needle practices.^[51]

As of 2024, at least ten countries currently offer safe injection sites, including Australia, Canada, the United States, Denmark, France, Germany, Luxembourg, The Netherlands, Norway, Spain and Switzerland. In total, there are at least 120 sites operating.^[52][53]

Many species of animals use injections for self-defence or catching prey. This includes venomous snakes which inject venom when they bite into the skin with their fangs. Common substances present in snake venom include neurotoxins, toxic proteins, and cytotoxic enzymes. Different species of snakes inject different formulations of venom, which may cause severe pain and necrosis before progressing into neurotoxicity and potentially death.^[54] The weever is a type of fish which has venomous spines covering its fins and gills and injects a venom consisting of proteins which cause a severe local reaction which is not life-threatening.^[55] Sting rays use their spinal blade to inject a protein-based venom which causes localized cell death but is not generally life-threatening.^[56]

Some types of insects also utilize injection for various purposes. Bees use a stinger located in their hind region to inject a venom consisting of proteins such as melittin, which causes a localized painful and itching reaction.^[57] Leeches can inject an anticoagulant peptide called hirudin after attaching to prevent blood from clotting during feeding. This property of leeches has been used historically as a natural form of anticoagulation therapy, as well as for the use of bloodletting as a treatment for various ailments.^[58] Some species of ants inject forms of venom which include compounds which produce minor pain such as the formic acid, which is injected by members of the Formicinae subfamily.^[59] Other species of ants, including Dinoponera species, inject protein-based venom which causes severe pain but is still not life-threatening.^[60] The bullet ant (Paraponera clavata) injects a venom which contains a neurotoxin named poneratoxin which causes extreme pain, fever, and cold sweats, and may cause arrhythmias.^[61]

Plants may use a form of injection which is passive, where the injectee pushes themselves against the stationary needle. The stinging nettle plant has many trichomes, or stinging hairs, over its leaves and stems which are used to inject a mix of irritating chemicals which includes histamine, serotonin, and acetylcholine. This sting produces a form of dermatitis which is characterized by a stinging, burning, and itching sensation in the area.^[62] Dendrocnide species, also called stinging trees, use their trichomes to inject a mix of neurotoxic peptides which causes a reaction similar to the stinging nettle, but also may result in recurring flares for a much longer period after the injection.^[63] While some plants have thorns, spines, and prickles, these generally are not used for injection of any substance, but instead it is the act of piercing the skin which causes them to be a deterrent.^[64]

• Dart injection
• Jet injector
• Injection port
• Lethal injection
• Needlestick injury
• Needle remover
• Safety syringe
• Trypanophobia

Wikimedia Commons has media related to Injections (medicine).

• Information about injections from the Merck Manual
• FDA Center for Drug Evaluation and Research Data Standards Manual: Route of Administration