Antipruritic

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Antipruritics, abirritants, [1] or anti-itch drugs, are medications that inhibit the itching (Latin: pruritus ) often associated with sunburns, allergic reactions, eczema, psoriasis, chickenpox, fungal infections, insect bites and stings like those from mosquitoes, fleas, and mites, and contact dermatitis and urticaria caused by plants such as poison ivy (urushiol-induced contact dermatitis) or stinging nettle. It can also be caused by chronic kidney disease and related conditions. [2]

Contents

Abirritants consist of a large group of drugs belonging to different classes with varying mechanisms to treat itch. They may work either directly or indirectly to relieve itch, and evidence on their effectiveness varies from one class to another. [3] Some alternative medicines are also used to treat itch. [4] [5] Side effects of abirritants also vary depending on the class of the drug. Even before the emergence of modern evidence-based medicine, abirritants have already been used in many civilizations, but practices and choice of drugs may differ by culture. [6]

Types

A number of drug classes are available as abirritants for itching relief, but there is no one single specific abirritant to treat all forms of itch. [7] Treatments may vary depending on the cause. Commonly prescribed abirritants can be broadly divided into topical and systemic drugs, and may include a combination of one or more drugs, described as below.

Topical

Corticosteroid creams can be applied directly on the skin to treat itch. Tube of Hydrocortison, Oude Pekela (2019) 02.jpg
Corticosteroid creams can be applied directly on the skin to treat itch.

Topical formulations are preferred for treating localized itch caused by skin damage, inflammation or dryness. [8] Topical antipruritics in the form of creams and sprays are often available over the counter. The active ingredients usually belong to these classes:

MedicationMechanism of ActionExamples
Corticosteroids Suppresses itch originating from immune response and inflammation [10]
Antihistamines Antihistamines have anti-inflammatory properties that can relieve itching by suppressing the underlying inflammation [11]
Anesthetics Prevents the propagation of nerve signals that would otherwise cause an itching sensation [12]
Phosphodiesterase-4 inhibitors Suppresses inflammation to relieve itch [12]
Capsaicin Desensitizes nerves that cause itch [8]

Systemic drugs

Antihistamines are commonly used to treat itching associated with allergies. A strip of antihistamine.jpg
Antihistamines are commonly used to treat itching associated with allergies.

Generalized itch, or itching across the whole body, can be a symptom of a dermatological disorder or an underlying systemic problem. [13] Some systemic diseases can that cause generalized itch include diabetes, hypothyroidism, kidney diseases and liver diseases. [14] [13] It is usually treated with systemic agents instead of topical agents. [15] Corticosteroids and antihistamines mentioned above can also be used to treat generalized itch. [16] Common systemic abirritants are listed below:

Gabapentin is an anticonvulsant which can also be used to treat itch. Gabapentin.jpg
Gabapentin is an anticonvulsant which can also be used to treat itch.
MedicationMechanism of ActionExamples
CorticosteroidsSuppresses itch originating from immune response and inflammation [10]
AntihistaminesAntihistamines have anti-inflammatory properties that can relieve itching by suppressing the underlying inflammation [11] [17]
μ-opioid receptor antagonistsBlocks the μ-opioid receptor, the stimulation of which causes itch in clinical settings such as itch due to liver diseases [18]
AntidepressantsReduces itch by mediating serotonin and histamine levels in the body. [19] Two main classes of antidepressants are utilized to relieve itch:
ImmunosuppressantsSuppresses the immune system to reduce inflammation and hence reduce itch [20]
AnticonvulsantsMechanism of action is unclear, but is thought to prevent itching by desensitizing calcium channels in nerves [21]
Thalidomide Thalidomide suppresses itching through a number of ways:
  • Acts as a central depressant;
  • Reduces inflammation;
  • Modulates immune response; and
  • Modulates nerve signal transmission [22]
Butorphanol Butorphanol activates the κ-opioid receptor and blocks the μ-opioid receptor, inhibiting generalized pruritus due to an imbalance between the μ- and κ-opioid systems

Oral antipruritics are usually prescription drugs. Those more recently described include:

Substances proposed to act antipruritically, but not used medically

Alternative treatments

A number of herbs have been used to treat itching such as cannabis, pigweed (Portulaca oleracaea), ashoka (Saraca asoca), and fig (Ficus carica). [5]

Other unconventional forms of treatment with potential efficacy for treating systemic itch include topical cannabinoids [33] and H4 antihistamines. [34]

Effectiveness

Despite the availability of many forms of treatment, there is only a limited number of case series or small-scale studies examining the efficacy of abirritants. [19] There is a lack of evidence on treatment for chronic pruritus of unknown origin. [35] [36] There is also little to no evidence on the efficacy and safety of using abirritants during pregnancy. [37]

Treating itch associated with disease

Some abirritants work by indirectly treating itch through treating the causative medical conditions, which means that the itching associated with the condition will often subside when it is properly treated. This includes antihistamines and corticosteroids, which are effective in treating inflammatory disorders of the skin, in particular atopic dermatitis. [38] Successful treatment of atopic dermatitis with either corticosteroids or antihistamines would resolve the associated itching. [39]

Treating itch directly

Some abirritants treat pruritus directly without necessarily treating the causative medical condition. Abirritants that directly treat itching and are established to be effective are reported here in the table below:

MedicationEffectiveness
Gabapentin Gabapentin was found to be effective in decreasing the severity of uremic pruritus compared to placebo. [40]
Butorphanol Continuous intravenous butorphanol reduced the incidence of morphine-induced pruritus significantly. [41]
Thalidomide Thalidomide is effective in treating chronic refractory pruritus among patients who had failed conventional therapy (corticosteroids or antihistamines), with a 50% or greater reduction in symptoms and a shorter time to improvement. [22]
μ-opioid receptor antagonistsμ-opioid receptor antagonists such as naltrexone and nalmefene demonstrated significant improvement in treating patients with cholestatic pruritus, or itch arising from urticaria and atopic dermatitis. [18]

Traditional Chinese medicine

Dictamnus is one of the many herbs used to treat itch in Traditional Chinese Medicine. Dictamnus albus SLO.jpg
Dictamnus is one of the many herbs used to treat itch in Traditional Chinese Medicine.

Traditional Chinese medicine is extensively used in Asia for relief of itch. It is believed that itching is caused by irritations from wind, dampness or blood stasis, and can be relieved by the use of herbs such as chrysanthemum, gardenia fruit or mung bean. [42] Sometimes these herbal remedies are used in combination with acupuncture and moxibustion, [4] but their efficacy is still unclear. [43] Sericin cream and oral omega-3 fatty acid supplements may show benefit in reducing itch. [36]

Adverse effects

Each class of abirritants has its own set of potential adverse effects.

Systemic corticosteroids

Systemic corticosteroid treatment can cause redistribution of fat tissue, leading to moon face. CushingsFace.jpg
Systemic corticosteroid treatment can cause redistribution of fat tissue, leading to moon face.

Systemic corticosteroid use has been associated with a wide range of potential adverse effects. In a review article, the following common complications were noted for prolonged use: redistribution of fat tissues (moon face), high blood sugar, infections, delayed wound healing, and HPA axis suppression, where the body's natural production of hormones like corticotropin-releasing hormone and adrenocorticotropic hormone is suppressed as a response to the increased level of corticosteroids in the blood. [44]

There is a lack of data on adverse effects associated with corticosteroid use of a shorter period and lower dose. [44]

Topical corticosteroids

Both local and systemic side effects can result from topical corticosteroid use, especially in prolonged treatment. [39]

Local side effects can occur regularly from prolonged use, [45] which include skin atrophy (thinning), stretch marks, infections, lighter skin color, and sudden decrease in efficacy of the drug. [39] [45]

Systemic side effects are far less prevalent than local ones. [45] Prolonged high potency corticosteroids use on thin skin, especially in children, increases the risk of systemic side effects since thin skin allows for greater absorption. [46] One commonly cited systemic side effect from topical use is HPA axis suppression. [46] A meta-analysis of topical corticosteroid use in children concluded that low-potency corticosteroid at recommended dosages and duration do not cause clinically significant HPA suppression. [47]

Antihistamines

Antihistamines target the molecule histamine by blocking the histamine H1 receptor. [48] First-generation antihistamines like diphenhydramine and chlorpheniramine are able to move from the blood into the brain across the blood–brain barrier, where they block the H1 receptor, reducing the neurotransmitter effect of histamine, leading to central nervous system side effects such as drowsiness and confusion. [48] Second generation antihistamines, such as fexofenadine and cetirizine are less able to move from blood circulation into the brain and are therefore associated with fewer side effects in usual doses. [48]

μ-Opioid receptor antagonists

μ-opioid receptor antagonists are usually well-tolerated and have no abuse potential since they do not cause physical dependence. [18] Side effects are dose-dependent and generally limited to the first two weeks of treatment. [49] [50] [51] Opioid withdrawal symptoms are rare and may include severe lightheadedness, depersonalization and anxiety. [18]

Antidepressants

Serotonin reuptake inhibitors, including both serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs), are generally well tolerated. [52] Common side effects include:

Immunosuppressants

Immunosuppressants may cause immunodeficiency, resulting in an increased susceptibility to infection. Other side effects include bone marrow suppression, increased risk of cardiovascular disease and increased risk of cancer. [54]

Capsaicin

Being the main chemical that causes heat in chili pepper, the main side effect of capsaicin is a burning sensation that usually persists for several days. A topical anaesthetic can be used to reduce the sensation. In addition, the topical anaesthetic can also provide anti-itch effect on its own. [55]

History

Squill was used to treat itch and is commonly listed in ancient pharmacopeia. Scilla cilicica - Taurus Squill 04.jpg
Squill was used to treat itch and is commonly listed in ancient pharmacopeia.

Abirritants have an extensive history in treating itch. The history of abirritants dates back to the Byzantine period, when Alexander of Tralleis, a famous physician, recommended crushed rue and alum mixed in honey for topical application to the scalp for itching caused by scabby conditions of the head. [6]

During the 7th century, Paul of Aegina, a famous Greek physician, described a list of drugs for treatment of itch including plants such as the squill, metallic components, and goat droppings which were applied externally. These drugs are common in ancient pharmacopeia. [56]

The Lorscher Azneibuch written in the monastery of Lorsch in the 7th century described many preparations of abirritants for both systemic and topical use, such as an ointment prepared from stinging nettle seeds. [57]

Mercury-coated girdles were used in the 17th century as an expensive treatment to alleviate symptoms of itch caused by scabies, but mercury toxins in the blood often caused other troubling symptoms in patients. [58]

In the 20th century, many new abirritants for external use emerged, including salicylic acids, naphthol, tar, carbolic acid, thymol, and menthol, which were mostly available in the form of ointments. Alcohol and opium were also commonly prescribed. [6]

See also

Related Research Articles

<span class="mw-page-title-main">Dermatitis</span> Inflammation of the skin

Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved can vary from small to covering the entire body. Dermatitis is often called eczema, and the difference between those terms is not standardized.

<span class="mw-page-title-main">Corticosteroid</span> Class of steroid hormones

Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.

<span class="mw-page-title-main">Lichen simplex chronicus</span> Human skin disorder

Lichen simplex chronicus (LSC) is thick leathery skin with exaggerated skin markings caused by sudden itching and excessive rubbing and scratching. It generally results in small bumps, patches, scratch marks and scale. It typically affects the neck, scalp, upper eyelids, ears, palms, soles, ankles, wrists, genital areas and bottom. It often develops gradually and the scratching becomes a habit.

<span class="mw-page-title-main">Itch</span> Sensation that causes desire or reflex to scratch

Itch is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response patterns are different. Pain creates a withdrawal reflex, whereas itches leads to a scratch reflex.

<span class="mw-page-title-main">Seborrhoeic dermatitis</span> Skin disease

Seborrhoeic dermatitis is a long-term skin disorder. Symptoms include flaky, scaly, greasy, and occasionally itchy and inflamed skin. Areas of the skin rich in oil-producing glands are often affected including the scalp, face, and chest. It can result in social or self-esteem problems. In babies, when the scalp is primarily involved, it is called cradle cap. Seborrhoeic dermatitis of the scalp may be described in lay terms as dandruff due to the dry, flaky character of the skin. However, as dandruff may refer to any dryness or scaling of the scalp, not all dandruff is seborrhoeic dermatitis. Seborrhoeic dermatitis is sometimes inaccurately referred to as seborrhoea.

<span class="mw-page-title-main">Hives</span> Skin disease characterized by red, raised, and itchy bumps

Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasting skin change. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs.

<span class="mw-page-title-main">Allergic conjunctivitis</span> Medical condition

Allergic conjunctivitis (AC) is inflammation of the conjunctiva due to allergy. Although allergens differ among patients, the most common cause is hay fever. Symptoms consist of redness, edema (swelling) of the conjunctiva, itching, and increased lacrimation. If this is combined with rhinitis, the condition is termed allergic rhinoconjunctivitis (ARC).

<span class="mw-page-title-main">Desonide</span> Chemical compound

Desonide (INN) is a low-potency topical corticosteroid anti-inflammatory that has been available since the 1970s. It is primarily used to treat atopic dermatitis (eczema), seborrheic dermatitis, contact dermatitis and psoriasis in both adults and children. It has a fairly good safety profile and is available as a cream, ointment, lotion, and as a foam under the tradename Verdeso Foam. Other trade names for creams, lotions, and ointments include Tridesilon, DesOwen, Desonate. It is a group VI corticosteroid under US classification, the second least potent group.

Aquagenic pruritus is a skin condition characterized by the development of severe, intense, prickling-like epidermal itching without observable skin lesions and evoked by contact with water.

<span class="mw-page-title-main">Atopic dermatitis</span> Long-term form of skin inflammation

Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which can thicken over time. AD may also simply be called eczema, a term that generally refers to a larger group of skin conditions.

<span class="mw-page-title-main">Pruritic urticarial papules and plaques of pregnancy</span> Chronic rash that occurs during pregnancy

Pruritic urticarial papules and plaques of pregnancy (PUPPP), known in United Kingdom as polymorphic eruption of pregnancy (PEP), is a chronic hives-like rash that strikes some women during pregnancy. Some skin changes are known to occur in people who are pregnant while other skin conditions, or dermatoses, that people have prior to getting pregnant will become altered or symptoms will increase. Pruritic urticarial papules and plaques of pregnancy (PUPPP) is one of many skin conditions that is specific to pregnancy and occurs in about 1 in every 160 (0.625%) of pregnancies.

<span class="mw-page-title-main">Prurigo nodularis</span> Medical condition

Prurigo nodularis (PN), also known as nodular prurigo, is a skin disease characterised by pruritic (itchy) nodules which usually appear on the arms or legs. Patients often present with multiple excoriated lesions caused by scratching. PN is also known as Hyde prurigo nodularis, Picker's nodules, atypical nodular form of neurodermatitis circumscripta, lichen corneus obtusus.

<span class="mw-page-title-main">Mometasone</span> Steroid medication

Mometasone, also known as mometasone y 3 s, is a steroid medication used to treat certain skin conditions, hay fever, and asthma. Specifically it is used to prevent rather than treat asthma attacks. It can be applied to the skin, inhaled, or used in the nose. Mometasone furoate, not mometasone, is used in medical products.

<span class="mw-page-title-main">Clobetasone</span> Chemical compound

Clobetasone (INN) is a corticosteroid used in dermatology, for treating such skin inflammation as seen in eczema, psoriasis and other forms of dermatitis, and ophthalmology. Topical clobetasone butyrate has shown minimal suppression of the hypothalamic–pituitary–adrenal axis.

<span class="mw-page-title-main">Notalgia paresthetica</span> Neuropathy causing itching between the shoulder blades

Notalgia paresthetica or Notalgia paraesthetica (NP) (also known as "Hereditary localized pruritus", "Posterior pigmented pruritic patch", and "subscapular pruritus") is a chronic sensory neuropathy. Notalgia paresthetica is a common localized itch, affecting mainly the area between the shoulder blades (especially the T2–T6 dermatomes) but occasionally with a more widespread distribution, involving the shoulders, back, and upper chest. The characteristic symptom is pruritus (itch or sensation that makes a person want to scratch) on the back, usually on the left hand side below the shoulder blade (mid to upper back). It is occasionally accompanied by pain, paresthesia (pins and needles), or hyperesthesia (unusual or pathologically increased sensitivity of the skin to sensory stimuli, such as pain, heat, cold, or touch), which results in a well circumscribed hyperpigmentation of a skin patch in the affected area.

Senile pruritus is one of the most common conditions in the elderly or people over 65 years of age with an emerging itch that may be accompanied with changes in temperature and textural characteristics. In the elderly, xerosis, is the most common cause for an itch due to the degradation of the skin barrier over time. However, the cause of senile pruritus is not clearly known. Diagnosis is based on an elimination criteria during a full body examination that can be done by either a dermatologist or non-dermatologist physician.

<span class="mw-page-title-main">Topical steroid withdrawal</span> Medical condition

Topical steroid withdrawal, also known as red burning skin and steroid dermatitis, has been reported in people who apply topical steroids for 2 weeks or longer and then discontinue use. Symptoms affect the skin and include redness, a burning sensation, and itchiness, which may then be followed by peeling.

<span class="mw-page-title-main">Oclacitinib</span> Janus kinase inhibitor


Oclacitinib, sold under the brand name Apoquel, is a veterinary medication used in the control of atopic dermatitis and pruritus from allergic dermatitis in dogs at least 12 months of age. Chemically, it is a synthetic cyclohexylamino pyrrolopyrimidine janus kinase inhibitor that is relatively selective for JAK1. It inhibits signal transduction when the JAK is activated and thus helps downregulate expression of inflammatory cytokines. While oclacitinib is effective, its long-term safety is currently unknown.

<span class="mw-page-title-main">Topical glucocorticoids</span>

Topical glucocorticoids are the topical forms of glucocorticoids. Topical glucocorticoids are used in the treatment of many skin conditions. They provide anti-inflammatory, antimitotic, and immune-system suppressing actions through various mechanisms.

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