Antipruritic
Antipruritics, abirritants,
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.
Topical
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- Antihistamines such as diphenhydramine (Benadryl) and hydroxyzine
- Corticosteroids such as hydrocortisone topical cream, see topical steroid
- Counterirritants, such as mint oil, menthol, or camphor[9]
- pramoxine, or benzocainein topical creams or lotions
| Medication | Mechanism of Action | Examples |
|---|---|---|
| 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
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:
| Medication | Mechanism of Action | Examples |
|---|---|---|
| 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][17] |
|
| μ-opioid receptor antagonists | Blocks the μ-opioid receptor, the stimulation of which causes itch in clinical settings such as itch due to liver diseases[18] | |
| Antidepressants | Reduces itch by mediating serotonin and histamine levels in the body.[19] | Two main classes of antidepressants are utilized to relieve itch:
|
| Immunosuppressants | Suppresses the immune system to reduce inflammation and hence reduce itch[20] | |
| Anticonvulsants | Mechanism 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:
| |
| 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:
- animal models of other prurituses[23]
- Oclacitinib, a janus kinase inhibitor used to control pruritus in dogs.
Substances proposed to act antipruritically, but not used medically
- Burow's solution, an astringent aqueous solution of aluminium triacetate, is shown to soothe and to relieve itching.[24]
- Olive oil
- poison sumac.[31]
- Paste of sodium bicarbonate (baking soda) and water, applied topically[32]
- Ammonium hydroxide (household ammonia), applied topically[32]
- Papain-based topical creams.
Alternative treatments
A number of herbs have been used to treat itching such as
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:
| Medication | Effectiveness |
|---|---|
| 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 antagonists | μ-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
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 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 (
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.
Antihistamines
Antihistamines target the molecule histamine by blocking the
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:
- Sexual dysfunction, which is the most common side effect of all serotonin reuptake inhibitors, manifesting as delayed ejaculation, inability to achieve orgasm and decreased libido.[52]
- Gastrointestinal effects such as nausea and vomiting, which depend on the dose and usually resolve within the first two weeks of treatment.[52]
- Central nervous system disturbances such as anxiety, insomnia and sedation.[52]
- Suicide risk: a combined analysis of placebo-controlled trials of various antidepressants including SSRIs in children and adolescents showed a doubled risk of suicide in those taking antidepressants.[53] In response, the United States Food and Drug Administration issued a warning in 2004 regarding the elevated risk of suicidal thoughts and behavior in children and adolescents.[53]
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
Abirritants have an extensive history in treating itch. The history of abirritants dates back to the
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
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
See also
References
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External links
- Paus, R. (2006). "Frontiers in pruritus research: scratching the brain for more effective itch therapy". Journal of Clinical Investigation. 116 (5): 1174–1185. PMID 16670758.
