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| {{drugbox | | {{Details0|Diphenhydramine (oral)}} |
| | IUPAC_name = 2-benzhydryloxy-''N'',''N''-dimethyl-ethanamine | | {{Details0|Diphenhydramine (Injection)}} |
| | image = Diphenhydramine_Structure.svg
| | {{Details0|Diphenhydramine (topical)}} |
| | CAS_number = 58-73-1
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| | ATC_prefix = D04
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| | ATC_suffix = AA32
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| | ATC_supplemental = {{ATC|D04|AA33}}, {{ATC|R06|AA02}}
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| | PubChem = 3100
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| | DrugBank = APRD00587
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| | C=17 | H=21 | N=1 | O=1
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| | molecular_weight = 255.355 g/mol
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| | bioavailability = 86% bound to plasma protein
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| | protein_bound = 98 to 99%
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| | metabolism = Various cytochrome P450 liver enzymes (cyp 2D6 (80%) ,cyp 3A4 (10%)<br />
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| | elimination_half-life = 2-8 hours
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| | pregnancy_category = B
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| | legal_status = Over-the-counter, non-regulated
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| | routes_of_administration = Oral, parenteral (IM), suppository
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| | excretion = 94% through the urine, 6% through feces
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| }}
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| {| border="1" cellpadding="3" cellspacing="0" width="250px" align="right" style="border-collapse: collapse; margin: 0 0 0 0.5em"
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| </table><table bgcolor="#ffffff" border="1" cellpadding="3" cellspacing="0" width="167px" align="right" style="border-collapse: collapse; clear: right; margin: 0 0 0 0.5em">
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| |'''Indicated for:'''<br/>
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| * [[Antihistamine|Antihistaminic]]
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| * [[Motion sickness]]
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| * [[Sedative]]/[[Hypnotic]]
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| '''Other uses:'''<br/>
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| * Halting allergic reactions, controlling [[extrapyramidal]] side-effects induced by [[antipsychotic]]s
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| |'''[[Contraindication]]s:'''<br/>
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| * Use in neonates and premature infants
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| * Use in nursing mothers
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| * Use as a local anesthetic
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| * Use in people with hypersensitivity to diphenhydramine hydrochloride and other antihistamines of similar chemical structure
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| |-
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| |'''[[Recreational drug use|Non-medical]] use/abuse:'''<br/>
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| *Used as a deliriant/hallucinogen
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| |'''[[Adverse drug reaction|Side effects]]:'''
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| <div style="background: #ffcc99">
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| '''''{{red|Severe:}}'''''
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| * [[Myocardial infarction]] (Heart Attack), serious [[cardiac arrhythmia|ventricular dysrhythmias]], [[coma]] and [[death]]
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| </div>
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| '''''Atypical [[sensation]]s:'''''
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| *Feelings of heaviness, hearing disturbance
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| '''''[[Cardiovascular]]:'''''
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| *Hypertension in sensitive individuals
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| '''''[[Ear]], [[nose]], and [[throat]]:'''''
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| *Dryness of the nose and throat, heartburn
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| '''''[[Endocrinal]]:'''''
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| *Increased or decreased appetite
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| '''''[[Eye]]:'''''
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| *Dryness of the eyes, redness of the eyes, yellowing of the eyes
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| '''''[[Gastrointestinal]]:'''''
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| *Constipation, nausea
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| '''''[[Hematological]]:'''''
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| *Hepatotoxicity in extremely large dosages
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| '''''[[Muscle|Musculo]][[skeletal]]:'''''
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| *Incoordination, slow muscle response, [[fasciculations]] (twitching), restlessness, extrapyramidal side-effects, restless-leg syndrome
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| '''''[[Neurological]]:'''''
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| *Confusion, clouded thinking, drowsiness, hallucinations, delirium, euphoria, short-term memory loss
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| '''''[[Psychological]]:'''''
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| *Agitation, anxiety, emotional lability, depression, excitability (especially in children), paranoia
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| '''''[[Respiration (physiology)|Respiratory]]:'''''
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| *Decreased respiration
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| '''''[[Skin]]:'''''
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| *[[Photosensitivity]], flushing
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| '''''[[Urogenital]] and [[reproductive]]:'''''
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| *Urinary retention, sexual dysfunction, vaginal dryness, decreased libido
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| '''''Miscellaneous:'''''
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| *?
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| |}
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| {{SI}}
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| {{CMG}} | |
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| ==Overview==
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| '''Diphenhydramine hydrochloride''' (trade name '''[[Benadryl]]''', as produced by [[J&J]], or '''Dimedrol''' outside the U.S. & Canada. '''[[Nytol]]''' as a sleeping pill) is an [[Over-the-counter drug|over-the-counter]] (OTC) [[antihistamine]], [[sedative]] and [[hypnotic]]. It may also be used for the treatment of [[extrapyramidal]] side effects of [[typical antipsychotic]]s. It is a member of the [[ethanolamine]] class of [[antihistaminergic]] agents.
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| Diphenhydramine was the first known antihistamine, invented in 1943 by Dr. [[George Rieveschl]].
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| The brand Benadryl is currently [[trademark]]ed in the [[United States]] by [[Pfizer]], however many drug store chains and retail outlets manufacture less-costly [[Generic drug|generic versions]] under their own store brands.
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| == Pharmacological action ==
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| Diphenhydramine works by blocking the effect of histamine at [[H1 receptor|H1]] [[transmembrane receptor|receptor]] sites. This results in effects such as the reduction of [[smooth muscle]] contraction, making diphenhydramine a popular choice for treatment of the symptoms of [[Hay fever|allergic rhinitis]], [[hives]], [[motion sickness]], and insect bites and stings. | |
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| In the 1960s it was found that diphenhydramine inhibits [[reuptake]] of the [[neurotransmitter]] [[serotonin]]. This discovery led to a search for viable [[antidepressant]]s with similar structures and fewer side effects, culminating in the invention of [[fluoxetine]] (Prozac), a [[selective serotonin reuptake inhibitor]] (SSRI). A similar search had previously led to the synthesis of the first SSRI [[zimelidine]] from [[chlorpheniramine]], also an antihistamine.
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| == Common use and dosage ==
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| Diphenhydramine is a [[Antihistamine#First-generation H1-receptor antagonists|first-generation antihistamine]] drug. Despite being one of the oldest antihistamines on the market, it is largely the most effective antihistamine available either by prescription or over-the-counter, and has been shown to exceed the effectiveness of even the latest prescription drugs.<ref>{{cite journal | author = Raphael GD, Angello JT, Wu MM, Druce HM | title = Efficacy of diphenhydramine vs desloratadine and placebo in patients with moderate-to-severe seasonal allergic rhinitis. | journal = Ann Allergy Asthma Immunol | volume = 96 | issue = 4 | pages = 606-614 | year = 2006 | id = PMID 16680933}}</ref> Consequently, it is frequently used when an allergic reaction requires fast, effective reversal of the often dangerous effects of a massive histamine release. However, it is not always the drug of choice for treating allergies.
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| It is known that diphenhydramine contains [[sedative]] properties. Many new antihistamines have been introduced without the side effect of sedation. The drug is also used as a [[sleep aid]] and is an ingredient in many sleep aids, such as [[Unisom]] gelcaps (however, the tablet form of Unisom contains [[Doxylamine]], a different active ingredient<ref>{{cite web|url=http://www.chattem.com/qna/unisomFAQ.asp#FAQ1162|title=Chattem: Unisom}}</ref>), and most notably [[Tylenol PM]] where it is combined with [[Acetaminophen]] ([[Paracetamol]]), and Nytol and Sominex which have diphenhydramine as the only active ingredient. Several generic and store brands of antihistamines and sleep aids also contain solely diphenhydramine.
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| Diphenhydramine is widely used in [[Over-the-counter drug|nonprescription]] sleep aids with a maximum recommended dose of 50mg (as the [[hydrochloride]] salt) being mandated by the FDA. In the [[United Kingdom]], [[Australia]], [[New Zealand]], [[South Africa]], and other countries, a 50 to 100mg recommended dose is permitted. | |
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| There are also topical formulations of diphenhydramine available, including creams, lotions, gels, and sprays. They are used to relieve itching, and have the advantage of causing much less systemic effect (i.e. drowsiness) than oral forms.
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| ==Side effects==
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| Like many other first generation antihistamines, diphenhydramine is a potent [[anticholinergic]] agent. This leads to profound drowsiness as a very common side-effect, along with the possibilities of motor impairment ([[ataxia]]), dry mouth and throat, flushed skin, rapid or irregular heartbeat ([[tachycardia]]), blurred vision at nearpoint due to lack of accommodation ([[cycloplegia]]), abnormal sensitivity to bright light ([[photophobia]]), pupil dilatation ([[mydriasis]]), urinary retention ([[ischuria]]), constipation, difficulty concentrating, short-term memory loss, visual disturbances, hallucinations, confusion, erectile dysfunction, and delirium. Some side effects such as twitching may be delayed until the drowsiness begins to cease and the person is in more of an awakening mode. Diphenhydramine also has [[local anesthetic]] properties, and has been used for patients allergic to common [[local anesthetics]] like [[lidocaine]].<ref>http://www.postgradmed.com/issues/1999/08_99/smith.htm</ref> Severe, prolonged twitching and muscle spasm have also been experienced.
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| The most common cardiac dysrhythmias associated with diphenhydramine overdose are sinus bradycardia, elongated S-T segment interval, and premature ventricular contraction.
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| Diphenhydramine is very similar in its effects to [[dimenhydrinate]] (Dramamine<sup>®</sup>), its [[8-chlorotheophylline]] salt, although the latter is approximately 60% the potency in terms of required dosage and is slightly less sedating.
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| Some patients have an allergic reaction to diphenhydramine in the form of hives.
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| ==Recreational use==
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| Those who use diphenhydramine [[recreational drug use|recreationally]] take a higher dose than recommended (usually between 225mg and 450mg)<ref>http://www.erowid.org/pharms/diphenhydramine/diphenhydramine_dose.shtml</ref> for its [[deliriant]] effects. Diphenhydramine is also a component of the recreational form of [[heroin]] known as "[[cheese (recreational drug)|cheese]]" or "chiva". The mental effects are described by many as "dreaming while awake" involving visual and auditory hallucinations which, unlike those experienced with most [[psychedelic drug]]s, often cannot be readily distinguished from reality. Diphenhydramine generally has a low abuse profile due to the frequently unpleasant nature of the hallucinations. People who consume a high recreational dose can possibly find themselves in a hallucination which places them in a familiar situation with people and friends and rooms they know, while in reality being in a totally different setting. Inexperienced users of hallucinogens are liable to [[panic]]. Many users report a side effect profile consistent with [[tropane]] [[alkaloid|glycoalkaloidal]] poisoning.
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| This is due to [[receptor antagonist|antagonism]] of [[muscarinic]] [[acetylcholine]] receptors in both the [[central nervous system|central]] and [[autonomic nervous system]] which inhibits various [[signal transduction]] pathways. In the [[Central Nervous System|CNS]], diphenhydramine readily crosses the [[blood-brain barrier]], exerting effects within the [[visual cortex|visual]] and [[primary auditory cortex|auditory cortex]].
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| Other [[Central Nervous System|CNS]] effects occur within the [[limbic system]] and [[hippocampus]], causing [[confusion]] and temporary [[amnesia]]. Toxicology also manifests in the [[autonomic nervous system]], primarily at the [[neuromuscular junction]], resulting in [[ataxia]] and [[extrapyramidal]] side-effects, and at [[sympathetic nervous system|sympathetic]] post-[[ganglion]]ic junctions, causing [[urinary retention]], pupil dilation, [[tachycardia]], irregular [[urination]], and dry skin and [[mucous membranes]]. Considerable overdosage can lead to [[myocardial infarction]] (heart attack), serious [[cardiac arrhythmia|ventricular dysrhythmias]], [[coma]] and [[death]]. Such a side-effect profile is thought to give [[ethanolamine]]-class antihistamines a relatively low abuse liability. The specific antidote for diphenhydramine poisoning is [[physostigmine]], usually given by IV in hospital.
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| ==See also==
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| *[[Akathisia]]
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| *[[Acrivastine]] (UK Benadryl Benadryl Allergy Relief)
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| *[[Cetirizine]] (UK Benadryl Once-A-Day)
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| ==External links==
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| *[http://media.pfizer.com/files/products/uspi_benadryl.pdf Prescription Information] ([[PDF]])
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| *[http://www.umm.edu/altmed/drugs/diphenhydramine-043500.htm DiphenhydrAMINE] University of Maryland Medical Center - Includes comprehensive dosage recommendations
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| ==References==
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| ===Notes===
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| <references/>
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| ===Sources===
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| * Bruce G. Charlton, ''[http://www.hedweb.com/bgcharlton/sdtm.html Self-management of psychiatric symptoms using over-the-counter (OTC) psychopharmacology: the S-DTM therapeutic model - self-diagnosis, self-treatment, self-monitoring]''. ''Medical Hypotheses'' 2005; 65: 823-828.
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| * J.A. Lieberman, ''History of the use of antidepressants in primary care''. Primary Care Companion, [[Journal of Clinical Psychiatry]] [[2003]]; 5 (supplement 7).
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| {{Antihistamines}}
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| {{Antipruritics}}
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| {{Deliriants}}
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| [[de:Diphenhydramin]]
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| [[ja:ドリエル]]
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| [[ru:Димедрол]]
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| [[th:ไดเฟนไฮดรามีน]]
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| [[Category:Drugs]]
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| [[Category:Antiemetics]]
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| [[Category:Deliriants]]
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| [[Category:H1 receptor antagonists]]
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| [[Category:Muscarinic antagonists]]
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| [[Category:Sedatives]]
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| [[Category:Hypnotics]]
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| [[Category:Tardive dyskinesia]]
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| [[Category:Drugs]]
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| [[pl:Difenhydramina]]
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| {{jb1}}
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| {{WH}}
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| {{WS}}
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