Peringatan Keamanan

Overdose is expected to result in effects similar to the adverse effects that are ordinarily associated with the use of diphenhydramine, including drowsiness, hyperpyrexia, and anticholinergic effects, among others L5266, L5269, L5281, L5287, F3394. Additional symptoms during overdose may include mydriasis, fever, flushing, agitation, tremor, dystonic reactions, hallucinations and ECG changes L5287. Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, arrhythmias, coma and cardiovascular collapse L5287. Moreover, with higher doses, and particularly in children, symptoms of CNS excitation including hallucinations and convulsions may appear; with massive doses, coma or cardiovascular collapse may follow F3394.

Although diphenhydramine has been in widespread use for many years without ill consequence, it is known to cross the placenta and has been detected in breast milk F3394. This medication should therefore only be used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing fetus or suckling infant F3394.

Pharmacokinetic studies indicate no major differences in the distribution or elimination of diphenhydramine compared to younger adults F3394. Nevertheless, diphenhydramine should be used with caution in the elderly, who are more likely to experience adverse effects L5287. Avoid use in elderly patients with confusion L5287.

The results of a review on the use of diphenhydramine in renal failure suggest that in moderate to severe renal failure, the dose interval should be extended by a period dependent on Glomerular filtration rate (GFR) F3394.

After intravenous administration of 0.8 mg/kg diphenhydramine, a prolonged half-life was noted in patients with chronic liver disease which correlated with the severity of the disease F3394. However, the mean plasma clearance and apparent volume of distribution were not significantly affected F3394.

LD50=500 mg/kg (orally in rats). Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death.

Diphenhydramine

DB01075

small molecule approved investigational

Deskripsi

Diphenhydramine - perhaps known most commonly as its brand name formulation Benadryl - is a first-generation H1 receptor antihistamine that is used extensively for the treatment of seasonal allergies, insect bites and stings, and rashes L5263, L5266, L5269, F3379. However, it also has antiemetic, antitussive, hypnotic, and antiparkinson properties L5269, F3352. As histamine receptors exist both peripherally and in the central nervous system, diphenhydramine has been shown to cause sedation due to its competitive antagonism of histamine H1 receptors within the central nervous system L5263, L5266, L5269, F3379, A174541. While its use in allergy therapy can sometimes fall out of favor due to its sedative effect, diphenhydramine has been repurposed for use within many non-prescription over-the-counter sleep aids and cough-and-cold medications that have been marketed for "night time" use L5263, L5281, L5287.

Diphenhydramine is also used in combination with DB14132 as the anti-nausea drug DB00985 where it is utilized primarily for its antagonism of H1 histamine receptors within the vestibular system A1540.

Diphenhydramine has also been shown to be implicated in a number of neurotransmitter systems that affect behaviour including dopamine, norepinephrine, serotonin, acetylcholine, and opioid A1539. As a result, diphenhydramine is being investigated for its anxiolytic and anti-depressant properties.

Struktur Molekul 2D

Berat 255.3547
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The elimination half-life ranges from 2.4-9.3 hours in healthy adults [F3394, L5287]. The terminal elimination half-life is prolonged in liver cirrhosis [L5287].
Volume Distribusi Diphenhydramine is widely distributed throughout the body, including the CNS [F3394]. Following a 50 mg oral dose of diphenhydramine, the volume of distribution is in the range of 3.3 - 6.8 l/kg [F3394].
Klirens (Clearance) Values for plasma clearance of a 50 mg oral dose of diphenhydramine has been documented as lying in the range of 600-1300 ml/min [F3394].

Absorpsi

Diphenhydramine is quickly absorbed after oral administration with maximum activity occurring in approximately one hour A644, L5287. The oral bioavailability of diphenhydramine has been documented in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration A644, L5287.

Metabolisme

Diphenhydramine undergoes rapid and extensive first-pass metabolism F3394, L5287, A174577. In particular, two successive N-demethylations occur wherein diphenhydramine is demethylated to N-desmethyldiphenhydramine (the N-desmethyl metabolite) and then this metabolite is itself demethylated to N,N-didesmethyldiphenhydramine (the N,N-didesmethyl metabolite) F3394, A174577. Subsequently, acetyl metabolites like N-acetyl-N-desmethyldiphenhydramine are generated via the amine moiety of the N,N-didesmethyl metabolite A174577. Additionally, the N,N-didesmethyl metabolite also undergoes some oxidation to generate the diphenylmethoxyacetic acid metabolite as well F3394, L5287, A174577. The remaining percentage of a dose of administered diphenhydramine is excreted unchanged F3394, L5287, A174577. The metabolites are further conjugated with glycine and glutamine and excreted in urine L5287. Moreover, studies have determined that a variety of cytochrome P450 isoenzymes are involved in the N-demethylation that characterizes the primary metabolic pathway of diphenhydramine, including CYP2D6, CYP1A2, CYP2C9, and CYP2C19 A174574. In particular, CYP2D6 demonstrates higher affinity catalysis with the diphenhydramine substrate than the other isoenzymes identified A174574. Consequently, inducers or inhibitors of these such CYP enzymes may potentially affect the serum concentration and incidence and/or severity of adverse effects associated with exposure to diphenhydramine A174574.

Rute Eliminasi

The metabolites of diphenhydramine are conjugated with glycine and glutamine and excreted in urine L5281, L5287. Only about 1% of a single dose is excreted unchanged in urine L5281, L5287. The medication is ultimately eliminated by the kidneys slowly, mainly as inactive metabolites L5281, L5287.

Interaksi Makanan

2 Data
  • 1. Avoid alcohol.
  • 2. Take before a meal. Take 30 minutes before a meal or 30 minutes before departure for motion sickness.

Interaksi Obat

2278 Data
Buprenorphine Diphenhydramine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
Doxylamine Doxylamine may increase the central nervous system depressant (CNS depressant) activities of Diphenhydramine.
Dronabinol Dronabinol may increase the central nervous system depressant (CNS depressant) activities of Diphenhydramine.
Droperidol Droperidol may increase the central nervous system depressant (CNS depressant) activities of Diphenhydramine.
Hydrocodone Diphenhydramine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Magnesium sulfate The therapeutic efficacy of Diphenhydramine can be increased when used in combination with Magnesium sulfate.
Methotrimeprazine Diphenhydramine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
Metyrosine Diphenhydramine may increase the sedative activities of Metyrosine.
Minocycline Minocycline may increase the central nervous system depressant (CNS depressant) activities of Diphenhydramine.
Nabilone Nabilone may increase the central nervous system depressant (CNS depressant) activities of Diphenhydramine.
Orphenadrine Diphenhydramine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
Paraldehyde Diphenhydramine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
Perampanel Perampanel may increase the central nervous system depressant (CNS depressant) activities of Diphenhydramine.
Pramipexole Diphenhydramine may increase the sedative activities of Pramipexole.
Ropinirole Diphenhydramine may increase the sedative activities of Ropinirole.
Rotigotine Diphenhydramine may increase the sedative activities of Rotigotine.
Rufinamide The risk or severity of adverse effects can be increased when Rufinamide is combined with Diphenhydramine.
Suvorexant Diphenhydramine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
Tapentadol Tapentadol may increase the central nervous system depressant (CNS depressant) activities of Diphenhydramine.
Thalidomide Diphenhydramine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
Zolpidem Diphenhydramine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Aclidinium The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Aclidinium.
Mianserin Mianserin may increase the anticholinergic activities of Diphenhydramine.
Mirabegron The risk or severity of urinary retention can be increased when Diphenhydramine is combined with Mirabegron.
Potassium chloride The risk or severity of gastrointestinal ulceration can be increased when Diphenhydramine is combined with Potassium chloride.
Pramlintide The risk or severity of reduced gastrointestinal motility can be increased when Pramlintide is combined with Diphenhydramine.
Secretin porcine The therapeutic efficacy of Secretin porcine can be decreased when used in combination with Diphenhydramine.
Tiotropium The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Tiotropium.
Topiramate The risk or severity of hyperthermia and oligohydrosis can be increased when Diphenhydramine is combined with Topiramate.
Umeclidinium The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Umeclidinium.
Benzylpenicilloyl polylysine Diphenhydramine may decrease effectiveness of Benzylpenicilloyl polylysine as a diagnostic agent.
Betahistine The therapeutic efficacy of Betahistine can be decreased when used in combination with Diphenhydramine.
Hyaluronidase (ovine) Hyaluronidase (ovine) can cause an increase in the absorption of Diphenhydramine resulting in an increased serum concentration and potentially a worsening of adverse effects.
Hyaluronidase (human recombinant) Hyaluronidase (human recombinant) can cause an increase in the absorption of Diphenhydramine resulting in an increased serum concentration and potentially a worsening of adverse effects.
Hyaluronidase Hyaluronidase can cause an increase in the absorption of Diphenhydramine resulting in an increased serum concentration and potentially a worsening of adverse effects.
Methadone The risk or severity of adverse effects can be increased when Methadone is combined with Diphenhydramine.
Sodium oxybate Diphenhydramine may increase the central nervous system depressant (CNS depressant) activities of Sodium oxybate.
Atomoxetine The metabolism of Atomoxetine can be decreased when combined with Diphenhydramine.
Glycopyrronium The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Glycopyrronium.
Linezolid The risk or severity of serotonin syndrome can be increased when Linezolid is combined with Diphenhydramine.
Botulinum toxin type A The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Botulinum toxin type A.
Glucagon Diphenhydramine may increase the gastrointestinal motility reducing activities of Glucagon.
Sulpiride Diphenhydramine may increase the anticholinergic activities of Sulpiride.
Botulinum toxin type B The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Botulinum toxin type B.
Mirtazapine Diphenhydramine may increase the serotonergic activities of Mirtazapine.
Eluxadoline The risk or severity of constipation can be increased when Diphenhydramine is combined with Eluxadoline.
Ramosetron The risk or severity of constipation can be increased when Diphenhydramine is combined with Ramosetron.
Ethanol Diphenhydramine may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
Azelastine Diphenhydramine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
Brimonidine Brimonidine may increase the central nervous system depressant (CNS depressant) activities of Diphenhydramine.
Sertraline The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Sertraline.
Sibutramine The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Sibutramine.
Nefazodone The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Nefazodone.
Zimelidine The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Zimelidine.
Dapoxetine The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Dapoxetine.
Milnacipran The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Milnacipran.
Desvenlafaxine The risk or severity of serotonin syndrome can be increased when Desvenlafaxine is combined with Diphenhydramine.
Seproxetine The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Seproxetine.
Levomilnacipran The risk or severity of serotonin syndrome can be increased when Diphenhydramine is combined with Levomilnacipran.
Indalpine The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Indalpine.
Alaproclate The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Alaproclate.
Citalopram The risk or severity of QTc prolongation can be increased when Diphenhydramine is combined with Citalopram.
Phentermine Phentermine may decrease the sedative activities of Diphenhydramine.
Benzphetamine Benzphetamine may decrease the sedative activities of Diphenhydramine.
Diethylpropion Diethylpropion may decrease the sedative activities of Diphenhydramine.
Lisdexamfetamine The risk or severity of serotonin syndrome can be increased when Diphenhydramine is combined with Lisdexamfetamine.
Mephentermine Mephentermine may decrease the sedative activities of Diphenhydramine.
MMDA MMDA may decrease the sedative activities of Diphenhydramine.
Midomafetamine Midomafetamine may decrease the sedative activities of Diphenhydramine.
2,5-Dimethoxy-4-ethylamphetamine 2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Diphenhydramine.
4-Bromo-2,5-dimethoxyamphetamine 4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Diphenhydramine.
Tenamfetamine Tenamfetamine may decrease the sedative activities of Diphenhydramine.
Chlorphentermine Chlorphentermine may decrease the sedative activities of Diphenhydramine.
Methylenedioxyethamphetamine Methylenedioxyethamphetamine may decrease the sedative activities of Diphenhydramine.
Dextroamphetamine Dextroamphetamine may decrease the sedative activities of Diphenhydramine.
Metamfetamine Metamfetamine may decrease the sedative activities of Diphenhydramine.
Iofetamine I-123 Iofetamine I-123 may decrease the sedative activities of Diphenhydramine.
Ritobegron Ritobegron may decrease the sedative activities of Diphenhydramine.
Mephedrone Mephedrone may decrease the sedative activities of Diphenhydramine.
Methoxyphenamine Methoxyphenamine may decrease the sedative activities of Diphenhydramine.
Gepefrine Gepefrine may decrease the sedative activities of Diphenhydramine.
2,5-Dimethoxy-4-ethylthioamphetamine 2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Diphenhydramine.
Phendimetrazine Phendimetrazine may decrease the sedative activities of Diphenhydramine.
Amphetamine Amphetamine may decrease the sedative activities of Diphenhydramine.
Desomorphine The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Desomorphine.
Morphine The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Morphine.
Hydromorphone The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Hydromorphone.
Oxycodone The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Oxycodone.
Butorphanol The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Butorphanol.
Dextropropoxyphene The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Dextropropoxyphene.
Pentazocine The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Pentazocine.
Sufentanil The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Sufentanil.
Alfentanil The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Alfentanil.
Fentanyl The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Fentanyl.
Nalbuphine The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Nalbuphine.
Levorphanol The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Levorphanol.
Remifentanil The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Remifentanil.
Diphenoxylate The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Diphenoxylate.
Oxymorphone The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Oxymorphone.
Dezocine The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Dezocine.

Target Protein

Histamine N-methyltransferase HNMT
Histamine H1 receptor HRH1
Muscarinic acetylcholine receptor M2 CHRM2

Referensi & Sumber

Synthesis reference: Alison B. Lukacsko, Joseph J. Piala, "Effect of a combination of a terbutaline, diphenhydramine and ranitidine composition on gastrointestinal injury produced by nonsteroidal anti-inflammatory compositions." U.S. Patent US5260333, issued December, 1983.
Artikel (PubMed)
  • PMID: 16680933
    Raphael GD, Angello JT, Wu MM, Druce HM: Efficacy of diphenhydramine vs desloratadine and placebo in patients with moderate-to-severe seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2006 Apr;96(4):606-14.
  • PMID: 25493135
    Abdi A, Rose E, Levine M: Diphenhydramine overdose with intraventricular conduction delay treated with hypertonic sodium bicarbonate and i.v. lipid emulsion. West J Emerg Med. 2014 Nov;15(7):855-8. doi: 10.5811/westjem.2014.8.23407. Epub 2014 Sep 19.
  • PMID: 11835984
    Halpert AG, Olmstead MC, Beninger RJ: Mechanisms and abuse liability of the anti-histamine dimenhydrinate. Neurosci Biobehav Rev. 2002 Jan;26(1):61-7.
  • PMID: 4329456
    Jaju BP, Wang SC: Effects of diphenhydramine and dimenhydrinate on vestibular neuronal activity of cat: a search for the locus of their antimotion sickness action. J Pharmacol Exp Ther. 1971 Mar;176(3):718-24.
  • PMID: 15023018
    Flake ZA, Scalley RD, Bailey AG: Practical selection of antiemetics. Am Fam Physician. 2004 Mar 1;69(5):1169-74.
  • PMID: 2866055
    Paton DM, Webster DR: Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clin Pharmacokinet. 1985 Nov-Dec;10(6):477-97.
  • PMID: 17020955
    Akutsu T, Kobayashi K, Sakurada K, Ikegaya H, Furihata T, Chiba K: Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metab Dispos. 2007 Jan;35(1):72-8. doi: 10.1124/dmd.106.012088. Epub 2006 Oct 4.
  • PMID: 22337782
    Rodrigues WC, Castro C, Catbagan P, Moore C, Wang G: Immunoassay screening of diphenhydramine (Benadryl(R)) in urine and blood using a newly developed assay. J Anal Toxicol. 2012 Mar;36(2):123-9. doi: 10.1093/jat/bkr015.

Contoh Produk & Brand

Produk: 3179 • International brands: 18
Produk
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    Tablet, film coated • - • Oral • US • OTC
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    Tablet, film coated • - • Oral • US • Generic • OTC • Approved
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    Powder, for solution • - • Oral • US • OTC
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Menampilkan 8 dari 3179 produk.
International Brands
  • Aleryl
  • Alledryl
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  • Belix
  • Benylan — Biogen
  • Dermodrin — Montavit
  • Desentol — Meda
  • Dibondrin — Montavit
  • Dimedrol — Zdorovie
  • Diphen — Wockhardt

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