Soniphen Capsule/Soniphen Injection

Soniphen Capsule/Soniphen Injection Mechanism of Action

diphenhydramine

Manufacturer:

Amherst Lab

Distributor:

Medichem

Marketer:

Amherst Parenterals
Full Prescribing Info
Action
Pharmacology: Diphenhydramine HCl is an ethanolamine antihistamine with anticholinergic (antimuscarinic), antitussive, anti-emetic, anti-vertigo, sedative and hypnotic properties. Diphenhydramine acts predominantly as a competitive but reversible inhibitor of histamine at the H1 receptor sites. The antitussive effect of diphenhydramine is due to a central mechanism involving suppression of the medullary cough center. The antiemetic and anti-motion sickness effects of diphenhydramine result from its central anticholinergic and central nervous system (CNS) depressant properties. Likewise, its activity on parkinsonian syndrome and drug-induced extrapyramidal reactions are related to its central anticholinergic effects. Anti-vertigo action is by central antimuscarinic effect on the vestibular apparatus and the integrative vomiting center and medullary chemoreceptor trigger zone of the mid brain. The exact mechanism for CNS depressant action is not known, but it is thought to cause indirect reduction of stimuli to the brain stem reticular formation.
Pharmacokinetics: Injectable diphenhydramine has a rapid onset of action. After intravenous (IV) injection of a single 50 mg dose over a 1-minute period in healthy adults, plasma diphenhydramine concentration one hour after the injection ranged from 99-196 ng/mL. A single oral dose of diphenhydramine HCl is quickly absorbed with maximum activity occurring in approximately one hour. The duration of activity after an average dose of diphenhydramine is from 4-6 hours. After single oral doses of 50 and 100 mg in healthy adults, peak plasma concentrations of 37-83 ng/mL and 81-159 ng/mL, respectively, have been reported. After oral administration of diphenhydramine dosages of 25 mg every 4 hours or 50 mg every 6 hours, peak steady-state plasma concentrations of the drug were 55 or 85 ng/mL, respectively, and minimum steady-state plasma concentrations were 27.5 or 30 ng/mL, respectively. Diphenhydramine is widely distributed throughout the body, including the CNS. The drug crosses the placenta and has been detected in milk, although the extent of distribution into milk has not been quantified. Diphenhydramine is approximately 80-85% bound to plasma proteins in vitro. Less extensive protein binding of the drug has been reported in healthy Asian adults and in adults with liver cirrhosis. After IV administration, diphenhydramine's volume of distribution is 4.5 L/kg, its half-life 8.4 hours, and its clearance, 6.2 mL/min/kg. In a study among Caucasian and Asian patients, diphenhydramine 50 mg given orally showed greater peak plasma concentrations among Asians compared with Caucasians. Plasma protein binding was 85.2% in Caucasians and 76% in Asians. Asians had higher mean volumes of distribution and mean clearance values. Diphenhydramine is rapidly and almost completely metabolized. After oral administration, the drug undergoes substantial first-pass metabolism in the liver. Diphenhydramine appears to be metabolized principally to diphenylmethoxyacetic acid, which may further undergo conjugation. The drug also undergoes dealkylation to form the N-demethyl and N,N-didemethyl derivatives. Diphenhydramine and its metabolites are excreted principally in urine. Plasma concentrations of diphenhydramine appear to decline in a monophasic manner, although some pharmacokinetic data suggest a polyphasic elimination. The terminal elimination half-life of diphenhydramine has not been fully explained, but appears to range from 2.4-9.3 hours in healthy adults.
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