Does occasional use of anticholinergic drugs such as Benadryl have serious neurological ris… by Connie b. Dellobuono
Answer by Connie b. Dellobuono:
Toxicity of meds is greater for over 60 yrs old and under 6 yrs old. Benadryl gave rise to creation of Prozac.
Diphenhydramine (DPH, DHM) is a first-generation antihistamine mainly used to treat allergies. It is also used in the management of drug-induced parkinsonism and other extrapyramidal symptoms. The medication has a sedating effect and is FDA-approved as a nonprescription sleep aid. It possesses anticholinergic, antitussive, antiemetic, and sedative properties.
Diphenhydramine was first synthesized by George Rieveschl and first made publicly available through prescription in 1946. Diphenhydramine is marketed under the trade name Benadryl by McNeil Consumer Healthcare in the U.S., Canada, and South Africa (trade names in other countries include Dimedrol, Daedalon, and Nytol). It is also available as a generic medication.
Diphenhydramine is a first-generation antihistamine used to treat a number of conditions including allergic symptoms and itchiness, the common cold, insomnia, motion sickness, and extrapyramidal symptoms. Diphenhydramine also has local anesthetic properties, and has been used as such in people allergic to common local anesthetics such as lidocaine.
Diphenhydramine has been found to have a higher efficacy in treatment of allergies than some second-generation antihistamines (such as desloratadine) but a similar efficacy with others (such as cetirizine).
njectable diphenhydramine is typically used in addition to epinephrine for anaphylaxis. As of 2007 it was the most commonly used antihistamine for acute allergic reactions in emergency departments. As of 2007 its use for this purpose has not been properly studied.
Also, topical formulations of diphenhydramine are available, including creams, lotions, gels, and sprays. These are used to relieve itching, and have the advantage of causing fewer systemic effects (e.g., drowsiness) than oral forms.
Diphenhydramine is used to treat Parkinson's disease-like extrapyramidal symptoms caused by antipsychotics.
Because of its sedative properties, diphenhydramine is widely used in nonprescription sleep aids for insomnia. The drug is an ingredient in several products sold as sleep aids, either alone or in combination with other ingredients such as acetaminophen (paracetamol). An example of the latter is Tylenol PM. Diphenhydramine can cause minor psychological dependence. Diphenhydramine can cause sedation and has also been used as an anxiolytic.
Diphenhydramine also has antiemetic properties, which make it useful in treating the nausea that occurs in vertigo and motion sickness.
The most prominent side effect is sedation. A typical dose creates driving impairment equivalent to a blood-alcohol level of 0.1 which is higher than the 0.08 limit of most drunk driving laws.
Diphenhydramine is a potent anticholinergic agent. This activity is responsible for the side effects of dry mouth and throat, increased heart rate, pupil dilation, urinary retention, constipation, and, at high doses, hallucinations or delirium. Other side effects include motor impairment (ataxia), flushed skin, blurred vision at nearpoint owing to lack of accommodation (cycloplegia), abnormal sensitivity to bright light (photophobia), sedation, difficulty concentrating, short-term memory loss, visual disturbances, irregular breathing, dizziness, irritability, itchy skin, confusion, increased body temperature (in general, in the hands and/or feet), temporary erectile dysfunction, and excitability, and although it can be used to treat nausea, higher doses may cause vomiting. 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. It has been implicated in the occasional development of restless leg syndrome.
Torsades de pointes can occur as a side effect of diphenhydramine
Acute poisoning can be fatal, leading to cardiovascular collapse and death in 2–18 hours, and in general is treated using a symptomatic and supportive approach. Diagnosis of toxicity is based on history and clinical presentation, and in general specific levels are not useful. Several levels of evidence strongly indicate diphenhydramine (similar to chlorpheniramine) can block the delayed rectifier potassium channel and, as a consequence, prolong the QT interval, leading to cardiac arrhythmias such as torsades de pointes. No specific antidote for diphenhydramine toxicity is known, but the anticholinergic syndrome has been treated with physostigmine for severe delirium or tachycardia. Benzodiazepines may be administered to decrease the likelihood of psychosis, agitation, and seizures in patients who are prone to these symptoms.
Some patients have an allergic reaction to diphenhydramine in the form of hives. However, restlessness or akathisia can also be a side effect made worse by increased levels of diphenhydramine, especially with recreational dosages. As diphenhydramine is extensively metabolized by the liver, caution should be exercised when giving the drug to individuals with hepatic impairment.
Long term anticholinergic use is associated with an increased risk for cognitive decline and dementia among older people.
Diphenhydramine is not recommended for patients older than 60 or children under the age of six, unless a physician is consulted. These populations should be treated with second-generation antihistamines such as loratadine, desloratadine, fexofenadine, cetirizine, levocetirizine, and azelastine. Due to its strong anticholinergic effects, diphenhydramine is on the "Beers list" of drugs to avoid in the elderly.
Diphenhydramine is category B in the FDA Classification of Drug Safety During Pregnancy. It is also excreted in breast milk. Paradoxical reactions to diphenhydramine have been documented, in particular among children, and it may cause excitation instead of sedation.
Topical diphenhydramine is sometimes used especially on patients in hospice. This use is without indication and topical diphenhydramine should not be used as treatment for nausea because research does not indicate this therapy is more effective than alternatives.
Measurement in body fluids
Diphenhydramine can be quantified in blood, plasma, or serum. Gas chromatography with mass spectrometry (GC-MS) can be used with electron ionization on full scan mode as a screening test. GC-MS or GC-NDP can be used for quantification. Rapid urine drug screens using immunoassays based on the principle of competitive binding may show false-positive methadone results for patients having ingested diphenhydramine. Quantification can be used to monitor therapy, confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest, or assist in a death investigation.
Mechanism of action
Overview of diphenhydramine targets and effects
Diphenhydramine is an inverse agonist of the histamine H1 receptor. It is a member of the ethanolamine class of antihistaminergic agents. By reversing the effects of histamine on the capillaries, it can reduce the intensity of allergic symptoms. It also crosses the blood–brain barrier and inversely agonizes the H1 receptors centrally. Its effects on central H1 receptors cause drowsiness.
Like many other first-generation antihistamines, diphenhydramine is also a potent antimuscarinic (a competitive antagonist of muscarinic acetylcholine receptors) and, as such, at high doses can cause anticholinergic syndrome. The utility of diphenhydramine as an antiparkinson agent is the result of its blocking properties on the muscarinic acetylcholine receptors in the brain.
Diphenhydramine also acts as an intracellular sodium channel blocker, which is responsible for its actions as a local anesthetic. Diphenhydramine has also been shown to inhibit the reuptake of serotonin. It has been shown to be a potentiator of analgesia induced by morphine, but not by endogenous opioids, in rats.