Antihistamines history

The history of histamine [51-45-6] (1), and the development of antihistamines have been reviewed (1,2). Histamine was the first to be... 

Antihistamines such as diphenhydramine are known for their sedating properties and are frequently used over-the-counter medications (usual doses 25-50 mg) for difficulty sleeping. Diphenhydramine is approved by the FDA for the treatment of insomnia and can be effective at reducing sleep latency and increasing sleep time.43 However, diphenhydramine produces undesirable anticholinergic effects and carryover sedation that limit its use. As with TCAs and BZDRAs, diphenhydramine should be used with caution in the elderly. Valerian root is an herbal sleep remedy that has inconsistent effects on sleep but may reduce sleep latency and efficiency at commonly used doses of 400 to 900 mg valerian extract. Ramelteon, a new melatonin receptor agonist, is indicated for insomnia characterized by difficulty with sleep onset. The recommended dose is 8 mg at bedtime. Ramelteon is not a controlled substance and thus may be a viable option for patients with a history of substance abuse. 

In AIT, patient selection is critical. The allergic cause of AR should be verified by history and skin or blood tests. Additionally, the responsible antigen(s) must be identified. Patients who may benefit from AIT include those who do not tolerate traditional drug therapy (e.g., nosebleeds with intranasal steroids and sedation with antihistamines), suffer from severe symptoms, have comorbid conditions (e.g., asthma and sinusitis), fail drug therapy, or prefer not to take long-term medication.11 22"24... 

Antihistamines help to initiate sleep and, depending on their half-life, may produce little hangover. They are not addictive and therefore may be preferred for patients with a history of substance abuse. Diphenhydramine is usually an effective hypnotic at 25-50 mg at bedtime. The same dose tends to be effective for hydroxyzine. 

Anticholinergic effects Antihistamines have varying degrees of atropine-like actions use with caution in patients with a predisposition to urinary retention, history of bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension. 

Contraindications Acute asthmatic attack, patients receiving MAO inhibitors, history of hypersensitivity to antihistamines... 

For those with a history of substance abuse or intolerance to benzodiazepines and the elderly, caution must be used in controlling anxiety. In these cases, benzodiazepines may exacerbate other conditions. Preliminary reports suggest that antipsychotics such as quetiapine may alleviate symptoms of anxiety. Other strategies include use of antihistamines such as hydroxyzine and diphenhydramine. 

Benzimidazoles substituted with an alkylamine at position 2 have a venerable history as Hi antihistaminic agents. The standard starting material for many benzimidazoles consists of phenylenediamine (40-1), or its derivatives. Reaction of that compound with chloroacetic acid can be rationalized by invoking initial formation of the chloromethyl amide (40-2). Imide formation with the remaining free amino group closes the ring to afford the 2-chloromethyl benzimidazole (40-3). Displacement of... 

Chlorpromazine s (CPZ) efficacy was discovered primarily by chance in exploratory clinical trials after it had been initially synthesized as an antihistamine. Its discovery, however, was not entirely fortuitous, because it was chosen for human investigation since it was mildly sedating. The concept of an antipsychotic, however, was unknown. CPZ s sedative properties then led the French anesthesiologist and surgeon Henri Laborit to use it in a lytic cocktail to reduce autonomic response with surgical stress (1). He also persuaded many clinicians to try it for the treatment of a wide variety of other disorders. In this context, he encouraged John Delay and Pierre Deniker (1952), who then administered CPZ to schizophrenic patients. The rest is history ( 2, 3). 

Hydroxyzine [hye DROX i zeen] is an antihistamine with antiemetic activity. It has a low tendency for habituation thus it is useful for patients with anxiety, who have a history of drug abuse. It is also often used for sedation prior to dental procedures or surgery. 

Both Vicks Sinex, which contains oxymetazoline, and Sudafed, which contains pseudoephedrine, should be stopped because these are contributing to some of his symptoms, (rebound effect). Recommend a once-a-day non-sedating antihistamine. However, only cetirizine is safe - the other antihistamines are contraindicated because of his history of porphyria. 

There is stunning similarity between the penclomedine story and the history of terfenadine (Seldane), a highly successful antihistamine product that was withdrawn from marketing. In early clinical studies of terfenadines, it was not appreciated that the major source of clinical benefit was its metabolite, fexofenadine (Allegra see structures in Chapter 1, Figure 1.2). It became obvious that the metabolite should have been the lead compound only after car-diotoxicity was subsequently discovered for the parent drug but not the metabolite. 

A 37-year-old woman with a 5-year history of multiple itchy nodules on the outer aspects of the upper parts of the arms at sites of previous vaccine injections had been receiving hyposensitization vaccines to treat recurrent extrinsic asthma and rhinitis for 10 years (56). Physical examination and a biopsy of one of the nodules were identical to those of the previous case. Patch tests with aluminium chloride were negative. Symptomatic relief was obtained with topical corticosteroids and oral antihistamines. The nodules persisted for at least 3 years. 

A 56-year-old Nigerian woman, with a previous history of sickle cell trait, osteoarthritis, and non-insulin-dependent diabetes mellitus, took amlodipine 5 mg/day for hypertension for 2 weeks and developed a lichenoid eruption (15). Histological examination confirmed the diagnosis of lichen planus. Amlodipine was withdrawn and there was rapid symptomatic and clinical improvement after treatment with glucocorticoids and antihistamines. 

However, cardiac dysrhjdhmias in patients taking antihistamines may be related to other factors, and in this case the patient was also taking another antihistamine and had a history of hepatitis. 

A 71-year-old man received intrathecal anesthesia using 0.3% cinchocaine 2 ml for a transurethral prostatectomy (8). He had a history of allergic rhinitis, and 2 months before had had an uneventful prostate biopsy and cystoscopy, also under spinal anesthesia with iso-baric bupivacaine. Within 45 minutes of the spinal injection he complained of periorbital itching, started to shake, and developed muscle rigidity. He rapidly became unconscious, with a systolic blood pressure of 40 mmHg and widespread erythema. He was treated with hydrocortisone and antihistamines and required an infusion of adrenaline. Intradermal testing after full recovery was positive with cinchocaine. 

Hypersensitivity reactions to etoposide or teniposide usually occur within minutes after intravenous administration, and are probably related to release of vasoactive substances by basophils and/or mast cells. Several reports have suggested that premedication with an antihistamine and/or a corticosteroid may prevent further hypersensitivity reactions, even in patients with a history of previous reactions. However, this strategy should not be followed when patients have had severe hypersensitivity reactions, such as long-lasting bronchospasm or severe hjrpotension (130,131). Etoposide was successfully restarted in 78% of patients who had had a hypersensitivity reaction, especially when the drug was infused at a slower rate after premedication with an antihistamine and/or a glucocorticoid (132). 

A visible effect of the solubility modifications happening after introduction of a carboxylic group is found in the history of antihistaminic compounds (Figure 20.49). The first generation of antihistaminic drugs, in which hydroxyzine, were lipophilic compounds. They were able to cross the BBB, and had a sedating action because they were not P-glycoprotein (P-gp) substrate (which means they were not considered as xenobiotics and pumped out of the brain). Nowadays, hydroxyzine is still used as anxiolytic. 

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