Antihistamines indications

Based on correlations of pKa values and lipophilicity data, it appears that compounds with a log D (the sum of the partition coefficients of both the ionized and unionized species) near 1.0 60.5 at pFI 7.4 are most efficacious, and their water-soluble salts also show a low incidence of ocular irritation. Relationships between partitioning characteristics of these and other antihistamines indicate (at least moderate) receptor affinity and that a particular range of optimal lipophilicity for topical ocular antihistamines with minimal ocular irritation (43). Some of these compounds are currently available (Table 37.9) or are being evaluated as nasal sprays, and some also are occasionally used as systemic antihistamines. 

The parent drug of this series, promazine (24), was prepared originally as an antihistamine. Following the identification of the more potent chloro analog as an antipsychotic, it too came into use for that indication. The drug is prepared by straightforward alkylation of phenothiazine with w-C3-chloropropyl)di-methylamine by means of sodium hydride in xylene. ... 

Although these drug s are sometimes used to treat allergies, a drug allergy can occur with the use of an antihistamine Symptoms that may indicate an allergy to these drugs include skin rash, urticaria, and anaphylactic shock. 

Although histamine has mixed excitatory and inhibitory effects on central neurons, those antihistamines (Hi-receptor antagonists) that enter the brain produce sedation this indicates that the predominant overall effect of histamine is excitatory. The preferred explanation for this rests on evidence that histaminergic neurons in the posterior hypothalamus are active in waking and silent in deep SWS and REM sleep. 

The in vivo antihistaminic activity results indicate that all test compounds protected the animals from histamine-induced bronchospasm significantly. Structural activity relationship (SAR) studies indicated that different alkyl substituents on the first position of the triazoloquinazohne ring exerted varied biological activity. 

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. 

Clinical trials have indicated that omalizumab, a recombinant humanized monoclonal IgE antibody approved for use in moderate to severe persistent asthma in patients with reactivity to a perennial allergen, is effective in the treatment of SAR.25-27 Omalizumab inhibits the binding of IgE to mast cell and basophil receptors, resulting in a reduction of allergic mediator release.25 Additionally, serum free IgE levels are decreased.2 27 In SAR patients, omalizumab improves quality of life and nasal symptoms and reduces antihistamine needs. The most effective dose in SAR appears to be omalizumab 300 mg administered subcutaneously every 3 to 4 weeks depending on baseline IgE levels.26,27... 

First-generation antihistamines are effective, but associated sedation and psychomotor impairment limit chronic use. Efficacy and safety of second-generation antihistamines in children have been demonstrated in clinical trials.33 Cetirizine is indicated for children 6 months of age and older, loratadine for children 2 years of age and older, and fexofenadine for children 6 years of age and older.15... 

Oral pseudoephedrine should not be used in children under 1 year of age due to safety concerns. Intranasal ipratropium can be used as intermittent therapy for mild rhinitis or as add-on therapy in more severe cases. AIT is recommended for persistent rhinitis, particularly severe disease, because studies have shown that children respond better than adults. Montelukast is indicated for children 2 years of age and older with SAR and for infants 6 months of age and older with PAR. Studies evaluating leukotriene receptor antagonists as monotherapy or in combination with antihistamines have contradictory results.33... 

All monoclonal antibodies end in the suffix -mab. The syllable before -mab indicates the source of the monoclonal antibody (see Table 85-4). When administering an antibody for the first time, one should consider the source. The less humanized an antibody, the greater is the chance for the patient to have an allergic-type reaction to the antibody. The more humanized the antibody, the lower is the risk of a reaction. The severity of the reactions may range from fever and chills to life-threatening allergic reactions (which have resulted in death). Premedication with acetaminophen and diphenhydramine is common before the first dose of any antibody. If a severe reaction occurs, the infusion should be stopped and the patient treated with antihistamines, corticosteroids, or other supportive measures. 

Examples abound regarding the role of serendipity in the discovery of new therapeutic approaches, which on closer examination usually turned out to be the result of clinicians paying attention to unexpected clinical effects rather than discounting them. For example, lithium was tried first for hypertension, chlorpro-mazine was initially developed as an anesthetic, and imipramine was originally regarded as an antihistamine and an antipsychotic agent. Without astute clinical observations, these drugs would not have found their niche, nor would clozapine have been revived for the benefit of millions of the most difficult to treat schizophrenic patients. Other examples include the expanded indications of newer... 

Motilium contains domperidone, v/hich is a dopamine antagonist and acts on the chemoreceptor trigger zone. It is ineffective in motion sickness. Stugeron contains cinnarizine Avomine and Phenergan contain promethazine and Kwells contains hyoscine hydrobromide. Cinnarizine and promethazine are antihistamines, which are indicated in motion sickness and hyoscine hydrobromide is an antimuscarinic agent that is also used in motion sickness. 

The application of a mild topical corticosteroid, such as hydrocortisone, is effective in patients presenting with multiple mosquito bites. Paracetamol, which is an antipyretic agent is not indicated in mosquito bites. Fusidic acid cream is an anti-infective agent and is indicated if the mosquito bites have been scratched and there is risk of infection. Benzocaine (anaesthetic) and mepyramine (antihistamine) may relieve itchiness but are less effective in multiple mosquito bites than hydrocortisone. 

Codeine, dextromethorphan and pholcodine are opioid cough suppressants indicated for dry cough. Sedating antihistamines, such as diphenhydramine, tend to have an antitussive action as well. Vitamin C is not used in the management of cough but may be used as a prophylaxis against colds. 

Furuncles (boils) are caused by staphylococci. Fusidic acid is very effective against boils. Hydrocortisone is a lov/-potency corticosteroid. Aciclovir (antiviral) is indicated for the treatment and prophylaxis of herpes infections. Promethazine is an antihistamine cream and zinc oxide acts as a barrier v/hen used in creams. 

Carbocisteine is classified as a mucolytic as it reduces sputum viscosity and aids its elimination. Carbocisteine is therefore indicated for use in chesty cough. Pholcodine, dextromethorphan and the sedating antihistamines, such... 

Blockade of histamine receptors. Allergic reactions are predominantly mediated by H receptors. Hi antihistamines (p. 114) are mostly used orally. Their therapeutic effect is often disappointing. Indications allergic rhinitis (hay fever). 

Figure 6. Heat map of a small cluster of related antihistaminic drugs. 149 pharmacological assays are clustered on the X-axis and 10 compounds are clustered on the Y-axis. Clustering is performed using Pearson correlation and complete linkage using a pICso data set. For nonhits with primary screening % inhibition values of less than 20%, a default pICso value of 3.5 was used. Non-hits and above 20% inhibition received a default pICso value of 4.0. The pICso values range from the default value of 3.5 (blue-green) to 9 (red). Black spaces indicate data that is missing due to compound interference with the detection method.

Hj antihistamines are clinically used in the treatment of histamine-mediated allergic conditions. Specifically, these indications may include allergic rhinitis, allergic conjunctivitis, allergic dermatological conditions (contact dermatitis), pruritus (atopic dermatitis, insect... 

Respiratory disease In general, antihistamines are not recommended to treat lower respiratory tract symptoms, because their anticholinergic effects may cause thickening of secretions and impair expectoration. However, several reports indicate antihistamines can be safely used in asthmatic patients with severe perennial allergic rhinitis. 

Discontinue antihistamines approximately 4 days prior to skin testing procedures these drugs may prevent or diminish otherwise positive reactions to dermal reactivity indicators. 

Uses Severe, systemic fungal Infxns oral cutaneous candidiasis Action Binds ergosterol in the fungal membrane to alter permeability Dose Adults Peds. Test dose 1 mg IV adults or 0.1 mg/kg to 1 mg IV in children then 0.25-1.5 mg/kg/24 h IV over 2-6 h (range 25-50 mg/d or qod). Total dose varies w/ indication PO 1 mL qid Caution [B, ] Disp Inj SE -1- K /Mg from renal wasting anaphylaxis reported, HA, fever, chills, n hrotox, -1- BP, anemia, rigors Notes -1- In renal impair pre-Tx w/ APAP antihistamines (Benadryl) X SE Interactions T Nephrotoxic effects W/ antineoplastics, cyclosporine, furosemide, vancomycin, aminoglycosides, T hypokalemia W/ corticost oids, skeletal muscle relaxants EMS May cause electrolyte imbalances, monitor ECG OD May effect CV and resp Fxn symptomatic and supportive... 

The indications for Hi-antihistaminics are derived from their mechanism of action all conditions in which a histamine release, mainly as sequel of an allergic reaction (bronchial asthma, hey fever, urticaria, allergic reactions to food or drugs), dominates the clinical symptoms. They can be used pro-phylactically or in acute situations, even by intravenous application. 

Geriatric Considerations - Summary A preferred agent for older adults when an antihistamine is indicated. 

Enantiomerically pure diarylmethylamines are important intermediates in the synthesis of biologically active compounds such as 28 or 29 (Fig. 2.1.3.8). Among several drug candidates, Cetirizine hydrochloride (28) stands out as a commercially important nonsedative antihistamine agent. Binding studies indicate that... 

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