Antihistamines effects

Attachment of the basic side chain to the phenothiazine nucleus by means of a carbonyl function apparently abolishes the usual CNS or antihistamine effects shown by most compounds in this class. The product azaclorzine instead is... 

Tharion, WJ, McMenemy, DJ and Rauch, TM (1994) Antihistamine effects on the central nervous system, cognitive performance and subjective states. Neurophsychobiol. 29 97-104. 

Antihistamines. After alcohol, antihistamines are the most commonly self-administered sleep medications. Foremost among these is diphenhydramine (Benadryl), which is also available as a component in a variety of over-the-counter nighttime medications including Tylenol PM and Excedrin PM. Prescription antihistamines like hydroxyzine (Vistaril, Atarax) are also occasionally used to treat insomnia. Finally, it is the antihistamine effect of some antidepressants and anti-psychotics that contribute to their utility as sedative-hypnotics. 

Medications that enhance norepinephrine activity are used to treat depression and ADHD. Boosting norepinephrine can also produce numerous side effects including nervousness and anxiety, insomnia, and loss of appetite. With mirtazapine and the TCAs, these side effects are usually not a problem because these antidepressants also block histamine receptors. Their antihistamine effects promote increased appetite and drowsiness that tend to offset the side effects that might be experienced from increased norepinephrine activity. 

The most significant problems with antihistamines are sedation and weight gain. Except for stimulants, there are no medications that counteract these effects. We do recommend the use of a stimulant to counteract antihistamine effects. 

These include trazodone and a derivative of its metabolite nefazodone, both of which are strongly sedative, an effect which has been attributed to their potent alpha-1 receptor antagonism rather than to any antihistaminic effects. A main advantage of these drugs in the treatment of depression is that they appear to improve the sleep profile of the depressed patient. Their antidepressant activity is associated with their weak 5-HT reuptake inhibition and also a weak alpha-2 antagonism. However, unlike most of the second-generation antidepressants, neither drug is effective in the treatment of severely depressed patients. Furthermore, there is some evidence that trazodone can cause arrythmias, and priapism, in elderly patients. 

Attachment of the basic side chain to the phenothiazine nucleus by means of a carbonyl function apparently abolishes the usual CNS or antihistamine effects shown by most compounds in this class. The product azaclorzine instead is described as an anti anginal agent. Reduction of proline derivative 106 with lithium aluminum hydride gives the corresponding fused piperazine 107. Use of that base to alkylate the chloroamide 109, obtained from acylation of phenothiazine with 3-chloropropionyl chloride, leads to azaclorzine (110). ... 

Chlorpromazine emerged from a series of compounds that aroused interest mainly on account of their antihistaminic effects, and partly their... 

H -antagonists are well absorbed from the gastrointestinal tract. Following oral administration, antihistaminic effect is manifested within 30 minutes, peak plasma concentration is achieved in 2 to 3 hours and effects usually last 4 to 6 hours. However, drugs in piperazine subgroups especially chlorcyclizine and meclizine, the actions persists for 8 to 12 and 12 to 24 hours respectively. 

Fexofenadine inhibited antigen-induced bronchospasm and histamine release from mast cells. No anticholinergic or alpha adrenergic-receptor blocking effects were observed. Moreover, no sedative or other CNS effects were observed. Fexofenadine does not cross the blood-brain barrier. It inhibits skin wheal and flare responses produced by histamine injection. Following single and twice daily oral administration, antihistaminic effects occurred within 1 hour, achieved a maximum at 2-3 hours, and lasted a minimum of 12 hours. 

Sedation is common, particularly at initiation of treatment and is largely related to antihistamine and antiadrenergic effects. Weight gain may also be related to antihistamine effects. Some recent evidence suggests there can be impairment of psychomotor function but in the treatment of patients with depression this must... 

Chlorpromazine has direct effects on the CTZ and may also depress temperature control and prevent shivering. The effects are due to inhibition of dopamine centrally. It may potentiate the effects of hypnotics, sedatives and anaesthetic agents. It is rarely used in anaesthetic practice today. Promethazine was first developed for its antihistamine effects but is more commonly used for its sedative/anticholinergic, anti-emetic actions, and prevention of motion-related sickness. The sedative actions are quite marked and last longer than the anti-emetic effects. 

Elevations of TCA levels may occur when combined with CYP2D6 inhibitors or from constitutional factors. About 7% of the Caucasian population in the USA has a CYP2D6 polymorphism that is associated with slow metabolism of TCAs and other 2D6 substrates. Combination of a known CYP2D6 inhibitor and a TCA in a patient who is a slow metabolizer may result in additive effects. Such an interaction has been implicated, though rarely, in cases of TCA toxicity. There may also be additive TCA effects such as anticholinergic or antihistamine effects when combined with other agents that share these properties such as benztropine or diphenhydramine. Similarly, antihypertensive drugs may exacerbate the orthostatic hypotension induced by TCAs. 

Gentiana dahurica Fisch. G. lutea L. G. macrophylla Pall. Jue Chuang (Gentian) (root) Gentianine, gentianidine, gentianol.33 Treat rheumatism and fever, antipyretic, anti-inflammatory, antihypersensitivity and antihistaminic effects. 

Colchichine is a natural material produced by the autumn crocus and meadow saffron. Its mechanism of CH3 action, as far as it is known, is three-fold it interferes with microtubule-spindle formation in the proliferation of the cells responsible for inflammation it has an antihistaminic effect it prevents the release of an inflammatory glycoprotein... 

Normal adult dosage when taken orally for antihistamine effects. 

Johnston, C.S., Martin, L.J., and Cai, X. Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis. J Am Coll Nutr, 11,172-176,1992. 

In addition to their well-established antipsychotic properties, the neuroleptics have a number of clinically important properties that include their antiemetic and antinauseant actions, their antihistaminic effects and their ability to potentiate the actions of analgesics and general anaesthetics. 

Ortho-substitution decreases the antihistamine effects, but increases the antimuscarinic properties the ortho-methyl analogue of diphenhydramine (orphenadrine) was successfully introduced as an anti-Parkinson medicament. 

Primary drug Secondary drug ANTIHISTAMINES Effect Mechanism Precautions... 

Mast cell stabilizers prevent the mast cell from degranulating and therefore the subsequent release of mediators. However, once the mast cells have already degranulated, mast cell stabilizers are ineffective against the released mediators. Combination drugs with both mast cell-stabilizing and antihistamine effects provide both longterm treatment and a more rapid relief of symptoms. Drugs with this dual-action or multiaction mechanism include azelastine, epinastine, ketotifen, and olopatadine (Table 13-7). 

Benzatropine and etybenzatropine (ethylbenzatropine) are anticholinergic drugs. They represent attempts to combine atropine-like and antihistaminic effects in single molecules. The dose is determined individually and varies from 0.5 to 6 mg/day for benzatropine and 6 to 30 mg/day for etybenzatropine. Although the adverse reactions are essentially those of the anticholinergic drugs, sedation is very likely to occur and these drugs should not be used in patients who need to drive motor vehicles. Benzatropine has also been reported to cause rash, peripheral numbness, and muscular weakness. 

Chlorphenoxamine is an antihistamine closely related to diphenhydramine with a similar metabolic pathway (1). It appears to have been developed in the hope of producing a greater effect in Parkinson s disease by combining both anticholinergic and antihistaminic effects in a single molecule (2). 

O Hanlon JF, Ramaekers JG. Antihistamine effects on actual driving performance in a standard test a summary of Dutch experience, 1989-94. Allergy 1995 50(3) 234-42. 

Prototypical agent amitriptyline Inhibits norepinephrine and serotonin reuptake Hepatic metabolism with renal elimination High anticholinergic and antihistamine effects imipramine has high orthostasis profile 2nd degree amines (nortriptyline, desipramine) and doxepin have moderate anticholinergic effects... 

Studies of the ginseng extract ginsenocide Rbl in a rat peritoneal mast cell model have demonstrated potent antihistaminic effects. 

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