Main unwanted side effect of sedating antihistamines
Desloratadine is the most potent antihistamine (Ki 0.4 n M) followed by levocetirizine (Ki 3 n M) and fexofenadine (Ki 10 n M) (the lower the concentration, the higher potency).
Although these are often considered to be fixed values, they may be influenced by temperature and p H, and therefore, they can differ in physiologic and pathologic conditions.
For example, in inflammation the p H of the tissues is reduced from 7.4 to 5.8, leading to a 2-to 5-fold increase in the affinity of fexofenadine and levocetirizine for H-receptors but no change in the affinity of desloratadine.
As shown in Figure 2, histamine receptors are situated on the cellular membranes of cells, including vascular and airways smooth muscle, mucous glands, and sensory nerves, all of which are surrounded by the extracellular fluid.
During this time, knowledge of the nature and diversity of receptors was rudimentary to say the least and it was only several decades later that the existence of more than one species of histamine receptor was discovered.
This review will concentrate on the histamine H-receptor is a member of the superfamily of G-protein coupled receptors.
Consequently, the preferred term to define these drugs is "H-antihistamines derive from the same chemical stem from which cholinergic muscarinic antagonists, tranquilizers, antipsychotics, and antihypertensive agents were also developed, they have poor receptor selectivity and often interact with receptors of other biologically active amines causing antimuscarinic, anti-α-adrenergic, and antiserotonin effects.
In February 2009, the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom advised that cough and cold remedies containing certain ingredients, including first-generation H-antihistamines, should no longer be used in children younger than 6 years because the balance of benefit and risks has not been shown to be favorable.
Reports submitted to regulators stated that more than 3000 people have reported adverse reactions to these drugs and that diphenhydramine and chlorpheniramine were mentioned in reports of 27 and 11 deaths, respectively.-antihistamine, patients seek attributes that include good efficacy, a rapid onset of action, a long duration of action, and freedom from unwanted effects.
When activated, these neurones stimulate H-receptors in all of the major parts of the cerebrum, cerebellum, posterior pituitary, and spinal cord where they increase arousal in the circadian sleep/wake cycle, reinforce learning and memory, and have roles in fluid balance, suppression of feeding, control of body temperature, control of the cardiovascular system, and mediation of stress-triggered release of adrenocorticotrophic hormone and β-endorphin from the pituitary gland.
It is not surprising then that antihistamines crossing the blood-brain barrier interfere with all of these processes.However, levocetirizine may cause somnolence in susceptible individuals while fexofenadine has a relatively short duration of action requiring twice daily administration for full all round daily protection.