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inhibit the release of histamine. The term antihistamine usually refers to the classical H1 receptor blockers. Reversible & competitive H1 receptor antagonists block the binding of histamine to its receptors. These compounds do not influence the formation or release of histamine. [Cromolyn which inhibits the
release of histamine from mast cells and is useful in the treatment of asthma.]
Many are available without prescription, both alone and in combination formulations such as cold pills and sleep aids.
Different antihistamines antihistaminesThree generations of
Each generation improved on the previous one. Share general characteristics and properties. The first generation drugs are still widely used because they are effective and inexpensive. However, the other agents, because they do not penetrate the blood-brain barrier (???), show less CNS toxicity than the older drugs.
First generation antihistamines Small, lipophilic molecules that could cross the
blood brain barrier. Highly sedating. Not specific to the H1 receptor (lack of selectivity for the H1 receptor), most also have considerable anticholinergic activity which can provide an antiemetic effect (particularly against motion sickness) by blocking the muscarinic actions of acetylcholine.
Used to treat motion sickness
May increase appetite and wt. gain Reduction of allergic reactions
Marked potential for producing hypotension
Indication s- Mainly used for IgE mediated hypersensitivity
Allergic rhinitis Allergic conjunctivitis Allergic dermatological conditions (contact dermatitis) Urticaria Angioedema Pruritus (atopic dermatitis, insect bites) - Anaphylaxis - adjunct only (as other autacoids are mainly responsible, not histamine)
- Nausea and vomiting - Insomnia
Commonly used first generation antihistamines:
Chlorpheniramine Cyclizine Diphenhydramine Dimenhydrinate Doxepin Doxylamine Hydroxyzine Meclizine Promethazine ⇒ Common anticholinergic side effects: Blurred vision Dry mouth Constipation Tachycardia Urine retention Confusion and memory impairment
Second generation antihistamines first generation antihistamines Modifications of the
to eliminate side effects, resulted in the second generation antihistamines. More selective for peripheral H1 receptors. Little or no anticholinergic or antiemetic effects. Poorly penetrate the CNS, thus little or no sedation.
Commonly used antihistamines:
Terfenadine (Terfenadine is a prodrug, generally completely metabolized to the active form fexofenadine ) Loratadine Cetirizine Mizolastine Astemizole
“Next” generation antihistamines Metabolite derivatives or active enantiomers of
existing drugs. Safer, faster acting or more potent than second generation drugs. Examples: Fexofenadine (Active form of terfenadine) Desloratadine (Desloratadine is the metabolite of loratadine) Levocetirizine (active isomer of cetirizine)
Why antihistamines are not effective in bronchial asthma and systemic anaphylaxis?
Bronchial asthma: Main mediators: leukotriens activating factor (PAF). Anaphylaxis: Main mediators: autacoids histamine.
For these reasons antihistamines are not effective against bronchial asthma and anaphylaxis. Main drug-
H1 antihistamines antagonize all actions of histamine except for those mediated by H2 receptors. The action of all of the H1 receptor blockers is qualitatively similar. However, most of these blockers have additional effects unrelated to their blocking of H1 receptors; these effects probably reflect binding of the H1 antagonists to cholinergic, adrenergic, or serotonin receptors. Some of these actions are of therapeutic value and some are undesirable.
Therapeutic uses Allergic conditions: H1 Blockers are useful in
treating allergies caused by antigens acting on IgE-antibody sensitized mast cells. For example, antihistamines are the drugs of choice in controlling the symptoms of allergic rhinitis and urticaria because histamine is the principal mediator.
receptor blockers, such as diphenhydramine, dimenhydrinate, cyclizine, meclizine and hydroxyzine are the effective agents for the prevention of the symptoms of motion sickness. The antihistamines prevent or diminish vomiting and nausea mediated by both the chemoreceptor and vestibular pathways. Promethazine has perhaps the strongest muscarinic-blocking activity among these agents and is among the most effective of the H1 antagonists in combating motion sickness.
Somnifacients: Although they are not the medication of choice, some of the first-generation antihistamines, such as diphenhydramine and doxylamine have strong sedative properties and are used in the treatment of insomnia.
The use of first-generation H1 antihistamines is contraindicated in the treatment of individuals working in the job where wakefulness is critical.
Sedation: The most frequently observed adverse reaction is sedation. This effect is prominent in first-generation antihistamine such as chlorpheniramine, diphenhydramine, hydroxyzine and promethazine. These drugs binds to H1 receptor and block the neurotransmitter effect of histamine in the CNS. Sedation is less common with the higher generation drugs that do not readily enter the CNS.
Dry mouth: Oral antihistamines also exert weak anticholinergic effects, leading not only to a drying of the nasal passage but also to a tendency to dry the oral cavity. Blurred vision can also occur with some drugs.
Drug interactions: Interaction of H1 receptor blockers with other drugs can cause serious consequences, such as the potentiation of the effects of all other CNS depressants, including alcohol. Persons taking MAO inhibitors should not take antihistamines, since the MAO inhibitors can exacerbate the anticholinergic effects of the antihistamines.
Actions not caused by histamine receptor blockade
Sedation: A common effect of first-generation H1 antagonists is sedation. At ordinary dosages, children occasionally (and adults rarely) manifest excitation rather than sedation. At very high toxic dose levels, marked stimulation, agitation, and even convulsions may precede coma. Second-generation H1 antagonists have little or no sedative or stimulant actions. These drugs (or their active metabolites) also have far fewer autonomic
Antinausea and antiemetic actions Several first-generation H1 antagonists have significant activity in preventing motion sickness. They are less effective against an episode of motion sickness already present. Certain H1 antagonists, notably doxylamine, were used widely in the past in the treatment of nausea and vomiting of pregnancy.
Anticholinoceptor actions Many of the first-generation agents have significant atropine-like receptors. This action may be responsible for some of the (uncertain) benefits reported for nonallergic rhinorrhea but may also cause urinary retention and blurred vision. effects on peripheral muscarinic
Adrenoceptor-blocking actions Alpha-receptor-blocking effects can be demonstrated for many H1 antagonists, for example promethazine. This action may cause orthostatic hypotension in susceptible individuals. Beta-receptor blockade is not observed.