Antihistamines and H1 Blockers

• Antihistamines, also known as H1 blockers, primarily treat allergic reactions such as urticaria, angioedema, and allergic rhinitis
• These conditions are related to increased histamine release
• H1 blockers work by blocking histamine's effects in tissues with H1 receptors, alleviating allergy symptoms

Histamine and Allergic Reactions

• Histamine is a small molecule mainly produced by mast cells and basophils
• It causes local inflammation and vasodilation upon release
• Histamine is present in the brain as a neurotransmitter
• It is produced by enterochromaffin cells in the stomach to increase gastric acid secretion
• For an allergic reaction to occur, an allergen activates B cells
• Activated B-cells produce IgE antibodies that bind to mast cells
• Mast cells become "primed" and release histamine into local tissue upon subsequent allergen exposure

Histamine Receptors

• There are 4 types of histamine receptors: H1, H2, H3, and H4
• H1 receptors are the focus for antihistamines used for allergies
• H1 receptors are found on endothelial cells, smooth muscle cells, sensory nerve endings, and in the brain
• Stimulation of H1 receptors on endothelial cells causes blood capillaries to dilate and become leaky, leading to redness and edema
• Stimulation of H1 receptors on smooth muscle cells in the lungs results in bronchoconstriction
• Stimulation of H1 receptors on sensory nerve endings leads to pain and itching
• In the brain, H1 receptors promote wakefulness and appetite suppression

Pharmacology of Antihistamines

• Antihistamines block histamine receptors
• They are subdivided into H1 blockers, which are used to treat allergies, and H2 blockers, which are primarily used to treat gastric problems like heartburn
• H1 blockers reversibly inhibit H1 receptors
• They are subdivided into first-generation and second-generation H1 blockers

First-Generation H1 Blockers

• Include medications that contain letters "-en" and end with the suffix "-ine" or "-ate" like diphenhydramine, chlorpheniramine, and dimenhydrinate
• Primarily used to treat allergic reactions
• High lipid solubility allows them to cross the blood-brain barrier and block H1 receptors in the brain
• Can cause cognitive side effects like sedation, therefore they can be also used as a short-term treatment for sleeping problems
• Diphenhydramine can be used to treat nausea and vomiting in motion sickness
• Due to anticholinergic properties, diphenhydramine can be useful in treating conditions with extrapyramidal symptoms, such as Parkinsonism
• Common side effects include antihistaminic effects like sedation, increased appetite, and weight gain; antimuscarinic effects like dilated pupils, blurry vision, and dry mouth; and anti-α-adrenergic effects like orthostatic hypotension and dizziness

Second-Generation H1 Blockers

• Include medications that end with the suffix “-adine”, like fexofenadine, desloratadine, and loratadine, with one exception - cetirizine
• Primarily used to treat allergic reactions
• Less lipid solubility than first-generation H1 blockers, causing fewer cognitive side effects
• Antimuscarinic side effects also tend to be less severe
• Second-generation is preferable to the first-generation H1 blockers

. 1st Generation Antihistamines: • Agents: Hydroxyzine, Cycizine, Clemastine • Mechanism of Action: These drugs competitively inhibit H1 receptors in the respiratory tract. They also have some affinity for alpha-1 adrenergic and serotonin receptors, which contributes to additional sedative and anticholinergic effects. • Indications: Used for treating allergies, insomnia, and motion sickness. • Side Effects: Common side effects include decreased sweat and urine production, dry mouth, blurred vision, constipation, confusion, and agitation. • Contraindications: Should be avoided in individuals with asthma, heart failure, or those who are breastfeeding. 2nd Generation Antihistamines: • Agents: Cetirizine, Levocetirizine • Mechanism of Action: These selectively antagonize peripheral H1 receptors and are less likely to cross the blood-brain barrier, reducing sedation. • Indications: Mainly used for anaphylaxis and seasonal allergies. • Side Effects: May cause headaches, dry mouth, and reduced liver metabolism. • Contraindications: Avoid in patients with polymorphic ventricular tachycardia, as these drugs can prolong the QT interval on an ECG.