creation date: 2025-09-08 16:21
tags: Pharmacology
Antihistamines
H1 Antihistamines
Mechanism of Action
H1 antihistamines target H1 histamine receptors which are found on:
- Smooth muscles, especially on bronchial and nasopharyngeal lining
- Vascular endothelial cell surfaces
- Central nervous system
- Heart
In normal function, a bound histamine causes:
- Increased capillary dilation and permeability → hypotension and edema
- Increased bronchiolar smooth muscle contraction → bronchoconstriction
- Increased nasal and bronchial mucus production
- Increased activation of peripheral nociceptive receptors → pain and pruritus
- Decreased conduction at AV node
The antihistamine acts as competitive, reversible antagonist to:
- Inhibit increased vascular permeability and allergic bronchial constriction
- Sedation (especially first-generation due to crossing blood-brain barrier)
Side Effects
- Sedation (less in 2nd generation due to limited CNS activity)
- Anticholinergic effects (less pronounced in 2nd generation)
- Anti-alpha-adrenergic effects (eg. orthostatic hypotension)
- Headaches
First-Generation
Duration 4-6h
Indications
- Allergies
- Anaphylactic shock
- Insomnia (used as sedative)
- Nausea (antiemetic central effect)
- Pruritus
- Motion sickness
Contraindications
- Benign prostatic hyperplasia (due to urinary retention risk)
- Closed angle glaucoma
- Pyloric stenosis
Examples
- Diphenhydramine (Benadryl)
- Chlorpheniramine (Chlor-Tripolon)
- Hydroxyzine (Atarax)
- Triprolidine (Actifed)
- Promethazine (Phenergan)
Second-Generation
Lasts 12-24 hours
Indications
- Allergies
- Pruritus
- Anaphylactic shock
Contraindications
- Childhood and pregnancy (except loratadine)
Examples
- Certirizine (Reactine)
- Loratadine (Claritin)
- Desloratadine (Aerius)
- Fexofenadine (Allegra)
- Levocetirizine (Xyzal)
- Acrivastine (Semprex-D)
H2 Antihistamines
Mechanism of Action
H2 antihistamines target H2 histamine receptors. These are found on:
- Gastric parietal cells (primarily)
- Vascular smooth muscle
- Neutrophils
- CNS
- Heart
- Uterus
Normal histamine function on the H2 receptor include:
- Increased gastric acid secretion
- Positive inotropism and enhanced automaticity (spontaneous cardiac depolarization)
- Smooth muscle relaxation → vasodilation
Antihistamine acts as a competitive, reversible antagonist on the parietal cells which has downstream effect of decreasing phosphorylation and activation of H+/K+ ATPase, resulting in reduced gastric acid secretion.
Side Effects
Side effects in H2 antihistamines are rare. Listed side effects are from cimetidine (dc in Canada):
- Antiandrogenic effects
- Inhibition of cytochrome P450
- Headaches, dizziness, confusion (crosses blood-brain barrier)
- Can cross placenta
- Reduces renal creatinine excretion
Details
Indications
- Anaphylactic shock (in conjunction with H1 antihistamines)
- Symptomatic treatment of peptic ulcer (less effective than PPIs)
- GERD (alternative NERD maintenance therapy or conjunction with PPI)
- Gastritis
- Zollinger-Ellison syndrome (gastrin-secreting neuroendocrine tumour)
Contraindications
Relative CI include:
- Pregnancy (placental crossing but considered safe)
- Nursing mothers
- Children
Examples
- Cimetidine (Tagamet) - discontinued in Canada
- Ranitidine (Zantac) - was taken off shelves due to carcinogen suspicion but has recently returned
- Famotidine (Pepcid)
- Nizatidine (Axid)