A Midsummer Night’s Diphenhydramine Antihistamines

2.1 – “A Midsum Midsummer mer Night’s D Diphenhydramine iphenhydramine iphenhydramine”: ”: Antihistam Antihistamines ines • Histamine is a biologically active amine that plays an important role in gastric acid secretion, functions as a NT, and mediates allergic inflammation. Most tissue histamine is stored in mast cells & basophils. Once mast cells are exposed to IgG, they will burst open at exposure to specific antigens (like an irritated beehive). • H1 receptor is involved in allergic response. o coupled to GqPCR (one Q-shaped dandelion). o Mediates type 1 allergic reaction → hives & allergic rhinitis (fairy dust making Hermia sneeze and break out in hives) ▪ ↑nasal & bronchial mucus production (dripping nose) ▪ Endothelia H1 receptors stimulate extravasation of fluid. Mediate pain, puritis, vasodilation, seen in allergies. Urticaria results from increased vascular permeability (bloody sap) o Causes constriction of bronchial smooth muscle (constricting lung branch). ▪ Asthma is in part a hypersensitivity to this effect. • Non-mast cell associated histamine functions as a neurotransmitter, acting via CNS H1 receptors to regulate sleep & arousal, neuroendocrine & CV regulation (brain shaped tree). • H2 receptors are coupled to GsPCR →↑cAMP (2 S-shaped handles on honeypot). Located on gastric principal cells and activate gastric acid secretion (stomach shaped honey pot leaking yellow honey) Antihis Antihistamines tamines (Hermia swatting away bees) • Antihistamines work at the H1 receptor, located in vascular endothelial cells, bronchial airways, and CNS. • First generation: Diphenhydramine & dimenhydrinate (diphenhydramine salt) (dragonfly fairy), chlorpheniramine (colored beetle, Queen Tatiana), hydroxyzine, cylizine, promethazine (cuisine) o Indications ▪ Used as initial treatment for type 1 allergic reactions. Blockade of H1 prevents type 1 responses. ▪ Treat vestibular nausea/motion sickness. Are lipophilic so easily enter CNS, acting on H1 receptors in the vestibular system and brainstem (sailor outfitted fairies riding current in front of brain tree) ▪ As an extension of antimuscarinic effects, can acutely suppress anti-pyramidal effects cause by antipsychotics (e.g. dystonia, drug induced parkinsonism) (parking cone) i.e. Help reestablish dopaminergic/cholinergic balance. (Antipsychotics interfere with dopaminergic transmission via nigrostriatal tract.) o Adverse effects ▪ Cause drowsiness (Lysander sleeping). Sufficiently potent as to treat insomnia. ▪ antagonize many other Rs in the periphery & CNS, including muscarinic Rs → significant antimuscarinic effects (Mad Hatter’s Tea Party) • Urinary retention, dry mouth, pupillary dilation, constipation, exacerbation of glaucoma, & delirium ▪ Anti-serotonergic effects: antagonize serotonin R in the CNS, stimulating appetite & causing weight gain (chubby fairy asleep on branch) ▪ Antagonize α1 receptors → dizziness & hypotension (α candle & passed out fairy) ▪ Can cause cognitive impairment in the elderly d/t central antihistamine & antimuscarinic effects (delirious Egeus) • Second generation: fexofenadine, cetirizine, loratadine (fox, satyr, and rat respectively) o Less lipophilic, so do not cross the BBB and are generally less sedating (trio standing far away from brain tree). Also less antimuscarinic, anti-serotonergic, and anti-adrenergic activity. o Can be used to treat allergic rhinitis or urticaria with significantly fewer adverse effects.