Histamines

What is histamine classified as in terms of its physiological role?

Histamine is an autacoid and a paracrine hormone, meaning it acts locally and is rapidly degraded

How is histamine produced and how long does it act?

It's produced by specific cells in response to stimuli and has a short duration of action due to rapid metabolism

Which cells are known to release histamine?

Mast cells release histamine in response to IgE-mediated allergens and non-IgE triggers like trauma, cold, or certain drugs.

What is the role of mast cells in histamine release?

Mast cells release histamine in response to IgE-mediated allergens and non-IgE triggers like trauma, cold, or certain drugs.

How do basophils contribute to histamine-related responses?

Basophils also play a role in inflammatory reactions by releasing histamine.

What is the function of enterochromaffin-like (ECL) cells in relation to histamine?

ECL cells release histamine to stimulate stomach acid secretion via parietal cells.

What is the function of histaminergic neurons?

They promote arousal and wakefulness in the central nervous system.

In what form is histamine stored in mast cells and basophils?

Stored in cytoplasmic vesicles complexed with heparin, chondroitin sulfate, chemotactic factors, and proteases like tryptase.

How do ECL cells and histaminergic neurons manage histamine?

They synthesize and release histamine as needed, not stored pre-formed.

What are the types and locations of histamine receptors?

H1: Endothelium, airway/gut smooth muscle, CNS

H2: Stomach parietal cells, vascular smooth muscle

H3: CNS neurons and glial cells

H4: Immune and hematopoietic cells

What are common H1 receptor-mediated effects?

Edema, vasodilation, wheezing, diarrhea, itching, sneezing, rhinorrhea, and wakefulness

What are the clinical effects of H2 receptor activation?

Vasodilation (vascular smooth muscle relaxation) and increased stomach acid secretion.

What are the pathological roles of histamine?

Allergies (rhinitis, conjunctivitis, urticaria, anaphylaxis)

Drug reactions (e.g., opioids, vancomycin)

Hyperacidic states (ulcers, GERD, Zollinger-Ellison Syndrome)

What are the steps of a Type I hypersensitivity reaction?

1. Sensitization and IgE production

2. IgE binding to mast cells

3. Allergen re-exposure → IgE crosslinking

4. Mast cell degranulation and histamine release

5. Symptoms: rhinorrhea, itch, dyspnea, anaphylaxis

What are triggers for non-IgE histamine release?

Opioids, vancomycin, protamine, NMJ blockers, radiocontrast media

Physical agents: cold, heat, sunburn, exercise

What is the "Triple Response of Lewis" to a bee sting?

Reddening (vasodilation)

Wheal (localized edema)

Flare (pain, nerve stimulation, peripheral vasodilation)

What are classic H1-mediated symptoms of allergic rhinitis?

Sneezing, nasal itching, discharge, watery eyes.

What is the non-H1 symptom of allergic rhinitis?

What are common first-generation H1 antihistamine drug classes?

Ethanolamines: Diphenhydramine, Dimenhydrinate

Ethylenediamines: Pyrilamine

Alkylamines: Chlorpheniramine

Piperazines: Meclizine, Cyclizine

Phenothiazines: Promethazine

Miscellaneous: Clemastine

What are clinical uses of first-generation H1 antihistamines?

Allergies, cold/flu symptoms, insomnia, motion sickness, anti-emetic, adjunct in anaphylaxis.

What are side effects of 1st gen antihistamines?

Sedation (CNS H1 blockade)

Dry mouth, blurry vision, urinary retention (antimuscarinic)

Why are 1st gen antihistamines cautioned in glaucoma?

They can worsen narrow-angle glaucoma due to antimuscarinic effects.

What are the toxic signs of 1st gen antihistamine overdose?

Fever, delirium, flushed skin, dry mucosa, dilated pupils, drowsiness, CNS excitation (especially in kids)

What drugs interact adversely with 1st gen antihistamines?

Alcohol, benzodiazepines, MAOIs, tricyclic antidepressants, antipsychotics.

What is unique about dimenhydrinate (Dramamine)?

It is diphenhydramine + 8-chloro-theophylline (a CNS stimulant).

What is Diclegis used for?

Nausea and vomiting in early pregnancy (contains doxylamine + pyridoxine).

Which 1st gen antihistamines are least sedating?

Alkylamines like chlorpheniramine and brompheniramine.

What is hydroxyzine used for besides allergies?

Anxiety and chronic urticaria (due to anti-serotonergic and sedative effects).

Which 1st gen antihistamine is the precursor of cetirizine?

Hydroxyzine

What defines second-generation H1 antihistamines?

Peripheral selectivity, non-sedating, long half-life, low anticholinergic activity.

What caused the withdrawal of terfenadine?

It caused fatal arrhythmias when combined with CYP3A4 inhibitors like erythromycin.

What is fexofenadine's relation to terfenadine?

It is the active metabolite of terfenadine and does not prolong the QT interval.

What is the benefit of loratadine's long half-life?

Once-daily dosing due to its long-lived metabolite, desloratadine.

What is cetirizine derived from?

It is the active metabolite of hydroxyzine.

What is levocetirizine?

The active L-isomer of cetirizine; more potent and requires a lower dose.

Which second-gen H1 blocker has the lowest sedation profile?

Fexofenadine

What nasal sprays act as antihistamines and mast cell stabilizers?

Azelastine and olopatadine.

What are examples of antihistamine eye drops for allergic conjunctivitis?

Alcaftadine, azelastine, bepotastine, epinastine, ketotifen, olopatadine, emedastine.