H1 Receptor Antagonist SDL

H₂ blockers reduce gastric acid secretion by blocking ______ receptors on ______ cells in the stomach, and are used to treat conditions such as ______ and ______.

H2, parietal, GERD, peptic ulcers

You should care about learning H1 receptor antagonists (H1RAs) because:

• huge market impact: The global allergy treatment market was $24.65 billion in 2017 and is projected to grow to $40.36 billion by 2025.

• The U.S. accounts for about one-third of the total market revenue.

• There are major differences in the adverse effect (ADE) profiles of first- vs. second-generation H1RAs.

Histamine is primarily stored in the vesicles of the ______ cells.

mast

What are some common medications that can cause histamine release?

• Mechanical injury
• Morphine
• Antibiotics
• Radiocontrast
• Polypeptides
• Dextran
• Venoms

Histamine in the epidermis can produce what type of response?

wheal and flare response

Mast cells are located in tissues prone to ______.

injury

Histamine increases capillary permeability by causing ______ and ______ to leak into the extracellular space, which increases ______ flow and leads to ______.

plasma proteins, fluid, lymph, edema

The Triple Response of Lewis consists of:

(1) a localized ______ from direct vasodilation via H1 receptor–mediated NO,

(2) a ______ from histamine-induced axon reflex vasodilation, and

(3) a ______ from histamine-induced increased capillary permeability (edema).

red spot, flare, wheal

H1RA can be used to treat ________ and ____________.

allergic rhinitis, urticaria

Adverse Events: First Generation

• Sedation (Paradoxical Excitation in children)

• Dizziness

• Fatigue

• Tachydysrhythmias in overdose - rare

• Allergic reactions with topical use- use a topical corticosteroid instead

• peripheral antimuscarinic effects:

  • dry mouth

  • blurred vision

  • constipation

  • urinary retention
    

H1 receptor antagonists blunt histamine-induced ______ in vascular smooth muscle, decrease ______ ______ to reduce edema (wheal), and suppress histamine’s action on ______ ______ to reduce flare and ______.

vasodilation, capillary permeability, nerve endings, itching

H1RA should NOT be used alone to treat _______________ in asthma.

bronchoconstriction

______ generation H1RAs are better at treating motion sickness because they cross the ______ and also block ______ receptors.

first, BBB, muscarinic

______ generation H1RAs have a higher rate of CNS effects because they are ______ and cross the ______, leading to ______ ______.

first, lipophilic, BBB, CNS depression

Common Side Effects of H1 Receptor Antagonists

• Drowsiness / sedation

• Dizziness and slowed reaction time

• Dry mouth, blurred vision, constipation, urinary retention —> anticholinergic effects.

• Confusion / paradoxical excitation —> more common in elderly or children.

Counseling Suggestions / Alternatives

• Advise patients to avoid alcohol and other CNS depressants.

• Recommend non-sedating antihistamines —> second-generation H1RA for those who need to avoid drowsiness.

• For patients particularly sensitive to anticholinergic effects (elderly, BPH, glaucoma) —> second-generation H1RA

First-generation H1 receptor antagonists have more drug interactions because:

1st gen H1RAs cross the BBB, have multiple receptor targets, and affect drug metabolism, they carry a higher risk of drug interactions compared to 2nd gen H1RAs

Conditions where H1RAs should NOT be used as primary treatment

• Asthma – limited efficacy; not used as sole therapy.

• Anaphylaxis – only adjuvant; epinephrine is primary therapy.

• Angioedema – same as anaphylaxis; not first-line.

• Common cold – provide no real therapeutic value.

Four Common Uses of H1RAs

• Allergic rhinitis, urticaria, conjunctivitis – suppress histamine-mediated symptoms.

• Motion sickness – e.g., dimenhydrinate, cyclizine, meclizine, promethazine.

• Vertigo – e.g., dimenhydrinate, meclizine.

• Sedation – e.g., diphenhydramine (especially in OTC sleep aids).

First-generation H1 receptor antagonists have a higher rate of:

• Drowsiness / sedation → cross the blood–brain barrier

• Anticholinergic effects → dry mouth, constipation, urinary retention, blurred vision

• Impairment → slowed reaction time, diminished alertness, increased accident risk

First-Generation H1 Receptor Antagonists

• Diphenhydramine —> Benadryl

• Chlorpheniramine —> Chlor-Trimeton

• Brompheniramine —> Dimetapp

• Clemastine —> Tavist

Second-Generation H1 Receptor Antagonists

• Loratadine —> Claritin

• Cetirizine —> Zyrtec

• Fexofenadine —> Allegra

• Desloratadine —> Clarinex