PCOL P2 histamine

HISTAMINE AGONISTS

Definition

Histamine agonists are drugs that stimulate histamine receptors (H₁, H₂, H₃) and mimic the physiologic effects of histamine.

TYPES OF HISTAMINE AGONISTS

1. Histamine

Acts on H₁, H₂, H₃, and H₄ receptors

Produces typical histamine effects:

Vasodilation

Bronchoconstriction

Increased gastric acid secretion

2. R-α-Methylhistamine

Selective H₃ receptor agonist

Mainly used in research

Decreases histamine release via negative feedback

3. Betazole (Histalog)

Has 10× greater activity at H₂ receptors than H₁

Stimulates gastric acid secretion

Previously used to test gastric secretory function

4. Impromidine

Highly selective H₂ agonist

H₂ : H₁ activity ratio ≈ 10,000 : 1

Investigational drug

Powerful stimulant of gastric acid secretion

ADVERSE EFFECTS OF HISTAMINE AGONISTS

(due to excessive histamine activity)

Flushing and burning sensation

Skin wheals (urticaria)

Hypotension

Tachycardia

Bronchoconstriction

USES OF HISTAMINE AGONISTS

Allergy testing

Assess histamine sensitivity

Gastric secretory function test

Now largely replaced by Pentagastrin (Peptavlon)

👉 Pentagastrin is preferred due to fewer adverse effects

Pulmonary function testing

CONTRAINDICATIONS

❌ Bronchial asthma

❌ Active peptic ulcer disease

❌ Gastrointestinal bleeding

BETAHISTINE (Serc)

Mechanism of Action

H₁ agonist

H₁ receptors in blood vessels of the inner ear

↑ Blood flow → ↓ endolymphatic fluid pressure

Use

Management of vertigo

Especially in Ménière’s disease

MANAGEMENT OF HISTAMINE EFFECTS (BIG PICTURE)

Types

A. Physiologic Antagonist

Epinephrine

Drug of Choice (DOC) for anaphylactic shock

Opposes histamine effects by:

Bronchodilation

Vasoconstriction

Increased cardiac output

B. Pharmacologic Antagonists

1. H₁ Antagonists

Used for allergic conditions

2. H₂ Antagonists

Used for peptic ulcer disease (PUD)

HISTAMINE RELEASE INHIBITORS

Mechanism

Prevent mast cell degranulation

↓ Histamine release

Examples

Cromolyn sodium (Intal)

Nedocromil (Tilade)

Uses

Prophylaxis of asthma

Not useful for acute asthma attacks

H₁ ANTAGONISTS (ANTIHISTAMINES)

Mechanism of Action

Competitive antagonists of H₁ receptors

Block effects of histamine on:

Smooth muscle

Endothelium

Sensory nerves

PHARMACOKINETICS

Well absorbed orally

Onset of action: ~30 minutes

Duration of action

1st generation: 3–6 hours

2nd generation: 3–24 hours

Lipid soluble

Cross BBB (↑ in 1st gen, ↓ in 2nd gen)

Metabolized in the liver

Some are enzyme inducers (e.g., Cetirizine)

Some produce active metabolites

Hydroxyzine → Cetirizine

PHARMACOLOGIC ACTIONS OF H₁ ANTAGONISTS

Anticholinergic effects

Seen in ethanolamines, phenothiazines, ethylenediamines

↓ Mucus secretion

Block sensory nerve stimulation

Local anesthetic action

e.g., Dimenhydrinate, Promethazine

Relax histamine-induced bronchial smooth muscle contraction