Inflammation & Antiinflammatories: Histamine & Steroids

What is the primary function of histamine in physiological processes?

Which of the following is a systemic effect of histamine release?

What is the mechanism of action of H1 receptor antagonists?

Which of the following is a side effect of glucocorticoids?

What is the primary mechanism of action of glucocorticoids?

What is the function of prostaglandins?

What is the primary difference between older and newer H1 receptor antagonists?

Histamine is derived from the amino acid Tryptophan.

H2 receptor activation leads to bronchoconstriction.

Newer H1 receptor antagonists, such as Loratadine, can pass the blood-brain barrier.

Glucocorticoids increase PLA2 activity.

Beta adrenoceptor agonists are used to treat anaphylaxis.

Histamine

Derived from Histidine, found in Mast Cells, Basophils, and Neutrophils
Secretion by slow release is physiologically important for gut, cardiovascular, and lung function
Mass degranulation activated in response to activated antibody leads to anaphylaxis → mass drop in blood pressure

Histamine Receptors

H1 receptor activation:
- Bronchoconstriction
- Contraction of gut
- Vasodilation & ↑vascular permeability, dec.bp
- Stimulation of sensory nerves and release of peptide mediators in periphery → vasodilation
H2 receptor activation:
- Gastric acid secretion
- Heart rate
H3 receptor:
- Presynaptic nerve terminals
H4 receptor:
- Mast cells

Histamine Release

Local:
- Itching
- Redness
- Swelling
- Oedema
- Headache
- Vasodilation
- Bronchoconstriction
- Vomiting
- Diarrhea
Systemic:
- Huge Vasodilation
- Bronchoconstriction and spasm

Treatment of Histamine Release

Treated with Beta adrenoceptor agonists
Antihistamines:
- H1 receptor antagonists
- Older (can pass BBB): Promethazine, chlorpheniramine
- Also anti-muscarinic- sedative effects
- Newer (reduced muscarinic, don't pass BBB): Loratadine, fexofenadine
- Uses: anti-allergy, sedation, cough/cold remedies, antiemetic
- Side effects: Dry mouth, blurred vision, sedation

Steroids

Glucocorticoids:
- Prednisone
- Beclametasone
- Gene expression changes:
  - Decrease PLA2 activity
  - Decrease COX expression
Side effects:
- Diabetes
- Osteoporosis
- Peptic ulcers
- Immunosuppression
- Adrenal suppression
- Altered appearance – gain weight on face and trunk, wasted limbs
- Mental disturbance
- Topical - skin atrophy, hair growth

Explore the role of histamine in physiological processes and its receptors, including H1 receptor activation. Learn about histamine's effects on the gut, cardiovascular, and lung function, as well as its involvement in anaphylaxis. Test your knowledge of histamine and steroids in this lecture bite.