Autocoids

Question 1

List the major class of the autocoids

Answer 1

1. Endogenous amines
   - histamine, serotonin
2. Lipid-derived autocoids
   - prostaglandin, leukotriene
3. Endothethelium-derived agents
   - Nitric oxide (NO)
4. Biogenic peptides
   - angiotensin and kinins

Question 2

Mechanism of action of histamine

Answer 2

Histamine receptor: H1, H2, H3 & H4

H1 receptor antagonist (blocker) : cyclizine, Hydroxyzine. It used in motion sickness.

H2 receptor (gastric mucosa, cardiac muscle, mast cell and brain) :

• it couple with G protein
• increase in intracellular cAMP
• increase calcium influx

Question 3

Action of histamine with their receptors

Answer 3

H2 receptor:
Stomach: stimulation of gastric HCL seceretion

H1 receptor:
Exocrine: increase production of nasal and Bronchial mucus result in respiratory symptoms.

Bronchial smooth muscles:
Constriction of bronchioles results in symptoms of asthma and decreased lung capacity

Instestinal smooth muscle:
-constriction result in intestinal cramp and diarrhea

Sensory nerve endings: causes itching and pain

Receptor H1 & H2:
Cardiovascular system: lower systemic blood pressure by reducing peripheral resistance. Cause positive chronotropism (mediated by H2 receptor) & positive inotropism (mediated by H1 & H2 receptor)

Skin: dilation and increased permeability of the capillaries results in leakage of proteins and fluid into the tissues. It results in “triple response”: wheal formation, reddening due to local vasodilation, and flare.

Question 4

Histamine agonist uses

Answer 4

1. Pitolisant: narcolepsy

2. Betahistine (histamine analog) : used to control vertigo Meniere’s disease

Question 5

H1 receptor antagonist uses

Answer 5

Based on H1 action: used in itching, urticaria, hay fever, insect bite

Based on anticholinergic property:
Used in common cold, motion sickness, parkinsonism

Other drugs: drugs of choice in idiopathic pruritus, local anesthetic

Question 6

Histamine antagonism generation of drugs

Answer 6

First generation (penetrate CNS & cause sedation)

• chlorpheneramine
• diphenhydramine
• promethazine

Second generations (no penetration to CNS and sedation)

• cetrizine
• loratidine

Third generation
-levocetrizine

Question 7

H1 receptor antagonist adverse effect

Answer 7

H1 receptor has low specificity, it interacts with muscarinic receptors, alpha adrenoceptors, serotonin receptor

Adverse effect
-sedation, tinnitus, fatigue, blurred vision, dry mouth and tremor