Autocoids and Related Drugs
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- Introduction to autacoids and classification
- Histamine, 5-HT and their antagonists.
- Prostaglandins, Thromboxanes and Leukotrienes.
- Angiotensin, Bradykinin and Substance P. e. Non-steroidal anti-inflammatory agents
- Anti-gout drugs
- Antirheumatic drugs
INTRODUCTION:
- Histamine, serotonin, prostaglandins, & some vasoactive peptides belong to a group of compounds called autacoids .
- They all have the common feature of being formed by the tissues on which they act so they function as local hormones
- The autacoids also differ from circulating hormones in that they are produced by many tissues rather than in specific endocrine glands.
TYPES: The important autacoids include:
• Histamine,
• Hydroxytryptamine (5-HT, serotonin),
• Prostaglandins,
• Leukotrienes, and
• Kinins.
HISTAMINE
Histamine (Beta-aminoethyl-imidazole) is formed from decarboxylation of Imidazole ring containing amino acid histidine. Histamine is a basic amine, stored in mast cell and basophil granules, and secreted when C3a and C5a interact with specific membrane receptors or when antigen interacts with cell-fixed immunoglobulin E. Histamine plays a central role in immediate hypersensitivity (Type 1) and allergic responses.
The actions of histamine on bronchial smooth muscle and blood vessels account for many of the symptoms of the allergic response. In addition, certain clinically useful drugs can act directly on mast cells to release histamine, thereby explaining some of their untoward effects.
Histamine has a major role in the regulation of gastric acid secretion and also modulates neurotransmitter release. Stimulation of IgE receptors also activates phospholipase A2 (PLA2), leading to the production of a host of mediators, including platelet-activating factor (PAF) and metabolites of arachidonic acid. Leukotriene D4, which is generated in this way, is a potent contractor of the smooth muscle of the bronchial tree.
Kinins also are generated during some allergic responses. Thus the mast cell secretes a variety of inflammatory mediators in addition to histamine, each contributing to the major symptoms of the allergic response. Epinephrine and related drugs that act through b2 adrenergic receptors increase cellular cyclic AMP and thereby inhibit the secretory activities of mast cells. So are given in anaphylactic shock treatment. However, the beneficial effects of b adrenergic agonists in allergic states such as asthma are due mainly to their relaxant effect on bronchial smooth muscle.
Cromolyn or Cromoglicate sodium is used clinically because it inhibits the release of mediators from mast and other cells in the lung.
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