AUTOCOIDS AND AUTOCOID ANTAGONISTS
Autocoids are endogenous chemicals by which the body heals and correct itself during some stressful and painful situations.
Auto means in Greek 'self' and Akos means 'medicine or remedy' and hence by the name they are body's 'self medicines'.
Autocoids are considered as true hormones that are secreted locally and are not secreted into the blood. But they involve a variety of pharmacological actions. Hence they are also considered as local hormones.
There are many prototype autocoids are secreted in our body. They are,
1.Histamine
2.Serotonin
3.Prostaglandins
4.Kinins
and others like leukotrienes, and interleukins etc.etc.But here we will deal with the first three autocoids as they are the prototypes and not secreted into the blood.
1.Histamine and Antihistamines
Chemistry
Histamine is a bio-amine derived from the amino acid Histidine present in the protein-rich foods. Histidine an amino acid is decarboxylated by the enzyme L-histidine decarboxylase into histamine.
Histamine is widely present in the body in the granules of mast cells and basophils.
Mechanism and Effects
Histamine when released from the mast cells by external or internal allergen stimulants acts on its own receptors such as H-1 and H-2.
These receptors are located on our body cell surfaces and mediate numerous varieties of pharmacological responses.
Physiological Effects
1.Constriction of bronchioles(H1)
2. Constriction of intestinal smooth muscle(H1)
3.Stimulates sensory nerves mediating pain and itching(H1)
4.Lower Blood Pressure (H2)
5.Stimulates gastric acid secretions(H2)
6.Increases permeability of skin capillaries(H2)
Clinically histamine has no medical use. But medicinally antihistamines have a variety of use.
Classifications
A.H-1 Antagonists
1.Ethylenediamine:-Tripelennamine
2.Alkylamines:-Chlorpheniramine maleate
3.Azines:-Promethazine
4.Piperidines:-Cyproheptadines
B.H-2 Antagonists
These are heterogenous congeners of histamine
1.Cimetidine
2.Ranitidine
3.Famotidine
4.Nizatidine
In general action of histamine on
1.H-1 Receptors
1.Allergy
2.Anaphylactic reactions such as bronchoconstriction, vasodilation, increased capillary permeability, and spasmodic contractions of Gastrointestinal smooth muscles.
2.H-2 Receptors
1.Increased gastric acid secretions
2.Increased pepsin secretion
3.Increased intrinsic factor (Castle's factor) formation
H-1 Antagonists
Competitively the inhibit the action of histamine on these receptors by their similarity of structures. Thus they limit the histamine effect on bronchial smooth muscle, capillaries, and GI smooth muscle.
These drugs also prevent the allergy-induced itching and pain of the skin and mucous membranes.
H-2 Antagonists
They limit the histamine effect of gastric acid secretions.
Therapy
Histamine has no medicinal and clinical value, yet it can be used as a diagnostic agent to test gastric function. However other gastric stimulants safer as diagnostic agents.
H-1 antagonists are mostly used as anti-allergic agents to reduce itching, urticaria, seasonal cold, and conjunctivitis.
H-2 antagonists are used to relieving from hyper acid secretions.
Toxicity
H-1 Antagonists:-
1.CNS depression
2.Sedation
3.Tiredness
4.Nausea and Vomiting
5.Anticholinergic effects such as dry mouth, urinary retention, and constipation.
Teratogenic effects(not suitable in pregnancy and lactation)
Peripheral H-1 antagonists such as terfenadine and astemizole are devoid of sedation fatigue and anticholinergic side effects.
But these drugs on elevation in plasma have serious cardiovascular effects such as QT prolongation in ECG, cardiac arrest, torsades de points, and ventricular arrhythmias.
Terfenadine is contraindicated with ketoconazole, macrolides as these compounds will reduce its liver metabolism and elevate plasma levels of terfenadine.
H-2 Antagonists:-
1.CNS effects like confusion and dizziness
2.Hepatic failure
3.Kidney failure
4. High doses of cimetidine cause androgenic effects like impotence and gynecomastia in men and galactorrhea in women
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