Autocoid+&+Antihistamines

=Autacoid and Antihistamines =

**Youtube videos:** http://www.youtube.com/watch?v=y3bOgdvV-_M
http://www.youtube.com/watch?v=ywdk3BTjK2s

==== Histamine, polypeptides, and lipid-derived substances are compounds that have been collectively termed autacoids. They naturally occur in the body and form in the tissue they act upon. **Histamine-** ==== Histamines are amines that are stored in Mast cells in the intestinal mucosa. Histamines are released by these cells during an immune reaction. Histamines are synthesized by the intracellular decarboxylation of the amino acid histidine. Histamine is found in mast cells and in basophils and is released by either exocytosis or degranulation. Histamine can be metabolized two different ways the first way is by N-methyltransferases being converted into methylimidazole acetic acid by monoamine oxidase. The second way is oxidative deamination of histamine by diamine oxidase to produce imidazole acetic acid which is conjugated with ribose. Once inactivated they are excreted by the kidneys. Any physical or chemical agent that nonspecifically injures tissue can cause instant release of Histamine from mast cells in the affect area particularly skin. Histamine will continue to be released for several minutes causing acute inflammation. Two to four hours later the tissue can have prolonged permeability.


 * Types of Histamines:**
 * __H1 agonist__ causes: vasodialation, bronchconstriction, increased capillary permeability and pain/itching in cutaneous nerve endings
 * __H2 agonist__ causes: Increased gastric acid secretion.

**What is its pharmacologic effect on the cardiovascular system?** Arteriolar dilation, cutaneous flushing, intense headache “Histamine headache”, and hypotension.

**Pharmacologic Effects on nonvascular smooth muscle?** Contration of the nonvascular smooth muscle. The smooth muscle of the bronchioles and gastrointestinal tract and to a smaller degree other smooth muscle organs such as the uterus and bladder.

**Pharmacologic Effects on Exocrine glands?** Elicits the secretion of pepsin by the gastric mucosa. It stimulates the secretion of catecholamines by the chromaffin cells of the adrenal medulla. Histamine can also enhance the salivary and lacrimal gland secretion.

**What are the therapeutic uses for histamine?** There is currently no therapeutic application. Histamine can be used in the Diagnosis of achlorhydria (assessing of gastric acid production), and to test for pheochromocytoma.

**Adverse reactions and side effects of histamine?** Histamine toxicity can cause cutaneous flushing, hypotension, headache, visual disturbances, dyspnea, Gastrointestinal disturbances such as nausea, vomiting and diarrhea. In huge doses it can lead to shock and circulatory failure.

**Antihistamines**: common drugs that act as an antagonist to histamines. Antihistamines antagonize **H-1 receptors** and are also known as H1 blockers.
 * Rx: Loratidine (Claritin): long acting trycyclic antihistamine with a selective histamine H1 receptor antagonist. Advertised to be "non sedating." Onset of action: 1-3hours, half life: 12-15 hours, duration of action: 24hours. Adverse reactions include: headaches, somnolence, fatigue and xerostomia.
 * Rx: Fexofenadine (Allegra): non sedating, second generation histamine H1 antagonist. Is an active metabolite, Terfadine, resposible for arruthmias. Often used for seasonal allergies. Does NOT cross the blood brain barrier thus reducing sedation potential. Erythromycin (antibiotic) and ketoconazole (antifungal) medications should be used with caution due to their ability to increase the level of Fexofenadine. Onset of action: 15-30minutes, half life: 8hours, duration of action: 24hours.
 * Rx: Astemizole (Hismanal) long acting, non sedating antihistamine. Binds to H1 receptor sites in the GI tract, uterus, blood vessels and bronchial muscles. Duration of action: 2-5days
 * Cetrizine (Zyrtec): Non sedating H1 antagonist that competes with histamine on effector cells in the GI tract, blood vessels and respiratory tract. Onset of action: 15-30minutes, duration of action: 24hours. Ofter used for seasonal allergies.

-Nausea and vomiting < Anticholinergic -Preoperative sedation and OTC sleeping aid (the hypnotic agent in Tylenol PM and Advil PM is diphenhydramine (Benadryl) - Local anesthesia: Benadryl can be used as a LA. -Antiserotonergic- can inhibit the release of Seratonin.
 * Antihistamines are most commonly used to treat seasonal allergies, however, due to their side effects antihistamines are also used to treat:

**AUTACOIDS** Histamines were the first autacoid to be discovered due to its inflammatory, skin redness and swelling,edema, and anaphylatic reactions. .It is one of a heterogeneous group of biologically active, naturally occurring substances that act like hormones in nearby surrounding tissue. In addition to histamines, autacoids include another amine, polypeptide, and lipid-derived substances collectively**.** Autacoids have a brief duration, are not blood borne, and act near the site of synthesis. Autacoids are nonspecific and play an important role in the body. Antacoids can also be released during exercise allowing for heat loss. Most common Autocoids:


 * Histamines
 * Prostaglandins *Found in most body tissue and fluids
 * *Produced in response to many different stimuli
 * *Can relax or stimulate the smooth muscle (depends on the spectrum of prostaglandin)
 * *Prostacylin is produced in the vessel walls and inhibits platelet aggregation

*Found in most body tissues and fluids *Produced in response to many different stimuli * Can relax or stimulate smooth muscle (depends on the spectrum of prostaglandin) * Produce by platelets and stimulate platelet aggregation (vasoconstrictor)
 * Thromboxanes

**Pharmacologic and affects in Dentistry**:


 * Pharmacologic: Works in the CNS by increasing body temperature by releasing interleuken 1 which promotes the release and synthesis of prostaglandins
 * Dentistry: Prostaglandins is involved in periodontal disease by inducing inflammatory response of soft tissue, resorb bone and inhibit synthesis of new bone by inhibiting osteblasticactivity.