Autacoid+&+Antihistamines

**Autocoids**:
· Comes from the Greek words "autos" (self) and "akos" (cure) · Naturally occuring and nonspecific substances · Examples include: amines (histamine), polypeptides (angiotensin, bradykinin, kallidin), and lipid-derived substances (prostaglandins, leukotrienes, and platelet-activating factor) · Histamine was the first autocoid to be discovered

Histamines
Histamines are found most in tissues in the mast cell and in blood in basophils and are released by degranulation. __Highest in concentrations__: in the lungs, skin, and intestinal mucosa. __Lowest concentrations__: in the pancreas, spleen, liver, and kidney.

__Stimuli Triggering the Release__:
 * 1) Tissue Injury
 * 2) Allergic Reactions
 * 3) Drugs and other Foreign Compounds

__Metabolism__ - inactivated by methylation of the imidazole ring by the enzyme histamine-N-methyltransferase or oxidative deamination of histamine by diamine oxidase to produce imidazole acetic acid, much of which is subsequently conjugated with ribose.

__Pharmacologic Effects__ - Histamine causes the relaxation of vascular smooth muscle in smaller blood vessels, constriction of some larger blood vessels, stimulation of exocrine glands, especially those of the gastric mucosa. There are three histamine receptors (G protein-linked): __ Cardiovascular system(H2 mostly) - __ dilation of terminal arterioles, capillaries, and postcapillary venules and leads to a sharp decrease in peripheral resistance and a consequent __fall in blood pressure__. Cutaneous flushing, over the face and upper trunk, and a rise in skin temperature. Circulatory depression is predominate. __ Nonvascular smooth muscle- __ the smooth muscle, bronchioles and gastrointestinal tract is most sensitive to this action. People with asthma are highly susceptible to histamine. __ Exocrine glands- __ Histamine plays a major role in the physiological role in gastric secretion. Although histamine can enhance salivary and lacrimal gland secretion, this effect is minimal unless large doses are used.
 * __H1 Receptors__ - mediate effects on smooth muscle, leading to vasodilation, increased vascular permeability, and contraction of nonvascular smooth muscle.
 * __H2 Receptors__ - mediate stimulation of gastric acid secretion and may be involved in other effects, such as the direct cardiac stimulation and vasodilation seen after high doses of antihistamine.
 * __H3 Receptors__ - the function has not yet been established, but appear to antagonize stimulatory effects mediated by the activation of H1 receptors. Inhibits the release of norepinephrine.

__General Therapeutic Uses__ - There are no valid therapeutic applications but could be used as a diagnostic tool the assessment of gastric acid production.

__Adverse Effects__ - Effects are dose dependent, cutaneous flushing, hypotension, headache, visual disturbances, dyspnea, and gastrointestinal disturbances such as nausea, vomiting, and diarrhea. Massive dosages may lead to shock and circulatory failure.

__Pharmacologic effects__ – H1 antihistamines -can inhibit the contraction GI and bronchial smooth muscle. They antagonize the increase secretions of the salivary and lacrimal glands and the increase release of epinephrine. they appear to interact with the H1 receptors on the target cell, resulting in a decreased availabilityof these receptors for histamine (this can be reversed with increased concentration of histamine). __Adverse reactions__ – CNC depressant manifested by as drowsiness, lethargy, and decrease motor coordination. Ethanolamines and phenothiazines are the most sedative. GI distrurbances-nausea, vomiting, epigastric distress. P.373 __Toxicity__ – large doses can cause marked stimulation of CNS manifestations by hallucinations, excitement, __Uses__ – (H1):allergic conditions, they are most effective when given before the release of histamine.  H1 antihistamines: 1. Nasal allergies.  They relieve rihnorrhea, sneezing, lacrimation, itching of the eyes and nasal mucosa. 2. Acute and chronic urticaria. They are topically effective in treating pruritus and uticaria which can cause allergic dermatitis. 3. Epinephrine used for severe anaphylactic reaction. Antihistamines may be given after emergency is controlled. 4. Anti-motion sickness. 5. OTC sold as hypnotics that include H1 because of their sedative effect. 6. Reduction of tremors, muscle rigidity, headaches……. ==**__Use in dentistry__: H1-Promethazine, hydroxyzine, and diphenhydraminez may be used in conscious sedation as premedication for deep sedation. H1 antihistamines can also reduce postoperative nausea and vomiting .**==
 * Antihistamines** ̶  describe the: (H1, H2, H3, receptor antagonist )

**__Adverse effects__** **H1- disturbances in cardiac rhythm, hallucinations, excitement, tremors, and convulsions. Allergic reactions include urticarial, bullous, or petechial rashes.**
H2 antihistamines :

__Uses of H2__: inhibit both basal and stimulate secretion of gastric acid. Used on Gi disorders to relieve reduction of acid secretion may relieve symptoms.
==__Adverse effects H2__- minor symptoms: dizziness, lethargy, and fatigue. More serious- mental confusion, delirium, seizures. Cimetidine has been shown to increase blood concentrations of numerous drugs, including anticoagulation of the warfarin type, TCAs, and various benzodiazepines.==