Antihistamine and Antiinflamasi Steroid

Anggelia PuspasariPharmacology and Theraupetic DepartementMedical and Health Sciences FacultyUniversity JambiAntihistamineIntroducing1927 Best and colleagues isolated histamine from fresh tissue of the lung and liver

Histamine__Histos, Greek word for tissue

Distributed through the animal kingdom present in many venom, bacteria, plants etc

Histamine in Human BodyFormed by decarboxylation of the amino acid l-histidineForming and storage histamine mainly in mast cell and basophil cell___non mast cell storage:epidermis, gastric mucosa, neuron CNS, cell that regenrtaed and growth rapdlyLow [ ] in plasma or body fluid except LCSTissue contain large number of mast cell are skin, bronchial tree, mucosa of respiratory system dan intestinalHistamine receptor : H1, H2, H3, H4

Tissue and Organ System Effect of the HistamineNervous system Powerful stimulant of sensory nerve ending_pain and itchingIncreased weakfulnessCardiovascular system Decreased BP, Increased HR, Vasodilatation of the blood vessel_flushing, sense of warmth, headacheIncreased capilary permeability, permit transudation molecul outward_hivesBronchial smooth muscleBronchocontrictionTissue and Organ System Effect of the HistamineGIT smooth muscleContraction of intestinal smooth muscle in large dose_diarrheaOther smooth muscle organInsignificant effect on genitourinary tract and eye.Pregnant women can induced uterus contraction in large doseSecretory tissuePowerful stimulant of gastric acid secretion, gastric pepsinEnhanced salivary and lacrimal gland secretion in large doseStimulated chromaffin cells to secrete cathecolamineTriple response of lewisIntradermal injection of histamine causes red spot, edema and flare

Histamine in Allergic Response

Antagonist Histamine Action

Histamine AntagonistPhysiologic antagonists, especially epinephrine, have smooth muscle actions opposite to those of histamine, but they act at different receptorsRelease inhibitors reduce the degranulation of mast cells that results from immunologic triggering by antigen-IgE interaction__Cromolyn and nedocromil .Histamine receptor antagonists represent a third approach to the reduction of histamine-mediated responsesAntihistamineH1 receptor antagonistMechanismof actionCompounds that competitively block histamine at H1 receptors also block autonomic receptors.The H1 antagonists are conveniently divided into first-generation and second-generation agents. Distinguished by the relatively strong sedative effects , 2nd generation have less sedative effect.

Classes of The Drug (AH-1, 1st generation)

Classes of the Drug (AH1_2nd Generation)

PharmakokineticAbsorption Rapidly absorbed following oral administrationPeak plasma [ ] 1-3 hDOA usually 4-6 h, some of the drug longer (meclizine and 2nd gen)DistributionWidely distributed through the body, 1st generation enter CNS MetabolismExtensively metabolized, primarily by microsomal systems in the liverExcretionRenal Excretion in metabolite form 1st generation.Cetirizine and loratadine excreted in urine in ummetabolized form, fezofenadine excreted in feces.PharmacodynamicHistamine receptor BlockerAH1 inhibit most effect of histamin on smooth muscle (inhibit bronchocontriction, inhibit vasodilatation)AH1 strongly block the increased capillary permeability and formation of oedema and whealAH1 inhibit flare and itchAH1 dont suppress gastric secretion

PharmacodynamicNon Histamine receptor Blocker EffectAH1 can both stimulated and depress the CNS (older generetion)__sedation effect.Have antimuscarinic effect__lessened secretion in cholinergically innervated gland and reduce ongoing secretion, potent prevented motion sickness but can cause urinary retention and blurred vissionLocal anesthetic effect__promethazineAdrenoreceptor blocking action caused orthostatic hypotension__phenotiazine groupSerotonin blocking action__cyproheptadine

Indication/Clinical usesAllergic ResponseMotion Sickness and vestibular disturbances__diphenhydramine, promethazine, cyclizine and meclizineSedationAntinausea and antiemetic agent__Doxylamine_now withdraw from the marketAntiparkinsonism effect__diphenhydramineAdverse EffectThe most frequent side effect in the first-generation H1 antagonists is sedation.The next most frequent side effects involve the digestive tract. Dryness of the mouth and respiratory passages (sometimes inducing cough), urinary retention or frequency, and dysuria.Untoward central actions include dizziness, tinnitus, lassitude, incoordination, fatigue, blurred vision, diplopia, euphoria, nervousness, insomnia, and tremors.azelastine, hydroxyzine, and fexofenadine showed teratogenic effects in animal studies whereas others (e.g.,chlorpheniramine, diphenhydramine, cetirizine, and loratadine) did not.

ToxicityIn acute poisoning with H1 antagonists, their central excitatory effects constitute the greatest danger.Lend the syndrome a remarkable similarity to that of atropine poisoning.Deepening coma with cardiorespiratory collapse and death usually within 2 to 18 hours. Treatment is along general symptomatic and supportive lines.Drug InteractionDrug interaction with inhibitor CYP450 enzyme (macrolide, azole antifungal or calcium antagonist)__increased plasma[ ] __induced arrythmia, especially for terfenadine Drug Interaction with inducer CYP450 enzym benzodiazepin exe__decreased plasma [ ]CYP inhibitor enzym__Alcohol or other CNS depressants produces an additive effect that impairs motor skillsTERIMAKASIH