Following drugs, which act on H,, receptors have active metabolite except
Ans. b (Mizolastine) (Ref KDT 6th/158)KDT 6th/1S9:Mizolastine: is nonsedating antihistaminic is effective in allergic rhinitis and urticaria by single daily dosing despite a t 1/2 of 8-10 hr and no active metabolite.anticholinergic action can be graded as:HighLowMinimal/ AbsentPromethazineChlorpheniramineClemastineDiphenhydramineHydroxyzineTerfenadineDimenhydrinateTriprolidineAstemizolePheniramineCyclizineLoratadineCyproheptadine CetirizineSECOND-GENERATION ANTIHISTAMINICSThe second-generation antihistaminics (SGAs) are H, receptor blockers marketed after 1980with following properties:# Higher H1 selectivity: no anticholinergic side effects.# Absence of CNS depressant property.# Additional antiallergic mechanisms apart from histamine blockade: some also inhibit late phase allergic reaction by acting on leukotrienes or by anti-platelet activating factor effect.# They have poor antipruritic, antiemetic and antitussive actions.Terfenadine (withdrawn by most manufacturers).# It is the first SGA,- highly H1 selective,- rapid onset (1-2 hr) and- moderate duration (12-24 hr) of action - good for short term and intermittent use.# Terfenadine, but not its carboxy metabolite (the active H1 blocker), blocks cardiac K+ channels in overdose and has produced polymorphic v. tach (torsade de pointes).# The risk is markedly increased in liver disease or when inhibitors of CYP 3A4 (which generates the carboxy metabolite) are administered concurrently -Erythromycin, clarithromycin, ketoconazole and itraconazole are the most important drugs precipitating terfenadine cardiotoxicity, while azithromycin and fluconazole are probably safe.# Similar incidences have been reported with astemizole, but not with other SGAs except ebastine.Fexofenadine (active metabolite of terfenadine)# Does not block delayed rectifier K+ channels in the heart--does not prolong QTc interval.# Therefore it has been introduced as a substitute of terfenadine free of arrhythmogenic potential.# But it is not entirely safe in patients with long QT, bradycardia or hypokalemia.# Fexofenadine do not cross BBB- no sedation or impair psychomotor performance and is free of atropinic side effects.# Duration of action 24 hours.# Though erythromycin and ketoconazole increase its blood levels, but no arrhythmias have been observed.Astemizole# Actions of astemizole are similar to terfenadine, but it has slow onset (2-4 hr) and long duration (2-5 days) of action.# It is 97% plasma protein bound and metabolized with a tV2 of 20 hr.# Astemizole is better used for maintenance therapy.# Not suitable for rapid control of symptoms.# In perennial rhinitis it has shown better efficacy than terfenadine and chlorpheniramine.# Increased appetite, weight gain and flatulence occur in some patients. It shares the ventricular tachycardia producing potential of terfenadine. The risk is enhanced by coadministration of selective serotonin reuptake inhibitors, quinidine, some macrolides, azole antifungals and HIV protease inhibitors.Loratadine# Another long-acting selective peripheral H] antagonist that lacks CNS depressant effects; faster acting than astemizole.# It is partly metabolized by CYP3A4 to an active metabolite with a longer t 1/2 of 17 hr, but in contrast to terfenadine/ astemizole, it has not produced cardiac arrhythmia in overdose.# No interaction with macrolides or antifungals has been noted.# Good efficacy has been reported in urticaria and atopic dermatitis.Desloratadine# It is the major active metabolite of loratadine effective at half the dose.# Non-interference with psychomotor performance and cardiac safety are documented.Cetirizine# It is a metabolite of hydroxyzine with marked affinity for peripheral Hl receptors; penetrates brain poorly, but subjective somnolence has been experienced at higher doses.# It is not metabolized; does not prolong cardiac action potential or produce arrhythmias when given with erythromycin/ ketoconazole.# Cetirizine also inhibits release of histamine and of cytotoxic mediators from platelets as well as eosinophil chemotaxis during the secondary phase of the allergic response.# Superior efficacy in urticaria / atopic dermatitis.# It is indicated in upper respiratory allergies, pollinosis, urticaria,atopic dermatitis; also as adjuvant in seasonal asthma.Azelastine# This newer H1 blocker has good topical activity;# Also inhibits histamine release and inflammatory reaction triggered by LTs and PAF; and has bronchodilator property.# After intranasal application it has been shown to down-regulate ICAM-1 expression on nasal mucosa.# Its metabolism is inhibited by CYP 3A4 inhibitors.# Given by nasal spray for seasonal and perennial allergic rhinitis it provides quick symptomatic relief lasting 12 hr.# Stinging in the nose and altered taste perception are the local side effects.# Some somnolence after nasal use and weight gain noted after oral use.Mizolastine# This recently marketed nonsedating antihistaminic is effective in allergic rhinitis and urticaria by single daily dosing despite a t 1/2 of 8--10 hr and no active metabolite.Ebastine# Another newer SGA that rapidly gets converted to the active metabolite carbastine having a t 1/2 of 10-16 hr. It is nonsedating and active in nasal and skin allergies.# Animal studies have found it to prolong Q-Tc interval, which makes it liable to arrhythmic potential and CYP3A4 interaction, but actual reports are still few.H2 antagonist: The first H2 blocker Burimamide was developed by Black in 1972. Metiamide was the next, but both were not found suitable for clinical use. Cimetidine was introduced in 1977 and gained wide usage. Ranitidine, famotidine, roxatidine, and many others have been added subsequently. They are primarily used in peptic ulcer and other gastric hypersecretory states and are described.H3 antagonist: Though a selective H3 antagonist thioperamide has been developed, it has not found any clinical utility.
Loratidine
Mizolastine
Azelastine
Ebastine
Anti Histaminics