ANTIBIOTICS, ANALGESICS AND ANTIMICROBIALS IN CHILDREN

Children because of skill developing immunity are more prone to infections. Oral cavity is one such area where a variety of bacterial, viral, fungal etc. infections are commonly encountered in children. Those conditions in majority of cases makes the use of antimicrobials mandatory. Hence a thorough knowledge of various drugs used in different conditions and their side effects is necessary. Drugs must be used only when definitely indicated and after balancing the possible benefit and risk ratio. t is

always beneficial for the dentist ! physician to use only those drugs with which he!she is familiar. "dministration of drugs does not mean a way to produce good oral health. nfact an injudicious use of any drug for that matter is potentially harmful. t is easy to administer drugs but at the same time it is difficult to control their side effects by removing them from the body. #ome of the general guidelines for use of drugs is given below$

Guidelines for Drug Therap ! %. There should be a genuine indication for the use of a drug in the patient. &. Drugs prescribed should be$ ' ' ' ' (inimum. "ppropriate and familiar. ne)pensive. Of good *uality. generic name should be used for

+. ,referably prescription.

-. Optimum dosage is used to achieve desired clinical effects with minimum adverse effects. .. " short gun therapy is to be avoided. /. "s far as possible oral route is preferred over other route in children. 0. "dverse drug reactions should be anticipated,

monitored and appropriately managed. Combinations of drugs may be necessary in certain conditions when the causative agent is not known. " multituding therapy is also used as a measure to minimi1e

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drug adverse reactions and to prevent development of drug resistance. #ome of the antibiotics commonly used in pedodontics and pediatrics and antimicrobials in general are discussed below. Cal"ula#ion of Dose! The dose in children is similar to that of adults with respect to body weight. The only difference is in infant that is because of$ ' ' ' ' ' Decreased gastric acid. Decreased plasma protein binding. Decreased flow to muscles. mmature kidney and liver functioning. ncreased e)tracellular fluid compared to adults.

The dose is determined by using body surface areas and weight. #ome of the formulae used for the calculation of dosage for children are$ %. Clarks rule$ Child dose Childs weight in bs ! %.2 ) adult dose &. 3oung rule$ Child dose 4"ge of child ! "ge 5 %&6 ) adult dose

An#i$i"ro%ial Agen#s! #ome of the antimicrobial agents used in various orofacial and general infections of the body include the following$ %. 7'lactamase inhibitors$ ' ' ' ,enicillins. Cephalosporins. 7acitracins.

&. "minoglycosides$ ' ' ' #treptomycin. 89ntamycin. "mikacin etc.

+. (acrolides$ ' ' ' ' 9rythromycin. Clindamycin. :o)ithromycin. "rithromycin etc.

-. #ulfonamides$ ' ' Trimethoprim #ulfametho)a1ole ; co trima)a1ole

.. Tetracyclines$ /. "ntifungal agents$ ' ' <ystatin. "mphotericin 7 -

' '

=etakena1ole. Oncano1ole etc.

0. "ntiviral agents$ ' ' "cycloutr >idovudine etc.

These given agents are of prime correction in oral and facial infections. #ome of other antimicrobial agents used in general infections include$ %. "nti tubercular agents. &. "nti leprocy agents. +. "nti helmintics. -. "nti malarials. .. anti proto1oals. 7. ?actamase nhibitors$ ' ' ' ,enicillins. Cephalosporins. 7acitracins.

&eni"illins! 9ven after introduction of a number of antibiotics penicillines enjoy the first place in initial preference against infections in orofacial as well as general parts. 7ased on its pure form as ben1yl penicillin and its modification

penicillins are classified as follows$

%. ,enicillinase #ensitive$ 7en1yl penicillin 8 4sodium or potassium6$ ' ' ' ' %22,222 units per oral /h .2'/2,222 units!kg!day m /h 7en1athane penicillin %.& mega units ! +'- weeks. ,rocain penicillin +22,222 units ! %&.&-hrs m.

&. "cid resistant penicillins$ ' ' ,heno)y methyl penicillins or penicillin @. Dose %2mg !kg!day.

+. ,enicillinase resistant penicillins$ (ithicillin %22mg!kg!day m! u of /hr O)acillin .2'%22mg!kg!day ,O! @ of / hr. Clo)acillin .2'%22mg!kg!day ,O! @ of / hr. -. 9)tended spectrum penicillins$ "mpicillin .2'%22mg!kg!D ,O or A / hr. "mo)ycillin &.'.2mg!kg!day ,O / hourly. Carbenicillin .2'.22mg!kg!day m! A / hourly. Ticarcillin .2'+22mg!kg!day A in vision -'/ hours. ,ipercacillin hourly. %22'+22mg!kd!day A in vision -'B

,enicillins have bactericidal properly by interfering with synthesis of cell membrane of growing bacterias. Thus creating a defective all membrane. This defect in cell membrane makes it more prone for phagocytosis. <atural penicillins with procain groups are poorly absorbed from stomach because of their inactivation by acid. t is therefore preferable to administer them by parentally. (ajority of oral preparations are less than complete dose through 8 T and reach to peak plasma concentration at +2'/2 minutes. They bind reversibly with free alumin in plasma and e)erted in active forms in urine. The half life of pencillin 8 is +2 minutes whereas e)tended spectrum penicillins like amo)ycyllin it is .2'/2 minutes. Therapeu#i" 'ses! ,enicillins are used against a wide variety of infections of the body including infections in the oral cavity. #ome of the applications include$ %. #treptococcal infections$ ' ' ' ' #t. pharyngitis. #t. abscesses. nfective endocarditis. Otitis media and sinusitis. 0

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,neumonia meningitis.

&. #taphylococcal infections$ @ast majority of staphyloccal infections are produced by penicillinase producing species. n case of

staphylaccal abscess penicillin 8 is ineffective and thus penicillinase resistant penicillins like mithecillin and o)acillin are used. Anfe"#ions (i#h Anaero%es! ,enicillins possess very little action on anaerobes. (ost of the infections of dental origin are of mi)ed variety and penicillins can be effectively administered in treating these infections. +. (iningococcal infections ; ,enicillin 8. -. 8onococcal infections ; "mo)ycyllin and "mpicillin. .. #yphilis ; Congenital syphilis in infants should be treated with procaine penicillin 8 for %2 days with .2,222 units!kg!day. ,rimary, secondary and tertiary syphilis of less than % year duration. ,rocaine penicillin 8. &.- million units ! day m.

,lus ,robenecid %gm !day orally for %2 days. /. "ctinomycosis$ "lthough rare in children any form of actinomycosis should be treated with %&' &2 million units of ,encillin 8 A ! day for / weeks. 0. Diphtheria$ ,rocaine ,enicillin 8 &.+ million units!day %2'%& days in divided doses. Ad)erse Rea"#ions! %. "llergy$ "lthough rare penicillins in sensitive patients produce severe anaphyla)is. The prevalence of such reactions is very rare accounting % in %222 individuals. The reaction may be life threatening. &. #uprainfections$ ,rolonged usage may had to decreased immunity by acting on normal flora suppressing the growth of only sensitive organisms. Thus the resistant organisms are free to grow producing infections. 9)$ candidiasis. +. 7itter taste of milk in lactating mother from ampicillin. C

-. ,seudomembraneous colitis leading to diarrhea. Cephalosporins! Cephalosporins are the ne)t group of antibiotics

considered. 7ased on the period of their introduction from old to recent products they are divided into three generations as first, second and third generation. #ome of these drugs according to generations and their doses in children include$ %. Dirst generation cephalosporins$ ' ' ' Cephale)in &.'.2mg!kg!D ,.O. / hr. Cepha1oline &.'.2mg!kg!D m. A B'%& hr. Cefadro)il +2mg!kg!D ,.O. %& hrly.

&. #econd generation cephalosporins$ ' ' ' Caphaclor &2'-2mg!kg!D ,.O. /'Bhr. Cephamandole .2'%.2mg!kg!D m, A B'%& hr. Ceauro)ime +2'%22mg!kg!D m! A B'%&hr.

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+. Third generation cephalosporins$ ' ' ' ' ' Cefota)ime %22'%.2mg!=g!D m! A B'%&hr. Cefoper1one .2'&22mg!kg!D m B'%& hr. (o)alactum .2'&22mg!kg!D m ! A /'B hrly. Cefta1idime .2'%22mg!=g!D @ %& hrly. Cefti1o)ime +2'/2mg!kg!D A B'%& hrly.

The first generation cephalosporins have got same spectrum of activity as that of penicillins. These agents may even be active against 7'lactamase producing

staphylococcus. #ome strains may not be active. "s the generation changes from to and the

spectrum of activity is increased. The second generation cephalosporins are more active against gram've bacilli in addition to the activity of first generation products. The second generation cephalosporins are active against: ' ' ' ' ?t. influen1a. 9nterobacter. 9'coli. =lebsiella species etc.

The half life of majority of cephalosporins is +2'.2 minutes and are e)creted mainly through kidnies. %%

The third generation cephalosporins like cefato)ime are highly resistant to beta'lactamase and are very much effective against gm5ve and gm've organisms. These drugs have got good activity against pseudomonas species. The half life of these drugs is more than that of and

generation cephalosporins i.e. %'& hours. These drugs in severe infections have to be administered -'B hourly. Therapeu#i" 'ses! %. Dental infections ; abscess. &. "s prophyla)is for bacterial endocarditis. +. nfections from gm've organisms. -. 8onorrhea. .. (iningitis. /. =lebsialla, streptococcus pneumonas etc. Side Effe"#s! %. "naphyla)is. &. <ausea vomiting. +. #uprainfections on indiscriminate usage.

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-. #ome of the third generation cephalosporins produce blood dyscriasis by reducing platicle functions. .. Diarrhea etc. A$inogl "osides! The antibiotics belonging to this group are not widely used in dental infections. 7ut in some conditions they are very effective. They are composed of various aminosugars linked by glycoside linkage and are prepared by fermentation of various species of streptomyces. These antibiotics are not given by oral route and and A route is most commonly preferred route m for

administration. (ost of these drugs are highly polar , cations and hence very poorly absorbed from 8 T. ?ess than %E is absorbed from 8 T. These are e)creted mainly through urine. The major drawback of these drugs is the severe to)icity produced by these drugs. "minoglycosides cause ; ototo)icity which involve both auditory and vestibular functions of Bth cranial nerve. The ne)t to)icity is

nephroto)icity by impaired renal functions.

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Hypersensitivity is the ne)t adverse effect seen. #ome of the aminoglycosides and their doses are$ %. #treptomycin -2mg!kg!D m %& hr. &. 8entamycin -'Bmg!kg!D m! A B'%& hrly. +. "mikacin %.'&2mg!kg!D m! A B'%& hrly. -. Tobramycin /'0..mg!kg!D m! A /'B hrly. .. #isomycin +mg!kg!D m! A B hrly. Dosage should be reduced and intervals between doses should be increased in case of renal damage. Indi"a#ions! n cases of infections caused by aerobic gm've

microorganisms. Me"hanis$ of a"#ion! They act by interfering with ribosomal function and thus protein synthesis. They are bactericidal in action. Ma"rolides! The first drugs of preference in patients allergic to penicillins for treatment of infections are macrolides. The drugs belonging to macrolides include$

%-

%. 9rythromycin .2mg!kg!D ,O. /'B hr. &. Cleandomycin .2mg!kg!D ,O. %& hrs. +. :o)ithromyin +2'.2mg!kg!D ,O %& hrs. -. @ancomycin +2'-2 A /'B hrs. .. "1ithromycin %2 ,O once daily. /. Clarithromycin %. ,O %& hrly. 0. Clindamycin %2'-2 A / hrly. B. ?inkomycin +2'/2 ,O / hrly. C. ,olymy1in 7 &2222 A!=g!D ,O. B hrly. (acrolides are the compounds with comple) structures with unusual nitrogen containing sugars and a larger

molecule weight 4F0226. (ost of the macrolides are given by oral route and are better absorbed from small intestine. The mechanism of action includes inhibition of protein synthesis between +2. and .2. fractions of ribosomes the pharmacological activity makes the bacteriostatic at lower doses and at higher doses these drugs act as bactericidal drugs.

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Therapeu#i" uses! 9rythromycin among the macrolides is most commonly used drug. The uses in dentistry include$ %. Dental infections with gm5ve and ;ve aerobic

organisms including$ ' ' ' &. "pical abscess. ,eriodontal abscess. ,ulpitis etc. nfections caused by staph aureus, streptococcus, mycoplasma, pneumoniae, Chlamydia, C. diaphtheria, Tetanus bacilli, 7. pertusis etc. 9rythromycin is generally safe and preferred in

patients allergic to penicillin and cephalosporins. available in . salts namely$ %. 9rythromycin base. &. 9rythromycin stearate. +. 9rythromycin 9stolate. -. 9rythromycin ethyl succinate. .. 9rythromycin lactobionate.

t is

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The main side effects with erythromycin include

problems and a cholastatic hepatitis like condition where the mucosmembrane and sclera of chilb become yellow with yellowish discoloration of urine. The condition disappears as the drug is withdrawn. "1ithramycin has got increased activity against gm've organisms along with the spectrum of erythromycin and is better tolerated as compared to erythromycin. @ancomycin acts as cidal drug against staphylococci. Clindamycin or lincomycin may give rise to

pseudomembraneous colitis. *uinalones! Guinalones cover a wider area of gm5ve and ;ve aerobic organisms. They are mostly used by oral route and are better absorbed in 8 T. The mechanisms of action of *uinalones is they act by inhibiting the en1yme. D<" gyrase thus interfering with D<" synthesis. The activity thus is cidal in nature. #ome of the *uinalones include$

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%. <ilidi)ic acid .2'/2mg!kg ,O B hrly. &. Ciproflo)acin %.'&2mg!kg ,O %& hrly. 0'%2mg!kg A %& hrly. +. <orflo)acin %2mg!kg ,O %& hrly. -. Oflo)acin &22mg 4adults6 %& hrly. Therapeu#i" uses! %. Dental infections caused by gm5ve and ;ve aerobic bacterias. &. Tonsilitis, pharyngitis. +. A:T . -. Arinary tract infiltration. .. "ny systemic infections e)$ typhoid. The use of *uinalones in children is not indicated. t is because, all the species of *uinalones produce arthropathy in immature children. The metabolism of theophyllin is inhibited by children when used in pregnant female or

liproflo)acin and when two drugs are used concurrently to)icity may occurs.

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Broad Spe"#ru$ An#%io#i"s! Tetracyclines: Tetracyclines are classified under broad spectrum antibiotics because of their additional spectrum of activity involving pseudomonas. :ickettsia mycoplasma and

Chlamydia. #ome atypical bacteria and amebae. #ome of the tetracycline products are$ ' ' ' ' ' ' Chlor tetracycline. O)ytetracycline. Demeclocycline. (ethacycline. Do)ycycline. (inocycline.

(ajority of tetracyclines are given orally and few products like o)ytetracycline can be given by m route. The mechanism of actions of these tetracyclines is by interfering with protein synthesis. The site of action is +2. fraction of ribosomes. These drugs a pharmacologically bacteriostatic in nature.

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On

oral

administration

tetracyclines

are

absorbed

incompletely but ade*uately form 8 T distributed throughout the body and e)creted unchanged in urine. The absorbtion of tetracyclines is better in empty stomach and is disturbed by the presence of antacids, calcium magnesium and iron salts. "luminium hydro)ide gels and bismuth subsalicylate. The main mechanism

involved is chelation of divalent and trivalent cations. Effe"#s on Cal"ified Tissues! This makes the main reason for avoiding Ttcln in children. Ase of these drugs by children for a short term therapy or long term therapy may develop brown inversible

discolorations of involved teeth. The larger the dose relative to body weight more marked will be the discoloration. The risk of this problems on teeth are more when the child is given this drug during the period of & months and C2 years when majority of teeth are getting calcified. The total dose of drug rather than duration of treatment is the main factor of consideration.

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The main mechanism of this discoloration is because of the chelating property and the formation of tetracycline ; calcium or the phosphate comple). "s the time progresses the yellow fluorescence is replaced by brown discoloration which is indicative of o)idation product of antibiotic. This discoloration is permanent and its formation is hastened by light treatment of infections with :icket sialchlamydae, mycoplasma pneumonia, amaebiosis. Ad)erse Rea"#ions! %. 8 T ; These drugs produce severe 8 varying degrees. They include$ ' ' ' 9pigastric burning and distress. "bdominal and vomiting. Diarrhea in some cases. The problem increases with increases in dose of the drug. &. ,hototo)icity$ Demeclocycline and do1eycyclines producee to)ic problems of

reactions of skin to sunlight in treated patients.

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+. Hepatic to)icity$ The jaundice followed by diffuse infiltration of fat in liver is a complication with prolonged tetracycline

therapy. ,regnant women are particularly susceptible for

hepatic damage. -. :enal to)icity$ 7y inhibiting protein synthesis treatment in pregnancy causes pigmentation of primary teeth. The period of greatest risk is from mid pregnancy to -'/ months postnatally. n addition to teeth tetracyclines may also get

deposited in skeleton during gestation and throughout childhood. " -2E of depression in bone growth has been demonstrated. This can be reversible in case of a short doe for a lesser period. Dosage$ %. Tetracycline &.'.2mg!kg!D ,.O. / hourly. %.'&.mg!kg!D m B'%& hrly &. Do)ycyclin %..'&mg!kg!D ,.O. %&'&- hrly. &&

Chlora$pheni"ol "nother drug under broad spectrum antibiotics is chloromphenicol because of its intended activity on H. nfluen1a species. The drug can be administered by oral m or v route and e)creted mainly through kidnies. The drug acts by protein synthesis inhibition and is bacteriostatic. Therapeu#i" uses! %. <ot indicated in children. &. n treatment of H. influen1a infection. +. n treatment of 9nteric fever. Ad)erse rea"#ions! %. (ost common adverse reaction of child is bone marrow depression after prolonged usage and it is dose related. " more severe bone marrow aplasia may occurs due to single larger dose or prolonged usage. This shows aplastic anemia. t is totally unpredictable and terminates fatally in many cases.

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&. Hypersensitivity$ +. n infants and children if the drug is used

indiscriminately it may lead to 8rey'7aby syndrome resulting in$ ' ' ' ' "bdominal distension. @omitting. :efusal to suck and Dyspnea. The baby develops gray colour due to cyanosis and peripheral circulatory collapse with death in around half of the cases. Dosage$ ' ' Chloramphenicol ; .2'%22mg!kg!D ,.O. m, v / hrly. 9ye drops ; 2..'%E

Sulfona$ides! #ulfonamides are the most economic group of

antibiotics. The common sulfonamide is a mi)ture of Trimethoprim and #ulphametho)a1ole and is Co'

&-

trima)ada1ole. They are the first group of antibiotics introduced and were widely used. An#i$i"ro%ial Spe"#ru$! 8m positive and gram negative organisms like st. pyogens, st. pneumonia, H. influen1a, <ocardia,

"ctinomycos camphylobacter grganulomatosis etc. The utility of these drugs is reduced because of increased resistance in organisms and increased reports of allergic reactions. Me"hanis$s! #ulfonamides are competitive antagonists for

paraaminobemoic acid and interferes with synthesis of folic acid in the bacterial cells. The pH action is H7acteriostaticI. Dosage: The co'trima)a1ole available contains trimethoprim and sulphametha)o1ole in a ratio of %$.. 9ach tablet contains B2mg of Trimethoprim and -22mg of sulfametha)a1ole. Dosage ; Trimethoprim /mg!kg!D ,.O. %& hourly.

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An#ipro#o+oal Agen#s! "lthough a number of antiproto1oal drugs are available the drug of choice in dentistry for trating severe infections caused specially by anaerobic organisms is metronida1ole. Tinida1ole is the recent introduction in treating anaerobes. Me#ranida+ole! (etranida1ole has got a wider antiproto1oal and wide antimicrobial properties. The drug is given usually by oral route but can some times be given by proto1oal infections. On oral administration the drug is absorbed promptly and completely and attains peak plasma levels after % hour of its administration. The plasma half life of the drug is about B hours and e)creted mainly through urin. An#i$i"ro%ial spe"#ru$! (etranida1ole is a cidal drug and is effective against$ %. Trichomonas, amaebae and histiolytica. @ infusion in the treatment of severe

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&. Drom dental point of view the drug is effective against anaerobic organisms including bacteriods,

fusobacterium, clostridia, 7. fragylis, Chlamydia. Clini"al Appli"a#ions! %. n the management of ; TrichomoniasisJ "maebiasis and other proto1oal infections. &. n treating infections like caused by anaerobic periodontal

microorganisms abscess etc. Ad)erse Effe"#s!

dental

abscess,

%. (utagenesis, carcinogenesis$ ndiscriminate use of metranida1ole for a prolonged period of time may cause change in mutation pattern of normal cells. This condition may be reversal in initial periods. &. One of the side effects that makes it to avoid in children is the metallic taste in saliva, which is not well tolerated by children. +. <ausea and vomiting. -. n some patients it may cause blood dysiasis. &0

Dosage$ n infections and amebiasia &2mg!kg!D B hourly ,.O. Tinida1ole ; .2mg!kg!D ,.O. once daily. H persensi#i)i# ! 7ody immune mechanisms as provided e)hibited by inflammatory reactions is a well known process. n certain conditions these body immune mechanisms may be seen as an e)aggerated or e)cessive manner leading to tissue damage and thus proving harmful to the body. These processes are called as HHypersensitivity :eactionsI. HThe term hypersensitivity refers to the injurious conse*uences in the sensiti1ed host following contact with specific antigensI. <ormally in the process of immunity the focus of attention is antigen and its fate i.e. whether bacterial death is the result or neutrali1ation of bacterial to)ins. 7ut in cases of hypersensitivity reactions the focus of attention is not the antigen as such but at the same time is concerned with what happens to the host as a result of immune reactions.

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Dor the induction of hypersensitivity reactions the host is re*uired to get e)posed to the antigen atleast once before the reactions. This initial e)posure sensiti1es host to the concerned antigen and is called as sensiti1ing dose or priming dose. Classifi"a#ion! Coombs and Gell: 7ased on the mechanism of pathogenesis involved in the Coomb and 8ell in %C/+ classified H.#. reactions in to four groups, namely$ %. Type &. Type +. Type ; mmediate hypersensitivity ; "naphylactic. ; Cytoto)ic or cell stimulation ; mmune comple) or to)ic comple) disease.

-. Type @ ; Delayed hypersensitivity. T pe I rea"#ion Reageni" The mechanism here is antibodies are fi)ed on the surface of tissue cells 4mast cells and basophils6 in

sensiti1ed individuals. The antigen combines with all fi)ed antibody leading to release of a variety of 4vasoactive

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amines6 pharmacologically active substances which produces clinical reaction. Anaph la,is ' ' ' t is a classical immediate type of reaction. The term anaphyla)is was coined by :icket in %C2&. Theobald #mith observed a triangular phenomenon in 8uinea pigs in %C2& following injection of to)in antito)in mi)tures. 9hrlich named this as Theobald #mith phenomenon and showed that this kind of reactions are produces not only by to)in initiation mi)tures but also even by injection of normal serum. ' #ensiti1ation is most effective when injected parentally may occur by any route including ingestion and even inhalation. ' n sensitive individuals a minute *uality of antigen is sufficient to cause a severe reaction. ' ' "ntigens as well as heptens can induce anaphyla)is. " minimal interval of &'+ weeks is needed between sensiti1ing dose and shocking dose.

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#hocking dose is more effective when injected @ and less when intraperitonially and subcutaneously and least when intradermally.

Clini"al -ea#ures! ' Due to smooth muscular contraction and increased vascular permeability. ' Tissues or organs affected by anaphylactic reaction are known as Htarget tissuesI or Hshock organsI. n man fatal anaphyla)is is very rare, immediately after administration of antigen the symptoms begin as$ ' ' ' ' tching of scalp and tongue. Dlushing of skin over whole body. Difficulty in breathing due to bronchial spasm. There may be nausea, vomiting, abdominal pain, diarrhea, some times blood in stool etc. ' "cute hypotension, loss of consciousness followed by death as last conse*uence.

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Me"hanis$ of Anaph la,is! "naphyla)is can be passively transferred from a sensitive donor to normal recipient by injection of serum. The circulating antibodies are responsible for this passive transfusion. Hemocytotrophic g and antibody is the major g

antibody responsible for anaphylactic reactions. Other have ony a small role.

g and molecules are bound to a mast cells in tssues and basophils in circulation on e)posure to an antigen the g and combines with antigen bridging the gap between two cells. This crosslinking increases the permeability of these cells to calcium ions causing dedgranulation of cells

including biologically active substances within the granules. These biologically active substances has their

pharmacological action are responsible for various reactions. The substances are mediators of reaction and of two types$ %. ,rimary ; Histamin, serotonin, heparin ; 9ainophil chemotact factor of anaphyla)isJ neutrophilJ various proteolytic en1ymes.

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&. #econdary ; slow releasing substance of anaphyla)is, prostaglandins, platelet activating factor. Media#ors of Anaph la,is! Primary Mediators of Anaphylaxis: a6 Histamin$ t is the most important vasoactive amine in

anaphyla)is. t is the most important vasoactive amine in anaphyla)is. t is formed by De cabo)ylation of histidine found in mast cells basophils and pts. On secretion into skin it stimulation sensory nerve endings causing$ ' ' ' ' tching, burning sensation. @asodilatation and hyperemia by a)on refle)es. 9dema by causing increased vascular permeability. t produces severe smooth muscle contraction including vasculative intesting and especially of bronchioles. ' t stimulates secretions.

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b6 #eratonis 4#.H.T.6 ' t is a base derived from dedcarbo)ylation of

tryptophan in mast cells, basophils in small intestine. ' t causes vaso constriction, smooth muscle contraction and increased permeability. ' ts role in humans is minimum.

+-