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Antibiotics
1. 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. It is
always beneficial for the dentist / physician to use only those
drugs with which he/she is familiar. Administration of drugs
does not mean a way to produce good oral health. Infact an
injudicious use of any drug for that matter is potentially
harmful. It is easy to administer drugs but at the same time it
is difficult to control their side effects by removing them
from the body.
Some of the general guidelines for use of drugs is
given below:
1
2. Guidelines for Drug Therapy:
1. There should be a genuine indication for the use of a
drug in the patient.
2. Drugs prescribed should be:
- Minimum.
- Appropriate and familiar.
- Inexpensive.
- Of good quality.
3. Preferably generic name should be used for
prescription.
4. Optimum dosage is used to achieve desired clinical
effects with minimum adverse effects.
5. A short gun therapy is to be avoided.
6. As far as possible oral route is preferred over other
route in children.
7. Adverse 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. A
multituding therapy is also used as a measure to minimize
2
3. drug adverse reactions and to prevent development of drug
resistance.
Some of the antibiotics commonly used in pedodontics
and pediatrics and antimicrobials in general are discussed
below.
Calculation 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.
- Immature kidney and liver functioning.
- Increased extracellular fluid compared to adults.
The dose is determined by using body surface areas
and weight. Some of the formulae used for the calculation of
dosage for children are:
1. Clarks rule: Child dose Childs weight in Ibs / 150 x
adult dose
2. Young rule: Child dose (Age of child / Age + 12) x
adult dose
3
4. Antimicrobial Agents:
Some of the antimicrobial agents used in various
orofacial and general infections of the body include the
following:
1. B-lactamase inhibitors:
- Penicillins.
- Cephalosporins.
- Bacitracins.
2. Aminoglycosides:
- Streptomycin.
- GEntamycin.
- Amikacin etc.
3. Macrolides:
- Erythromycin.
- Clindamycin.
- Roxithromycin.
- Arithromycin etc.
4. Sulfonamides:
- Trimethoprim
- Sulfamethoxazole – co trimaxazole
5. Tetracyclines:
6. Antifungal agents:
- Nystatin.
- Amphotericin B
4
5. - Ketakenazole.
- Oncanozole etc.
7. Antiviral agents:
- Acycloutr
- Zidovudine etc.
These given agents are of prime correction in oral and
facial infections. Some of other antimicrobial agents used in
general infections include:
1. Anti tubercular agents.
2. Anti leprocy agents.
3. Anti helmintics.
4. Anti malarials.
5. anti protozoals.
B. Lactamase Inhibitors:
- Penicillins.
- Cephalosporins.
- Bacitracins.
Penicillins:
Even after introduction of a number of antibiotics
penicillines enjoy the first place in initial preference against
infections in orofacial as well as general parts. Based on its
pure form as benzyl penicillin and its modification
penicillins are classified as follows:
5
6. 1. Penicillinase Sensitive:
Benzyl penicillin G (sodium or potassium):
- 100,000 units per oral 6h
- 50-60,000 units/kg/day Im 6h
- Benzathane penicillin 1.2 mega units / 3-4 weeks.
- Procain penicillin 300,000 units / 12.24hrs Im.
2. Acid resistant penicillins:
- Phenoxy methyl penicillins or penicillin V.
- Dose 10mg /kg/day.
3. Penicillinase resistant penicillins:
Mithicillin 100mg/kg/day Im/Iu of 6hr
Oxacillin 50-100mg/kg/day PO/IV of 6 hr.
Cloxacillin 50-100mg/kg/day PO/IV of 6 hr.
4. Extended spectrum penicillins:
Ampicillin 50-100mg/kg/D PO or IU 6 hr.
Amoxycillin 25-50mg/kg/day PO 6 hourly.
Carbenicillin 50-500mg/kg/day Im/ IU 6 hourly.
Ticarcillin 50-300mg/kg/day IU in vision 4-6 hours.
Pipercacillin 100-300mg/kd/day IU in vision 4-8
hourly.
6
7. Penicillins 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.
Natural penicillins with procain groups are poorly
absorbed from stomach because of their inactivation by acid.
It is therefore preferable to administer them by parentally.
Majority of oral preparations are less than complete
dose through GIT and reach to peak plasma concentration at
30-60 minutes. They bind reversibly with free alumin in
plasma and exerted in active forms in urine. The half life of
pencillin G is 30 minutes whereas extended spectrum
penicillins like amoxycyllin it is 50-60 minutes.
Therapeutic Uses:
Penicillins are used against a wide variety of infections
of the body including infections in the oral cavity. Some of
the applications include:
1. Streptococcal infections:
- St. pharyngitis.
- St. abscesses.
- Infective endocarditis.
- Otitis media and sinusitis.
7
8. - Pneumonia meningitis.
2. Staphylococcal infections:
Vast majority of staphyloccal infections are
produced by penicillinase producing species. In case of
staphylaccal abscess penicillin G is ineffective and thus
penicillinase resistant penicillins like mithecillin and
oxacillin are used.
Anfections with Anaerobes:
Penicillins possess very little action on anaerobes.
Most of the infections of dental origin are of mixed
variety and penicillins can be effectively administered in
treating these infections.
3. Miningococcal infections – Penicillin G.
4. Gonococcal infections – Amoxycyllin and Ampicillin.
5. Syphilis – Congenital syphilis in infants should be
treated with procaine penicillin G for 10 days with
50,000 units/kg/day.
Primary, secondary and tertiary syphilis of less than 1
year duration.
Procaine penicillin G. 2.4 million units / day Im.
8
9. Plus
Probenecid 1gm /day orally for 10 days.
6. Actinomycosis:
Although rare in children any form of actinomycosis
should be treated with 12- 20 million units of Pencillin G
IU / day for 6 weeks.
7. Diphtheria: Procaine Penicillin G 2.3 million units/day
10-12 days in divided doses.
Adverse Reactions:
1. Allergy:
Although rare penicillins in sensitive patients produce
severe anaphylaxis. The prevalence of such reactions is
very rare accounting 1 in 1000 individuals. The reaction
may be life threatening.
2. Suprainfections:
Prolonged 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. Ex: candidiasis.
3. Bitter taste of milk in lactating mother from ampicillin.
9
10. 4. Pseudomembraneous colitis leading to diarrhea.
Cephalosporins:
Cephalosporins are the next group of antibiotics
considered. Based on the period of their introduction from
old to recent products they are divided into three generations
as first, second and third generation.
Some of these drugs according to generations and their
doses in children include:
1. First generation cephalosporins:
- Cephalexin 25-50mg/kg/D P.O. 6 hr.
- Cephazoline 25-50mg/kg/D Im. IU 8-12 hr.
- Cefadroxil 30mg/kg/D P.O. 12 hrly.
2. Second generation cephalosporins:
- Caphaclor 20-40mg/kg/D P.O. 6-8hr.
- Cephamandole 50-150mg/kg/D Im, IU 8-12 hr.
- Ceauroxime 30-100mg/kg/D Im/IU 8-12hr.
10
11. 3. Third generation cephalosporins:
- Cefotaxime 100-150mg/Kg/D Im/IU 8-12hr.
- Cefoperzone 50-200mg/kg/D Im 8-12 hr.
- Moxalactum 50-200mg/kg/D Im /IU 6-8 hrly.
- Ceftazidime 50-100mg/Kg/D IV 12 hrly.
- Ceftizoxime 30-60mg/kg/D IU 8-12 hrly.
The first generation cephalosporins have got same
spectrum of activity as that of penicillins. These agents may
even be active against B-lactamase producing
staphylococcus. Some strains may not be active.
As the generation changes from I to II and III 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:
- Lt. influenza.
- Enterobacter.
- E-coli.
- Klebsiella species etc.
The half life of majority of cephalosporins is 30-50
minutes and are excreted mainly through kidnies.
11
12. The third generation cephalosporins like cefatoxime
are highly resistant to beta-lactamase and are very much
effective against gm+ve and gm-ve organisms. These drugs
have got good activity against pseudomonas species. The
half life of these drugs is more than that of I and II
generation cephalosporins i.e. 1-2 hours. These drugs in
severe infections have to be administered 4-8 hourly.
Therapeutic Uses:
1. Dental infections – abscess.
2. As prophylaxis for bacterial endocarditis.
3. Infections from gm-ve organisms.
4. Gonorrhea.
5. Miningitis.
6. Klebsialla, streptococcus pneumonas etc.
Side Effects:
1. Anaphylaxis.
2. Nausea vomiting.
3. Suprainfections on indiscriminate usage.
12
13. 4. Some of the third generation cephalosporins produce
blood dyscriasis by reducing platicle functions.
5. Diarrhea etc.
Aminoglycosides:
The antibiotics belonging to this group are not widely
used in dental infections. But 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 Im
and IU route is most commonly preferred route for
administration. Most of these drugs are highly polar , cations
and hence very poorly absorbed from GIT. Less than 1% is
absorbed from GIT.
These are excreted mainly through urine.
The major drawback of these drugs is the severe
toxicity produced by these drugs. Aminoglycosides cause –
ototoxicity which involve both auditory and vestibular
functions of 8th
cranial nerve. The next toxicity is
nephrotoxicity by impaired renal functions.
13
14. Hypersensitivity is the next adverse effect seen. Some
of the aminoglycosides and their doses are:
1. Streptomycin 40mg/kg/D Im 12 hr.
2. Gentamycin 4-8mg/kg/D Im/IU 8-12 hrly.
3. Amikacin 15-20mg/kg/D Im/IU 8-12 hrly.
4. Tobramycin 6-7.5mg/kg/D Im/IU 6-8 hrly.
5. Sisomycin 3mg/kg/D Im/IU 8 hrly.
Dosage should be reduced and intervals between doses
should be increased in case of renal damage.
Indications:
In cases of infections caused by aerobic gm-ve
microorganisms.
Mechanism of action:
They act by interfering with ribosomal function and
thus protein synthesis. They are bactericidal in action.
Macrolides:
The first drugs of preference in patients allergic to
penicillins for treatment of infections are macrolides. The
drugs belonging to macrolides include:
14
15. 1. Erythromycin 50mg/kg/D PO. 6-8 hr.
2. Cleandomycin 50mg/kg/D PO. 12 hrs.
3. Roxithromyin 30-50mg/kg/D PO 12 hrs.
4. Vancomycin 30-40 IU 6-8 hrs.
5. Azithromycin 10 PO once daily.
6. Clarithromycin 15 PO 12 hrly.
7. Clindamycin 10-40 IU 6 hrly.
8. Linkomycin 30-60 PO 6 hrly.
9. Polymyzin B 20000IU/Kg/D PO. 8 hrly.
Macrolides are the compounds with complex structures
with unusual nitrogen containing sugars and a larger
molecule weight (>700).
Most 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 305 and 505 fractions of ribosomes the
pharmacological activity makes the bacteriostatic at lower
doses and at higher doses these drugs act as bactericidal
drugs.
15
16. Therapeutic uses:
Erythromycin among the macrolides is most commonly
used drug. The uses in dentistry include:
1. Dental infections with gm+ve and –ve aerobic
organisms including:
- Apical abscess.
- Periodontal abscess.
- Pulpitis etc.
2. Infections caused by staph aureus, streptococcus,
mycoplasma, pneumoniae, Chlamydia, C. diaphtheria,
Tetanus bacilli, B. pertusis etc.
Erythromycin is generally safe and preferred in
patients allergic to penicillin and cephalosporins. It is
available in 5 salts namely:
1. Erythromycin base.
2. Erythromycin stearate.
3. Erythromycin Estolate.
4. Erythromycin ethyl succinate.
5. Erythromycin lactobionate.
16
17. The main side effects with erythromycin include IT
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.
Azithramycin has got increased activity against gm-ve
organisms along with the spectrum of erythromycin and is
better tolerated as compared to erythromycin.
Vancomycin acts as cidal drug against staphylococci.
Clindamycin or lincomycin may give rise to
pseudomembraneous colitis.
Quinalones:
Quinalones cover a wider area of gm+ve and –ve
aerobic organisms.
They are mostly used by oral route and are better
absorbed in GIT.
The mechanisms of action of quinalones is they act by
inhibiting the enzyme. DNA gyrase thus interfering with
DNA synthesis. The activity thus is cidal in nature.
Some of the quinalones include:
17
18. 1. Nilidixic acid 50-60mg/kg PO 8 hrly.
2. Ciprofloxacin 15-20mg/kg PO 12 hrly.
7-10mg/kg IU 12 hrly.
3. Norfloxacin 10mg/kg PO 12 hrly.
4. Ofloxacin 200mg (adults) 12 hrly.
Therapeutic uses:
1. Dental infections caused by gm+ve and –ve aerobic
bacterias.
2. Tonsilitis, pharyngitis.
3. URTI.
4. Urinary tract infiltration.
5. Any systemic infections ex: typhoid.
The use of quinalones in children is not indicated. It is
because, all the species of quinalones produce arthropathy in
immature children when used in pregnant female or
children.
The metabolism of theophyllin is inhibited by
liprofloxacin and when two drugs are used concurrently
toxicity may occurs.
18
19. Broad Spectrum Antbiotics:
Tetracyclines:
Tetracyclines are classified under broad spectrum
antibiotics because of their additional spectrum of activity
involving pseudomonas. Rickettsia mycoplasma and
Chlamydia. Some atypical bacteria and amebae.
Some of the tetracycline products are:
- Chlor tetracycline.
- Oxytetracycline.
- Demeclocycline.
- Methacycline.
- Doxycycline.
- Minocycline.
Majority of tetracyclines are given orally and few
products like oxytetracycline can be given by Im route.
The mechanism of actions of these tetracyclines is by
interfering with protein synthesis. The site of action is 305
fraction of ribosomes. These drugs a pharmacologically
bacteriostatic in nature.
19
20. On oral administration tetracyclines are absorbed
incompletely but adequately form GIT distributed throughout
the body and excreted 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. Aluminium hydroxide
gels and bismuth subsalicylate. The main mechanism
involved is chelation of divalent and trivalent cations.
Effects on Calcified Tissues:
This makes the main reason for avoiding Ttcln in
children.
Use 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 2 months and 90
years when majority of teeth are getting calcified. The total
dose of drug rather than duration of treatment is the main
factor of consideration.
20
21. The main mechanism of this discoloration is because of
the chelating property and the formation of tetracycline –
calcium or the phosphate complex. As the time progresses
the yellow fluorescence is replaced by brown discoloration
which is indicative of oxidation product of antibiotic. This
discoloration is permanent and its formation is hastened by
light treatment of infections with Ricket sialchlamydae,
mycoplasma pneumonia, amaebiosis.
Adverse Reactions:
1. GIT – These drugs produce severe GI problems of
varying degrees. They include:
- Epigastric burning and distress.
- Abdominal and vomiting.
- Diarrhea in some cases.
The problem increases with increases in dose of the
drug.
2. Phototoxicity:
Demeclocycline and dozeycyclines producee toxic
reactions of skin to sunlight in treated patients.
21
22. 3. Hepatic toxicity:
The jaundice followed by diffuse infiltration of fat in
liver is a complication with prolonged tetracycline
therapy.
Pregnant women are particularly susceptible for
hepatic damage.
4. Renal toxicity:
By inhibiting protein synthesis treatment in pregnancy
causes pigmentation of primary teeth. The period of
greatest risk is from mid pregnancy to 4-6 months
postnatally.
In addition to teeth tetracyclines may also get
deposited in skeleton during gestation and throughout
childhood. A 40% of depression in bone growth has been
demonstrated. This can be reversible in case of a short
doe for a lesser period.
Dosage:
1. Tetracycline 25-50mg/kg/D P.O. 6 hourly.
15-25mg/kg/D Im 8-12 hrly
2. Doxycyclin 1.5-2mg/kg/D P.O. 12-24 hrly.
22
23. Chloramphenicol
Another drug under broad spectrum antibiotics is
chloromphenicol because of its intended activity on H.
Influenza species.
The drug can be administered by oral Im or Iv route
and excreted mainly through kidnies.
The drug acts by protein synthesis inhibition and is
bacteriostatic.
Therapeutic uses:
1. Not indicated in children.
2. In treatment of H. influenza infection.
3. In treatment of Enteric fever.
Adverse reactions:
1. Most common adverse reaction of child is bone marrow
depression after prolonged usage and it is dose related.
A more severe bone marrow aplasia may occurs due to
single larger dose or prolonged usage. This shows aplastic
anemia. It is totally unpredictable and terminates fatally
in many cases.
23
24. 2. Hypersensitivity:
3. In infants and children if the drug is used
indiscriminately it may lead to Grey-Baby syndrome
resulting in:
- Abdominal distension.
- Vomitting.
- Refusal 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 – 50-100mg/kg/D P.O. Im, Iv 6 hrly.
- Eye drops – 0.5-1%
Sulfonamides:
Sulfonamides are the most economic group of
antibiotics. The common sulfonamide is a mixture of
Trimethoprim and Sulphamethoxazole and is Co-
24
25. trimaxadazole. They are the first group of antibiotics
introduced and were widely used.
Antimicrobial Spectrum:
Gm positive and gram negative organisms like st.
pyogens, st. pneumonia, H. influenza, Nocardia,
Actinomycos camphylobacter grganulomatosis etc.
The utility of these drugs is reduced because of
increased resistance in organisms and increased reports of
allergic reactions.
Mechanisms:
Sulfonamides are competitive antagonists for
paraaminobemoic acid and interferes with synthesis of folic
acid in the bacterial cells. The pH action is “Bacteriostatic”.
Dosage:
The co-trimaxazole available contains trimethoprim
and sulphamethaxozole in a ratio of 1:5. Each tablet contains
80mg of Trimethoprim and 400mg of sulfamethaxazole.
Dosage – Trimethoprim 6mg/kg/D P.O. 12 hourly.
25
26. Antiprotozoal Agents:
Although a number of antiprotozoal drugs are available
the drug of choice in dentistry for trating severe infections
caused specially by anaerobic organisms is metronidazole.
Tinidazole is the recent introduction in treating anaerobes.
Metranidazole:
Metranidazole has got a wider antiprotozoal and wide
antimicrobial properties.
The drug is given usually by oral route but can some
times be given by IV infusion in the treatment of severe
protozoal infections.
On oral administration the drug is absorbed promptly
and completely and attains peak plasma levels after 1 hour of
its administration. The plasma half life of the drug is about 8
hours and excreted mainly through urin.
Antimicrobial spectrum:
Metranidazole is a cidal drug and is effective against:
1. Trichomonas, amaebae and histiolytica.
26
27. 2. From dental point of view the drug is effective against
anaerobic organisms including bacteriods,
fusobacterium, clostridia, B. fragylis, Chlamydia.
Clinical Applications:
1. In the management of – Trichomoniasis; Amaebiasis
and other protozoal infections.
2. In treating infections caused by anaerobic
microorganisms like dental abscess, periodontal
abscess etc.
Adverse Effects:
1. Mutagenesis, carcinogenesis:
Indiscriminate use of metranidazole for a prolonged
period of time may cause change in mutation pattern of
normal cells.
This condition may be reversal in initial periods.
2. 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.
3. Nausea and vomiting.
4. In some patients it may cause blood dysiasis.
27
28. Dosage:
In infections and amebiasia 20mg/kg/D 8 hourly P.O.
Tinidazole – 50mg/kg/D P.O. once daily.
Hypersensitivity:
Body immune mechanisms as provided exhibited by
inflammatory reactions is a well known process. In certain
conditions these body immune mechanisms may be seen as
an exaggerated or excessive manner leading to tissue damage
and thus proving harmful to the body. These processes are
called as “Hypersensitivity Reactions”.
“The term hypersensitivity refers to the injurious
consequences in the sensitized host following contact with
specific antigens”.
Normally in the process of immunity the focus of
attention is antigen and its fate i.e. whether bacterial death is
the result or neutralization of bacterial toxins. But 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.
28
29. For the induction of hypersensitivity reactions the host
is required to get exposed to the antigen atleast once before
the reactions. This initial exposure sensitizes host to the
concerned antigen and is called as sensitizing dose or
priming dose.
Classification:
Coombs and Gell:
Based on the mechanism of pathogenesis involved in
the Coomb and Gell in 1963 classified H.S. reactions in to
four groups, namely:
1. Type I – Immediate hypersensitivity – Anaphylactic.
2. Type II – Cytotoxic or cell stimulation
3. Type III – Immune complex or toxic complex disease.
4. Type IV – Delayed hypersensitivity.
Type I reaction Reagenic
The mechanism here is antibodies are fixed on the
surface of tissue cells (mast cells and basophils) in
sensitized individuals. The antigen combines with all fixed
antibody leading to release of a variety of (vasoactive
29
30. amines) pharmacologically active substances which produces
clinical reaction.
Anaphylaxis
- It is a classical immediate type of reaction.
- The term anaphylaxis was coined by Ricket in 1902.
- Theobald Smith observed a triangular phenomenon in
Guinea pigs in 1902 following injection of toxin
antitoxin mixtures. Ehrlich named this as Theobald
Smith phenomenon and showed that this kind of
reactions are produces not only by toxin initiation
mixtures but also even by injection of normal serum.
- Sensitization is most effective when injected parentally
may occur by any route including ingestion and even
inhalation.
- In sensitive individuals a minute quality of antigen is
sufficient to cause a severe reaction.
- Antigens as well as heptens can induce anaphylaxis.
- A minimal interval of 2-3 weeks is needed between
sensitizing dose and shocking dose.
30
31. - Shocking dose is more effective when injected IV and
less when intraperitonially and subcutaneously and
least when intradermally.
Clinical Features:
- Due to smooth muscular contraction and increased
vascular permeability.
- Tissues or organs affected by anaphylactic reaction are
known as “target tissues” or “shock organs”.
In man fatal anaphylaxis is very rare, immediately
after administration of antigen the symptoms begin as:
- Itching of scalp and tongue.
- Flushing 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.
- Acute hypotension, loss of consciousness followed by
death as last consequence.
31
32. Mechanism of Anaphylaxis:
Anaphylaxis 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 Ig and antibody is the major
antibody responsible for anaphylactic reactions. Other Ig
have ony a small role.
Ig and molecules are bound to a mast cells in tssues
and basophils in circulation on exposure to an antigen the Ig
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:
1. Primary – Histamin, serotonin, heparin – Eainophil
chemotact factor of anaphylaxis; neutrophil; various
proteolytic enzymes.
32
33. 2. Secondary – slow releasing substance of anaphylaxis,
prostaglandins, platelet activating factor.
Mediators of Anaphylaxis:
Primary Mediators of Anaphylaxis:
a) Histamin:
It is the most important vasoactive amine in
anaphylaxis. It is the most important vasoactive amine in
anaphylaxis. It is formed by De caboxylation of histidine
found in mast cells basophils and pts.
On secretion into skin it stimulation sensory nerve
endings causing:
- Itching, burning sensation.
- Vasodilatation and hyperemia by axon reflexes.
- Edema by causing increased vascular permeability.
- It produces severe smooth muscle contraction including
vasculative intesting and especially of bronchioles.
- It stimulates secretions.
33
34. b) Seratonis (S.H.T.)
- It is a base derived from dedcarboxylation of
tryptophan in mast cells, basophils in small intestine.
- It causes vaso constriction, smooth muscle contraction
and increased permeability.
- Its role in humans is minimum.
34