Antibiotics and analgesics in pediatric dentistry almost cover all basic pharmacology and recent drugs which are used in pediatric dentistry. although it contains some not used cephalosporins but we should have some knowledge about that.

1. ANTIBIOTICS AND ANALGESICS
PRESENTED BY: DR. PARIKSHIT S. KADAM
(JR-1)

2. CONTENT
• Introduction
• General pharmacology
• Definition
• History
• Classification
• Penicillins
• Cephalosporins

3. • Chloramohenicol
• Macrolides
• Tetracyclins
• Aminiglycosides
• Sulfonamides
• Cotrimoxazole
• Fluroqunolones

4. • Clindamycin
• Vancomycin
• Metroniadazole
• Pediatric dosage formulas
• Antibiotic sensitivity test
• References

5. INTRODUCTION
• Antibiotics are one of the most frequently used as well
as misused drugs.
• Their importance is magnified in the developing
countries, where infective diseases predominate.
• If discontinued prematurely, the surviving bacteria can
restart an infection that may be resistant to the original
antibiotic.

6. • In dentistry, antibiotics are used mainly in the
following purposes:
1. As adjuncts to therapy for oro-facial infection
2. To prevent local infection associated with dental
procedures
3. To prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body

7. GENERAL PHARMACOLOGY
• Drug:- single active chemical entity present in a medicine that is
used for diagnosis, prevention, treatment/cure of a disease
• Acoording to WHO (1996) “ drug is a any substance or product
that is used or is intended to be used to modify or explore
physiological systems or pathological states for the benefit of the
recipient”.

8. PHARMACY
• It is an art and science of compounding and dispensing drugs or
preparing suitable dosage forms for administrations of drug to
man or animal.
• It includes collections, identification, purification, isolation,
synthesis, standardization and quality control of medicinal
substances.

9. TOXICOLOGY
• It is a study of poisonous effect of drugs and other chemicals (
household, environmental pollutants, industrial, agricultural,
homicidal) with emphasis on detection, prevention and treatment
of poisonings.

10. DRUG NOMENCLATURE
• Chemical Name
• Nonproprietary Name
• Proprietary Name

11. PHARMACOKINETICS
1. Absorption
2. Distribution
3. Metabolism
4. Excretion

12. BIOAVAILIBILITY
• It is the fraction of administered drug that reaches the systemic
circulation in the unchanged form.
1. AUC- tells about extent of absorption
2. Tmax- time to reach maximum con.
3. Cmax- maximum concentration of drug that can be obtained
• Bioequivalance

13. DISTRIBUTION
• The extent of distribution of drug depends on its:
1. Lipid solubility
2. Ionization at physiological ph
3. Extent of binding to plasma and tissue proteins
4. Differences in the regional blood flow
• Volume of distribution can be defined as “ the volume that
would accommodate all the drug in the body, if the
concentration throughout was the same as in plasma”.

14. METABOLISM
• Metabolic reactions occur with the help of microsomal or non-
microsomal enzymes
• Phase I and phase II
• Phase I – Oxidation, reduction, Hydrolysis, cyclization
• Phase II – Acetyalation, methylation, sulfation

15. EXCRETION
Excretion of drug through kidneys occur by
1. Glomerular filtration
2. Tubular reabsorption
3. Tubular secretion

16. • Rate of elimination is the amount of drug eliminated per unit time.
• The clearance of a drug is the theoretical volume of plasma from
which the drug is completely removed in unit time
• It can be calcualted as CL = rate of elimination/C

17. ORDER OF KINETICS
• First order:- The rate of elimination is directly proportional to drug
concentration, constant fraction of drug present in the body is
eliminated in unit time
• Zero order:- The rate of elimination remains constant irrespective
of drug concentration
• Plasma half life:- time taken to reduce the plasma concentration to
half of the original value.

18. PHARMACODYNAMICS
• Deals with the effect of drug on body
1. Enzyme inhibition
2. Receptors

19. ROLE IN PEDIATRIC DENTISTRY
• Most common clinical situations in dentistry amenable
to drug therapy in children are pain and infection.
• The necessity to adjust the dosages of medications to
accommodate their lower weight and body size.

20. DEFINITION
• Antibiotics are the substances produced by
microorganisms, which suppress the growth or kill
other microorganism at very low concentration without
causing any harm to host.
• The term antibiotic means "against life”

21. HISTORY
• Term 'antibiosis', - Jean Paul Vuillemin 1877
• Renamed antibiotics - Selman Waksman,1942.
• 1928 Alexander Fleming - penicillin, chemotherapy.
• Gerhard Domaqk in 1932 in Germany- first
sulfonamide & received Noble Prize the 1939.

22. • Penicillin was commercially available-1941 golden age
of antibiotics .
• Florey and Chain purifying penicillin, in 1942.
• Chemical structure of penicillin - Dorothy Crowfoot
Hodgkin in 1945.
• Chlortetracycline- introduced in 1948 [for rickettsial
infections]

23. CLASSIFICATION OF ANTIBIOTICS
Effectiveness
Gram +ve
penicillin ,
erythromycin
Gram –ve
aminoglycosid
es
cephalosporin
s
Gram +ve
and –ve
ampicillin,
amoxycillin
Acid fast
bacilla
Streptomycin
Fungi
Nystatin

24. BASED ON MECHANISM OF
ACTION

27. PENCILLIN
• First antibiotic to be used in 1941.
• Obtained originally from the fungus Penicillium
notatum.
• Presently obtained from P.chrysogenum.
• Has wide therapeutic range and is a safest drug.
• Most commonly used penicillin is Penicillin G or
Benzyl Penicillin.

28. • 60% bound to plasma albumin
• Narrow spectrum, bactericidal - bind to peptidoglycan
• Absorbed from duodenum and eliminated by kidney.
• Food interferes absorption - oral 30 min before or 2-3
hr after food.

29. CLASSIFICATION
Penicillin
Natural Penicillin G
Semisynthetic
Penicillinase resistant
penicillins
Methicillin, Cloxacillin
Acid resistant
penicillins
Phenoxymethyl
penicillin
Extended spectrum
penicillins
Carboxypenicillins
Beta lactamase
inhibitors
Clavulanic acid,
Sulbactam

30. ON DURATION OF ACTION
• Short acting- Procaine benzyl penicillin[1-3hr]
• Intermediate acting- Fortified Benzyl penicillin [12-24 hr]
• Long acting- Benzathine penicillin [12- 15 days]

31. MECHANISM OF ACTION
• Penicillin interfere with the synthesis of bacterial cell wall.
1. Penicillin binding proteins(PBPs)
2. Inhibition of transpeptidase
3. Production of autolysins

32. • The bacteria synthesises UDP-N-acetyl muramic acid
and UDP-N-acetyl glucosamine.
• The cross linking of peptidoglyacamns provides
stability and rigidity to the cell wall.
• The penicillin inhibit the transpeptidases so that cross
linking does not take place.

33. • The enzymes and related proteins constitute the
penicillin binding proteins(PBPS) which are located in
the bacterial cell membrane.
• Each organism has several PBPS obtained from
different species differ in their affinity towards
different b- lactam antibiotics.
• When bacteria divide in presence of a b-lactam
antibiotic- cell wall deficient forms are produced.

34. • As the interior of the bacterium is hyperosmotic, the
CWD forms swell and bursts.
• This is how b-lactam antibiotics exerts bactericidal
action.
• Lytic effect of these antibiotics may also due to
depression of some bacteria autolysins which normally
function during cell division.

35. • The peptidoglycan cell wall is unique to bacteria.
• No such substance is synthesized by higher animals.
This is why penicillin is practically nontoxic to man.
• In gram-positive bacteria, the cell wall is almost
entirely made up of peptidoglyacan while in gram-
negative bacteria it is made up of alternating layer of
lipoprotein and peptidoglyacan.

36. PENICILLIN-G
• It is narrow spectrum antibiotic; activity is limited
primarily to gram-positive bacteria and few others.
• Antibacterial Spectrum:-
1. Cocci:- streptococcia except viridans and group D.
Staph. Aureus, N. gonorrhoeae, N. mengitidis.
2. Bacilli:- B. anthracis, Corynebacterium diphtheriae,
all Clotridia and Listeria.

37. • Bacterial resistance
o Many bacteria are inherently insensitive to PnG
because in them the target enzyme and PBPS are
located deeper under lipoprotein barrier where PnG is
unable to penetrate or they have low affinity for PnG.
o The primary mechanism of acquired resistance is
production of penicillinase.

38. PENICILLINASE
• It is a narrow spectrum b-lactamase which opens the b-
lactam ring to inactivate PnG.
• Majority of staphylococci and some strains of
gonococcia, E. coli, H. influenza produces
penicillinase.

39. PHARMACOKINETICS
• It is acid labile and destroyed by gastric acid.
• Only 1/3rd of oral dose is absorbed in the active form,
absorption from i.m. site is rapid and complete; peak
plasma level is attained in 30 min.
• It is disributed mainly extracellularly; reaches most
body fluids but penetration in serous cavities and CSF
is poor.

40. • About 60% is plasma protein bound.
• Because of rapid excretion, very little PnG is metabolised.
• Plasma t1/2 of PnG in healthy adult is 30 min, in neonates it is
longer.

41. PREPERATIONS AND DOSE
• Sod. Penicillin G ( crystalline penicillin) injection 0.5-5 MU
i.m/i.v. 6-12 hourly.
• Respiratory penicillin G injections
1. Procaine penicillin G inj. – 0.5-1 MU i.m. 12-24 hourly.
2. Fortified procaine penicillin G inj.:- contains 3 lac U
procaine penicillin and 1 lac sod. Penicillin G.
3. Benzathine penicillin G: 0.6- 2.4 MU i.m. every 2-4
weeks.

42. ADVERSE EFFECTS
• Local irritation and toxicity.
• Hypersensitivity
• Uses
• Dental infections
• General medical uses

43. SEMISYNTHETIC PENICILLIN
• Produced by chemically combining specific side chains
or by incorporating specific precursors in culture.
• Aim is as follows:
• Poor oral efficacy
• Susceptibility to penicillinase
• Narrow spectrum of activity
• Hypersensitivity reactions

44. PENICILLINASE RESISTANCE
PENICILLINS
• These antibiotics have side chains that protect b-lactam
ring from attack by staphylococcal penicillinase.
• Cloxacilline
• Oxacillin

45. METHICILLIN
• Highly penicillinase resistance but not acid resistance
• Largely replaced by cloxacillin.
• Methicillin resistant staphyococci are resistant to all
betalactum antibiotics

46. CLOXACILLIN
• Highly penicillinase resistance as well as acid
resistance.
• Should not be used as substitute for PnG.
• More active than methicillin against penicillinase
producing staph, but not against MRSA.
• Infrequently used in dentistry because staphalococcal
infections are rare in oral cavity

47. • It is incompletely but dependably absorbed from oral
route, especially when taken in empty stomach.
• 90% plasma protein bound.
• Elimination primarily by kidney, also partly by liver.
• T1/2 is about 1 hour.

48. DOSE
• 0.25-0.5 g orally every 6 hours.
• For severe infections 0.25-1 g may be injected i.m. or
i.v.
• KLOX, BIOCLOX, CLOPEN

49. NAFICILLIN
• More active than methicillin
• But less active than benzyl penicillin
• 87% is plasma protein bound
• Excreted by the liver

50. ACID RESISTANT PENICILLIN
• Penicillin V
• Acid stable, oral absorption is better.
• Peak blood level is reached in 1 hour and plasma t1/2 is 30-
60 min.
• Suitable for nonserious dental infections but not for severe.
• Dose: 125-250 mg 6 hourly.
• CRYSTAPEN-V, KAYPEN.

51. EXTENDED SPECTRUM PENICILLINS
• These are active against a variety of gram-negative
bacilli.
• They are grouped according to the nature of side chain
substitution and spectrum of activity into amno-/
carboxy-ureido- penicillin.

52. AMINIOENICILINS
• This group has an amino substitution in the side chain.
• These are not resistance to penicillinase.

53. AMPICILLIN
• Active against all organisms sensitive to PnG.
• Many gram-negative bacilli eg. H. influenza, E. coli,
salmonella.
• Cocci eg. Pneumococci, gonococci and meningococci.

54. PHARMACOKINETICS
• Not degraded by gastric acid; oral absorption is incomplete
but adequate, Food interferes in absorption.
• It is partially excreted in bile and primary channel of
excretion is kidney but tubular secretion is slower than PnG.
• Plasma t1/2 is 1 hour.
• Dose: 0.5-2 g oral/ i.m. /i.v. depend on severity of infection,
every 6 hours
• Children 25-50 mg/kg/day.

55. USES
• Broader spectrum of action covering both gram-positive and
gram-negative aerobic as well as anaerobic bacteria.
• Urinary tract infections, respiratory tract infections,
meningitis, gonorrhoea, typhoid fever, bacillary dysentery.
• Adverse effects
• Diarrhoea, rashes.

56. BACAMPICILLIN
• It is ester of ampicillin which is completely absorbed
from git.
• It is a prodrug and is largely hydrolysed during
absorption, thus higher plasma level are attained.
• Dose: 400-800 mg BD; PENGLOBE 200 mg tab.

57. AMOXICILLIN
• Oral absorption is better; food does not interfere with
absorption; higher and more sustained blood levels are
produced.
• More active against penicillin resistance strep. Pneumoniae.
• First choice of drug for prophylaxis of local wound
infection as well as distant infection following dental
surgery.

58. • Dose: 0.25-1 g TD oral/ i.m. or slow i.v.injection.
• Children 25-50 mg/kg/day.
• AMOXYLIN, NOVAMOX, SYNAMOX .

59. CARBENICILLIN
• Active against Pseudomonas aeruginosa.
• It is neither penicillinase resistant nor acid resistant.
• It is inactive orally and has to be administered i.m. or i.v.
• The t1/2 is 1 hour.
• Indicated in serious infections caused by Pseudomonas or
proteus, eg. Burns, urinary tract infection and septicaemia.

60. • High doses have caused bleeding by interfering platelet
function.
• CARBELIN 1 g, 5 g per vial inj.

61. PIPERACILLIN
• This antipseudomonal penicillin is about 8 times more
active than carbencillin.
• Good activity against Klebsiella and some Bacteroids.
• Used in serious gram negative infections.
• T1/2 is 1 hour.
• Dose: 100-150 mg/kg/day in 3 divided doses.
• PIPRAPEN 1g, 2 g vials.

62. BETA-LACTAMASE INHIBITORS
• Beta-lactmases are a family of enzymes produced by
many gram-positive and gram-negative bacteria that
inactivate beta-lactam antibiotics by opening the beta-
lactam ring.
• Different beta-lactamse differ in their substrate
affinities.

63. CLAVULANIC ACID
• Obtained from Streptomyces clavuligerus, it has a beta-
lactam ring but no antibacterial activity of its own.
• It inhibits a wide variety of beta-lactamases produced by
both gram-positive and gram-negative bacteria.
• Clavulanic acid is a progressive inhibitor: inhibition increses
with time so called as suicide inhibitor.

64. PHRMACOKINETICS
• Rapid oral absorption and bioavailability of 60%.
• Its elimination T 1/2 is 1 hour and tissue distribution
matches amoxicillin with which it is combined.
• It is eliminated mainly by glomerular filtration.

65. USES
• Skin and soft tissue infections, dental infections and
gonorrhoea.
• Side effects are same as amoxicillin
• AUGMENTIN, ENHANCIN, AMONATE

66. SULBACTAM
• It is semisynthetic beta-lactamase inhibitor related
chemically as well as in activity to clavulanic acid.
• It also progressive inhibitor.
• Sulbactam does not induce chromosomal beta-lactmases,
while clavulanic acid can induce.
• Oral absorption is inconsistant so it is given parenterally.
• It is combined with ampicillin

67. • This combination is indicated in PPNG gonorrhoea and
mixed aerobic-anaerobic infections.
• SULBACIN, AMPITUM: Ampicillin 1 g +sulbactam
0.5 g per vial inj.
• Adverse effects are pain at site of injection,
thrombophlebitis of injected vein, rash and diarrhoea.

68. TAZOBATAM
• It is similar to sulbactam and its pharmacokinetics matches with
that of piperacillin with which it is combined
• Used in sever infections like peritonitis, pelvi/urinary/respiratory
infections.
• Dose: 0.5 g combined with piperacillin 4 g injected i.v. over 30
min 8 hourly.
• PYBACTAM, TAZACT, TAZOBID.

69. CEPHALOSPORINS
• Semisynthetic antibiotic derived from ‘ cephalosporin-C’ obtained
from a fungus Cephalosporium.
• Chemically related to penicillins.
• Effective against both gram +ve and gram –ve organisms.
• Bactericidal drugs.
• Inhibit cell wall synthesis

70. CLASSIFICATION
First
• Parenteral-
• Cephalothin
• Cefazolin
• Cephaloridine
• Oral-
• Cephalexin
• Cephadine
• Cefadroxil
Second
• Parenteral
• Cefuroxim
• Cefoxitin
• Oral
• Cefaclor
• Cefuroxim
axetal
Third
• Parenteral-
• Cefotaxim
• Ceftizoxime
• Ceftraxone
• Cefoperazone
• Oral-
• cefexim
Fourth
• Parenteral-
• Cefepime
• Cefiperome

71. CEFAZOLIN
• More active against klebicella, E.coli.
• Susceptable to staphylococcal beta lactamases.
• Preffered for surgical prophylaxis.
• T ½ - 2 hr.
• Dose: 0.5 g 8 hourly for mild cases, 1 g 6 hourly for sever cases
i.m. or i.v; for surgical prophylaxis 1.0 g ½ hour before surgery.
• ALCIZON, ORIZOLIN, REFLIN 0.25 g.

72. CEPHALEXIN
• Orally effective first generation cephalosporin.
• Has similar spectrum of activity.
• Little bound to plasma, attains high concentration in bile and
excreted unchanged I urine.
• Used as an alternative to amoxicillin in dentistry.
• T ½ - 1hr.
• Dose: 0.25 g-1 g 6-8 hourly, for children 25-100 mg/kg/day.
• CEPHACILLIN 250, SPORIDEX.

73. CEPHADROXIL
• Has good tissue penetration including in alveolar bone.
• Exerts more sustained action at the site of infection and can be
given 12 hourly despite T1/2 of 1 hr.
• Excreted unchanged in urine
• Frequently selected for dental infections
• Dose: 0.5-1 g BD.
• DROXYL 0.5, CEFADROX 0.5.

74. CEFUROXIME
• Highly resistant to beta lactamases (gram negative organisms)
• Well tolerated by i.m. route and has been used in some mixed
infections as well as for single dose i.m. therapy of gonorrhoea
due to PPNG.
• Dose: CEFOGEN, SUPACEF 250 mg, vial inj; 0.75-1.5 g i.m. or
i.v. 8 hourly, for children 30-100 mg/kg/day.

75. CEFUROXIME AXETIL
• Ester of cefuroxime , effective orally though absorption is
incomplete.
• Activity depend upon in vivo hydrolysis and release of
cefuroxime.
• Frequently chosen for dental infections
• Dose: 250-500 mg BD, for children half dose
• CEFTUM, SPIZEF 125, 250 500 mg, tab and 125 mg/5ml susp.

76. CEFACLOR
• Given orally and more active than first generation.
• Dose: KEFLOR, VERCEF, DISTACLOR 250 mg cap, 125
mg/5ml fry syr, 50 mg/ml ped. Drops.

77. CEFPROZIL
• Oral absorption is good
• Active against strep. pyogens, strep. Pneumoniae, H. influenza.
• Indicated in bronchitis, ENT and skin infections.
• Dose: 250-500 mg BD, child dose is 20 mg/kg/day.
• ORPROZIL, ZEMETRIL 250, 500 mg tabs, REFZIL 125 mg/5ml
and 250 mg/5 ml syr.

78. CEFOTAXIME
• 3rd generation,
• Potent action on aerobic gram-negative as well as gram-positive bacteria but
not on anaerobes.
• Indicated in meningitis, life-threating hospital-acquired infections,
septicaemias and infections in immunocompromised patients.
• Deacetylated in the body; metabolite exerts weaker but synergistic action with
parent drug.
• The plasma T1/2 is 1 hr.
• DOSE: 1-2 g i.m. or i.v. 6-12 hourly.
• OMNATAX, ORITAXIM, CLAFORAN 0.25, 0.5 g per vial inj.

79. CEFTIZOXIME
• Have similar antibiotic activity and same indications as that of
cefotaxime.
• Not metabolised and excreted by kidney at slower rate.
• T1/2 is 1.5-2 hr.
• Dose: 0.5-1 g i.m./i.v. 8 or 12 hourly.
• CEFIZOX, EPOCELIN 0.5 and 1 g per vial inj.

80. CEFTRIAXONE
• Longer duration of action, penetration in CSF is good and it is
eliminated equally in urine ad bile.
• Shown high efficacy in a wide range of serious infections
including bacterial meningitis, multiresistant typhoid fever,
abdominal sepsis and septicaemias.
• Hypoprothrombinaemia and bleeding are specific side effects.
• Dose: OFRAMAX, MONOCEF, MONOTAX 0.25, 0.5 per vial
inj; 1-2 g i.v. or i.m./day.

81. CEFTAZIDIME
• Highly active against pseudomonas aeruginosa and specific
indications are febrile neutropenic patients and burns.
• Plasma T1/2 is 1.5-1.8 hr.
• Adverse effects are neutropenia, thrombocytopenia, rise in plasma
transaminase and blood urea.
• Dose: 0.5-2 g i.m. or i.v. every 8 hr, children 30mg/kg/day.
• FORTUM, CEFAZID, ORZID 0.25, 0.5 and 1 g per vial inj.

82. CEFOPERAZONE
• Indicated in severe urinary, biliary, respiratory, skin-soft tissue
infections, meningitis and septicaemias.
• Primarily excreted in bile; T1/2 is 2 hr.
• It has hypoprothrombinaemic action but does not affect platelate
function.
• A disulfiram-like reaction with alcohol has been reported.
• Dose: 1-2 g i.m./i.v. 12 hourly.
• MAGNAMYCIN 0.25 g, 1 g, 2 g inj; CEFOMYCIN, NEGAPLUS 1
g inj.

83. CEFIXIME
• Orally active 3rd genration highly active against
Enterobacteriaceae, H. influenza, strep. pyogenes,.
• Longer acting and T1/2 is 3 hr.
• Indicated in respiratory, urinary and biliary infections.
• Stool changes and diarrhoea are prominent side effects.
• Dose: TOPCEF, ORFIX 100, 200 mg tab/cap, TAXIM-O 100 mg,
200 mg tabs, 50 mg/ 5ml dry syr.

84. CEFPODOXIME PROXETIL
• Orally active ester prodrug of cefpodoxime.
• Highly active against Enterobacteriaceae and strptococci, it
inhibits staph. aureus.
• Mainly indicated in respiratory, urinary, skin and soft tissue
infections.
• Dose: 200 mg BD.
• CEFOPROX, CEPODEM, DOXCEF 100, 200 mg tab,
100mg/5ml dry syr.

85. CEFDINIR
• Orally active and has good activity against many beta lactamase
producing organisms.
• Most respiratory pathogens including gram-positive cocci are
susceptible.
• Indicated in pneumonia, acute exacerbations of chronic bronchitis,
ENT and skin infections.
• Dose: 300 mg BD
• SEFDIN, ADCEF 300 mg cap, 125 mg/5 ml susp.

86. CEFTIBUTEN
• Orally active against gram-positive and few gram-negative
bacteria but not staph. aureus.
• Indicated in respiratory, ENT and orodental infections.
• Dose: 200 mg BD or 400 mg OD
• PROCADAX 400 mg cap, 90 mg/5ml powder for oral suspension.

87. FOURTH GENERATION
• Latest group characterised by non-susceptibility to inducible
chromosomal beta-lactamse while retaining high activity against
Enterobacteriaceae and spectrum of 3rd generation compounds.

88. CEFEPIME
• Developed in 1990.
• Has same antibacterial spectrum to tat of 3rd generation
compounds but highly resistant to beta-lactamse.
• Due to high potency and extended spectrum it is effective in many
serious infections like hospital-acquired pneumonia, febrile
neutropenia, bacteraemia and septicaemia.
• Dose: 1-2 g i.v. 8-12 hourly
• KEFAGE, CEPIME 0.5 mg, 1 g inj.

89. TOXICITY
• Hypersensitivity reactions
• Cross-reactivity with penicillin
• Cefamandole, cefoperazone, cefotetan may causes
hypoprothrombinemia and dislufiram like reaction with alcohol

90. CHLORAMPHENICOL
• Inhibit protein synthesis by binding to 50s ribosomal subunits and
causing the inhibition of peptidyl transferase.
• Bacteriostatic with wide spectrum of antimicrobial activity
• Resistance develop to this drug due to formation of inactivating
enzyme acetyl transferase
• Drug of choice for typhoid
• Irreversible myelosuppression and grey baby syndrome are side
effects.

91. MACROLIDES
• These are antibiotics having a macrocyclic lactone ring with attached sugars
• Bind to 50s ribosome and block translocation of peptide chain from A to P
site.
• Uses
1. C = Chancroid
2. L = Legiionella infections
3. A = Atypical pneumonia
4. W = Whooping cough by bordetella pertusis

92. ADVESRSE EFFECTS
1. M = Motiline recession
2. A = Allergy
3. C = Cholestasis
4. R = Reversible ototoxicity.

93. ERYTHROMYCIN
• Isolated from streptomyces erythreus in 1952, and is employed
mainly as an alternative to penicillin
• Bacteriostatic at low but can be cidal at high concentration
depends upon organism and its rate of multiplication
• Partially destroyed by gastric juice, (enteric coated tablets)
• Plasma T1/2 is 1.5 hr
• Dose: 250-500 mg 6 hourly, children 30-60 mg/kg/day.
• ERYSEF 250, ERYTHROCIN 250.

94. ROXITHROMYCIN,CLARITHROMYCIN
 Similar spectrum of erythromycin
 More resistant to acid hydrolysis
 Better tissue level are achieved

95. AZITHROMYCIN
• This azalide congener of erythromycin has an expanded spectrum,
improved pharmacokinetcs, better tolerability and drug interaction
profiles
• Acid stable, rapid oral absorption, larger tissue distribution and
intracellular penetration
• Indicated in orodental infections, pharyngitis, tonsilitis, sinusitis
• Side effects are mild gastric upset, abdominal pain, headache and
dizziness.

96. TETRACYCLINS
• Bind to 30s ribosomal subunit and inhibit the binding
of aminoacyl t RNA to A- site.
• All tetracyclines are excreted in urine except
doxycyclin.

97. USES
1. R = Ricketssial fever and relapsing fever
2. B = Brucellosis
3. C = Cholera and chlamydia
4. IN = Granuloma inguinale
5. P = Plasma
6. L = LGV, Lyme’s disease, Leprosy.
7. A = Atypical pneumonia
8. S = SIADH
9. M = Maleria
10. A = Amoebiasis

98. TOXICITY
1. K = Kidney failure
2. A = Antianabolic effect
3. P = Photosensitivity
4. I = Insipedus diabetes
5. L = Liver toxicity
6. D = Dentition
7. E = Expired
8. V = Vestibular dysfunction

99. AMINOGLYCOSIDES
• Bactericidal inhibitors of protein synthesis.
• These binds to 30s and 50s ribosomes and freeze initiation,
interfere with polysome formation and causes misleading of
mRNA code
• Penetration across cell membrane depends on oxygen transport.

100. • Not absorbed orally and do not cross BBB.
• Excreted primarily by glomerular filtration
• Resistance develop due to formation of inactivating enzymes
which acetylate, phospholyarate or adenyalte the
aminoglycosides.
• Amikacin and netilmicin are resistant.

101. • Systemic aminoglycosides:- streptomycin, Gentaycin, Sisomicin,
Amikacin, Kanamycin, Netilmicin, Tobramycin
• Topical aminoglycosides:- Neomycin, Framycetin

102. USES
• Gentaycin, Tobramycin, Amikacin are effective against gram
negative organisms
• Streptomycin is first line drug for the treatment of tuberculosis,
plague and tularemia
• Netilmicin is used for serious infections only
• Neomycin can also be used orally for gut sterilization in hepatic
encephalopathy

103. SULPHONAMIDES
• These drugs are bacteriostatic and act by inhibiting folate synthase
compititively
• Selective toxicity to bacteria is due to mammalian cells do not
synthesise folic acid and utilize preformed folic acid in diet
• Not effective in presence of pus

104. • These drug hepatic metabolism by acetylation and can cause SLE.
• Drug undergoes acetylation are SHIP.
• S = Sulfonamide including dapsone
• H = hydralazine
• I = Isoniazid
• P = Procainamide

105. CLASSIFICATION
• Sulfisoxazole
• sulfamethiazole
• sulfacytine
Short acting
• sulfamethoxazole
• sulfadiazine
Intermediate
acting
• sulfadoxineLong acting

106. USES
• Sulfacetamide is used for ocular infections whereas mafenide and
silver sulfadiazine are used in burn patients.
• Sulfadiazine can be used for nocardiosis and sulfisoxazole for UTI
• Sulfasalazine and olsalazine are used for treatment of ulcerative
colitis.
• Sulfadoxine and pyrimethamine is used for maleria.

107. ADVERSE EFFECTS
1. A = Aplastic anaemia
2. B = Billrubin displacement
3. C = Crystalluria
4. R = Rash
5. A = Acetylation
6. S = SLE
7. H = Hemolysis in G-6PD defficiency

108. COTRIMOXAZOLE
• Fixed drug combination of trimethoprim and sulfamethoxazole in
a ratio of 5:1
• Bactericidal and acts by sequential blockade at two steps in the
DNA synthesis.

109. USES
• Effective in UTI, respiratory tract infections, tonsilitis,
pharyngitis, sinusitis and otitis media
• Drug of choice for pneumocystis nocardiosis

110. ADVERSE EFFECTS
• Nausea, vomiting, stomatitis, headache and reshes
• Blood dyscrasias occurs rarely
• Neonatal haemolysis and methaemoglobinaemia can occur.

111. QUINOLONES
• Synthetic antimicrobial having a quinolone structure
• Nalidixic acid is first derivative which is introduced in mid 1960s.
• Active against gram negative bacteria
• Acts by inhibiting bacterial DNA gyrase and s bactericidal

112. • Absorbed orally, partially metabolised in liver and excreted in
urine
• Plasma T12 is 8 hrs
• Resistance to nalidixic acid develops rapidly

113. USES
• Primarily used as urinary antiseptic and in diarrhoea
• Poor activity against oral pathogens so no utility in dentistry.
• Adverse Effects:-
• GI upset and rashes
• Headache, drowsiness, vertigo, occasionally seizures in children

114. FLUROQUINOLONES
• These are quinolones antimicrobials having one or more fluorine
substitutions
• First generation fluroquinolones introduced in 1980s having one
fluoro substitution
• In the 1990s, compound with additional fluoro and other
substitutions have been developed.

115. CLASSIFICATION
first
• Norfloxacin
• lomefloxacin
second
• Ciprofloxacin
• ofloxacin
third
• Levofloxacin
• Pefloxacin
• gatifloxacin
fourth
• Moxifloxacin
• Fleroxacin
• garenofloxacin

116. ACTION
• The FQs inhibit the enzyme bacterial DNA gyrase which nicks
double-stranded DNA, introduces negative supercoiling of the
strands when they separate to permit replication alone.

117. CLINDAMYCIN
• Is a lincosamide
• Binds to 50s ribosomes, effective against anaerobic bacteria
• Widely distributed in tissue fluids and tissues, including bone.
• An excellent alternative drug in penicillin-resistant anaerobic
infections
• Used in Osteomyelitis of the jaws
• Antimicrobial activity in colon is for 5days.

118. • Side effects are rashes, urticaria, abdominal pain but major
problem is diarrhoea
• Dose: 150-300 mg QID oral, 200-600 mg i.v. 8 hourly
• DALCAP 150 mg, CLINCIN 150

119. VANCOMYCIN
• It is glycopeptide antibiotic discovered in 1956 as a penicillin
substitute
• Bactericidal , acts by inhibiting bacterial cell wall synthesis
• Not absorbed orally, after i.v. administration it is widely
distributed, penetrated serous cavities, inflamed meninges and is
excreted mainly unchanged by glomerular filtration with T1/2 is 6
hours

120. • Systemic use is restricted to serous MRSA infections for which it
is most effective drug
• Used in dialysis patients and those undergoing cancer
chemotherapy
• Systemic toxicity is high and can cause nerve deafness, kidney
damage, fall in BP and skin allergy
• VANCOCIN-CP, VANCOGEN 500 mg/vial inj

121. NITROIMIDAZOLES
• Metronidazole, the protype member of this class was introduced in
1959 for trichomonas vaginitis and later found to be an effective
antiprotozoal drug
• Effective against gram negative bacteria only
• Inhibit cell-mediated immunity to induce mutagenesis and to
cause radiosensitization

122. • Almost completely absorbed from the small intestine
• Widely distributed in the body attaining therapautic concentration
in vaginal secretion, semen, saliva and CSF
• Metabolism occurs in liver and excreted through urine
• Plasma T1/2 is 8 hrs

123. USES
• Oro-dental infection
• Drug of choice for ANUG
• Periodontitis, pericoronitis, acute apical infection and in some
endodontic infections
• Protozoal infections, drug of choice for all forms of amoebiasis
including acute dysentery, chronic intestinal amoebiasis and liver
abscess

124. ADVERSE EFFECTS
• Anorexia, nausea, bitter or metallic taste and abdominal cramp are
the most common complications
• Looseness of stool is occasionally, urticaria, flushing, heat, itching
occur in allergic subjects
• Prolonged administration may cause peripheral neuropathy and
CNS effects
• DOSE: FLAGYL, METROGYL, METRON, ARISTOGYL 200.

125. TINIDAZOLE
• Equally effective as metronidazole but metabolism is slower, T1/2
is 12 hrs; duration of action is longer
• Better tolerated and incidance of side effects is lower
• TINIBA 300, 500 mg tab.

126. SOURCES OF DRUG
• Plants
• Animals
• Microbes
• Minerals
• Synthetic chemicals
• Biotechnological products

127. DOSAGE FORMS OF DRUG
Solid
• Powders
• Tablets
• Pills
• Capsules
• Lozenges
• Suppositors
Liquid
• Aqueous
• Suspensions
• Elixirs
• Drops
• Lotions
• Injections
Semisolid
• Ointments
• Pastes
• Gels

128. ROUTES OF DRUG ADMINISTRATION
Routes
Local
Topical
Deeper tissue
Arterial supply
Systemic
Oral Sublingual Rectal Cutaneous Inhalation Nasal Parental
Subcutaneous
Intramuscular
Intravenous
Intradermal

129. PRINCIPLES OF DRUG ACTION
• Stimulation
• Depression
• Irritation
• Replacement
• Cytotoxic action

130. ACTION-EFFECT SEQUENCE
• Drug action is initial combination of the drug with its receptor
results in conformational change in the latter
• Drug effect is the ultimate change in biological functions brought
about as a consequence of drug action

131. COMBINED EFFECT OF DRUG
Synergism
• Additive
• Supradditive
Antagonism
• Physical
• Chemical
• Physiological

132. DRUG DOSAGE
• Standard dose
• Regulated dose
• Target level dose
• Titrated dose

133. FACTORS MODIFYING DRUG
ACTION
• Body size
• Age
• Sex
• Species and race
• Genetics
• Route of administration

134. • Environmental factors and time of administration
• Psychological factor
• Pathological states
• Cumulation
• Tolerance

135. CLINICAL TRIALS
• Phase I – Human pharmacology and safety
• Phase II – Therapeutic exploration and dose ranging
• Phase III – Therapeutic conformation
• Phase IV – Post marketing surveillance

136. PEDIATRIC DOSAGE FORMULAS
• Nomogram Method
Pediatric
dose
=
Child's BSA in M2
1.73M2
x Adult
Dosage
Fried's Rule
Pediatric =
dose
child's age in months
150
x Adult Dose
Young's Rule
Pediatric =
dose
child's age in years
child's age in years + 12 years
x Adult
Dose
Clarks Rule
Pediatric=
dose
child's weight
150 lbs
x Adult Dose

137. • Colling’s rule =
• Dilling’ rule =
• Bestedo’s rule =
Pediatric =
dose
Age at next birthday
24
x Adult Dose
Pediatric =
dose
Age of child
20
x Adult Dose
Pediatric =
dose
Age of child + 3
30
Of fraction of Adult
Dose

138. • Augsberger’s rule:
{[(1.5× weight in kg) + 10]/100}× adult dose = Child dose
{[(4× age in year) +n20]/100} × adult dose = child dose
• Catzel’s rule
Age % of adult dose
1 25
3 35
7 50
12 75

139. • Gabius’s rule
1. 1 year = 1/12th of adult dose
2. 2 year = 1/8th of adult dose
3. 3 year = 1/6th of adult dose
4. 4 year = 1/4th of adult dose
5. 7 year = 1/3rd of adult dose
6. 14 year = 1/2nd of adult dose
7. 20 year = 2/3rd of adult dose
8. 21year = adult dose

140. GOLDEN RULES FOR ANTIBIOTIC
USAGE
• Don't use antibiotics unnecessarily
• Avoid broad spectrum Antibiotics as far as possible
• Don’t prolong the antibiotic therapy unnecessarily
• In cases of chronic infections like Tuberculosis,
Leprosy, etc employ multiple drug regime.

141. REQUIRING AB COVERAGE DOESNOT REQUIRE AB
COVERAGE
• Procedures involving manipulation of
gingival tissue
• Suture removal
• Extractions
• Periodontal procedures
• Implant placement
• Implantation of avulsed teeth
• Prophylactic cleaning
• Orthodontic band
• Restoration without retraction
chord
• LA injection through non infected
tissue
• Impressions
• Orthodontic brackets

142. THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY
(AAPD)
ANTIBIOTIC PROPHYLACTIC REGIMEN JULY ,2015
Children not allergic to penicillin Amoxicillin 50 mg/kg + clavulanic
acid 6.25 mg/kg (maximum 2 g)
oral route 1 hour before dental
treatment.
Children not allergic to penicillin
and with problems for oral drug
dosing
Amoxicillin 50 mg/kg + clavulanic
acid 5 mg/kg (maximum 2 g) IV or
IM, 30 minutes before dental
treatment.
Children allergic to penicillin Clindamycin 20 mg/kg (maximum
600 mg) oral route 1 hour before
dental treatment
Children allergic to penicillin and
with problems for oral drug dosing
Clindamycin 15 mg/kg (maximum
600 mg) IV or IM, 30 minutes before
dental treatment

143. ANTIBIOTIC SENSITIVITY TESTING
• This test determines the effectiveness of antibiotics against
microorganisms (e.g., bacteria) that have been isolated from cultures.
• Sensitivity analysis may be performed along with:
1. Blood culture
2. Urine culture (clean catch) or urine culture (catheterized
specimen)
3. Sputum culture
4. Throat culture
5. Wound and other cultures

144. Procedure
Prophylaxis
risk patient
(YES/NO)
Prophylaxis
healthy
patient
(YES/NO)
Staples for absolute rubber dam isolation YES NO
Intraligamentous anesthesia YES YES
Truncal anesthesia YES NO
Extractions YES YES
Hemorrhagic dental repair: placement of splints and wedges YES NO
Orthodontic band placement YES NO
Pulp treatment in deciduous and young permanent teeth YES YES
Hemorrhagic crown trimming: stripping, preformed crown
placement
YES NO
Planells-del Pozo P, Barra-Soto MJ, Santa Eulalia-Troisfontaines E. Antibiotic
prophylaxis in pediatric odontology. An update. Med Oral Patol Oral Cir Bucal
2006;11:E352-7.

145. COMMON REASONS FOR
ANTIBIOTIC FAILURE
• Failure to surgically eradicate the source of the
infection.
• Too low blood antibiotic concentration.
• Inability of the antibiotic to penetrate to the site of
infection.
• Impaired/inadequate host defence.
• Inappropriate choice of antibiotic.
• Limited vascularity or blood flow.

146. • Decreased tissue pH or oxygen tension.
• Emergence of antibiotic resistance.
• Delay in diagnosis.
• Incorrect diagnosis.
• Antibiotic antagonism.

147. ANTIBIOTICS WITH SPECIFICATION
• Effective against odontogenic infections -------- Penicillin,
Clindamycin, Erythromycin, Cefadroxil, Metronidazole, Tetracyclines
• Amoxicillin ------ first choice antibiotic against endocarditis
prophylaxis
• Child is allergic to penicillin ------ Macrolides, Clarithromycin and
Azithromycin
• Metronidazole ------ Against anaerobic bacteria
• Cefadroxil ------- Commonly used under cephalosporin
• Tetracyclines ------- Limited use in dentistry

148. MEDICINE Dental use UTI RTI
Amoxicillin √ √ √
Cloxacillin √ √ √
Sulfonamides √
Cotrimoxazole √ √
Quonolones √
Ciprofloxacin √ √

149. CAUSES OF FAILURE IN TREATMENT
OF INFECTION
• Inadequate surgical treatment
• Depressed host defences
• Presence of foreign body
• Antibiotic problems
• Drug not reaching infection
• Dose not adequate
• Wrong bacterial diagnosis
• Wrong antibiotic

150. AVAILIBILITYAND TRADE NAMES
• Capsules: Novamox LB(250mg, 500mg), Mox
(125mg, 250mg, 500mg)
• Dispersible tablets: Wymox( 250mg), Blumox (125mg,
250mg, 500mg)
• Kid tab : Wymox(125mg), Lamoxy (125mg).
• Syrups: Novamox (125mg, 250mg/5ml).
• Drops : Novamox(100mg/ml).
• Injections : Mox, Hipen(250mg, 500mg).

151. CLOXACILLIN
• Capsules: Klox, clopen, Bioclox( 250mg, 500mg),
Novaclox (Amox 250mg+ Clox 250mg), Mox kid
( Amox 125mg +Clox 125mg)
• Syrups: klox, clopen (125mg/5ml)
• Injections: Klox, Bioclox (inj 250mg, 500mg vials).

152. AMPICILLIN
• AMPILIN, ROSCILLIN, BIOCILIN
• 250, 500 mg cap
• 125-250 mg/ 5ml dry syr
• 100mg/ml pediatric drops
• 1.0 g per vial inj.

153. COMBINATION
• AUGMENTIN, ENHANCIN, AMONATE- Amox
250mg+ CA 125mg
• AUGMENTIN- Amox 1g+CA 0.2g, 0.5g 0.1g vial

154. CEPHALEXIN
• Capsules: Sporidex, Ceff, Sepexin, Phexin (250mg,
500mg).
• Kid tab: Sporidex, Ceff(125mg).
• Syrups: Sporidex, Ceff syrup (125mg/5ml,
250mg/5ml).
• Drops : Phexin (100mg/ml).

155. CEFADROXIL
Capsules: Cefedrox (0.5 g ), Kefloxin (0.5 g).
Dispersible tablets: Droxyl, Cefoxid (125mg, 250mg).
• Kid tab: Cefadrox, Kefloxin, Kidrox (125mg).
• Suspension: Kidrox (250mg/5ml), Cefoxid
(125mg/5ml).
• Drops : Kidrox (100mg/ml).

156. ERYTHROMYCIN
• Tablets : Erythrocin, Althrocin.( 100mg, 250mg,500mg
)
• Kid tab : Althrocin (125mg)
• Dispersible : Althrocin (250mg), eltocin (125mg)
• Suspension: Erythrocin (125mg/5ml)
• Drops : Althrocin, erythrocin (100mg/ml)

157. CLINDAMYCIN
• Capsules : Dalacin C (150mg, 300mg).
• Injections : Dalacin C (150mg/ml).

158. CIPROFLOXACIN
• Tablets: Cifran, Ciplox, Ciprolet (100mg, 250mg,
500mg, 750mg).
• Injections : 20mg/10ml.(50ml, 100ml,200ml).
• Suspensions : Ciprolar susp 125mg/5ml.

159. METRONIDAZOLE
• Tab : FLAGYL, METROGYL, METRON,
ARISTOGYL, ALDEZOLE (200mg, 400mg.)
• Suspensions: Flagyl, Metrogyl susp(200mg/5ml).
• Injections: Metrogyl, Metronidazole IV (500mg/100ml
infusion).

160. TINIDAZOLE
• Tablets : Tini 300mg, 500mg, 1 gm, Tiniba (300, 500
mgs).
• Suspensions: Tini susp 75mg/5ml.
• Injections: Tiniba, Tinipidi 800mg/400ml infusion.

161. NYSTATIN
• Mycostatin 5,00,000 U tab
FLUCONAZOLE
• Tablets: FUNGAL, ZOCON(50mg, 150mg, 200mg).
• Dispersible tablets: FLUZIDE 50mg DT.
• Injections: SYSCAN, FORCAN 200mg/100ml IV
infusion.
• Eye drops: SYSCAN 0.3%

162. ACYCLOVIR
• ZOVIRAX 200mg tab, 250mg/ vial for iv inj
• CYCLOVIR 200mg tab, 5% skin cream
• HERPEX 200mg tab, 3% eye oint, 5% skin cream
• OCUVIR 200 400 800mg tab
• ACIVIR DT 200 400 800 mg tab
• VALCIVIR 500, 1000 mg tab

163. CLASSIFICATION OF BACTERIA
Gram positive
cocci
Staphalococcus
Coagulase + Coagulase -
streptococcus
Beta hemolytic
Gamma
hemolytic
Alpha hemolytic
bacilli
Bergey’s Manual of Systemic Bacteriology: International journal of systemic
Bacteriology; July 1985:408.

164. Gram
negative
bacteria
Rods
Aerobes
Facultative
anaerobe
Anaerobe
cocci spirochetes
Aerobe Anaerobe
Bergey’s Manual of Systemic Bacteriology: International journal of systemic
Bacteriology; July 1985:408.

165. Single Dose 30 to
60 min. Before
Procedur
Situation Agent Adults Children
Oral Amoxicillin 2 g 50 mg/kg
Unable to take oral
medication
Ampicillin OR
Cefazolin or ceftriaxone
2 g IM or IV
1 g IM or IV
50 mg/kg IM or IV
50 mg/kg IM
Allergic to penicillins
or ampicillin—oral
Cephalexin OR
Clindamycin OR
Azithromycin or
clarithromycin
2 g
600 mg
500 mg
50 mg/kg
20 mg/kg
15 mg/kg
Allergic to penicillins
or ampicillin and unable
to take oral medication
Cefazolin or ceftriaxone
or Clindamycin
1 g IM or IV
600 mg IM or IV
50 mg/kg IM or IV
20 mg/kg IM or IV
Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O’gara PT, Rigolin VH.
2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of
the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American
College of Cardiology. 2017 Jul 3;70(2):252-89.

166. ANALGESICS

167. INTRODUCTION
• Pain plays a major role specially in treating kids.
• Poorly controlled pain contributes to anxiety among the
pediatric patient about future treatment.
• Management of dental pain in pediatric patients is
important

168. CONCEPTS ABOUT PAIN IN
CHILDREN
• Children have high tolerance to pain.
• Pain perception low because of biologic immaturity.
• More sensitive to side effects of analgesics.
• Special risk for addiction to narcotics .

169. DEFINITION
• Pain is an unpleasant sensory and emotional experience
associated with actual or potential tissue damage, or
described in terms of such damage (IASP by Merskey
1994)
• Odontogenic pain is caused by physical stimuli or the
release of inflammatory mediators

170. TYPES OF PAIN
Acute pain
• Sharp pain of short
duration
• Cause easily identifiable
• Localized in small area
• Subsides once the
healing process is
accomplished
Chronic pain
• Intermittent or constant
pain with different
intensities
• Longer periods
• Difficult to treat
Grichnik KP, Ferrante FM. The difference between acute and chronic pain.
The Mount Sinai journal of medicine, New York. 1991 May;58(3):217-20.

171. TYPES OF FIBRES
A-alpha
• Myelinated
• NCV- 70-
120m/sec
• Proprioception
A-beta
• Myelinated
• NCV – 36-
72m/sec
• Proprioception
A-delta
• Transmits
information that
is often
interpreted by the
brain as burning
or stinging pain
• pain impulses
due to
mechanical
pressure
• Large diameter,
Myelinated
• NCV – 4-
30m/sec
• Short duration,
sharp, prickling,
localized
C- fibers
• transmits painful
that is often
interpreted by the
brain as
throbbing or
aching
• Pain impulses
due to chemicals
or mechanical
• Small diameter,
unmyelinated
• NCV - 0.5-
2m/sec
• Delayed onset,
diffuse, aching,
throbbing
Johnsen DC, Harshbarger J, Rymer HD. Quantitative assessment of neural
development in human premolars. The anatomical record. 1983 Apr;205(4):421-429.

172. DENTAL PAIN
• Teeth are innervated by Aδ and C fibres and the dual mechanism
operating through Aδ processes most likely operates in the
trigeminal nuclei.
• Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network
Other inflammatory mediators
Cohen’s Pathways of pulp by Stephan Cohen, 10th edition

173. During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
 Oral Sedation
 Preoperative
Analgesics
• IV Sedation
• Nitrous Oxide
• Local Anesthesia
• Analgesic
Prescription
• Opioids
• Non-opioids

174. ANALGESICS
• Selectively relives pain by acting in the CNS or on
peripheral pain mechanisms without significantly
altering the consciousness
• Relive pain without affecting cause
• Two groups
• Opioids
• Non opioid/ NSAIDs

175. CLASSIFICATION
ANALGESICS
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-
selective
COX
Inhibitors
Preferential
COX-2
Inhibitors
Selective
COX-2
Inhibitors
Analgesic –
antipyretics with
poor
antiinflammatory
action
Natural opioids Semi-synthetic
opioids
Synthetic opioids
Essential of medical pharmacology by KD Tripathi,7th edition

176. OPIOID ANALGESICS
• Opioids are among the world's oldest known drugs.
• The term "opioid" originated in the 1950s.
• It combines "opium" + "-oid" meaning "opiate-like" ("opiates" being morphine and
similar drugs derived from opium).
• Opium was also known to the Greeks. It was valued by Hippocrates(c. 460 – c. 370
BC) and his students for its sleep-inducing properties and used for the treatment of
pain.
• A dark brown, resinous material obtained from poppy ( Papaver somniferum)
capsule.
• Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S.
Crystal structure of the µ-opioid receptor bound to a morphinan antagonist. Nature. 2012 May;485(7398):321.

177. CLASSIFICATION
• BASED ON RECEPTOR OCCUPATION
• Agonist
• Natural- Morphine, Codeine
• Synthetic- Pethidine, Methadone
• Antagonist- Naloxone, Naltrexone
• Mixed Agonist- Antagonist- Pentazocine,
Nalbuphine, Buprenorphine
Essential of medical pharmacology by KD Tripathi,7th edition

178. • SOURCE
• Natural- Morphine, Codeine
• Semisynthetic- Heroin, Oxymorphine
• Synthetic- Pethidine, Fantanyl, Diphenoxylate,
Methadone, Tramadol

179. • CHEMICAL NATURE
• The Phenantherene Group- Morphine, Codeine,
Thebaine
• The Benzylisoquinolone Group- Papaverine,
Noscapine, Narcine

180. MORPHINE
• Morphine is a pain medication of the opiate family which is
found naturally in a number of plants and animals.
Egwim O. The Prevalence and Determinants of Controlled Substance Discrepancies in a Level I Trauma
Hospital. Stefano GB, Ptacek R, Kuzelova H, Kream RM. Endogenous morphine: up-to-date review
2011. Folia biologica. 2012 Mar 1;58(2):49.

181. PHARMACOLOGIC ACTIONS
CNS
• Depressant
• Stimulants
CVS
• Vasodilatation
GIT
• Gastric
motility
decreased
• Secretions
decreased
Respiratory
• Depression
• Reduces
sensitivity to
CO2

182. PHARMACOKINETICS
• High first pass metabolism
• Plasma binding- 30%
• Freely crosses placenta and affect foetus more than the
mother
• Primarily metabolized in liver
• T1/2 – 2-3 hours

183. INDICATIONS
• Treatment of moderate to severe pain eg: due to renal
colic, severe trauma, major surgery or cancer.
• Acute pulmonary edema.
• As adjunct to general anesthesia.
• Post operative analgesia.

184. ADVERSE EFFECTS
• Sedation, mental clouding, lethargy
• Allergic reactions: urticaria, pruritis
• Apnoea
• Acute morphine poisoning

185. PRECAUTIONS AND
CONTRAINDICATION
• Infants and elderly are more susceptible to the
respiratory depressant action of morphine.
• Dangerous in patients with respiratory insufficiency.
• Bronchial asthma.
• Head injury
• Hypotensive state

186. DOSE
• Dose orally: 10-50mg,
• Parenteral -10-15mg IM or SC,
2-6mg IV.
• Children: 0.1-0.2mg/kg.
• Injection: MORPHINE SULPHATE 10 mg/ml
• Tablets: Morcontin 10, 30, 60, 100 mg

187. CODEINE
• Most commonly prescribed narcotic for moderate to
severe pain.
• Less potent than morphine
• Orally well absorbed , Single dose act for 4-6 hours
• Codeine may be given alone or in combination with
another analgesic. It is prudent to combine the two
types of analgesics for enhanced activity.

188. DOSE
• Codeine +acetaminophen –for pediatric analgesia.
• Children: 0.5 to 1.0 mg/kg given every 4 to 6 hrs as needed.
• Adults : 30 to 60 mg given every 4 to 6 hrs as needed
• Codex 10 mg, planokus (codein+ cholophenalamine) for dry
cough

189. INDICATIONS
• Post-operative analgesia after tooth extraction
• Cough depression
Adverse effects
• Nausea, sedation, dizziness, constipation
• Cramps
• Respiratory depression when given in high doses

190. RECENT DRUGS
• Alfentanil
• Remifentanil
• Tramadol

191. ALFENTANIL
• Rapid onset (within 1-1.5mins)
• Metabolized in liver
• Half-life - 1-2 hrs
Dosage of Alfentanil:
• Infant more than 3 months and child
• IV: 1-2 mcg/kg/dose
Route : IV
• Available as injections: Inj 500 mcg/ml

192. Uses:
• Short, painful procedures requiring intense analgesia
• Remifentanil for longer neurosurgical procedures
Availability and trade names:
• ALFENTA (Alfentanil)
• ULTIVA(Remifentanil)

193. TRAMADOL
• IV 100mg Tramadol=10mg morphine IM
• Good oral availability
• T1/2- 3-5 hours
• SIDE EFFECTS
• Dizziness
• Nausea
• Sleeplessness

194. • INDICATIONS
• Mild to medium intensity short lasting pain due to
diagnostic procedures, injuries
• Chronic pain
• Not effective in severe pain
• DOSE
• Adult – 50-100 oral/ im/ slow iv
• Children- 1- 2 mg/kg 4-6 hourly

195. • Capsule: CONTRAMAL, DOMADOL, TRAMAZAC
50 mg
• Tablets: 100 mg
• Injection: 50 mg/ml in 1 and 2 ml ampules.
• Ultracet ( Tramadol 37.5 mg + Paracetamol 325 mg)

196. ABUSE LIABILITY OF OPOIDS
• Exaggerated fear of “addicting” patients exists
• Physical dependance on opioids are a consequence of long term
medical use
• Such long term use is not prevalent for managing pain of pulpal
origin

197. DRUG INTERACTIONS OF OPOIDS
• Opioid + CNS depressant supra-additive
• Opioid + phenothiazine increased respiratory
depression
• Tricyclic antidepressant + opioid increased hypotension
• Local anaesthetic + opioid safe (however large doses
have supra-additive effect)

198. WITHDRAWAL REACTIONS
Acute Action
• Analgesia
• Respiratory Depression
• Euphoria
• Relaxation and sleep
• Decreased blood pressure
• Constipation
• Pupillary constriction
• Drying of secretions
Withdrawl Sign
• Pain and irritability
• Hyperventilation
• Dysphoria and depression
• Restlessness and insomnia
• Fearfulness and hostility
• Increased blood pressure
• Diarrhoea
• Pupillary dilation
• Lacrimation, runny nose

199. SIDE EFFECTS OF OPIODS
Short term
• Dulling of Pain
• Euphoria
• Slow Nervous system
• Slowed heart rate
• Loss of cough reflex
• Nausea
• Overdoses can lead to death
• Possibility of stroke
• Overall slowdown of
biological systems
Long Term
• Addiction and very strong
withdrawal effects
• Constipation
• Loss of libido
• Disruptions in menstruation
• Loss of appetite
• Problems associated with
buying street drugs i.e.
sharing needles AIDS and
prostitution.

200. NON OPIOID ANALGESICS/ NSAIDS
• Analgesic, Antipyretic & Anti-inflammatory actions
• Primarily on peripheral pain mechanisms
• Compared to morphine - weaker analgesics (except for
inflammatory pain)
• Do not depress CNS
• Does not produce physical dependence
• Have no abuse liability

201. MECHANISM OF ACTION
Membrane (Phospholipids)
Arachidonic Acid
Prostaglandins Leukotrienes
Phospholipase A2
Cyclo-oxygenase Lipoxygenase

202. CYCLOOXYGENASE
COX-1 COX-2
NON
SELECTIVE
COX
INHIBITOR
SELECTIVE
COX 2
INHIBITOR
Found in
almost
all
tissues
Found in
brain
and
kidney
Pain
Inflammation
Fever

203. PHARMACODYNAMICS
• Analgesia
• Antipyretic
• Anti-inflammatory
• Dysmenorrhoea
• Antiplatelet aggregatory
• Gastric mucosal damage
• Renal effects

204. Nonselective cox
inhibitors
• salicyclates
• Anthranilic acid
• Propionic acid
• Aryl-acetic
• Oxicam
• Pyrrolo-pyrole
• Indole derivatie
• Pyrazolone
derivative
Preferential cox-2
inhibitors
• Nimesulide
• Meloxicam
Selective cox-2
inhibitors
• Celecoxib
• Etoricoxib
Analgesic-antipyretic
with poor
antiinflammatory
• Paraaminophenol
derivatives
• Pyrazolone
derivative
• Benzoxazone
derivative

205. SALICYCLATES
• Aspirin is one of the most widely used medications globally, with an
estimated 40,000 tonnes(50 to 120 billion pills) consumed each year
• It is on the World Health Organization's (WHO's) List of Essential
Medicines, the safest and most effective medicines needed in a health
system
• Rapidly converted in the body to salicylic acid which is responsible
for most of its action
• Only drug amongst NSAIDs which irreversibly inhibit COX
Jones A (2015). Chemistry: An Introduction for Medical and Health
Sciences. John Wiley & Sons. pp. 5–6. ISBN978-0-470-09290-3.

206. PHARMACOLOGICALACTION
• Analgesic
• Antipyretic
• Anti-inflammatory
• Respiration is stimulated
• CVS
• GIT
• Blood

207. PHARMACOKINETICS
• Absorption: Stomach and Small intestine, Poor water solubility
• Solubility higher at high pH(alkaline medium)
• Rapidly deacetylated in the gut wall, liver and plasma to release
salicyclic acid
• 80% plasma protein bound
• Slowly enters in brain but freely crosses placenta
• Excretion: Urine
• T ½ 15-20min

208. USES
• Analgesic, Antipyretic, Anti inflammatory
• Acute rheumatic fever
• Rheumatoid arthritis
• Osteoarthritis
• Post myocardial infarction and post stroke patients

209. OTHER USES
• Pregnancy-induced hypertension
• Patent ductus arteriosus
• Familial colonic polyposis
• Prevention of colon cancer

210. ADVERSE EFFECTS
• At analgesic dose(0.3-1.5 gm/day) causes nausea,
vomiting, epigastric pain, increased blood loss in stool.
• Idiosyncrasy and hypersensitivity: Infrequent
• Salicylism at anti-inflammatory doses.
• Reye’s syndrome.
• Acute salicylate poisoning

211. PRECAUTIONS & CONTRAINDICATION
• Reye’s syndrome
• Should be stopped 1 week before elective surgery
• In Chronic liver diseases
• During pregnancy & avoided in breast feeding
• Avoided in G-6-PD deficient individuals
• Avoided in diabetics

212. DOSAGE
• Tablets: ASPIRIN 350 mg, COLSPRIN 100, 325, 650
mg, ECOSPRIN 75, 150, 325 mg, DISPIRIN 350 mg,
LOPRIN 75, 162.5 mg
• Injection: BIOSPIRIN- lysine acetylsalicyclate 900 mg
+ glycine 100 mg/ vial for dissolving 5 ml water and
i.v. inj.

213. THE EFFECT OF ASPIRIN ON BLEEDING
AFTER EXTRACTION OF TEETH
• Objective: The aim of this study was to determine if ASA was associated with
bleeding after dental extraction.
• Patients and methods: One hundred and eighty-nine subjects were divided into
four groups. Group 1A subjects who received ASA, underwent simple
extraction. Group 1B subjects who received ASA, underwent surgical
extraction. Group 2A subjects who did not receive ASA, underwent simple
extraction which served as control group. Group 2B subjects who did not
receive ASA, underwent surgical extraction which also served as control
group.
Nooh N. The effect of aspirin on bleeding after extraction of teeth. The Saudi dental
journal. 2009 Jul 1;21(2):57-61.

214. • Results: The results showed that Group 1B was the only group
which showed bleeding after 24 h. All groups had similar results
after 48 h and 5 days post-operatively.
• Conclusion: The study concluded that subjects who received 81
mg ASA daily could undergo dental extraction without bleeding
risks
Nooh N. The effect of aspirin on bleeding after extraction of teeth.
The Saudi dental journal. 2009 Jul 1;21(2):57-61.

215. PROPIONIC ACID DERIVATIVE
• Ibuprofen was the first member of this class and
introduced in 1969.
• Ibuprofen was discovered in 1961 by Stewart
Adams and initially marketed as Brufen
• Analgesic effect is independent of anti-inflammatory
activity and has both central and peripheral effect.
• Rated as the safest (SADR reporting system in U.K.)
Halford, GM; Lordkipanidzé, M; Watson, SP (2012). "50th anniversary of the discovery
of ibuprofen: an interview with Dr Stewart Adams". Platelets. 23 (6): 415–22.

216. USES
• Dental pain
• Rheumatoid arthritis, osteoarthritis and other musculo-skeletal
• Soft tissue injuries, fractures
ADEVERSE EFFECTS
• Gastric discomfort, nausea, vomiting
• Headache, dizziness, blurring of vision

217. PHARMACOKINETICS:
• Well absorbed orally
• 99% bound to plasma proteins.
• Metabolized in liver by hydroxylation and glucuronide
conjugation
• Excreted in urine as well as bile.
Bushra, R; Aslam, N (July 2010). "An overview of clinical pharmacology of Ibuprofen". Oman
Medical Journal. 25 (3): 1555–1661.

218. Dosage in children:
• For fever and pain : 10-15 mg/kg/dose
Availability and trade names:
• Tablets : Brufen, Ibugesic (200mg, 400mg, 800mg), Ibusynth
(200mg, 400mg), Ibugesic plus = ibu 400 mg+ pcm 325 mg,
Ibuclin junior 100, 125 mg.
• Suspensions: Ibugesic plus = ( ibu 100 mg+ pcm 125 mg)
Febrilix susp 100mg/5ml

219. PARACETAMOL
• Paracetamol has analgesic and antipyretic actions with
weak anti-inflammatory activity
• It is typically used for mild to moderate pain relief
"Acetaminophen". The American Society of Health-System Pharmacists. Archived from
the original on 5 June 2016. Retrieved 16 September 2016.

220. MECHANISM OF ACTION
• Poor inhibitor of PG synthesis in peripheral tissues
• More active on COX in the brain.
• Inability to inhibit COX in the presence of peroxides which
are generated at the sites of inflammation, but are not
present in the brain.
• It does not stimulated respiration or affect acid-base
balance.
Ghanem, CI; Pérez, MJ; Manautou, JE; Mottino, AD (July 2016). "Acetaminophen from liver to
brain: New insights into drug pharmacological action and toxicity". Pharmacological Research. 109:
119–31.

221. PHARMACOKINETICS:
• Well absorbed orally
• 1/4th - protein bound in plasma
• Uniformly distributed in the body.
• Plasma t1/2 - 2-3 hrs.
Prescott, L.F. (October 1980). "Kinetics and metabolism of paracetamol and phenacetin". British
Journal of Clinical Pharmacology. 10 Suppl 2: 291S–298S

222. USES
• Over-the-counter drug
• Mild to moderate fever.
• Mild to moderate pain.
Adverse Effects
• Fatal hepatic necrosis and renal impairment.
• Hypersensitivity.
• Acute paracetamol poisoning

223. DOSAGE
• Children:
• 3 months-1 year = 60-120mg.
• 1 year-5years = 120-250mg.
• 6 years-12years = 250-500mg.
• The above dose should be given 3-4 times daily when required.

224. AVAILABILITYAND TRADE NAMES
• Tablets: Crocin, Calpol, Metacin, Pyrigesic(500mg),
Fepanil(500mg), Dolo 650, P-125.
• Syrups: 120mg/5ml, Fepanil (150mg/ml-60ml bottle)
• Drops : 100mg/ml.
• Paracetamol suppository: 80mg, 170mg.

225. DICLOFENAC SODIUM
• Potent anti-inflammatory, analgesic and antipyretic
actions.
• Available as its sodium or potassium salt.
• Sodium salt-enteric-coated - ensure optimum -
bioavailability, but this lead to some delay in the onset
of action.
• The potassium salt is absorbed rapidly and action sets
in much earlier.

226. MECHANISM OF ACTION
• Inhibits PG synthesis
• The anti-platelet action is short lasting
• Neutrophil chemotaxis and super oxide production at the
inflammatory site are reduced
Pharmacokinetics
• well absorbed orally
• 99% protein bound
• metabolized and excreted both in urine and bile.
• The plasma t1/2 - 2 hours

227. INDICATIONS
• Inflammatory and degenerative arthritis
• Dental pain
• Musculo-skeletal conditions - low back pain.
Side effects
• Abdominal pain
• Peptic ulcer
• Fluid retention
• Renal impairment
Dutta, NK; Mazumdar, K; Dastidar, SG; Park, JH (October 2007). "Activity of diclofenac used alone
and in combination with streptomycin against Mycobacterium tuberculosis in mice". International
journal of antimicrobial agents. 30 (4): 336–40.

228. DOSAGE :
• Children over 1 year-1-3 mg/kg/day in divided doses.
• Route: orally and IV.
Availability and trade names:
• Tablets : Voveron, Jonac, Nac (50mg), aceclofenac 50mg.
• Dispersible tablets: Nac 50mg DT.
• Injections: Voveron, Jonac, Nac inj25mg/ml.
• Suppository: Jonac supp 12.5mg, 100mg.
• Dynapar, Dynapar s, Enzoflame

229. KETOROLAC
• Potent analgesic and modest anti-inflammatory activity
• Equal efficacy of morphine in postoperative pain
• Inhibits PG synthesis and relives pain by peripheral
mechanism
Mallinson TE. A review of ketorolac as a prehospital analgesic. Journal of Paramedic
Practice. 2017 Dec 2;9(12):522-526.

230. PHARMACOKINETICS
• Rapidly absorbed after oral and IM administration
• Highly plasma protein bound
• 60% excreted unchanged in urine
• Major metabolic pathway is glucuronidation
• Plasma t1/2 is 5-7 hrs
Indications:
• Postoperative, dental and acute musculoskeletal pain

231. DOSAGE
Children 0.5mg/kg/dose 6hr
Availability and trade names:
• Tablets: Ketorol, ketanov(10mg)
• Dispersible tablets: ketoral (10mg,DT)
• Injections: ketanov-1ml(30mg/ml)
Side effects:
• Gastritis, bleeding, impaired platelet aggregation

232. NIMESULIDE
• Newer NSAID
• Inhibits cyclo-oxygenase
• Weak inhibitor of prostaglandin synthesis but has
potent anti-inflammatory activity
Gupta, P; Sachdev, HP (June 2003). "Safety of oral use of nimesulide in children: systematic
review of randomized controlled trials". Indian pediatrics. 40 (6): 518–531

233. PHARMACOKINETICS:
• Completely absorbed orally
• 99%plasma protein bound
• Extensively metabolized
• Excreted mainly in urine
• T 1/2 - 2-5 hrs
Bernareggi, Alberto (October 1998). "Clinical pharmacokinetics of
nimesulide". Clinical Pharmacokinetics. 35 (4): 247–274.

234. INDICATIONS
• Musculo-skeletal pain
• Dental pain
Contraindicated:
• Patients with active peptic ulcer
• Moderate to severe hepatic impairment
Side effects:
• Epigastric pain
• Hepatotoxicity
• Renal failure

235. DOSAGE:
• Children -5mg/kg/day in 2 or 3 divided doses
• Availability and trade names:
• Tablets : Nise, Orthobid 100mg, Pronim 100mg
• Dispersible tablets: Nimulid (50mg, 100mg), Nise, Nimica(50mg),
Nimset(100)mg
• Suspensions: Nise, Nimulid, Nimcet, Nimica susp 50mg/5ml

236. MEPHENAMIC ACID
An analgesic, antipyretic and weaker anti-inflammatory
drug
Inhibits COX as well as antagonises certain actions of
PGs
 Exerts peripheral as well as central analgesic action

237. PHARMACOKINETICS:
Oral absorption is slow but almost complete
Highly bound to plasma proteins
Excreted in urine as well as bile
Plasma t1/2 - 2-4 hours

238. USES
 Primarily as analgesic in muscle, joint and soft tissue pain where
strong anti-inflammatory action is not needed
 Rheumatoid and osteoarthritis
Side effects
 Diarrhoea
 Epigastric distress
 Skin rashes, dizzines and other CNS manifestations
 Haemolytic anaemia is rare but serious complication

239. AVAILABILITYAND TRADE NAMES
• Dose: 250-500 mg
• Capsules: MEDOL 250, 500 mg
• Tablets: MEFTAL 250, 500 mg, PONSTAN 125, 250,
500 mg
• Suspension: MEFTAL 100 mg/5ml
• Syrup: PONSTAN 50 mg/ml

240. PRESCRIPTION WRITING
• Therapeutic transactions between physician and patient
• The ancient symbol, Rx signifying the appeal
• Accurate diagnosis; proper selection of medication,
dosage form and route of administration; proper size
and timing of dose; precise dispensing; accurate
labeling; and correct packaging all must be provided.

242. Term or Phrase Abbreviation Meaning
aqua Aq. Water
cum c. with
bis in die b.i.d. twice a day
dispensa disp. dispense
et et and
in vitro in vit in glass
hora somni h.s. at bedtime
non repetatur non. rep do not repeat
omni die o.d. daily
omni mane o.m. every morning
omni nocte o.n every night
post cibos p.c. after meals
quater in die q.i.d four times a day
recipe Rx take
si opus sit s.o.s. if necessary
ter in die t.i.d. three times a day

243. CONCLUSION
• Children are not men or women; they are almost as different
creatures, in many respects, as if they never were to be the one or the
other; they are as unlike as buds are unlike flowers, and almost as
blossoms are unlike fruits” – W.S. Landor
• During the course of dental treatment, when it is necessary to
prescribe pharmacologic agents for the pediatric patient, a drug
should be selected that is not only effective but also available in a
readily acceptable form.
• Using drug when needed and avoiding when it is not needed is one of
the successful trait of a successful practitioner.

244. REFERENCES
• K.D.Tripathi, Essentials of medical pharmacology,7th edition
2011: 1-58
• Tong DC, Rothwell BR. Antibiotic prophylaxis in dentistry: a
review and practice recommendations. The Journal of the
American Dental Association. 2000 Mar 1;131(3):366-74.
• Sweeney LC, Dave J, Chambers PA, Heritage J. Antibiotic
resistance in general dental practice—a cause for concern?.
Journal of Antimicrobial chemotherapy. 2004 Apr 1;53(4):567-76.

245. • Elias GP, Antoniali C, Mariano RC. Comparative study of rules
employed for calculation of pediatric drug dosage. Journal of
Applied Oral Science. 2005 Jun;13(2):114-119.
• del Pozo PP, Soto MJ, Troisfontaines ES. Antibiotic prophylaxis in
pediatric odontology. An update. Med Oral Patol Oral Cir Bucal.
2006;11:E352-7.
• Review of pharmacology by Gobind Rai Garg and Sparsh Gupta,
10th edition:2016

246. • Planells-del Pozo P, Barra-Soto MJ, Santa Eulalia-Troisfontaines E.
Antibiotic prophylaxis in pediatric odontology. An update. Med Oral
Patol Oral Cir Bucal 2006;11:E352-7.
• Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM,
Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S. Crystal
structure of the µ-opioid receptor bound to a morphinan antagonist.
Nature. 2012 May;485(7398):321
• opioid: definition of opioid in Oxford dictionary (American English)
(US)". www.oxforddictionaries.com. Retrieved 2016-02-14. Opioid:
1950s

247. • Duarte, Danilo Freire (February 2005). "Uma breve história do ópio e dos
opióide". Revista Brasileira de Anestesiologia. 55 (1). Retrieved 23
August 2018. Astyrakaki E, Papaioannou A, Askitopoulou H. References to
anesthesia, pain, and analgesia in the Hippocratic Collection. Anesthesia &
Analgesia. 2010 Jan 1;110(1):188-94.
• Egwim O. The Prevalence and Determinants of Controlled Substance
Discrepancies in a Level I Trauma Hospital. Stefano GB, Ptacek R, Kuzelova
H, Kream RM. Endogenous morphine: up-to-date review 2011. Folia
biologica. 2012 Mar 1;58(2):49.
• Jones A (2015). Chemistry: An Introduction for Medical and Health Sciences.
John Wiley & Sons. pp. 5–6.

248. • Warner TD, Mitchell JA (October 2002). "Cyclooxygenase-3
(COX-3): filling in the gaps toward a COX
continuum?" Proceedings of the National Academy of Sciences of
the United States of America. 99 (21): 13371–3.
• "WHO Model List of Essential Medicines (19th
List)"(PDF). World Health Organization. April
2015. Archived (PDF) from the original on 13 December 2016.
Retrieved 8 December 2016
• Nooh N. The effect of aspirin on bleeding after extraction of teeth.
The Saudi dental journal. 2009 Jul 1;21(2):57-61.

249. • Johnsen DC, Harshbarger J, Rymer HD. Quantitative
assessment of neural development in human premolars. The
anatomical record. 1983 Apr;205(4):421-429
• Cohen’s Pathways of pulp by Stephan Cohen, 10th edition
• Halford, GM; Lordkipanidzé, M; Watson, SP (2012). "50th
anniversary of the discovery of ibuprofen: an interview with
Dr Stewart Adams". Platelets. 23 (6): 415–22.