Antibiotics and analgesics

Antibiotics and analgesics

1. Dr. Firas Kassab
Dr. Firas Kassab

2. INTRODUCTION
DEFINATION OF ANTIBIOTICS
CLASSIFICATION OF ANTIBIOTICS
MECHANISM OF ACTION
PRINICIPLE OF ANTIBIOTIC ADMINSTRATION
AVOIDING RESISITENCE TO ANTIBIOTICS
THERAPEUTIC USE OF ANTIBIOTICS IN OMF
PROPHYLACTIC ANTIBIOTICS
PHARMACODYNAMIC RESPONSE OF
ANTIBIOTICS IN CHILDREN
ANTIBIOTIC RESISTANCE
ALLERGY TESTING
TRIPLE ANTIBIOTIC PASTE
CONTENTS
Dr. Firas Kassab

3. ANALGESICS
CLASSIFICATION OF ANALGESICS
•Non opioid analgesics (NSAIDS)
•Opioid analgesics
OTHER DRUGS WITH ANALGESIC
EFFECT
•Corticosteroids
•Local anesthetics
PAIN MANAGEMENT STRATEGIES
REVIEW OF LITERATURE
PRESCRIPTION WRITING
CONCLUSION
REFERENCES
CONTENTS
Dr. Firas Kassab

4. •Prescribe mainly orofacial infections. ( originate from
odontogenic infections).

•prescribing it is a important aspect of dental practice.

•7% and 11% of all common antibiotics (betalactams,
macrolides, tetracyclines,clindamycin,metronidazole).

•National Center for Disease Control and Prevention estimate
that approximately one-third of all outpatient antibiotic
prescriptions are unnecessary
Introduction
Dr. Firas Kassab

5. 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.

penicillin was commercilly 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]
HISTORY
Dr. Firas Kassab

6. What is an Antibiotic?
Antibiotic is a chemical substance produced by a
microorganism that inhibits the growth of or kills other
microorganisms.


Antimicrobial agent is a chemical substance
derived from a biological source or produced
by chemical synthesis that kills or inhibits the
growth of microorganisms.
Dr. Firas Kassab

7. CLASSIFICATION BASED ON SUSCEPTIBILITY OF ORGANISMS
I. Antibiotics effective against :
1) Gr +ve bacteria
Eg: penicillin , erythromycin
2) Gr -ve bacteria
Eg: aminoglycosides,cephalosporins
3) Gr +ve & Gr –ve bacteria
Eg: ampicillin, amoxycillin, tetracycline,
chloramphinicol,cephalsporins
4) Acid fast bacilli
Eg : Streptomycin
5) Fungi
Eg : Nystatin
CLASSIFICATION OF ANTIBIOTICS
Dr. Firas Kassab

8. II) Based on mechanism of action
1. Inhibitors of cell wall synthesis -Eg: Penicillin, cephalosporins,
vancomycin,bacitracin.
2. Inhibitors of protein synthesis
➢Affect the function of 30s or 50s (reversable inhibition of protien
synthesis)- Eg: Chloramphenicol, erythromycin,tetracyclin,
clindamycin.[static drugs]
➢Bind to 30s and alter protein synthesis- Eg: Aminoglycosides
[ Cidal drug]
3. Inhibitors of membrane function
Eg:nystatin,ampohoteresin-B [polyene antifungals]
4. Anti-metabolites
5. Inhibitors of nucleic acid synthesis
Dr. Firas Kassab

9. MECHANISM OF ACTION
Tetracyclins
chloramphinicol
aminoglycosides
clindamycin

Penicillins
cephalosporins
polymyxin
bacitracin polyenes

Intracellular
Extracellular
Dr. Firas Kassab

12. 1. Inhibitors of Cell Wall
synthesis
Beta-lactams
•Penicillins
•Cephalosporins
•Monobactams
•Carbapenems
Glycopeptides
Fosfomycins

13. •initial empirical management of odontogenic infections
thiazolidine ring fused with a beta lactum ring.
•6 amino-penicilanic acid- essential for the antibacterial activity
•60% bound to plasma albumin.[ inactive form]
•bactericidal -bind to peptidoglycan
•Narrow spectrum,
•absorbed- from duodenum.
•Food interferes absorption - oral 30 min before or 2-3 hr after
food.
•Parenteral administration- longer compaired to plasma.
•
High conc and eliminated -kidney
PENICILLIN
Dr. Firas Kassab

14. I) Natural penicillins :
Penicillin G (Benzyl penicillin),procain penicillin-g, benzathine penicillin.
II) Semisynthetic penicillin-
1.Acid resistant penicillins :
Phenoxymethyl penicillin (penicillin V)
2 . Penicillinase – resistant penicillins :
Acid labile : Methicillin, nafillin, cloxacillin, dicloxacillin
Acic resistant: flucloxacillin.
3. Extended spectrum penicillins :
a.Carboxypenicillins : Carbenicillin, ticarcillin,
b. Aminopenicillin : Amipicillin, amoxicilllin.
c. Ureidopenicillin : Mezlocillin, piperacillin.
4. Beta lactamase inhibitors : Clavulanic acid, Sulbactum.

CLASSIFICATION OF PENICILLIN
Dr. Firas Kassab

15. •Short acting-Procain benzyl penicillin[1- 3hr]
•Intermediate acting-Fortified Benzyl penicillin [12- 24 hr]
•Long acting- Benzathine penicillin [12- 15 days]
Penicillin V –
•potassium phenoxyethyl penicilllin, azidocillin - penicillinase
resistent acid labile form
• Potassium salt form
• More rapidly absorbed
• Less active than benzyl penicillin
• Not used in management of severe infection.

Dr. Firas Kassab

16. Dr. Firas Kassab

17. METHICILLIN-
•penicillinase producing organism
•S. aureus are sensitive.
•Methicillin resistant staphyococci are resistant to all
betalactum antibiotics

NAFICILLIN - more active than methicillin
•but less active than benzyl penicillin
•87%is plasma protein bound
•excreted by the liver

CLOXACILLIN-5-10 times more active than methicillin
•90- 95 / is plasma protien bound
•diclozacilln-blood level is twice as that of cloxacillin

18. Flucloxacillin-simillar to dicloxacillin,Less protein bound
•Staphyloccal resistant - production of a new PBP

Ampicilin-
•antibacterial activity is simillar to benzyl penicillin
•More active against gram negative micro-organisms
•It is water soluble and acid resistant
•Food do not interfere absorption, but incompletely absorbed
excreated by kidney
•In infants and children excretion is delayed
•Parenteral solution deteriorates fast

19. Talampicillin-
•is a carboxylic ester of ampicillin
•Rapidly absorbed from gut
•Hydrolysed by tissue esterase in to active form.
Amoxacillin-
•it is amio-p- hydroxy-benzyl penicillin
•Broad spectrum of activity similar to ampicillin
•Orally effective, and blood levels are twice as that of
ampicillin
•Absorption not affected by food
•Less protein bound
•excreate faster than ampicillin
•incidence of diarrhea is less than ampicillin.
Dr. Firas Kassab

20. Dr. Firas Kassab

21. Carbenicillin-
•weaker antibacterial spectrum than
• Advantage - against all strains of proteus, pseudomonas
aeruginosa.
•It is penicillinase susceptable.
•It’s acid labile and must be given parentarilly.

Ticarcillin-
•it is thienyle analogue of carbenicillin.
•antimicrobial activity is twice that of carbenicillin.

Dr. Firas Kassab

22. Piperacilllin-
• it is betalactamase sensitive.
•broad spectrum activity against gram negative
•it is acid labile.

Clavulanic acid –
•it is well absorbed on oral administration.
•weak antibacterial activity.
•potent and irreversible inhibitor of many betalactamase
• protect betalactum antibiotic from inactivation.
•Used in combination with amoxacillin and ticarcillin.
Dr. Firas Kassab

23. First generation-
More active
Second
generation-
Third generation

Forth generation
More active
against gram
positive organism
more selective
against gram
positive and gram
negative
organisms
Highly active
against gram
negative
otganisms

simillar
antibacterial
activity as that 0f
third generation
but highly
resistent to beta
lactamases

Parenteral-
Cephalothin
Cefazolin
Cephaloridine
Oral-
Cephalexin
Cephadine
Cefadroxil
Parenteral
Cefuroxim
Cefoxitin
Oral
Cefaclor
Cefuroxim axetal

Parenteral-
Cefotaxim
Ceftizoxime
Ceftraxone
Cefoperazone
Oral-
cefexim

Parenteral-
Cefepime
Cefiperome
Dr. Firas Kassab

24. Cephazolin-
•more active against klebicella , E.coli.
•Susceptable to staphylococcal beta lactamases.preffered for surgical
prophylaxis. T ½ - 2 hr.
•cephalexin- orally effective first generation cephalosporin.
•Has simillar spectrum of activity.T1/2- 1hr.

Cephadroxil
has good tissue penetration.
•Has sustained action at the site of infection.

Cefoxitin, cefuroxime
produced by actinomycete.
•Highly resistant to beta lactamases (gram negative organisms)
•treatment of anaerobic infection, surgical infection.
• T ½- 2 hr.

25. Cefuroxim axetil- orally effective.
Cefotaxime- 3
rd
generation
•anaerobic & somegram positive bacteria
•meningitis (gram negative bacilli),
• life threatning /hospital aquired infections.
•septicaemias and infections in
• immunocompromised patients.


Cefpirome- serious and resistant hospital
acquired
•effective on all gram negative bacterias .

26. Monobactams- inhibits gram negative
bacilli .
•It is resistant to gram negative beta-
lactemases .
•hospital acquired infections.
• T1/2 1.8 hrs


Imipenem - it is extremely potent and
most broad spectrum beta-lactam
antibiotic
Imipenem spectrum of activity
Dr. Firas Kassab

27. 2. Inhibitors of Protein Synthesis

•Aminoglycosides
•MLSK (Macrolides, Lincosamides, Streptogramins, Ketolides)
•Tetracyclines
•Glycylcyclines
•Phenicols
•Oxazolidinones
•Ansamycins
Dr. Firas Kassab

28. USES
•Gram-positives, except
Streptococus and Enterococcus.
•combine with aminoglycoside
(Gentamicin or Streptomycin) &
penicillin, ampicillin or
vancomycin for severe
enterococcal infections
(Synergy)
• In serious infection, with beta-
lactams or fluoroquinolones
•Gram-negative nosocomial
infections
•severe systemic infections
AMINOGLYCOSIDES
Dr. Firas Kassab

29. Dr. Firas Kassab
•Broad spectrum of action
•Rapid bactericidal effect
• Inhibitors of Protein Synthesis
• Related in structure and function
• Drugs differ based on location of radical groups attached to the 3 ring
basic structure

Kanamycin
•develops resistance quickly
•Hospital use only
• Nephrotoxic and toxic for ears
•Drug Dosage Adjustment:
•Monitoring mandatory.
•Control the serum level for peak -ensure the bactericidal effect and avoid
side effects

30. Group I-
•Chlortetracycline -Cl
•Tetracycline - OH,-H

•Oxytetracycline
Group II-
•Demeclocycline- OH,-H,-Cl
•Lymicyline
Grope III-
•Doxycycline – OH,-H,-CH3,-H
•Minocycline - -H, -H,- N(CH
3)
2
Dr. Firas Kassab

31. Broad spectrum antibiotic.
Low absorption through git.
Rapid renal excretion,
Low phototoxic
Marked alteration of intestinal bacteria.

Demiclocycline-
Intermediate potency.
High plasma binding capacity.
Slower renal excretion.
Highest phototoxic.
Doxicycline-
High potency.
Complete absorbtion from intestine.
High plasma binding.
T1/2- 18-24 hr.
Leaast alteration of intestinal flora.
Low toxixcity &metabolised in liver.
Tetracycline
Dr. Firas Kassab

32. •anti bacterial spectrum – similar penicillin.
•against penicilin resistant staphylococci.
•small intestine.
•partially destroyed by gastric juice, (enteric coated tablets)

•Various preparation- enteric coated tablets
Estolate form (most resistant by gastric acid)
Sterate
Ethylsuccinate [parenteral]
Glucoheptonate[parenteral ]
•drugs belonging to this group- olindomycin, Spiramycin
(Anti microbial -higher than erythromycin)
New macrolids- roxithromycin, clarithromycin
• Simillar spectrum of erythromycin
• More resistant to acid hydrolysis.
• Better tissue level are achieved.
Erythromycin (Macrolides )
Dr. Firas Kassab

33. •Chemically differ from the macrolide group -lactone ring contains a
nitrogen atom.
•simillar activity that of erythromycin.
•better tissue penetration.
•longer half life than erythromycin.

Clarithromycin-
•Differ from erythromycin only in methylation of hydroxyl group.
•Rapidly absorbed from gut.
•Has longer half life and better tissue penetration.
Azithromycin
(Newer macrolides [azalids] )

34. Is a lincosamide

•Widely distributed in tissue fluids and tissues, including bone.

•Avoid in the routine odontogenic infection

•An excellent alternative drug in penicillin-resistant anaerobic
infections

•Used in Osteomyelitis of the jaws

•Antimicrobial activity in colon is for 5days.
Clindamycin
Dr. Firas Kassab

35. Uses-
•for extra- intestinal
•severe salmonella infection.
• Empiric treatment of meningitis,
• crosses BBB well.
Toxicity:
•bone marrow aplasia
•Hematological abnormalities.
•Relatively small molecule, easily
enters Gram-positive and Gram-
negative Bacteria
•Spectrum of Action:Gram-positive
and Gram-negative bacteria,
Chlamydia, Mycoplasma and
Rickettsiae.
•Target is Ribosome
•Binds to 50S subunit - inhibits
elongation step of protein synthesis

36. 3. Inhibitors of Membrane Functions
•Polymixins
•Cyclic lipopeptides
Dr. Firas Kassab

37. Uses
•Gram-negative UTI, blood, CSF and
eye infections.
•used in combination against very
resistant Pseudomonas, KPC.
• High toxicity – neurotoxic and
nephrotoxic
Lipopeptides: Polymyxins Polymyxin B

38. Dr. Firas Kassab
•Target =Membrane phospholipids, LPS) & lipoproteins
• Outer and Cytoplasmic Membrane Effect
•More permeable membrane. leakage of
cellular molecules, inhibition of respiration and
increased water uptake leading to cell death.
•Gram-positives are naturally resistant (too thick to permit
access)

39. 4. Anti - Metabolites
•Sulphonomaides
•Trimethoprim
Dr. Firas Kassab

40. USES-
•UTI’s
• otitis media in children, chronic
bronchitis in adults,
• enteritis
•Travelers’ Diarrhea.
•Natural Resistance
•Enterococcus –poorly expressed
•S. pneumoniae
•Ps. aeruginosa (impermeability)
Anti-Metabolites
sulphonomides
Trimethoprim/Sulfametho xazole:

41. 5. Inhibitors of Nucleic Acid Synthesis

•Quinolines
•Furanes

42. • Small and hydrophilic
• easily diffuse n reach Target = Topoisomerases
• Rapid bactericidal activity

Quinolones

43. Dr. Firas Kassab
• 1st Generation Quinolones:
Gram-negatives, UTI
high concentrations -infection.

• Fluoroquinolones: Garenoxacin
Gram-negative and Gram-positive ( Anaerobes, Atypicals , S.pneumoniae and
Pseudomonas)

• Ciprofloxacin, Levofloxacin, Norfloxacin, Ofloxacin - More effective (lower
MIC values).
Spectrum -Staphylococci, Streptococci and Pneumococci (sparfloxacin).
More widespread tissue distribution .

Ciprofloxacin and Ofloxacin -systemic infections.
• Sparfloxacin, Gatifloxacin, Moxifloxacin
Trovafloxacin (removed cardiac arrhythmias, liver destruction, phototoxicity.)

•Gatifloxacin (Tequin®) removed from market 05/01/06 - diabetes.

44. Pencillins
Betalactums inhibit
final stage of
peptidoglycan
sysnthesis

Pencillin binds to
proteins and inhibit
PBP activity
•Weekens the cell
wall
•vulnerable to
damage by solutes in
surrounding
Glycopeptide
[vancomycin,
teicoplanin]
•Inhibits cell wall
synthesis in
bacteria- binding
with D- alanyl- D-
alanine terminus of
cell wall.

•Inhibits release of
the bulding block
unit from the carrier
•pervents
peptidoglycans
synthesis
Polyene
[amphotericin-B,
nystatin, hamycin,
natamycin]

high affinity for
ergosterol
•form a micropore in
the fungal wall

•Cell permiability is
through pores ions,
aminoacids, water
soluble substances
leak out.
Tetracyclins
[streptomyces
aureofaciens
]
•passive diffusion
porin proteins

•energy-dependent
system –(inner
cytoplasmic
membrane).

•Bind to 30s
•Prevent access to
aminoacyl t RNA to
the acceptor site on
the mRNA-ribosome
complex

•Inhibition of
protein
synthesis

45. Chloramphinicol
[streptomyces
venezuela
]
•facilitated
diffusion.
•prevent the binding
of the amino- acid-
containing end of
the aminoacyl
tRNAto the
accepor site on the
50s ribosome
•peptide bond
formation is
inhibited
•interruption of
protein synthesis
Macrolides
[streptomyces
erythreus]

•passive diffusion.
•Binds to 50s
ribosomes.
•inhibits
translocaation -
btwn synthesised
peptidyl tRNA
molecule moves
from the acceptor
site on the
ribosomes.
•Interruption of
protein synthesis.
Clindamycin-
•Binds to 50s ribosomes, has
simillar binding
site as that of
erythromycin
.
Aminoglycosides
[actinomyces sp]
•Diffuse by porin
protiens.
•Crsses cytoplasmic
membrane by ETC
blocked by reduction
of ph, hyperosmolarity.
•bind to polysome and
interfears with protein
synthesis
•misreading and
premature termination
of translation of
mRNA.
•aberrant protiens .
•altered permibility and
further drug
transport.

46. III) Classification based on spectrum of activity
➢Narrow spectrum
➢Eg: Penicillin G
➢Broad spectrum
➢Eg: Tetracyclines,chloramphenicol
" Imipenem
" Metranidazole
" Chloramphenicol " Vancomycin
" Clindamycin " Aminoglycosides
" Erythromycin " Cephalosporin(s)
" Tetracyclines " Penicillin(s)
" Bacteriostatic antibiotics " Bactericidal antibiotics
➢IV) Based on type of action
Dr. Firas Kassab

47. V) Based on the source of antibiotics
➢Fungi : Penicillin, Cephalosporin.
➢Bacteria : Polymyxin B, Bacitracin
➢Actinomycetes : Aminoglycosides, Tetracyclines
Chlorampheniol, Macrolides,polyenes
VI)Sources of Antibacterial Agents
• Natural - mainly fungal sources
• Semi-synthetic - chemically-altered natural
compound
• Synthetic - chemically designed in the lab
VII)Against anaerobes
•Chlormaphenicol
•Teicoplanin,Vancomycin ,Telavancin
•Metronidazole
•Thiamphenicol
Dr. Firas Kassab

48. •A. polyenes-
•Amphotricine B, nystatin, hamycin,natamycin
•B. heyerocyclic benzofuran-
•Griseofulvin
Dr. Firas Kassab

49. •Natamycin- 15mg/kg 12 hourly, infants- [8-30 days older] 15 mg/kg 8
hourly, children- 10mg/kg 6 hourly, adult- 125- 250mg/kg 6 hourly.
•pseudomembranus colitis- orally
•
Effective alternative for the treatment of endocarditis, in penicillin allergic
patients.

•Teicoplanin- used in osteomyelitis, endocarditis, methicillin resistant
strains infections.
•Can be given I.M

•Bacitracin- active against gram positive bacteria.
•Only topically used
•Used in opthalmical infection, infected ulcers, and in dressing of wound
after debridemant.

50. Nystatin- highly toxic
•Used for topically application.
•Not absorbed on oral administraton, can be used in monilial
diarrhoea [super infection]

Vancomycin- primarily active against gram positive bacteria.
•bacteriostatic drug, in combination with gentamycin or
tobramycin - bacteriocidal.
•Poorly absorbed after oral absorption, always given I.V.
•Half life 6 hr. Peak concentration is 60 micrograms/ml, higher
concentratio causes ototoxicity.

51. •Is not a first -line of antibiotic
•Causes potential toxicity- aplastic anemia,gray baby
syndrome.
•Indicated for life thratning conditions-bacterial
meningitis, rickettsial infections.

Chloramphinicol

52. USES-
•anaerobes in intra- abdominal abscess, (B.fragilis, spp, Fusobacterium
spp, Clostridium spp, Peptostreptococcus spp, Prevotella spp )
• bone and joint infections, septicemia,
•endometritis, or endocarditis.
•Pseudomembranous colitis due to Clostridium difficile
•Helicobacter pylori eradication therapy,
•MDR -peptic ulcer disease
•periapical abscess, periodontal abscess, acute pericoronitis of impacted or
partially erupted teeth; often used in conjunction with Amoxicillin

53. Dr. Firas Kassab
Adverse Effects
•Nausea, diarrhea, metallic taste
•IV adminstration- Thrombophlebitis

•Infrequent adverse effects
include: Hypersensitivity reactions (rash, itch,
flushing, fever), headache,
dizziness, vomiting, glossitis, stomatitis, dark
urine, and/or paresthesia.
•High doses and/or long-term systemic
•Leukopenia, neutropenia, peripheral
neuropathy
•CNS toxicity.

•
National Toxiology Program (NTP) -
human carcinogen
• Nitroimidazole antibiotic
•anerobic bacteria and protozoa
•antibiotic, amebicide, and antiprotozoal.
[

•DOC-mild-to -
moderate Cl.difficle infection

•MOA-taken up by diffusion, is selectively
absorbed by anerobic bacteria & protoza.

•non-enzymatically reduced by reacting
with reduced ferredoxin, which is
generated by pyruvate oxido-reductase.

•sulfinamides and thioether linkages with
cysteine enzymes deactivate these critical enzymes.

54. Quantitative Measure
• MIC = lowest concentration of antibiotic that inhibits growth
(measured visually)
• Interpretation of quantitative susceptibility tests is based on:
relationship of the MIC to the achievable concentration of
antibiotic in body fluids with the dosage given
•For treatment purposes, the dosage of antibiotic given should
yield a peak body fluid concentration 3-5 times higher than the
MIC
or
MIC x 4 = dosage to obtain peak achievable concentration
MIC-MINIMAL INHIBITORY
CONCENTRATION
Dr. Firas Kassab

55. Dr. Firas Kassab

56. Quantitative Measure
• MBC = lowest concentration of antibiotic that
kills bacteria
MBC – Minimum Bacterial Concentration
Dr. Firas Kassab

57. PRINCIPLES FOR CHOOSING THE APPROPRIATE
ANTIBIOTIC
•Identify the causative organism
•Empirical therapy
•70% infections- mixed flora
•5% aerobes
•25% anaerobes


Indications for obtaining cultures
✓Patient who has received treatment for three days without
improvement
✓postoperative wound infection
✓recurrent infection
✓actinomycosis is suspected
✓Osteomyelitis is present
Dr. Firas Kassab

58. ➢Broth dilution susceptability test using a micro dilution plate-
determine quantitative result.

➢Disc diffusion method -qualitative susceptability result.
➢Gradient diffusion test [ E- test]- qualitative susceptability result.
DETERMINATION OF ANTIBIOTIC
SENSITIVITY
Dr. Firas Kassab

59. 1) Proper dose
➢MIC
➢Over dosing
➢Underdosing

2) Selection of antibiotic-
➢Disc diffusion method is employed.
➢Use of specific narrow spectrum antibiotic
➢Use of least toxic antibiotic.

3) Proper time interval
➢Plasma half- life (T ½)
➢Elimination and frequency of dosing
➢4) Proper route of administration
•Oral route
•Parenteral routes
III) PRINCIPLES OF
ANTIBIOTIC
ADMINISTRATION
Dr. Firas Kassab

60. BACTERICIDAL RATHER THAN A BACTERIOSTATIC
DRUG
•Bactericidal - immunocompromosed conditions.
•Bacteriostatic- less chance of superinfection
USE OF SPECIFIC, NARROW -SPECTRUM ANTIBIOTIC
➢Decreases resistance, decreases superinfections
Dr. Firas Kassab

61. MINIMAL INHIBITORY CONCENTRATION (MIC)

Penicillin G Penicillin V Oxacillin Cefazolin Cephalexin
Streptococcus 0.005 0.015 0.02 0.2 1.0
Staphylococcus (non-penicillinase ) 0.03 0.03 0.3 0.6 6.0
Staphylococcus (penicillinase) R R 0.4 0.6 6.0
Penicillin G Erythromycin Clindamycin Metronidazole
Bacteroides oralis 1.6 0.1 0.1 2.8
Bacteroides melaninogenicus 1.0 0.4 0.01 3.0
Bacteroides fragilis R 2.0 0.2 3.1
Cefazolin Cephalexin Gentamicin
Escherichia coli 0.8 12.0 2.0
Proteus mirabilis 3.0 20.0 1.0
Klebsiella pneumoniae 3.0 20.0 1.5
Pseudomonas aeruginosa > 400.0 > 100.0 1.5
Dr. Firas Kassab

62. Pediatric dose =
Child's BSA in M
2

1.73M
2

x Adult
Dosage
Pediatric =
dose
child's age in months
150
x Adult Dose


Fried's Rule
Pediatric =
dose
child's age in years
child's age in years + 12 years
x Adult
Dose


Young's Rule
Clarks Rule
Pediatric= dose
child's weight (x)= x
150 lbs 150
x Adult Dose
Fluid Requirements = TBSA burned (%) x Weight (kg) x
4 mL (RL)
1 kg


Parkland's Formula:
Nomogram Method
Pediatric Dosage formulas
Dr. Firas Kassab

63. MAXIMUM DOSAGE FOR LIFE-THREATENING INFECTIONS
6 2 g Vancomycin
8 3-6 mg/kg Tobramycin
6 2 g Tetracycline
4 10-12 x 10
6
U Penicillin G
4-6 8-12 g Oxacillin
8 21 mg/kg Metronidazole
6 2-4 g Erythromycin
8 3-6 mg/kg Gentamicin
6 2-5 g Clindamycin
6 50 mg/kg Chloramphenicol
4 8-12 g Cephalothin
4 6-12 g Cefoxitin
6 4-8 g
Cefazolin
4 6-12 g Cefamandole
4 24-40 g Carbenicillin
4 12 g/day Ampicillin
8 15-25 mg/kg Amikacin
" Dosage interval (hr) Total daily dosage Antibiotic
Dr. Firas Kassab

64. PEDIATRIC DOSAGES OF COMMONLY USED ANTIBIOTICS
Drug
Daily dosage
Amoxicillin
20-25 mg/kg/day PO in 3 doses
Ampicillin
25-50 mg/kg/day PO, IM or Iv in 4 doses
Cephalothin
80-160 mg/kg/day PO, IM or IV in 6 doses
Cephalexin
25-50 mg/kg/day PO in 4 doses
Chloramphenicol
75-100 mg/kg/day IV in 4 doses
Clindamycin
10-20 mg/kg/day PO, IM, or IV in 3- 4 doses
Cloxacillin
50-100 mg/kg/day PO in doses
Dicloxacillin
12.5-50 mg/kg/day PO in 2 doses
Doxycycline
5.0 mg/kg/day PO in 2 doses
Erythromycin
30-50 mg/kg/day PO in 4 doses
Gentamicin
6.0 mg/kg/day IM in 3 doses
Metronidazole
30-40 mg/kg/day PO
Minocycline
4.0 mg ist day, then 4.0 mg/kg/day in 2 doses
Penicillin G
100,000 U/kg day IM or IV in 3 doses
Penicillin V
50 mg/kg/day PO in 3- 4 doses
Streptomycin
20-40 mg/kg/day IM in 3 doses
Tobramycin
3-5 mg/kg/day IM in 3 doses
Vancomycin
50 mg/kg/day IV in 4 doses

65. TOXIC EFFECTS OF ANTIBIOTIC
Some antibiotic kill / injure human cells

Penicillin
Amphotericin B
Cephaloridine
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis
Diarrhea Clindamycin
Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin
Myoclonic seizures Penicillin and cephalosporin
Vertigo Gentamicin
Deafness Tobramycin
Nervous system
Carbenicillin (and ticarcillin)
Aplastic anemia,Leukoplakia Chloramphenicol
Hematologic
" PROBLEM " ANTIBIOTIC
tubular necrosis
Decreased platelet aggregation
Dr. Firas Kassab

66. Antibiotic-associated colitis (AAC)
•Clindamycin, ampicilin-amoxicillin
•Cephalosporins
•Clinical features
➢Watery diarrhea
➢Cramping abdominal pain, fever and leukocytosis
➢Treatment :To discontinue the causative antibiotic, restore fluid
and electrolyte balance and administer anti-clostridia antibiotics
like the usual choice is oral vancomycin, metronidazole
Dr. Firas Kassab

67. Superinfection :
•Eg: overgrowth of Candida in the oral cavity
•broad-spectrum antibiotics results in decreased normal host flora
•Seen in the form of bacteremia, U T I, pneumonia owing to the over
growth of resistent micro-organisms- Klebicella, Aerobacter,
Pseudomonas, Candida.
•Oral signs- stomatitis, glossitis, black hairy tongue.[staphylococci,
streptococci, bacteroids, candida] .
•More common In compromised host-
Leukemias,AIDS,Agranulocytosis ,Uncontrolled diabeties,
corticosteroid therapy
Dr. Firas Kassab

68. UNFAVORABLE DRUG INTERACTIONS
Antibiotic
Other drug Effect
Aminglycoside Ethacrynic acid Increased ototoxicity
Cephaloridine Ethacrynic acid Nephrotoxicity
Furosemide
Tetracycline Coumarin Increased anticoagulation
Tetracycline Antacids Absorption inhibited
Bactericidal antibiotic Bacteriostatic antibiotic Decreased effectiveness
ampicillin

Estrogen-containing birth
control pills

Decreased effectiveness of birth control pills

Dr. Firas Kassab

69. Drugs to avoided in liver disorders-

•Erythromycin estolate
•Tetracyclin
•Taiampicillin
•Dose reduction-
•Chloramphinicol
•Metronidazole
•Clindamycin

70. PREGNANCY AND ANTIBIOTICS

Safe antibiotics
penicillins
cephalosporins
erythromycin
Drugs contraindicated in children-
Chloramphinicol
Tetracycline
Dr. Firas Kassab

71. MONITORING THE PATIENT
➢Adjunctive surgery
➢Fluid balance
➢Response to treatment :
➢The response begins by the second day, and initially it is a
subjective sense of feeling better.
➢From that time onward, objective signs of improvement occur
➢Duration of antibiotic therapy 2- 3 days
Dr. Firas Kassab

72. CAUSES OF FAILURE IN TREATMENT OF INFECTION
➢Inadequate surgical treatment
➢Depressed host defenses
➢Presence of foreign body
➢Antibiotic problems
▪Drug not reaching infection
▪Dose not adequate
▪Wrong bacterial diagnosis
▪Wrong antibiotic
Dr. Firas Kassab

73. Combination antibiotic therapy :
.
Indications :
•increase the antibacterial spectrum in life -threatening sepsis of
unknown cause.
•to increase the bactericidal effect against a specific organism.
•In the prevention of the rapid emergence of resistant bacteria

•Adjunctive treatment :
–Endodontic therapy or extraction
–Surgical drainage
–Many chronic dentoalveolar abscesses need curettage.
Dr. Firas Kassab

74. •Initial stage- Aerobic bacteria invade
•Severe infection- Aerobic and anaerobic bacteria invade

Abscess
•Advanced stage- anaerobic infection
Odontogenic infection, oral and
maxillofacial implications
Dr. Firas Kassab

75. Pericoronitis :
•Acute pericoronitis, if severe, may require antibiotic therapy.
•Treatment - debridement, drainage of the site,
penicillin 500 mg qid,
amoxacillin 500mg qid,
clindamycin 300mg qid


Dento Alveolar Abscess :Acute dentoalveolar abscess and cellulitis
Penicillin is the drug of choice


Therapeutic uses of antibiotics in maxillofacial
surgery
Dr. Firas Kassab

76. Soft tissue wounds
•open for six hours or more, (considered infected,)
•if primary closure is elected, a delayed primary closure is preffered
•delayed technique cannot be utilized,-antibiotic support is helpful.
•early primary closure -amoxicillin with clavulanic acid

Chronic inflammatory periodontal diseases-
•TOPICAL MEASURES - Tetracyclins, metronidazole 250mg tid, ,
penicillins500mg qid, cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin,
metronidazle400mg qid,
Dr. Firas Kassab

77. •Identify the causative organisms
•antibiotics for a much longer period -soft tissue infections
•Jaws that require special therapy
•Actinomycosis ,Fungal infections
For hospitalalized/ when inta-venous therapy is indicated-
Aqueous penicillin, 2 million Units IV Q6h, metronidazole 500mg q6h for 4 - 6 weeks
OR
Ampicillin/sulbactum 1.5 to 3.0 gm IV q6h for 2 days then amoxacillin/clavulanate
(augmentin)875, 125.mg PO bd for 4 to 6 weeks
FOR OUT PATIENT TREATMENT
penicillin V 2gm + metronidazole 500mg q8h for 2 to 4 weeks after last sequestrum
removal and patient with out symptons.
OR
cefoxitin 1 gm q8h IV OR IM
cephalexin 500mg q6h PO for 2 to 4 weeks
OR
clindamycin 600, 900mg q6h IV then clindamycin 300, 450 mg PO.
Dr. Firas Kassab

78. •therapeutic doses for 10 to 14 days
•should begin as early as possible after diagnosis
Pre-operatively
• penicillin 2 million units or cefazolin 0.5 gm-1.5 gm 12 hr [25- 50
mg/kg]
Post-operatively
•Penicillin 500mg 6 hr [30-40 mg /kg]
•Cephalexin 500mg 6 hr [25- 50 mg/kg]
•
In suspected intra-cranial contamination-
•Pre-operatively- naficillin 2-6 gm 6hr+ gentamycin 3-5mg/kg 8 hr
•Post-operatrively- cephalexin 500mg 6 hr[25-50 mg/kg]
Dr. Firas Kassab

79. Burke (1973) : “preventive antibiotics are indicated if there is a high probability that
a patient’s natural resistance to bacterial invasion will not overcome the combined
bacterial and physiological challenge of a surgical procedure”.

PROPHYLAXIS FOR WOUND INFECTION
IN ORAL AND MAXILLOFACIAL SURGERY
•Patient with normal defenses may require prophylaxis for some procedures :
•Long (over three hours)procedure requires the use of prophylactic.
•Bone graft procedures.
•implants of metal, plastic or other alloplastic material.
•Immucocompromised host.
•cytotoxic cancer chemotherapy.
•immunosuppressive drugs such as glucocorticoids, azathioprine (Imuran), or
cyclosporine.

•For intraoral procedures, the drug of choice is penicillin given parenterally, one or
two million units preoperatively and an additional dose every one and a half to two
hours. The last dose is given after complete recovery.
Dr. Firas Kassab

80. •procedure has risk of significant bacterial contamination and a high
incidence of infection.
•organism & antibiotic susceptibility of the causative organism must
be known.
•To be effective and to minimize adverse effects, the antibiotic must
be in the tissue at the time of contamination (operation) and it must
be continued for no more than four hours after cessation of
contamination.
•The drug must be given in dosages sufficient to reach four times the
MIC of the causative organisms.
Principles for the use of
prophylactic antibiotics
Dr. Firas Kassab

81. Developmental pharmacokinetics
•Slower GI but faster IM absorption
in infancy
•More body water vs lipid in early
life
•Limited protein binding in infants
•Larger liver/body weight ratio in
infants
•Immature enzymes in neonates
•Larger brain/body weight ratio and
higher blood–brain barrier
•permeability in younger children
•Immature renal function in infants
Pharmacodynamics respone of
drugs in children
Adverse effects
•Valproate hepatotoxicity increased
in young children (with learning
dif
ficulties and receiving multiple
AEDs)
•Thalidomide only causes
phocomelia while the limb is
forming
•Grey baby syndrome –
chloramphenicol in young children
•Tetracyclines only stain developing
enamel
Terence Stephenson,British Journal of Clinical Pharmacology,2005
Dr. Firas Kassab

82. THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY
(AAPD)
Antibiotic prophylactic regimens 2011
" Clindamycin 20mg/kg (maximum
600mg) IV or IM or cefazolin 25mg/kg
(maximum 1g) IV or IM within 30 min
before dental procedure " Children allergic to penicillin and
unable to take oral medications
" Clindamycin 20mg/kg (maximum
600mg) orally 1 h prior to dental
procedure " Children allergic to penicillin
Ampicillin 50mg /kg (maximum 2g)IV
or IM within 30 min before dental
procedure
Children not allergic to penicillin and
unable to take oral medications
Amoxicillin 50mg/kg (maximum 2g)
orally 1 hr prior to dental procedure Children not allergic to penicillin
Dr. Firas Kassab

83. PROPHYLAXIS REGIMEN IN PATIENTS WITH PROSTHETIC VALVE
I) Standard Regimen
A) Preoperatively : 30 minutes before surgery
Ampicillin 1.0-2.0 g IM or IV and
Gentamicin 1.5 mg/kg IM or IV
B) Postoperatively
Penicillin V 1.0 g PO 6 hours after initial dose or
Repeat preoperative regimen 8 hours after initial dose

Dr. Firas Kassab

84. II) Penicillin – allergic patient
A) Vancomycin
•Preoperatively : 1.0 g by slow IV drip (over 6 hour period).
•1 hour before surgery
•Postoperatively : No repeat doses

III) Pediatric dosage
A) Standard regimen
•Ampicillin : 50 mg/kg per dose
•Gentamicin : 2.0 mg/kg per dose
•Penicillin V : 500 mg per dose

B) Penicillin Allergic patient
•Vancomycin 20 mg/kg per dose
Dr. Firas Kassab

85. Under L.A
•Amoxacillin 3 gm or clindamycin 600mg 1 hr pre- operatively and
amoxacillin 1gm after 6 hr
Under G.A
•Amoxacillin 0.5 gm IM after 6 hr or 3 gm 4 hr + 1 gm probensid post-
operatively.
OR
•Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively.
•With previous history of infective endocarditis- Amox 1gm+
gentamycin 120mg IM and Amox 0.5 oral gm after 6 hr
OR
•Vancomycin IV 1gm + gentamycin 120 mg 6 hr post- operatively.
Surgical prophylaxis-

86. American Heart Association (AHA) -taking antibiotics for routine dental
procedures was no longer recommended.
Today antibiotics are only recommended for:
1.An artificial heart valve or who have had a heart valve repaired with artificial
material.
2.A history of endocarditis.
3.Certain congenital heart defects.
4.A heart transplant with abnormal heart valve function.
dentistry is the medical discipline guilty of some of the most antibiotics abuse.
•several negative consequences happen.
•Overuse promotes natural mutation of common bacteria, resulting in newer
resistant strains.
•Antibiotics -VERY useful to treat resistant bacterial infection, but remain
effective if urgent changes are made to curb the spread of antibiotic-resistant
bacteria and disease.

87. Bacteria already resistant
•Acinetobacter
•Anthrax
•Gonorrhea
•Group B streptococcus
•Klebsiella pneumonia
•Methicillin-resistant Staphlylococcus aureus (MRSA)
•Neisseria meningitides
•Shigella
•Streptococcus pneumoniae
•Tuberculosis (TB.
•Typhoid fever
•Vancomycin-resistant enterococci (VRE).
•Vancomycin-Intermediate/Resistant Staphylococcus aureus (VISA/VRSA)

88. •NO SINGLE TEST FOR ANTIBIOTIC ALLERGY.
•Except Penicillin, immunoreactive drug metabolites rarely
identified.
•IgE-mediated hypersensitivity.

• SKIN TESTING -
•Amoxycillin side chain–specific immune reactions warrant
specific amoxycillin skin testing.

•Intradermal skin testing is difficult to do in children under 10
years of age.
•Most nonpruritic maculopapular rashes will not be predicted by
skin testing.

89. •allergen is introduced into the skin

•contact with cutaneous mast cells

•Binding of the allergen occurs

•patient's mast cells are coated with IgE recognizing that specific allergen.

•then adjacent allergen-specific IgE -cross-linked on the mast cell surface & activated

•positive skin test,
•transient "wheal-and-flare" reaction (15 to 20 min)
•central area of superficial skin edema (wheal) surrounded by erythema (flare). pruritic
reaction represents the immediate phase.
•cutaneous mast cells are not activated, (no edema or erythema develo& the test is
negative)
• Falsely negative skin tests such as antihistamines

90. •BLOOD ALLERGY TESTING (ImmunoCAP) is available for penicillin G,
penicillin V, amoxicillin and Cefaclor
•most accurate -close to the time of the event.
•Tryptase elevation collected within 1– 4 hours after a reaction is
consistent with mast cell degranulation.
• blood count (looking for eosinophilia ) and biochemistry (looking for
raised liver enzymes)
•Eosinophilia and/or abnormal liver function tests -T-cell/non- IgE-
mediated reactions.
•results of allergy testing may become negative with time. Even in current
allergies
•For IgE-mediated antibiotic allergy, used where skin and intradermal
tests are negative, or H/O of low risk and alternative drugs are clearly
inferior.

•under medical supervision (clinical immunology/allergy specialist)

91. •Semi synthetic penicillins such as ticarcillin and piperacillin contain the
same nucleus as penicillin G.
•Cephalosporins share a common beta-lactam ring with the penicillins -
cross-reactivity is quite low.
•3-7% of those with penicillin allergy, may have allergic reactions to
cephalosporins as well.

•Monobactams such as aztreonam may be safely administered to
penicillin allergic subjects.

•carbapenems (imipenem) represent a significant risk to penicillin-
allergic patients.

92. Suggested management of penicillin hypersensitivity
Clinical situation Possible course of action
A clear history of an immediate (IgE-mediated) reaction
to penicillin (NB1) OR
A vague history
and an urgent situation (NB1)
1. Do not administer penicillin, a cephalosporin or a
carbapenem.
2. Reconsider clinical necessity for antibiotic therapy.
3. If treatment is definitely required, administer an
alternative antibiotic. Penicillin is definitely preferred,
undertake desensitisation.
A vague history of an immediate (IgE-mediated) reaction
to penicillin and a non-urgent situation (NB1)
Same as above
If a penicillin is definitely preferred, skin testing should
occur under the supervision of a clinical
immunology/allergy specialist. Negative-graded
challenge; if positive,- desensitisation program.
A clear history of a non-immediate reaction to penicillin
(NOT drug rash with eosinophilia and systemic symptoms
[DRESS], Stevens-Johnson syndrome or variants)
1. Reconsider clinical necessity for antibiotic therapy.
2. If treatment is definitely required, administer an
alternative non-penicillin antibiotic (e.g. cephalosporin,
aztreonam or non–beta-lactam antibiotic). If a penicillin is
definitely indicated, proceed with therapy, treating any
mild reactions symptomatically
A vague history of a non-immediate reaction to penicillin
(not DRESS, Stevens-Johnson syndrome or variants)
Same as above
A clear or vague history of DRESS, Stevens-Johnson
syndrome or variants
Same as above

93. • metronidazole, ciprofloxacin, and minocycline
•combination would be needed -diverse flora in root canal
•metronidazole -at a high concentration, it cannot kill all the bacteria, indicating the
necessity for combination of other drugs
•TAP first tested by Sato et al.
• Metronidazole (nitroimidazole) -a broad spectrum against protozoa &anaerobic bacteria.
•Minocycline (semisynthetic tetracycline) with a similar spectrum of activity.
• Ciprofloxacin, a synthetic fluoroquinolone, has a bactericidal mode of action
•increase in root thickness and length, resembling normal maturation of the root.
• the infected area requires a normal blood supply which is no longer in necrotic pulps.
•Therefore, local application of antibiotics most effective mode for delivering the drug.
•30% reduxtion in bacteria -2 weeks.
•successful treatment- sterilization of canals and healing of periapical pathology, immature
root development, necrotic pulps, and apical periodontitis
•managing non-vital young permanent tooth is based on the availability of viable stem
cells.
•drawbacks of this technique- Development of resistant bacterial strains and tooth
discoloration

94. Dr. Firas Kassab

95. Dr. Firas Kassab

96. During Intervention
Preoperative
Pain
Post-Operative
Oral Sedation

Preoperative
Analgesics

•IV Sedation

•Nitrous Oxide

•Local Anesthesia

•Analgesic Prescription
•Opioids
•Non-opioids

Dr. Firas Kassab

97. Algesia : It is defined as an ill defined, unpleasant
sensation, usually evoked by an external or internal
noxious stimuli.

Analgesic : A drug that selectively relieves pain by
acting in the CNS or peripheral pain mechanism,without significantly altering the conciousness.




Dr. Firas Kassab

98. 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
Dr. Firas Kassab

99. Dr. Firas Kassab

100. Dr. Firas Kassab

101. •Analgesia.
•Antipyresis.
•Antiinflammatory.
•Antithrombotic.
Dr. Firas Kassab

102. •Gastric mucosal damage.
•Bleeding: inhibition of platelet function.
•Limitation of renal blood flow.
•Delay / Prolongation of labour.
•Premature ductus arteriosus closure.
•Asthma & anaphylactoid reactions in susceptible
individuals.
Dr. Firas Kassab

103. •Non narcotic/non opioid/ aspirin like drugs.
•Weaker analgesics except for inflammatory pain.
•Analgesic, antipyretic & antiinflammatory properties.
•Physical Dependence, abuse liability
•Primary action: peripheral pain mechanism
interruption.



Dr. Firas Kassab

104. Dr. Firas Kassab

105. Non selective COX
inhibitors
(traditional NSAIDs)
Salicylates
Aspirin
Pyrazolone derivatives
Phenylbutazone, Oxyphenbutazone
Indole derivatives
Indomethacin
Propionic acid derivatives
Ibuprofen, Naproxen, Ketoprofen
Anthranilic acid derivative
Mephenamic acid
Aryl-acetic acid derivatives
Diclofenac
Oxicam derivatives
Piroxicam, Tenoxicam
Pyrrolo- pyrrole derivative
Ketorolac
Dr. Firas Kassab

106. Preferential COX-2 Inhibitors-Nimesulide, Meloxicam,
Nabumetone
SelectiveCOX-2 Inhibitors- Celecoxib, Rofecoxib, Va;decoxib,
Etoricoxib
Analgesic-AntipyreticBut Poor Antiinflammatory
Paraaminophenol Derivative Paracetamol (acetaminophen)
Pyrazolone derivative , metamizol ( dipyrone), propiphenazone
BENZOXAZOCINE DERIVATIVE :nefopam
Dr. Firas Kassab

107. •In England 18
th
century- Reverend Freudman first -cure of
agues(Fever)
•willow bark was a bitter glycoside - Salicin, 1
st
isolated in
1829 by Leroux, -antipyretic effect.
•Sodium salicylate was 1
st
used for -rheumatic fever
•And as antipyretic in 1875 &
•its utility in the gout soon followed.
•Hoffman -prepared acetyl salicylic acid.
•1899 introuduced by Dreses under the name aspirin.

NON-SELECTIVE COX INHIBITORs
Dr. Firas Kassab

108. •Acetyl salicylic acid.

•Rapidly converted in the body to salicylic acid which is
responsible for most of its action.

•Only drug amongst NSAIDs which irreversibly inhibit COX.



Dr. Firas Kassab

109. PHARMACOLOGICAL ACTIONS OF SALICYLATES

•Analgesic: 600mg equivalent to 60mg codeine.
•Antipyretic: promotes heat loss, resets hypothalamic
thermostat.
•Anti-inflammatory: 3-6gm/day; quenching of free radicals.
•Respiration is stimulated; dose dependant.
•Metabolic: inflammatory doses; may decrease blood sugar
in diabetics.
•CVS: no direct effect in therapeutic doses.
•GIT: irritate gastric mucosa.
•Blood: irreversibly inhibits thromboxane synthesis.
Dr. Firas Kassab

110. •Absorption: Stomach and Small intestine.
•Poor water solubility.
•Solubility higher at high pH(alkaline medium)
•80% plasma protein bound.
•Enters brain, crosses placenta.
•Excretion: Urine.
•T ½ 15- 20min.
Dr. Firas Kassab

111. •Analgesic, Antipyretic, Anti inflammatory.
•Acute rheumatic fever.
•Rheumatoid arthritis.
•Osteoarthritis.
•Postmyocardial infarction and post stroke
patients.
Dr. Firas Kassab

112. •Side 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 antiinflammatory doses.
•Reye’s syndrome.
•Acute salicylate poisoning: fatal dose 15-30g;
serum >50mg/dl.
Dr. Firas Kassab

113. PRECAUTIONS & CONTRAINDICATION

Reye’s syndrome.
Should be stopped 1 week before elective
surgery(Brennen et al. presented evidence suggesting
low-dose aspirin should be continued during dental
surgical procedures).
In Chronic liver diseases.
During pregnancy & avoided in breast feeding.
Avoided inG-6-PD deficient individuals.
Avoided in diabetics .
Dr. Firas Kassab

114. •Aminopyrine and antipyrine [1884]: agranulocytosis.
•Phenylbutazone and Oxyphenbutazone [1949].
•Potent antiinflammatory drug,but poor analgesic and
antipyretic action.
•Banned: risk of bone marrow depression.
PYRAZOLONE DERIVATIVES
Dr. Firas Kassab

115. •Potent and promptly acting analgesic and antipyretic.
•Few cases of agranulocytosis reported.

PROPIPHENAZONE
•Similar to metamizol.
Dr. Firas Kassab

116. •Potent anti-inflammatory drug, comparable to
phenylbutazone.
•Analgesic action is better than phenylbutazone, it
relieves only inflammatory or tissue injury related
pain.
•Highly potent inhibitor of PG synthesis and suppresses
neutrophil motility.

Dr. Firas Kassab

117. Pharmacokinetics
Absorbed orally.
•Rectal absorption is slow but dependable.
• 90% bound to plasma proteins
•Partly metabolized in liver to inactive products and excreted by kidney.
• Plasma t1/2 is 2-5 hours.
Adverse effects:
•High incidence of gastrointestinal & cardiovascular events
•Frontal headache, leukopenia , increased risk of bleeding
Contra indications:
•Pregnant women & children
Uses:
•– Acute gout, common drug in PDA closure.
Dr. Firas Kassab

118. •A prodrug that converts into an active sulfide metabolite.

•Antiinflammatory action < Indomethacin.

•At lower doses, selectively inhibit extrarenal
prostaglandin synthesis.
Dr. Firas Kassab

119. •Rated as the safest (SADR reporting system in U.K.)
•Better tolerated than aspirin.
•Anti- inflammatory,analgesic & antipyretic efficacy is lower than high
dose of aspirin.
•Most commonly used NSAID .
Dose: 400- 800mg TD, Ibuprofen
250mg BD-TD, Naproxen
•Naproxen : more potent, but inhibits platelet aggregation & prolong BT.
•200mg Ibuprofen has same analgesic effect as acetaminophen 650mg/
codeine 60mg
•400mg and 600mg doses produced greater levels of analgesia.



Dr. Firas Kassab

120. •Orally.

•90% plasma protein bound.

•Enter brain, synovial fluid, placenta.

•Liver – hydroxylation, glucoronide conjugation.

•Excreted in urine.
Dr. Firas Kassab

121. Therpeutic uses
•Rheumatoid arthritis, ankylosing spondylitis who cannot
tolerate aspirin.
•Soft tissue injuries, fractures ,vasectomy, tooth extraction, post
partum and post operatively
•It is available as an `Over The Counter Drug’
Adverse effects:
• Gastric discomfort, nausea & vomiting.
•Occult blood loss are rare.
• Rashes.
• Precipitate asthma.
Contraindicated:
•Not prescribed in pregnant women & should be avoided in peptic ulcer patients.
Dr. Firas Kassab

122. Dr. Firas Kassab

123. Drug MOA Route Bioa
vaila
bity
T ½ Uses AE
Mephnemic
Acid
Anthranilic
acid
derivative
Non
selectiv
e COX
inhibito
rs
Peripheral as well
as central analgesic
action
Oral 2-4
hours
muscle pain,
soft tissue pain
, joint pain
Diarrhoea.
Diclofenac
sodium- Aryl
acetic acid
derivatiove
(extensively
used)
Non
selectiv
e COX
inhibito
rs
Short antiplatelet
action.
Neutrophil
chemotaxis &
superoxide
production at is
reduced
Oral
and i.m.
Oral-
50mg
TDS

99% 2 hrs RA, OA,
bursitis, post
traumatic, post
operative
inflammatory
conditions.
Epigastric
pain ,nausea,
dizziness,
headache,
rashes.

Piroxicam
(oxicam
derivative)
(e.g.piroxica
m,tenoxicam)

Reversi
ble
inhibito
r of
cycloox
ygenas
e
Metabolized in liver
by hydroxylation
and glucuronide
conjugation.
Excreted in urine
and bile
Oral
20mg
OD
99% 2 days inhibits
platelet
aggregation-
prolonging
BT. Dec. IgM
rheumatoid
factor.
Dr. Firas Kassab

124. Dr. Firas Kassab
Drug MOA Route Bioav
ailabit
y
T
½
Uses AE
Ketorolac
pyrrolopyrro
le derivative

Non
selectiv
e COX
inhibit
ors

EFFICIECNC
Y EQUA TO
MORPHINE
Oral
and i.m.
Oral
10-20
mg
6hrly.
(5days)
60% 5-7
ho
urs
dental & acute
musculo- skeletal
pain (equals
morphine)
free of respiratory
depression
hypotensive
constipation
Nimesulide
( week
inhibitor)





Prefent
ial cox
2
inhibit
or
Free radical
scavanging
Reduced
generation of
superoxide
by
neutrophils
orally 99% 2-5
hrs
short lasting painful
inflammatory
conditions like
Sports injuries,
Sinusitis and other
ear, nose, throat
disorders.Dental
surgeries, Low
backache. Post-OP
pain and OA.

GI-
Epigastralgi
a
Hepato &
Nephrotoxic
ity
Fulminant
hepatic
failure
Celecoxib
. .
Selective COX-2
inhibitor
Slowly absorbed
orally 87-97%p
pb
11
hrs
RA,OA, musculo
skeletal pain.
abdominal
pain,
dyspepsia,
diarrhoea.

125. •Introduced in 1887.
•Acetaminophen- deethylated active metabolite of phenacetin.
•CNS-raises pain threshold.
•negligible anti-inflammatory action.
•Poor inhibitor of PG synthesis in peripheral tissues, but more
active on COX in brain.
•Gastric irritation is insignificant –except in overdose
•Does not affect function or clotting factors and is not
uricosuric.
ANALGESIC –ANTIPYRETICS WITH POOR
ANTIINFLAMMATORY ACTION
Dr. Firas Kassab

126. •Orally.
•1/3 is protein bound in plasma .
•Glucuronidation.
•Excreted rapidly in urine.
•Plasma t l/2 is 2-3 hours.
•Effects after an oral dose last 3-5hrs.
Dr. Firas Kassab

127. Adverse effects
•Nausea, rashes, leukopenia.
•Acute PCT poisoning – Dose >150 mg/kg or > 10g in
adult. Fatality >250mg/kg , jaundice starts after 2 days.
(In chronic alcoholics,even 5-6g/day taken for a few
days can result in hepatotoxicity)
N-acetylcysteine (150mg/kg iv) is the drug of choice.
Therapeutic Uses
•Headache.
•Musculoskeletal pain.
•Dysmenorrhoea.
•Safe in gastric irritation, ulceration, bleeding, pregnancy
& lactating mother.
Dr. Firas Kassab

128. Dr. Firas Kassab

129. Dr. Firas Kassab

130. Dr. Firas Kassab
For Elderly Patients:
•Acetaminophen is the drug of choice.
•Selective COX-2 inhibitors are the second option.
Liver & Kidney Disases:
•Regular strength Acetaminophe (2-2.5 grams in divided doses/ day)
•Codeine+Acetaminophen.
•Oxycodone/Hydrocodone+Acetaminophen .
Asthamatic Patients:
•Nimesulide is the drug of choice.

131. When additional pain control is
needed
Dr. Firas Kassab

132. •Mentioned in EBER’S papyrus 1500BC.
•THEOPHRATUS writings 300BC.
•GALEN 2
nd
century AD.
•Pharmacist – SERTURNER 1806 isolated active
component “morphine” from opium; named after
Greek god of dreams MORPHEUS.
Dr. Firas Kassab

133. •
NATURAL
Morphine
codeine
SEMI SYNTHETIC
Di acetyl morphine
pholcodeine
SYNTHETIC
Pethidine
Fentanyl
Methadone
Detropropoxyphene Tramadol
Dr. Firas Kassab

134. Dr. Firas Kassab

135. Pharmacological Action:
CNS: interacts primarily with μ opiod receptor
•Analgesia: strong analgesic; suppression of pain is selective,
without affecting other sensations; degree increases with dose.
•Sedation: drowsiness, higher doses induce sleep and coma.
Dr. Firas Kassab

136. •Mood & subjective effects: mental clouding, loss of
apprehension.
•Respiratory system: depresses RS in dose dependant
manner.
•Cough centre: depressed.
•Temperature regulating centre: hypothermia occurs in
cold surroundings.
•Vasomotor centre:fall in BP at higher doses.
•CVS: vasodilatation due to direct action decreasing tone of
blood vessels
•Neuro endocrine: hypothalamic action on pituitary is reduced
•GIT: constipation (direct action on intestines & in CNS)
•ANS: central sympathetic stimulation- causes mild
hyperglycaemia.


Dr. Firas Kassab

137. PHARMACOKINETICS

•First pass metabolism: high & variable.
•Concentrations in Liver, spleen, kidney>plasma.
•Crosses placenta.
•30% ppb.
•Metabolised in Liver by glucoronide conjugation.
•T ½ 2-3hrs.
•Elimination complete by 24hrs.

Dr. Firas Kassab

138. Adverse effects
•Side effects: sedation, mental clouding,
lethargy, dysphoria, blurring of vision.
•Idiosyncrasy and allergy: rare.
•Apnoea: in newborns if mother is on it during labor.
•Acute morphine poisoning: 50mg in non-tolerant adult.
Human lethal dose: 250mg.
•Tolerance and dependence: high.
Contraindication
•Infants more susceptible to resp depression.
•Respiratory disease.
•Head injury: intracranial tension
•Hypotensive and hypovolaemia: exaggerate fall in BP.
•Elderly male: chances of urinary retention.
•Liver, kidney disease.
Dr. Firas Kassab

139. •Codeine •Pethidine •Methadone •Tramadol
•Methyl morphine.
•60mg codeine
comparable to
600mg aspirin.
•Selective cough
supressant.
•Constipation is
the prominent side
effect at analgesic
dose.

Chemically
unrelated to
morphine.
•Nearly similar to
morphine in
analgesic
property,but more
than codeine.
•Not a cough
supressant.
•T ½ 2-3hrs.
•Side effects –
accumulation of
norpethidine(tremo
rs, mydriasis,
hyperreflexia).
Binds to tissue
protiens.
•T ½ 24-36hrs
•90% plasma
protein bound
•Liver –
demethylation
•1mg methadone
= 4mg morphine
•

2mg heroine
•
20mg pethidine
•Additional
mechanism of pain control.
•Medium intensity ,
short acting.
•Partially reversed
by opioid
antagonist
•T ½ 3-5hrs.
•100mg IV =
10mg IM morphine.
•Not effective in
severe pain.
Dr. Firas Kassab

140. Dr. Firas Kassab

141. •NSAID-OPIOID COMBINATION
•NSAID-NSAID COMBINATION
1000mg paracetamol + 600mg ibuprofen
Two general methods for drug combination :
1. Alternating regimen consisting of an NSAID
followed by an acetaminophen-opioid combination.
2. Single NSAID-opioid combination

e.g. Combunox (5mg oxycodone+400mg ibuprofen)
Dr. Firas Kassab

142. Dr. Firas Kassab

143. Dr. Firas Kassab
GLUCOCORTICOIDS

144. In the form of a paste mixed with antibiotics
•Dexamethasone solution.
•Kenacomb: Each gram contains 100 000 units nystatin,
2.5 mg neomycin base (as sulphate ), 0.25 mg gramicidin, and
1.0 mg triamcinolone acetonide
.
•Ledermix paste: triamcinolone 10mg, demeclocycline
calcium 30mg.
Dr. Firas Kassab

145. Dexamethasone
•Very potent & highly selective glucocorticoid.
•Long acting.
•Pituitary depression.
•Used in inflammatory & allergic condition.
•Dose: 8mg loading dose,followed by 4 mg every
eight hours (upto max. 5 days).

Dr. Firas Kassab

146. Dr. Firas Kassab

147. Dr. Firas Kassab
•Considerations for Effective “Three-D” Pain
Control

1. Diagnosis
2. Definitive dental treatment
3. Drugs


a. Pretreat with NSAIDs or acetaminophen when appropriate.

b. Use long-acting local anesthetics when indicated.
C. Use a flexible prescription plan.

d. Prescribe “by the clock” rather than as needed.

148. Dr. Firas Kassab

149. Dr. Firas Kassab

150. Procedure/ condition Initial choice If more needed
1.Canal debridement Aspirin/ NSAID Analgesic with ½ gm Codeine
2.Canal debridement where considerable
over- instrumentation has occurred*
Analgesic +½ gm Codeine Analgesic with 1gm Codeine

3.Canal fillings where overfillings has
occurred & periapical tissue is normal
Analgesic +½ gm Codeine

Analgesic with 1gm Codeine

4.Root amputation without flap Nothing ASA,NSAID
5.Periapical/amputational surgery with
minimal trauma
ASA,NSAID Analgesic with ½ gm Codeine

6.Extensive surgery with considerable
trauma
Vicodin ,Lortab [steroids] Meperedine,
7.Call after office hours with moderate
pain
Analgesic with 1g of cod.

Tradol, Vicodin

8. Call after office hours with severe pain

Vicodin ,Lortab

Demerol, Percodan/percocet
Dr. Firas Kassab

151. Dr. Firas Kassab

152. Antibiotic prophylaxis Infective endocarditis -updated by the American Heart Association (AHA)
and National Institute for Health (NIH) and Clinical Excellence. Aim To determine the specific
infective endocarditis antibiotic prophylaxis prescribing practices of dentists in Singapore.
Methods A questionnaire survey was sent through an email link and by postal mail. Statistical
analysis was carried out using SPSS 19.0. Results Responses were received from 458 dentists
The accuracy of prescriptions for 13 cardiac conditions and 12 dental procedures were
evaluated.. The median number of accurate answers for dental procedures was generally high,
both for dentists who followed the AHA 1999 guidelines (median = 10) and AHA 2007
(median = 9) guidelines. 82.8% felt that developing a local guideline would be beneficial to
the local dental community. Conclusion Dentists were accurate in their prescriptions of antibiotic
prophylaxis for dental procedures, but not for cardiac conditions. It may be helpful to attain a
consensus among local cardiologists and dentists to unify the antibiotic prophylaxis prescription
practices in Singapore.
Antibiotic prophylaxis prescribing
practices of dentists in Singapore.
International Dental Journal. Apr2014, Vol. 64 Issue 2, p108-114. 7p
Dr. Firas Kassab

153. The purpose of this in vitro study was to compare the ability of triple antibiotic paste (TAP) to
calcium hydroxide (CH) in disinfecting dentinal tubules.
Sixty root blocks were obtained from extracted single-rooted human teeth. The root canals
were enlarged with Gates-Glidden drills up to size 3 and were contaminated with (E.
faecalis), and then left for 21 days. The contaminated blocks were treated with saline (as
negative control), CH or TAP. Dentin debris was obtained at the end of first and 7th days,
using Gates-Glidden drills sizes 4 and 5 from two different depths of 100 and 200 um. The
vital bacterial load was assessed by counting the number of colony forming units (CFUs). The
data was analyzed with the Kruskal-Wallis H and Dunn Post-Hoc tests & Wilcoxon Signed
Ranks test (P<0.05).
Results: TAP significantly decreased the number of CFUs in both depths and time intervals
(P<0.001), while the CH group showed a moderate antibacterial effect.
Conclusion: TAP is more effective in disinfecting the canal against E. faecalis compared to CH.
The Ability of Triple Antibiotic Paste and
Calcium Hydroxide in Disinfection of Dentinal
Tubules.
Iranian Endodontic Journal. 2014, Vol. 9 Issue 2, p123-126. 4p.
Dr. Firas Kassab

154. •The authors recruited parent-child pairs visiting the Pediatric Clinic at the College of
Dentistry at The University of Tennessee Health Science Center, Memphis, and three
private dental offices. They made parents to measure 5 milliliters of liquid by using a
medicine cup with clear markings, a medicine cup with printed markings, a cylindrical
measuring spoon and an oral syringe,each device weighed before and after the
measuring exercise and compared the difference in weight with 5 mL. Results-McNemar
test revealed a significant difference in parents' ability to measure accurate doses with
the various devices.
• Conclusions- Medicine cups had a higher occurrence of dosing errors when compared with
the other devices.
• We improve pain management in pediatric patients by educating parents about accurate
measuring devices, weight-based dosing and correct interpretation of medication dosing
charts.
Parents' understanding of an accuracy in using
measuring devices to administer liquid oral pain
medication.
Journal of the American Dental Association (JADA). Feb2014, Vol. 145 Issue 2, p141-149.
Dr. Firas Kassab

155. •An 8-month-old boy underwent cleft palate repair and placement of bilateral
myringotomy tubes. His anesthetic course was uneventful, consisting of maintenance with
desflurane and fentanyl. He received acetaminophen for routine postoperative pain
management and was tolerating liquids and discharged home on postoperative day 1.
•Day 3, child - profoundly lethargic with multiple episodes of emesis ,45-second tonic-
clonic seizure in transport to the medical center, and initial lab results - total bilirubin
3.1 mg/dL, and a serum acetaminophen level -83 µg/mL. Aggressive measures -
blood products and periprocedural fresh frozen plasma, peracillin/tazobactam, and
intravenous infusions of N-acetylcysteine , sodium phenylacetate and sodium benzoate,
carnitine, and citrulline were administered. metabolic acidosis and acute hepatitis
began to correct by day 4, and discharged on day 15.
•Conclusion: This report challenges existing guidelines for acetaminophen administration
and emphasizes the importance of close follow-up and hydration after even relatively
minor surgery.
Acute Liver Failure Following Cleft Palate Repair: A
Case of Therapeutic Acetaminophen Toxicity.
Cleft Palate-Craniofacial Journal. Nov2013, Vol. 50 Issue 6, p747-750. 4p.
Dr. Firas Kassab

156. •therapeutic transactions between physician and patient.
•The art of prescription writing is an ancient inheritance.
•most significant written communications of the human race.
• The ancient symbol, Rx, signifying the appeal, Latin was adopted,
•Present- day prescription contain single ingredient, written in English, with doses given
in the metric system.
•ancient "Rx" and the Latin "Signatura," abbreviated as "Sig.," are all that remain of the
ancient art of the prescription.
•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.
Prescription Writing
Dr. Firas Kassab

157. •Form of the Written Prescription- Barest form- the superscription, the inscription, the subscription,
the signa, and the name of the prescriber - written within the confines of a form.
•Superscription- Date, the name, address and age of the patient; and the symbol Rx (an abbreviation
for "recipe," the Latin for "take thou."
•Inscription - body of the prescription, containing the name and amount or strength of each
ingredient.
•Subscription - The directions to the pharmacist, usually consisting of a short sentence such as:
"make a solution," "mix and place into 10 capsules," or "dispense 10 tablets."
•Signatura- From the Latin "signa,“, contains the directions to the patient. written in English;
however, physicians continue Latin abbreviations, e.g. "1 cap t.i.d . pc. Since the pharmacist always
writes the label in English, the use of such abbreviations or symbols should be discouraged.
•"take as directed”- avoided.
•directions to the patient - phrases as "for pain,for relief of headache, to relieve itching”
Dr. Firas Kassab

158. •Labeling- physician wants his patient to know the name of the drug, the box on the
prescription form marked "label" should be checked.
•Refills- The physician should designate the number of refills he wishes the patient to
have.
•Proprietary vs. Non-Proprietary ("Generic") Prescriptions - In recent years, some
hospitals and private physicians indicate willingness to pharmacist to dispense a non-
proprietary or "generic-named" preparation instead of the trade name item written on the
prescription. Some have a box on the prescription designated "N.P.P." e pharmacist can
sell a less expensive drug to the patient.
•The amount to be dispensed should be clearly stated and needed by the patient.
Excessive amounts should never be dispensed,
•It is far better to have several refills of a prescription than to have an excessive amount
prescribed at one time.
http://www.sh.lsuhsc.edu/fammed/outpatientmanual/prescripwriting-pdr.htm
Dr. Firas Kassab

159. Dr. Firas Kassab

160. Dr. Firas Kassab
Table 1. Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ad ad to, up to
ad libitum ad. lib. at pleasure
ana a.a. of each
ante cibos a.c. before meals
aqua aq. water
bis in die b.i.d. twice a day
collyrium collyr. eye lotion
cum c. with
cum aqua cum aq. with water
dentur tales doses d.t.d. give such doses
dispensa disp. dispense
et et and
gutta, guttae gtt. drop, drops
hora somni h.s. at bedtime
in vitro in vit. in glass
misce m. mix
non repetatur non. rep. do not repeat

161. Dr. Firas Kassab
oculus dexter o.d. right eye
oculus sinister o.s. left eye
omni die o.d. daily
omni mane o.m. every morning
omni nocte o.n. every night
per os p.o. by mouth
placebo placebo to please
post cibos p.c. after meals
pro re nata p.r.n. as the occasion arises
quantum sufficiat q.s. sufficient quantity
quater in die q.i.d. four times a day
recipe Rx take
semis ss _ one-half
sine s,s without
si opus sit s.o.s. if necessary
ter in die t.i.d. three times a day
trochiscus, torchisci troch. lozenge, lozenges
unguentum ungt. ointment
ut dictum ut dict. as directed

162. Dr. Firas Kassab

163. •The pharmacologic basis of therapeutics 10
th
Ed
Goodman & Gilman
•Essentials of Medical Pharmacology 5
th
Ed
K.D.Tripathi
•The short Textbook of Medical Microbiology – Satish
Gupte.
•Textbook of pharmacology - Topazian
•Text of pharmacology and pharmacothraputics -
Satoskar
•Principles of general medicine- Davidson
•Endodontic Therapy 6
th
Ed Franklin S.Weine
•Pathways of Pulp 10
th
Ed Stephen Cohen
• Endodontics 6
th
Ed. Ingle





Dr. Firas Kassab

164. •Haas DA. An update on analgesics for the management of
acute post-operative dental pain. J Can Dent Assoc
2002;68(8):476-82
•Mohammadi Z,Farhad A. Pharmacological strategies to
control post-operative endodontic pain.A review. Dent Res
J 2007;4(2):61-68
•Hargreaves K, Abott PV. Drugs for pain management in
dentistry. Aust Dent J 2005;50 Suppl 2:S14-S22
•Ong CK, Seymour RA. An evidence -based update of the use
of analgesics in dentistry. Periodontol 2000 2008;46:143-64
•Phero JC,Becker D. Rational use of analgesic
combinations. Dent Clin N Am 2002;46:691-705
•Roda RP,Bagan JV,Soriano YJ,Romero LG. Use of
nonsteroidal antiinflammatory drugs in dental practice.A
review. Oral Patol Oral Cir Bucal 2007;12:E10-8

Dr. Firas Kassab