Antibiotics & analgesics dentistry

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Antibiotics and Analgesics in dentistry

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  • Good work doctor. your mail id plz. drop me in renju.igids@gmail.com
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  • term 'antibiosis', - Jean Paul Vuillemin 1877 renamed antibiotics - Selman Waksman,1942.1928  Alexander Fleming -named penicillin, -chemotherapy. Alexander Fleming first sulfonamide Gerhard Domaqk in 1932 in Germany,Domagk received the 1939 Noble Prize for medicine.In 1939, World War II, Rene Dubos- first naturally derived antibiotic, tyrothricin1941 penicillin was commercilly available, golden age of antibioticsFlorey and Chain succeeded in purifying the first penicillin,in 1942, e chemical structure of penicillin was determined by  Dorothy Crowfoot Hodgkin in 1945. Clinical potential of microbial products as therapeutic agents in 1877 – Pasteur and JoubertChlortetracycline- introduced in 1948 [for rickettsial infections]
  • • It is important to understand the growth cycle and physiology of bacteria toappreciate how it influences antimicrobial action• Bacteria are all around us. Given good growing conditions, a bacteriumwill divide.• A new cell wall forms at the center and the "bug" splits into two daughtercells, both of which carry the same genetic information as the parent• If the environment is perfect, the two daughter cells can split into fourwithin 20 minutes• 1, 2, 4, 8, 16, 32, 64...• Typical bacterial growth cycle includes:Lag phaseExponential (log) phaseStationary phaseDeath phase
  • Gram-Negatives:1. Outer membrane entry through the:Porins: Hydrophilic ß-lactams tend to gain access into the periplasmicspace using these watery funnels (i.e., E. coli organism has about100,000 of these porins). Porins are transmembrane proteins. Theycomplex together to form water-filled channels through which lowmolecular weight (<600 daltons) hydrophilic substances readily diffuse.Such diffusion is passive and the concentration in the periplasmicspace can reach the level that prevails in the external environment aslong as there are no mechanisms to pump the drug back out or whichinactivate it.Phospholipids: This mode of entry is less common, but it seems toplay a significant part in the case of certain ß-lactams. Lipid bilayerssupport the diffusion of lipophilic compounds (certain ß-lactams arelipophilic). However, if the organism’s LPS (endotoxin) is branched(e.g., as in the case of Pseudomonas aeruginosa), such diffusion isblocked. This is called impermeability.2. Peptidoglycan entry3. Periplasmic space entry: ß-lactams may encounter ß-lactamases4. Cytoplasmic membrane PBP – boundNatural Resistance - Many Gram-negative organisms are naturally resistantto penicillin G and oxacillin because the drug is prevented from entering the cell by the LPS which blocks the porins.
  • Mode of actionTarget = Ribosome in cytoplasm1. Outer Membrane entry:Aminoglycosides are positively charged molecules which means theyrapidly enter bacteria (negatively charged) since the two charges attracteach other.The negative charge of bacteria is due to LPS in the outer membrane andthe peptidoglycan (notably the teichoic acid).2. Cytoplasmic Membrane entry:The drugs cross the cytoplasmic membrane via respiratory enzymes(involved in aerobic respiration).This is why bacteria without respiratory enzymes (strict anaerobes orfacultative anaerobes like streptococci) are naturally resistant toaminoglycosides.
  • Outer and Cytoplasmic Membrane Effect:positively charged molecules (cationic) which areattracted to the negatively charged bacteria.Cationic molecules attracted to the negatively charged bacteria.(LPS and peptidoglycan).
  • Anti-Metabolites• Called folate pathway inhibitors or anti-metabolitesFolic acid is essential for the synthesis of adenine and thymine, make up our genes, DNA and chromosomes.Humans do not synthesize folic acid. Good selective target.Sulfonamides• Bacteriostatic• Introduced in 1930’s – first effective systemic antimicrobial agent• Used for treatment of acute, uncomplicated UTI’sTrimethoprim/Sulfamethoxazole• TMP/SXT is bactericidal• Broad spectrum• Synergistic actionSulfonamides (sulfamethoxazole)-enzyme pteridinesynthetasetrimethoprim -enzyme dihydrofolic acid ReductaseTHFA is not produced by the bacteria. Sulfonamides, trimethoprim (alone/ combination) block folic acid -synthesis of adenine and thymidine -DNA, RNA. The combination SXT is synergistic bactericidal effect
  • Parkland's burn formula is most useful during the first twenty four hours of fluid resuscitation with second degree or greater burns. Ringers lactate is the fluid of choice and should be administered at 4 mL/kg of body weight per percentage of burn using total body surface area (TBSA) as a guide
  • A basic problem in diagnosing antibiotic allergy by immunological methods is the fact that most antibiotics are not complete antigens but rather haptenic metabolites of the parent drug coupled with a carrier tissue protein. With the exception of penicillin, immunoreactive drug metabolites have rarely been identified.The role of allergy testing is limited largely to immediate (IgE-mediated) hypersensitivity. The only validated skin testing approach involves the use of penicillin major and minor determinants (where available) in penicillin allergy. It is important to note that negative reactions may be seen if performed several months or years after the event. 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.Skin testing should only be performed by specialists due to the risk of anaphylaxis. Most nonpruriticmaculopapular rashes will not be predicted by skin testing.Blood allergy testing (ImmunoCAP) is available for penicillin G, penicillin V, amoxicillin and Cefaclor through commercial laboratories and is most accurate when measured close to the time of the event. Tryptase elevation on a sample collected within 1–4 hours after a reaction is consistent with mast cell degranulation. A blood count (looking for eosinophilia) and biochemistry (looking for raised liver enzymes) may also indicate that a reaction is related to drug administration. Eosinophilia and/or abnormal liver function tests are often due to T-cell/non-IgE-mediated reactions rather than IgE-mediated reactions.It is important to note that results of allergy testing may become negative with time from the event, and that testing may be negative even in patients who have current allergy. Thus a negative test in the presence of a convincing history does not guarantee safe administration.For IgE-mediated antibiotic allergy, antimicrobial introduction can be judiciously employed where skin and intradermal tests are negative, or in circumstances where history suggests a low risk and alternative drugs are clearly inferior. This should only be done under medical supervision, after consultation with a clinical immunology/allergy specialist. In these cases, the degree of suspicion surrounding possible life-threatening reactivity will dictate whether a desensitisation protocol (see Appendix 1) is preferable to oral challenge.
  • Components of the Penicillin Allergy TestPenicillin allergy testing involves the use of various skin testing techniques, including prick skin testingand intradermal skin testing, to penicillin and penicillin metabolites. Most allergy physicians perform skin testing with penicillin G (an injectable form of penicillin that is in liquid form), Pre-Pen (benzylpenicilloylpolylysine) - the major metabolite of penicillin after the body breaks down the drug, and a minor determinant mixture (MDM) containing other "minor" metabolites.MDM is not available commercially available at this time, although some allergists -- such as those working in university settings -- will make a "homemade" version. Penicillin testing that includes the use of MDM adds to the accuracy of the testing.Generally, prick skin testing is performed first, which is able to identify the most sensitive penicillin-allergic people. If prick skin testing is positive, then the person is considered to be allergic to penicillin, and no additional testing is done. If prick testing is negative, then intradermal skin testing is performed with the same materials. Intradermal skin testing identifies many more people with penicillin allergy, but is potentially dangerous in the most sensitive people. This is the reason why prick skin testing is performed first
  • NON OPIOID ANALGESICS
  • Vane and coworkers in 971, prostacyclin, thromboxane a2 cox 2 constitutional??? Macrophages MORE RECENTLY, IT HAS BEEN SHOWN TO BE UPREGULATED IN VARIOUS CARCINOMAS AND TO HAVE A CENTRAL ROLE IN TUMORIGENESIS.
  • Weaker analgesics except for inflammatory pain; but also on CNS to raise pain threshold.
  • 1899, 1949,1963, heralded recognised for cyclooxygenase inhibition ,most are organic acid
  • In England 18th century- Reverend Freudman first described in a letter to the president of the Royal Society -cure of agues(Fever) The active ingredient in the willow bark was a bitter glycoside called Salicin, 1st isolated in a pure from in 1829 by Leroux, -antipyretic effect. Sodium salicylate was 1st used for the treatment of rheumatic fever and as an antipyretic in 1875 and discovery of its uricosuric effects and of its utility in the gout soon followed. Hoffman a chemist to prepare acetyl salicylic acid. 1899 introuduced by Dreses under the name aspirin.
  • Obtundin of peripheral ner, Prevention of sensitization of neve; subcortcal effect to inc pain thresh; sweatin n vasodil; hyperglycaemia at toxic doses;in large chronic doses- cholesterol levels reduced; negative nitrogen balace
  • Salicylic acid 3-5hours
  • Dizzziness vertigo tinitusexcitement n mental confusio n, electrolyte imbalance; hepqtic encephalopathy in children
  • Pediatric formulations banned in india
  • Miosis, bradycardia, vasodilatation decrese tone of blood vessels, hypothalanmic control on pit, constipation, contraction, sympathetic stimulation mild hyperglycaemia
  • Respiratory support, maintenance of bp, gastric lavage pot perm naloxone 0.4 to 0.8 mg till bp picks upevery2 tp 3mins
  • Good activity by oral route
  • Analgesic monotherapy has shown equivocal success in treating dental pain.Primary goal is to lower doses of component drugs,thereby increasing analgesia without increasing the side effects.
  • INTRALIGAMENTARY, INTRAOSSEOUS METHYLPREDNISALONE (STABIDENT SYSTEM, X-TIP)
  • Journal of the American Dental Association (JADA). Feb2014, Vol. 145 Issue 2, p141-149.
  • One must remember that analgesics are a second best means of managing pain;the best means is to remove the source as quickly as possible. We have numerous analgesics at our disposal. Our goal should be to periodically assess patient’s pain & intervene as needed to adjust medications to balance analgesic efficacy against adverse effects. Rational prescribing will result in good pain management with minimal side effects.Antibiotics are basically given as an adjunct as not as the main cause of the treatment, undesirable use of antibiotics leads to its resistance and toxicity, so as dentist we should wisely prescribe antbiotics and analgesics as an adjunct and not as the sole treatment.
  • Antibiotics & analgesics dentistry

    1. 1. ANTIBIOTICS & ANALGESICS By R.Hemalatha 1st year Department of Pedodontics and Preventive Dentistry
    2. 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
    3. 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
    4. 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
    5. 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
    6. 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.
    7. 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
    8. 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
    9. 9. MECHANISM OFACTION Tetracyclins chloramphinicol aminoglycosides clindamycin Penicillins cephalosporins polymyxin bacitracin polyenes Intracellular Extracellular
    10. 10. 1. Inhibitors of Cell Wall synthesis Beta-lactams •Penicillins •Cephalosporins •Monobactams •Carbapenems Glycopeptides Fosfomycins
    11. 11. •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
    12. 12. 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
    13. 13. ON DURATION OF ACTION • 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. Pencillin spectrum of activity
    14. 14. 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
    15. 15. 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
    16. 16. 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.Amoxacillin spectrum of activity
    17. 17. 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.
    18. 18. 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.
    19. 19. Cephalosporins 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
    20. 20. 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.
    21. 21. Cefuroxim axetil- orally effective. Cefotaxime- 3rd 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 .
    22. 22. 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
    23. 23. 2. Inhibitors of Protein Synthesis •Aminoglycosides •MLSK (Macrolides, Lincosamides, Streptogramins, Ketolides) •Tetracyclines •Glycylcyclines •Phenicols •Oxazolidinones •Ansamycins
    24. 24. 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 •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 AMINOGLYCOSIDES
    25. 25. Broad spectrum antibiotics- Tetracycline 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(CH3)2
    26. 26. 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
    27. 27. •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 )
    28. 28. • 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] )
    29. 29. 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
    30. 30. CHLORAMPHENICOL 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
    31. 31. 3. Inhibitors of Membrane Functions •Polymixins •Cyclic lipopeptides
    32. 32. Uses •Gram-negative UTI, blood, CSF and eye infections. •used in combination against very resistant Pseudomonas, KPC. • High toxicity – neurotoxic and nephrotoxic •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) Lipopeptides: Polymyxins Polymyxin B
    33. 33. 4. Anti - Metabolites •Sulphonomaides •Trimethoprim
    34. 34. 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/Sulfamethoxazole:
    35. 35. 5. Inhibitors of Nucleic Acid Synthesis •Quinolines •Furanes
    36. 36. • Small and hydrophilic • easily diffuse n reach Target = Topoisomerases • Rapid bactericidal activity • 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 Quinolones
    37. 37. 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
    38. 38. Chloramphinic ol [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.
    39. 39. 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
    40. 40. 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
    41. 41. Anti-fungal antibiotics • A. polyenes- • Amphotricine B, nystatin, hamycin,natamycin • B. heyerocyclic benzofuran- • Griseofulvin
    42. 42. • 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. British journal of surgery 1980, vol 67
    43. 43. 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.
    44. 44. • 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
    45. 45. Metronidazole • 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. 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 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
    46. 46. 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
    47. 47. Quantitative Measure • MBC = lowest concentration of antibiotic that kills bacteria MBC – Minimum Bacterial Concentration
    48. 48. 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
    49. 49. ➢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
    50. 50. 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
    51. 51. BACTERICIDAL RATHER THAN A BACTERIOSTATIC DRUG •Bactericidal - immunocompromosed conditions. •Bacteriostatic- less chance of superinfection USE OF SPECIFIC, NARROW-SPECTRUM ANTIBIOTIC ➢Decreases resistance, decreases superinfections
    52. 52. 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
    53. 53. Pediatric dose = Child's BSA in M2 1.73M2 x Adult Dosage Pediatric = dose child's age in months 150 x Adult DoseFried'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
    54. 54. MAXIMUM DOSAGE FOR LIFE-THREATENING INFECTIONS 62 gVancomycin 83-6 mg/kgTobramycin 62 gTetracycline 410-12 x 106 UPenicillin G 4-68-12 gOxacillin 821 mg/kgMetronidazole 62-4 gErythromycin 83-6 mg/kgGentamicin 62-5 gClindamycin 650 mg/kgChloramphenicol 48-12 gCephalothin 46-12 gCefoxitin 64-8 gCefazolin 46-12 gCefamandole 424-40 gCarbenicillin 412 g/dayAmpicillin 815-25 mg/kgAmikacin " Dosage interval (hr)Total daily dosageAntibiotic
    55. 55. 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
    56. 56. TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill / injure human cells Penicillin Amphotericin B Cephaloridine Aminoglycosides Renal urinary system Erythromycin Pseudomembranous colitis DiarrheaClindamycin HepatitisTetracycline Gastrointestinal system VertigoVancomycin Myoclonic seizuresPenicillin and cephalosporin VertigoGentamicin DeafnessTobramycin Nervous system Carbenicillin (and ticarcillin) Aplastic anemia,LeukoplakiaChloramphenicol Hematologic " PROBLEM" ANTIBIOTIC tubular necrosis Decreased platelet aggregation
    57. 57. 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
    58. 58. 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
    59. 59. 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
    60. 60. Drugs to avoided in liver disorders- • Erythromycin estolate • Tetracyclin • Taiampicillin • Dose reduction- • Chloramphinicol • Metronidazole • Clindamycin
    61. 61. PREGNANCY AND ANTIBIOTICS Safe antibiotics penicillins cephalosporins erythromycin Drugs contraindicated in children-  Chloramphinicol  Tetracycline
    62. 62. 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
    63. 63. 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
    64. 64. 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.
    65. 65. • Initial stage- Aerobic bacteria invade •Severe infection- Aerobic and anaerobic bacteria invade Abscess •Advanced stage- anaerobic infection Odontogenic infection, oral and maxillofacial implications
    66. 66. 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
    67. 67. 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,
    68. 68. •Identify the causative organisms •antibiotics for a much longer period -soft tissue infections •Jaws that require special therapy •Actinomycosis ,Fungal infections Antibiotic regimen for osteomyelitis 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.
    69. 69. Regimen for fracture • 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]
    70. 70. 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.
    71. 71. •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
    72. 72. 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 difficulties 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
    73. 73. 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
    74. 74. 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
    75. 75. 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
    76. 76. 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-
    77. 77. Antibiotic Resistence Antibiotics in dentistry--a boon or bane? APUA Newsletter 15(1):1-5. Walton RE, Zerr M, 1997. 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.
    78. 78. 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) http://articles.mercola.com/sites/articles/archive/2011/03/11/consequence-of-antibiotics- overuse.aspx
    79. 79. ANTIBIOTIC ALLERGY TESTS •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. ASCIA HPIP Antibiotic allergy 2014,351.38 KB
    80. 80. Principle of skin testing •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 Penicillin skin testing , Solensky, Franklin Adkinson Jr, UpToDate, Feb 2014
    81. 81. •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) ASCIA HPIP Antibiotic allergy 2014,351.38 KB
    82. 82. Cross-reactivity •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. ASCIA HPIP Antibiotic allergy 2014,351.38 KB
    83. 83. 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- Same as above
    84. 84. Triple Antibiotic Paste • 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 J Phrm Bioallied Science Aug 2012,4(suppl2) S230-233
    85. 85. ANALGESICS
    86. 86. DENTAL PAIN 89
    87. 87. During InterventionPreoperative Pain Post-Operative PAIN CONTROL STRATEGY 90  Oral Sedation  Preoperative Analgesics • IV Sedation • Nitrous Oxide • Local Anesthesia • Analgesic Prescription • Opioids • Non-opioids
    88. 88. 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. 91
    89. 89. CLASSIFICATION 92 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
    90. 90. The major analgesic drug class for treating endodontic pain 93
    91. 91. NSAIDS
    92. 92. Beneficiary actions due to PG synthesis inhibition • Analgesia. • Antipyresis. • Antiinflammatory. • Antithrombotic. 95
    93. 93. Toxicities due to PG synthesis inhibition • 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.
    94. 94. NSAIDS • 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.
    95. 95. 98
    96. 96. 99 NonselectiveCOX inhibitors (traditionalNSAIDs) 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
    97. 97. 100 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
    98. 98. SALICYLATES: History • In England 18th century- Reverend Freudman first - cure of agues(Fever) • willow bark was a bitter glycoside -Salicin, 1st isolated in 1829 by Leroux, -antipyretic effect. • Sodium salicylate was 1st 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
    99. 99. ASPIRIN • 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.
    100. 100. 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.
    101. 101. Pharmacokinetics • 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.
    102. 102. Therapeutic Uses • Analgesic, Antipyretic, Anti inflammatory. • Acute rheumatic fever. • Rheumatoid arthritis. • Osteoarthritis. • Postmyocardial infarction and post stroke patients.
    103. 103. Adverse effects • 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.
    104. 104. 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.
    105. 105. • 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
    106. 106. METAMIZOL • Potent and promptly acting analgesic and antipyretic. • Few cases of agranulocytosis reported. PROPIPHENAZONE • Similar to metamizol.
    107. 107. INDOLE DERIVATIVES (Indomethacin, Sulindac ) • 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.
    108. 108. 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:
    109. 109. Sulindac • A prodrug that converts into an active sulfide metabolite. • Antiinflammatory action < Indomethacin. • At lower doses, selectively inhibit extrarenal prostaglandin synthesis. 112
    110. 110. Propionic acid derivatives Ibuprofen • 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. Hargreaves K,Abott PV; Aust Dent J 2005
    111. 111. Pharmacokinetics • Orally. • 90% plasma protein bound. • Enter brain, synovial fluid, placenta. • Liver – hydroxylation, glucoronide conjugation. • Excreted in urine.
    112. 112. 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.
    113. 113. Drug MOA Route Bioav ailabit y T ½ Uses AE Mephnemic Acid Anthranilic acid derivative Non selecti ve COX inhibito rs Peripheral as well as central analgesic action Oral 2-4 hou rs muscle pain, soft tissue pain , joint pain Diarrhoea. Diclofenac sodium- Aryl acetic acid derivatiove (extensively used) Non selecti ve 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 ) Revers ible inhibito r of cycloo xygena se Metabolized in liver by hydroxylatio n and glucuronide conjugation. Excreted in urine and Oral 20mg OD 99% 2 day s inhibits platelet aggregation -prolonging BT. Dec. IgM rheumatoid
    114. 114. Drug MOA Route Bioav ailabit y T ½ Uses AE Ketorolac pyrrolopyrrol e derivative Non selecti ve COX inhibito rs EFFICIECN CY EQUA TO MORPHINE Oral and i.m. Oral 10-20 mg 6hrly. (5days) 60% 5-7 hou rs dental & acute musculo- skeletal pain (equals morphine) free of respiratory depression hypotensive constipation Nimesulide ( week inhibitor) Prefen tial cox 2 inhibito r 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 . . Selecti ve COX-2 inhibito Slowly absorbed orally 87- 97%p pb 11h rs RA,OA, musculo skeletal pain. abdominal pain, dyspepsia, diarrhoea.
    115. 115. PARA-AMINO PHENOL DERIVATIVES (Paracetamol ) • 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
    116. 116. Pharmacokinetics • 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.
    117. 117. 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.
    118. 118. 122 J Can Dent Assoc 2002
    119. 119. 123 Haas DA.J Can Dent Assoc 2002
    120. 120. 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. 124
    121. 121. Opioids When additional pain control is needed
    122. 122. History of Opioids • Mentioned in EBER’S papyrus 1500BC. • THEOPHRATUS writings 300BC. • GALEN 2nd century AD. • Pharmacist – SERTURNER 1806 isolated active component “morphine” from opium; named after Greek god of dreams MORPHEUS.
    123. 123. CLASSIFICATION • NATURAL Morphine codeine SEMI SYNTHETIC Di acetyl morphine pholcodeine SYNTHETIC Pethidine Fentanyl Methadone Detropropoxyphene Tramadol
    124. 124. Mechanism Of Action 128
    125. 125. Morphine (Prototype) 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.
    126. 126. • 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. 130
    127. 127. 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.
    128. 128. 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.
    129. 129. •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(tre mors, 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.
    130. 130. 134 Haas DA.J Can Dent Assoc 2002
    131. 131. COMBINATION ANALGESIA 135 • 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)
    132. 132. OTHER DRUGS WITH ANALGESIC EFFECT 136
    133. 133. The potent antiinflammatory properties of glucocorticoids were first appreciated & utilized as an adjunct to endodontic therapy more than 50years ago. Used as an intracanal medicament & systemically as a means to decrease pain & inflammation in endodontic patients. 137 Ingle’s endodontics 6th Ed. GLUCOCORTICOIDS
    134. 134. Intracanal administration 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.
    135. 135. Systemic administration 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).
    136. 136. STRATEGY TO CONTROL DENTAL PAIN 140
    137. 137. • 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. 141 Cohen, 10th Ed.
    138. 138. 142 Cohen,10th Ed.
    139. 139. 143 Haas DA.J Can Dent Assoc 2002
    140. 140. 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 Vicodin ,Lortab Demerol,Weine,6th Ed.
    141. 141. Review of Literature
    142. 142. 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
    143. 143. 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.
    144. 144. • 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.
    145. 145. • 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.
    146. 146. •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 Prescription Writing http://www.sh.lsuhsc.edu/fammed/outpatientmanual/prescripwriting-pdr.htm
    147. 147. •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”
    148. 148. •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
    149. 149. 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
    150. 150. 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
    151. 151. CONCLUSION
    152. 152. REFERENCES • The pharmacologic basis of therapeutics 10thEd Goodman & Gilman • Essentials of Medical Pharmacology 5th 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 6th Ed Franklin S.Weine • Pathways of Pulp 10th Ed Stephen Cohen • Endodontics 6th Ed. Ingle
    153. 153. • 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:E10-8 157

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