ANTIBIOTICS INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com
Dr AMIT BYATNAL
CONTENTS •Introduction •History of Antibiotics •Classification of antimicrobial drugs •Problems with AMA •Choice of AMA •Principles of administration •Indications for antimicrobial agents used in dentistry
Beta lactam antibiotics Quinolones Tetracyclines Macrolides Nitroimidazoles Antifungal drugs Anti viral drugs Maxillofacial infections Conclusion References
INTRODUCTION ď Ź
Antimicrobial agents: Substances that will suppress the growth/ multiplication of bacteria and prevent their action.
Antibiotic agents: Chemical substances produced by microorganisms that have the capacity, in dilute solutions, to produce antimicrobial action.
HISTORYOF ANTIBIOTICS 1877 Louis Pasteur Inhibition of some microbes by others; anthrax (Bacillus anthracis)
1908 Gelmo Synthesized sulfanilamide (1st sulfonamide www.indiandentalacademy.com
1928 Fleming… Penicillin notatum inhibits growth ‘PENICILLINS’
1941 Chain n Florey Discovered properties of penicillin
1932 Domagk Prontosil Therapeutic value sulfonamides
1943, Selman Waksman isolated, Streptomyces griseus â€ŚStreptomycin www.indiandentalacademy.com
Classification A) Chemical structure Sulfonamides and related drugs
Sulfadiazine and others Sulfones – Dapsone (DDS), Paraaminosalicylic acid (PAS).
Nalidixic acid Norfloxacin Ciprofloxacin etc
Penicillins Cephalosporins Monobactams Carbapenems Oxytetracycline Doxycycline etc
Streptomycin Gentamicin Neomycin etc
Erythromycin Roxithromycin Azithromycin etc
Polymyxin-B Colistin Bacitracin Tyrothricin
Nicotinic acid derivatives
Isoniazid Pyrazinamide Ethionamide
Nystatin Amphotericin-B Hamycin
Miconazole Clotrimazole Ketoconazole Fluconazole
Rifampin Lincomycin Clindamycin Spectinomycin Sod. fusidate Cycloserine Viomycin Ethambutol Thiacetazone Clofazimine Griseofulvin
B) Type of organisms against which primarily active Antibacterial
Penicillins Aminoglycosides Erythromycin etc
Griseofulvin Amphotericin B Ketoconazole
Idoxuridine Acyclovir Amantadine Zidovudine etc
Chloroquine Pyrimethamine Metronidazole Diloxanide etc
Mebendazole Pyrantel Niclosamide Diethyl carbamazine etc
Aminoglycosides Bacitracin Cephalosporins Metronidiazole Vancomycin Penicillins Ciprofloxacin Streptomycin Cotrimoxazole
Chloramphenicol Clindamycin Erythromycin Sulfonamides Tetracycline Trimethoprim
Spectrum of activity Narrow spectrum Broad spectrum
Mechanism of action
Problems with use of AMA Toxicity -Local irritancy: -Systemic toxicity: -Therapeutic index- high, low, very low Hypersensitivity reactions : Drug resistance - Natural- lack of metabolic process or target site - Acquired – due to use over a period of time, mutations or gene transfer
Preventing Resistance to Drugs
Limit the use of antimicrobial agents to the treatment of specific pathogens sensitive to the drug being used
Notorious-Make sure doses are high enough, and the duration of drug therapy long enough , combination therapy
Be cautious about the indiscriminate, inadequate or unduly prolonged use of anti-infectives
Superinfection Nutritional deficiencies Masking of an infection
Choice of AMA agent- patient factors 1.Age : affect kinetics of drug.
Conjugation and excretion of chloremphenicol- gray baby syndrome Sulfonamides displace bilirubin from PBS- kernicterus Tetracycline accumulates in bone and teeth
2. Renal and hepatic failure: cautious use and dose reduction 3. Local factors: presence of pus and secretions- AMAs, surgical drainage reduces causative bacteria and suppresses anaerobic bacteria Presence of necrotic material and infection Hematomas – foster growth www.indiandentalacademy.com
4.Drug allergy 5.Impaired host defense 6.Pregnancy 7.Genetic factors
ď Ź ď Ź
Organism related considerations Drug factors 1. 2. 3. 4. 5. 6. 7. 8.
Spectrum of activity Type of activity Sensitivity of the organism Relative toxicity Pharmacokinetic profile Route of administation Evidence of clinical efficacy Cost www.indiandentalacademy.com
Microorganisms isolated from pulpal/periapical infections
Gram +ve cocci Staphylococci
Gram +ve Baccili Lactobaccili Corynebacterium Eikenella
Gram +ve cocci Peptostreptococcus
Gram –ve cocci Veillonella
Gram +ve baccilli Actinomyces Eubacterium Clostridia Propionibacterium
Gram -ve baccilli Bacteriodes Fusobacteria Porphyromonas Prevotella
denticola Treponema macrodentium Treponema oralis Treponema vincenti www.indiandentalacademy.com
PRINCIPLES OF ANTIBIOTIC THERAPY
PRINCIPLE 1: TO DETERMINE THE SEVERITY OF INFECTION PRINCIPLE 2: TO EVALUATE STATE OF PATIENT’S HOST DEFENSE MECHANISMS PRINCIPLE 3: TO TREAT INFECTION SURGICALLY PRINCIPLE 4: TO SUPPORT THE PATIENT MEDICALLY PRINCIPLE 5: CHOOSE AND PRESCRIBE APPROPRIATE ANTIBIOTIC PRINCIPLE 6: PROPER ANTIBIOTIC ADMINISTRATION www.indiandentalacademy.com
PRINCIPLES OF ANTIBIOTIC ADMINISTRATION 1. Proper dose : DRUG DOSAGE ‘Dose’ is the appropriate amount of a drug needed to produce a certain degree of response in a patient. Body size : Individual dose = BW(kg)/70 x average adult dose
Individual dose = BSA(m2
) /1.7x average adult dose
Age : The dose of drug for children is often calculated from the adults dose Young’s formula Child dose =
Age x adult dose Age +12
Dilling’s formula Child dose =
Age 20 x adult dose
Clarke’s rule Child dose =
wt in lb x adult dose 150 www.indiandentalacademy.com
NEONATES AND INFANTS Greater percentage of body weight compared with body water Greater volume of distribution Increased serum half lives Reduced gastric emptying Reduced plasma protein binding Reduced GFR
2) Proper time interval : 3) Proper route of administration :
Parenteral administration will produce the necessary serum level of antibiotics. Oral route results in the most variable absorption. For maximum absorption is taken in fasting stage.
4) Consistency in regard to route of administration :
When treating a serious, established infections, parenteral antibiotic therapy is frequently the method of choice.
Combination antibiotic therapy : The rationale for the use of 2 or more drugs together is to minimize the emergence of antibiotic resistant microorganisms to increase the certainty of a successful clinical outcome to treat mixed bacterial infections to prevent superinfection to treat severe infections of unknown etiology to decrease toxicity without decreasing efficacy
Isoniazid + ethambutol + streptomycin in treatment of tuberculosis. Rules : 2 bactericidal drugs produce, supraadditive effects, not antagonism. (1+1>2) The combination of a bacteriostatic and a bactericidal drug generally results in diminished effects. (1+1<2) 2 bacteriostatic drugs are never inhibitory. (1+1=2)
Results : ď Ź Indifference when the effect is equal to the single most active drug or equal to the arithmetic sum of the two, use is not justified. ď Ź Antagonism : when the combined drug effect is less than the algebraic sum of the effects on the individual drugs in the mixture. ď Ź Synergism : ability of two antibiotics acting together to markedly increases the rate of bactericidal action compared to either drug alone.
Adds nothing to therapeutic efficacy and may even reduce it (antagonism). Increase antibiotic toxicity and allergy. Increase the likelihood of superinfection Discourages specific etiologic diagnosis and promote false security. Encourage inadequate doses, particularly with fixed dose combination therapy. Increased cost Emergence of resistant bacterial strains Increase the environmental spread of antibiotic resistant bacteria.
FACTORS INFLUENCING ANTIBIOTIC THERAPY
Minimal Inhibitory Concentration Concentration-dependent Vs Timedependent antibiotics Post-antibiotic effects
MINIMAL INHIBITORY CONCENTRATION
Is the lowest antibiotic concentration that prevents growth of microorganism after an incubation period of 18 – 24 hours with a standard inoculum of 104 to 105 cu/ml
MINIMAL BACTERICIDAL CONCENTRATION Is the lowest concentration of drug that causes the complete destruction of the organisms or permits survival of less than 0.1% of the inoculum
RULE OF THUMB ď Ź
The concentration of the antibiotic in the blood should exceed the MIC by a factor of 2-8 times to offset the tissue barriers that restrict access to the infected site
CONCENTRATION DEPENDENT Vs TIME DEPENDENT ANTIBIOTICS
Aminoglycosides, metronidazole, fluoroquinolones Concentration dependent Bactericidal activity depends on the drug concentration www.indiandentalacademy.com
Beta-lactams and vancomycin Long time of exposure of the organisms Better the bactericidal activity
POSTANTIBIOTIC EFFECTS ď Ź
Is the persistent supression of microbial growth after short time exposure to an antimicrobial agent.
MECHANISM : Is the time necessary to recover from sublethal structural and metabolic alterations that prevents resumption of bacterial regrowth. www.indiandentalacademy.com
Indications for antimicrobial agents in dentistry Therapeutic indications Prophylactic indications
Dental procedure for which antibiotic prophylaxis is recommended to prevent infective endocardititis (AHA recommendation) Dental extractions Periodontal procedures Replantation procedure Implant placement Initial placement of orthodontic bands Intra ligamentary local anesthetic injection Incision and drainage Not recommended : 1.Restorative dentistry 2.LA injections 3.Intracanal endodontic treatment 4.Post-op suture removal 5.Oral radiographs www.indiandentalacademy.com
American Heart Association guidelines for antibiotic prophylaxis Standard general prophylaxis
Adults: 2 g Children: 50 mg per kg Taken orally one hour before the procedure
Patient is unable to take oral medications
Adults: 2 g Children: 50 mg per kg Given IM or IV within 30 minutes before the procedure
Patient is allergic to penicillin
Adults: 600 mg Children: 20 mg per kg Taken orally one hour before the procedure
or Azithromycin or clarithromycin
Patient is allergic to penicillin and is unable to take oral medication
Adults: 500 mg Children: 15 mg per kg Taken orally one hour before the procedure
Adults: 600 mg Children: 20 mg per kg Given IV or IM within 30 minutes before the procedure
BETA LACTAM ANTIBIOTICS CLASSIFICATION OF PENICILLIN I) Natural penicillins : Penicillin G (Benzyl penicillin) II) Acid resistant penicillins : Phenoxymethyl penicillin (penicillin V) III) Penicillinase â€“ resistant penicillins : Acid labile : Methicillin, naficillin, cloxacillin, dicloxacillin IV) Extended spectrum penicillins : Carboxypenicillins : Carbenicillin, ticarcillin Aminopenicillins : Ampicillin, amoxicillin Ureidopenicillins www.indiandentalacademy.com
BENZYL PENICILLIN (PENCILLIN G) Antibacterial activity
Inhibits the growth of susceptible organism. Mainly gram +ve, gram –ve cocci and some gram +ve bacilli with exception of enterococci. Cocci – Highly sensitive – Streptococci, Pneumococci, Staph. aureus, N. gonorrhoeae, N. meningitis Bacilli – B. anthracis, Corynebacterium diphtheriae, clostridium tetany and spirochetes Actinomyces israelii is moderately sensitive
Preparation and dose : PnG inj 0.5-5 MU i.m or i.v 6-12 hours Procaine pencillin inj 0.5, 1 MU dry powder in vial
ADVERSE REACTIONS : Miscellaneous reactions : Nausea and vomiting on oral PnG Sterile inflammatory reaction at the site of IM inj. Prolonged IV administration may cause thrombophlebitis Accidental IV administration of procaine PP cause anxiety, mental disturbances paraesthesia and convulsions
Major problem with PnG includes idiosyncratic, anaphylactic and allergic reactions
Other allergic reactions are
Skin rashes Serum sickness Renal disturbance Hemolytic disturbance Anaphylaxis Jarisch herxheimer reaction Super infection Hyperkalemia
Uses : PnG is the drug of choice for infections
Streptococcal infections Pneumococcal infections Meningococcal infections Gonorrhoea Syphilis Diphtheria Tetanus and gas gangrene Prophylactic uses
The major drawbacks of benzyl penicillin are
Inactivation by the gastric hydrochloric acid Short duration of action Poor penetration into CSF Activity mainly against gram +ve organism Possibility of anaphylaxis
Acid resistant pencillins : ď Ź 1. Potassium phenoxymethyl penicillin (penicillin V) Dose : infants 60 mg, children 125-250 mg given 6 hourly CRYSTAPEN-V, KAYPEN, PENIVORAL 65, 130, 125, 250 mg tablets 125 mg/5 ml dry ser
II) Pencillinase resistant pencillins : Methicillin
Effective in staphylococci It is given IM or IV (slow) in the dose of 1 gm every 4-6 hours. Haematuria, albuminuria and reversible interstitial nephritis are the special adverse effect of methicillin.
Weaker antibacterial activity. Distrubuted throught out the body, but highest concentration in kidney and liver. 30% excreted in urine. Oral dose for adults 2-4 gm divided into 4 portions children 50100mg/kg/day. IM adults 2-12 gm/day, children 100-300 mg/kg/day every 4-6 hours. BIOCLOX, KLOX, CLOCILIN 0.25, 0.5 gm cap, 0.5 gm/vial.
III) Extended spectrum pencillins : Amino pencillins Ampicillin – Antibacterial activity is similar to that of PnG that is more effective than PnG against a variety of gram-ve bacteria Drug is effective against H.influenzae strep.viridans, N.gonorrhea, Salmonella, shigellae, Klebsilla and enterococci. Absorption, fate and excretion : Oral absorption is incomplete but adequate Food interferes with absorption Partly excreted in bile and partly by kidney
Dose : 0.5-2 gm oral/IM or IV depending on severity of infection every 6 hours Children : 25-50 mg/kg/day AMPILIN, ROSCILLIAN, BIOCILIN – 250, 500 mg cap 100mg/ml ped drops, 250 mg/ml dry syr, 1 gm/vial inj. USES :
Urinary tract infections Respiratory tract infections Meningitis Gonorrhoea Bacillary dysentry Septicaemias SABE
Adverse effects :
Diarrhoea is frequent
Skin rashes is more common Unabsorbed drug irritates lower intestines Patient with history of hypersensitivity to PnG should not be given ampicillin.
This is a semisynthetic penicillin. (amino-p-hydroxy-benzylpenicillin) Antibacterial spectrum is similar to ampicillin. Oral absorption is better; food does not interfere; higher and more sustained blood levels are produced. It is less protein bond and urinary excretion is higher than that of ampicillin. Incidence of diarrhoea is less
Dose : 0.25-1 g TDS oral; AMOXYLIN, NOVAMOX, SYNAMOX, MOX, AMOXIL 250, 500 mg cap, 125 mg/5ml dry syr, 500 mg/vial inj. USES :
Oro-dental infections Upper RTI Bronchitis Urinary infection SBE Gonorrhoea
BETA LACTAMASE INHIBITORS CLAVULANIC ACID Obtained from STREPTOMYCES CLAVULIGERUS Betalactam ring – no antibacterial activity Suicide inhibitor –inactivated after binding to enzyme Permeates the outer layers of cell wall of gram-ve bacteria Pharmacokinetics : Oral absorption- rapid Bioavailability-60% Distribution similar that of amoxicillin Excretion-tubular secretion Used as : Amoxicillin+clavulanic acid (AUGMENTIN,ENHANCIN) Ticarcillin+clavulanic acid (TIMENTIN)
Adverse effects :
Pain-thrombophebitis Rashes and diarrhoea Mixed aerobic-anaerobic infections Dental infections caused by beta lactamase producing bacteria Gonorrhoea Skin/soft tissue infections
CEPHALOSPORINS Cephalosporium acremonium was the first source. They contain 7 amino cephalosporonic acid nucleus. Structurally they contain betalactam and dihydro thiazine rings. Mechanism of action : Act by inhibiting bacterial cell was synthesis and are bactericidal.
Classification Classified according to its antibacterial activity. First generation cephalosporin Good activity against gram +ve bacteria. (except enterococci). Most oral cavity anaerobes are sensitive. Parental Oral CEPHALOTHIN CEPHALEXIN CEFAZOLIN CEPHRADINE CEFADROXIL
Cephalaxin and Cephadroxil : Useful in treating community acquired, respiratory and urinary tract infections and in surgical prophylaxis. Infections of head and neck region. Dose: Oral 0.25 - 1g 6-8 hrly Children : 25-100mg/kg/day IM – 0.25g 8 hrly (mild cases) 1g 6 hrly (severe cases). Drops – cephaxin 125mg/5ml syrup. 100mg /ml ped. drops. SPORIDEX, CEPHAXIN, CEPHACILLIN, CEFADROX, DROXYL
Second generation cephalosporins : Increased activity against gram –ve organism. More active against anaerobes. Parenteral Oral CEFUROXIME CEFACLOR CEFOXITIN CEFUROXIME AXETIL More active against H. influenzae, E coli. Dose : 250mg, 125mg, 125mg/5ml syr. and 50 mg /ml ped. drops. KEFLOR, CEFTUM, CEFOGEN, FUROXIL.
Third Generation Cephalosporins High activity against gram –ve entrobacteriaceae, some inhibit Pseudomonas as well. Parenteral Oral Cefataxime Cefixime Ceftizoxime Cefpodoxime proxetil Ceftriaxone Cefdinir Ceftazidime Ceftibuten Cefoperazone Dose: 250mg, 500mg, 1000mg per vial inj CLAFORAN, CEFIZOX,MONOCEF,CEFAZID.
Fourth Generation Cephalosporins Similar to 3rd generation ,but is highly resistant to betalactamases. Due to high potency and extended spectrum, it is effective in many serious infections like hospital acquired pneumonia, bacteremia, septicaemia. Parentral Cefepime Cefpirome Dose: 1-2 g i.m/i.v 12hrly CEFROM, CEFROTH, KEFAGE
Adverse reactions : Local reactions – cause pain (IM) and cause thrombophlebitis (IV) Allergy – skin rashes Nephrotoxicity Bleeding disorders Intolerance to alcohol
Uses : Alternatives to penicillins. RTI, UTI and soft tissue infection Penicillinase producing staph infection. Septicaemias. Surgical prophylaxis Meningitis, gonorrhoea Typhoid Mixed aerobic and anaerobic infections Infection by odd organism or hospital infections Prophylactic treatment in neutropenic patients.
Dental infections Alternative to pencillins- hypersensitivity and resistance Oral – 1st and 2nd generation
Short acting(4-8hr)- Sulfadiazine Intermediate acting (8-12hr)- Sulfamethoxazole, Sulfamoxole Long acting(7 days)- Sulfadoxine, Sulfamethopyrazine Special purpose Sulfonamides – Sulfacetamide sod, Sulfasalazine, Mafenide, Silver sulfadiazine
Mechanism of action ď Ź
In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase, DHPS. DHPS catalyses the conversion of PABA (para-aminobenzoate) to dihydropteroate, a key step in folate synthesis. Folate is necessary for the cell to synthesize nucleic acids (nucleic acids are essential building blocks of DNA and RNA), and in its absence cells will be unable to divide. Hence the sulfonamide antibacterials exhibit a bacteriostatic rather than bactericidal effect.
Sulfonamides have the potential to cause a variety of untoward reactions, including urinary tract disorders, haemopoietic disorders, porphyria and hypersensitivity reactions. When used in large dose, it may develop a strong allergic reaction. One of the most serious is Stevens Johnson syndrome(or toxic epidermal necrolysis).
Entirely synthetic antimicrobials are active primarily against gram –ve bacteria. Nalidixic acid- low potency, modest blood and tissue levels, limited spectrum, high resistance Fluoroquinolones – high potency, expanded spectrum, better tissue penetrance, slow resistance.
Mechanism Quinolones and fluoroquinolones are bactericidal drugs, actively killing bacteria. Quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription.
•cinoxacin •nalidixic acid •oxolinic acid
Second generation ciprofloxaci nadifloxacin norfloxacin ofloxacin rufloxacin
Third generation gatifloxacin levofloxacin sparfloxacin temafloxacin tosufloxacin 4th generation •clinafloxacin •garenoxacin •gemifloxacin •sitafloxacin •trovafloxacin
CIPROFLOXACIN First generation FQ active against a broad range of bacteria especially gram –ve aerobic bacilli. Microbiological features : Rapid bactericidal activity and high potency. Relatively long post antibiotic effect Low frequency of mutational resistance. Protective intestinal streptococci and anaerobes are spared. Less active at acidic pH.
Adverse effect :
GIT – Nausea, vomiting, bad taste, anorexia, diarrhoea is infrequent. CNS- Dizziness, headache, restlessness, anxiety, insomnia and seizures are rare. Skin/hypersensitivity – rashes, pruritis, urticaria. Tendonitis and tendon rupture
Broad range of infections Minor cases, orodental -not indicated UTI Bacterial gastroenteritis Prophylaxis -Typhoid Bone, soft tissue, wound infection. Combinations- gram –ve septicaemias Tuberculosis
CIFRAN, CIPLOX, CIPROBID, CIPROLET 250, 500,750 mg tab, 200mg/100 ml IV infusion 3mg/ml eye drops.
Norfloxacin - Less potent than Ciprofloxacin.
- Used for Pseudomonas, Urinary and genital tract infections. NORFLOX -200,400mg
- Activity against gram –ve bacteria - Chlamydia and Mycoplasma - Alternative drug for Tuberculosis - Used mainly for Gonorrhea ZANOCIN -200,400mg www.indiandentalacademy.com
Levofloxacin - Sinusitis, Pylonephritis, soft tissue infections.
Gatifloxacin - Excellent activity against Streptococci pneumoniae - Indicated in community acquired pneumonia, exacerbation of chronic bronchitis, and other respiratory tract infections. - Used in urinary tract infectons and gonorrhhoea. GATIQIN – 200,400 mg tab www.indiandentalacademy.com
-Enhanced activity against gram â€“ve bacteria, Bacteroides fragilis, anaerobes and mycobacteria. - Indicated in Pneumonias, chronic bronchitis, sinusitis and other ENT infections. - Good efficacy in Mycobacterium avium infection in AIDS patients and Leprosy. - Higher incidence of phototoxic reactions. SPARTA, SPARDAC -100,200 mg tab
METRONIDAZOLE : Introduced in 1959 Broad spectrum- e.histolytica, giardia lamblia Anaerobic infections- chance discovery Tinidazole, secnidazole, ornidazole, satranidazole Cidal activity against protozoa and anaerobic bacteria such as B fragilis, Fusobacterium, h.pyroli, spirochetes Metronidazole is selectively toxic to anaerobic microorganisms.
Pharmacokinetics : Completely absorbed from the small intestine. Widely distributed in the body It is metabolized in liver Excreted in urine. 8hr
Adverse effects :
Anorexia, nausea, metallic taste and abdominal cramps Looseness of stool is occasional, Headache, glossitis, dryness of mouth, dizziness, rashes and transient neutropenia. Prolonged administration may cause peripheral neuropathy and CNS effects Thrombophlebitis
Contraindications : In neurological disease, blood dyscrasias, chronic alcoholism First trimister of pregnancy
Ornidazole Activity similar to Metronidazole but it is slowly metabolised . ď Ź Used in anaerobic infections, Amoebiasis, Giardiasis, Trichomonasis, and bacterial vaginosis. DAZOLIC -500mg tab, 500mg/100ml vial for i.v. infusion. ď Ź
Uses- Orodental infections
MZ 200-400mg TDS(15-30mg/kg/day) – anaerobes not inhibited by pencillin ANUG- MZ+Amox - 5days Periodontitis, pericoronitis, acute apical infections, endodontic infections- 5-7 days Aerobic and facultative bacteriaMZ+pencillin/cephalosporin/macrolides FLAGYL, METROGYL, METRON, ALDEZOLE 200, 400 mg tab, 200 mg/5ml susp. www.indiandentalacademy.com
TINIDAZOLE It is an equally efficacious congener of metronidazole Metabolism is slower and duration of action is longer Incidence of side effects is lower-Metallic taste, nausea, rashes TINIBA, TRIDAZOLE, 300, 500, 1000 mg tab, 800 mg/400 ml iv Dental infections: 0.5g(10mg/kg) BD for 5 days 2g orally followed 0.5g BD for 5days 800mg iv until oral therapy
Napthacene derivatives made up by fusion of 4 partially unsaturated cyclohexane radicals Tetracyclines are bacteriostatic. Classification Antimicrobial activity :
Gram+ve and –ve cocci are sensitive-R Gram+ve bacilli are inhibited Entero bacteriaceae are highly resistant Spirochetes are quite sensitive All rickettsiae and chlamydiae are highly sensitive www.indiandentalacademy.com
Classification According to source: Naturally-occurring Tetracycline Chlortetracycline Oxytetracycline Demeclocycline Semi-synthetic Doxycycline Lymecycline Meclocycline Methacycline Minocycline
According to duration of action: Short-acting (Half-life is 6-8 hrs) Tetracycline Chlortetracycline Oxytetracycline Intermediate-acting (Half-life is ~12 hrs) Demeclocycline Methacycline Long-acting (Half-life is 16 hrs or more) Doxycycline Minocycline Tigecycline
Mechanism of action
Tetracycline antibiotics inhibit protein synthesis by inhibiting the binding of aminoacyl-tRNA to the mRNAribosome complex. They do so mainly by binding to the 30S ribosomal subunit in the mRNA translation complex.[
Tetracyclines are widely used in treatment of periodontal diseases. Used in the treatment of Localised aggressive periodontitis.
Adverse effects :
GIT-epigastric burning, nausea, vomiting, diarrhea Liver damage Renal failure Phototoxicity Effects on teeth & bones- Ca tetracycline chelate Hypersensitivity Reactions Superinfection; Antianabolic effect
DOSE Tetracycline – 1-2g per day in adults Children over 8yrs -25 to 50mg /kg daily in 2 to4 divided dose TERRAMYCIN,RESTECLIN250,500mgcap,50mg/ml in10ml vial inj Ledermycin 150,300mg cap/tab DOXT, NOVADOX, TETRADOX-100mg cap. Cyanomycin 50,100 mg cap
Not to be used in pregnancy, lactation and in children Avoided in patients on diuretics Used cautiously in renal and hepatic insufficiency Beyond expiry date should not be used Do not mix injectable Tc with Pn- inactivation occurs
Local Drug Delivery Systems One of the alternative delivery system used to control release of drugs.
Tetracycline fibres -An ethylene/ Vinyl acetate copolymers of fibres of 0.5mm diameter containing Tetracycline drug. (12.7mg per 9inch) -Packed in periodontal pocket for 10 days. -Required to inhibit the growth of pathogens isolated from periodontal pockets.
-FDA approved 10% of Doxycycline in gel system using a syringe Atridox. Reduction in oral microbes. No overgrowth of foreign pathogens.
-Sustained release form of Minocycline microspheres(Arestin) for subgingival placement as an adjuvant to scaling and root planing.
-2% Encapsulated into bioresorbable microspheres is used. www.indiandentalacademy.com
ORODENTAL CONDITIONS Limited use- acute dental infections Periodontal diseases – collagenase Refractory periodontal disease – 2week tetracycline(1g/day) or doxycycline(0.10.2g/day) Juvenile periodontitis – 2-4 week
AMINOGLYCOSIDES These include amikacin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, streptomycin, tobramycin, and apramycin.
Mechanism of action Aminoglycosides work by binding to the bacterial 30S ribosomal subunit (some work by binding to the 50S subunit), inhibiting the translocation of the peptidyl-tRNA from the A-site to the P-site and also causing misreading of mRNA, leaving the bacterium unable to synthesize proteins vital to its growth. They kill bacteria by inhibiting protein synthesis. www.indiandentalacademy.com
Streptomycin Uses •Tuberculosis in combination with other anti-TB drugs. It is not the first line treatment. •Plague has historically been treated with it as the first line treatment. •Infective endocarditis caused by enterococcus when the organism is not sensitive to Gentamicin
MACROLIDES Macrocyclic lactone ring with attached sugars ERYTHROMYCIN-Streptomyces erythreus Alternative to pencillin Water solubility is limited-stable in cold Antibacterial activity : static- cidal Narrow spectrum antibiotic against penicillin resistant staphylococci Active against more gram+ve Mechanism of action :
Adults 250 - 500mg 6hrly Children 30 – 60mg/kg/day Erythromycin (base) - ERYSAFE 250 mg tab Erythromycin stearate -ERYTHROCIN – 250,500mg tab 100mg/5ml susp;100mg/ml ped drops E estolate- ALTHROCIN 125mg kid tab E ethylsuccinate- ERYNATE
Adverse effects : GIT – epigastric pain On high doses – hearing impairment Hypersensitivity reactions – rare Uses : Substitute for penicillin, pencillin resistant infections Oral adm, safe and effective Perio/periapical/NUG/extraction Prophylactic use
ROXITHROMYCIN Semisynthetic - long acting, stable macrolide Antibacterial spectrum similar to erythromycin Dose - 150-300mg BD 30min before food Children - 2.5-5mg/kg BD ROXID, ROXIBID 150,300mg tab 50mg kid tab,150 mg tab
Clarithromycin – CLARIMAC 250,500mg tab www.indiandentalacademy.com
CLINDAMYCIN It is lincosamide antibiotic having similar action (macrolide 50s) Bacteriostatic – low conc;Bacteriocidal – high conc Most active against gram+ve cocci, C.diphtheriae, Actinomyces Highly active against – anaerobes (B fragilis) Pharmacokinetics : Oral absorption – good Distribution – skeletal and soft tissues Excreted in urine
Adverse effects : Rashes ,Urticaria Abdominal pain Superinfection -Enterocolitis &Diarrhoea Uses : Anaerobic and mixed infections- alternative to Pn & macro Abscess and bone infections-staphy and bacteroids Infective endocarditis Doses : 150-300 mg QID oral ; 200-600mg I.v. 8 hourly DALCAP, CLINCIN, DALCIN, 150, 300 mg cap, 300mg/2ml and 600 mg/4ml inj. www.indiandentalacademy.com
Anti fungal drugs
Fungus Composed of a rigid cell wall made up of chitin and various polysaccharides, and a cell membrane containing ergosterol Protective layers of the fungal cell make the organism resistant to antibiotics Related groups of anti fungal agents 1.Antibiotics A. Polyenes B. Heterocyclic benzofuram 2.Antimetabolites 3. Azoles A.Imidazoles B.Triazoles 4.Allylamine 5.Topical agents
A polyene derived from Streptomyces noursei Binds to sterols of fungal cell membrane Topical antifungal agent- fungicidal 2nd choice to clotrimazole 1 lac units-4 times a day, 10-14 days Suspended with glycerine
Effective in the topical treatment. Esp, athletes foot, otomycosis and oral, cutaneous candidiasis. 10mg -3-4times a day. Gel or lotion-denture stomatitis Angular chelitis well tolerated although Local irritation and burning No systemic toxicity is seen after topical use. SURFAZ, CLOTRIN, CLODERM, 1% lotion, cream, powder 100mg tab. www.indiandentalacademy.com
Nonselective antiviral drugs-ribavirin www.indiandentalacademy.com
Indications: Herpes simplex virus (HSV) 1 and 2 infections; HSV encephalitis; shingles and chickenpox; ointment for herpes infections; cream for cold sores Actions: Inhibits viral DNA replication
Symptoms Rapid progressing- facial cellulitis-HI/SP Chronic/ slowly progressing-odontogenicstaphylococcal/mixed >101 F –nonodontogenic- hospitalization Colour:red/ violecious Swelling: indurated, non fluctuant or erythematous – cellulitis Pointed, fluctuant or productive- abscess
Management Upper face Outpatient: amoxicillin clavulanate or cefaclor orally Ceftriaxone- 1 day iv Inpatient : cefuroxime/ ampicillin+ sulbactam 7-10 days Odontogenic –pencillin/ clindamycin, surgical intervention Lower face Outpatient: cephalexin, amoxicillin clavuanate, erythromycin Inpatient : iv cefazolin, clindamycin
Some of the commonly used drugs
Amox-250,500mg-tid 250mg-Rs 67.50 500mg-Rs120.80
Children20-40mg/kg body weight-tid -125,250mg
Cephalexin(sporidex) 250,500mg 250mg-10tab-Rs66.50 500mg-10tab-Rs120.50 125mg,250mg/5ml 125mg;30ml-Rs34.50 250mg;30ml-Rs52.60
Sporidex dispersible tabs
Metrogyl 200mg;tab 10-Rs3.64 400mg;tab 10-6.31- given tid for 5-10 days Suspension; 200mg /5ml-30ml-Rs8.09
KNOW THE BUGS, KNOW THE DRUGS
List of references Essentials of medical pharmacology : KD TRIPATHI; 5th edi. Clinical pharmacology – Bennet & Brown 9th ed Oral & maxillofacial infections – Topazian 4th ed .Text book of pediatric dentistry – Damle 3rd ed Caranza Text book of periodontology 10th
Questions to ask before starting antibiotics •Does this patient actually need antibiotics? •What is best treatment? •What are the likely organisms? •Where is the infection? •How much, how often, what route, for how long? •How much does it cost? •Are there any problems in using antibiotics in this patient? www.indiandentalacademy.com
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