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http://www.med.cmu.ac.th/dept/ent/Internet_ENT2005/Teaching/postgrad/PDF_HIGHT_POST%20GRAD_ENT2549/OTOL_HIGH_801/Temporomandibular%20Joint%20Disorders.pdf

http://www.usc.edu/hsc/dental/rest/tooth_restorations/

http://www.4dent.org/video/alanezism/dental-abscess-an-animation-video_e2b213777.html

http://www.infodento.com/video/1

http://www.medicalnewstoday.com/healthvideos.php

http://www.medicalnewstoday.com/healthvideos.php

http://www.medicalvideos.us/videos/3058/the-endocrine-system

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http://www.humpath.com/spip.php?mot132

http://www.authorstream.com/Presentation/aSGuest29359-259985-introduction-virology-science-technology-ppt-powerpoint/

http://www.diacritech.com/samples/science_and_medical/anatomyB-4color.pdf

http://pharmacologycorner.com/ppt-lectures-opioids-mechanism-of-action-pharmacological-effect/

http://www.authorstream.com/Presentation/rbya-212539-impression-material-materials-presentation8-education-ppt-powerpoint/

http://www.authorstream.com/Presentation/saurabhchandra-247496-cast-restorations-dentistry-endodontics-operative-2-education-ppt-powerpoint/

http://emedicine.medscape.com/article/1081029-overview#aw2aab6b4

ANTIMICROBIAL DRUGS

— Antibiotics are products of microorganisms that react with and inhibit the growth of other microorganisms.

— An antibiotic should be

1. selectively toxic to pathogenic microorganisms,
2. should not incite an allergic response in the body,
3. should not upset the normal microbial population of various body sites, and
4. should not foster the development of drug resistance.

— A chemotherapeutic agent must have selective toxicity: it must kill or inhibit the microbial pathogen while damaging the host as little as possible.

— The degree of selective toxicity may be expressed in terms of

(1) the therapeutic dose, the drug level required for clinical treatment of a particular infection, and

(2) the toxic dose, the drug level at which the agent becomes too toxic for the host.

— The therapeutic index is the ratio of the toxic dose to the therapeutic dose.

— The larger the therapeutic index, the better the chemotherapeutic agent.

— A chemotherapeutic agent must have selective toxicity: it must kill or inhibit the microbial pathogen while damaging the host as little as possible.

— The degree of selective toxicity may be expressed in terms of

(1) the therapeutic dose, the drug level required for clinical treatment of a particular infection, and

(2) the toxic dose, the drug level at which the agent becomes too toxic for the host.

— The therapeutic index is the ratio of the toxic dose to the therapeutic dose.

— The larger the therapeutic index, the better the chemotherapeutic agent.

— A drug that disrupts a microbial function not found in eucaryotic animal cells often has a greater selective toxicity and a higher therapeutic index.

— For example, penicillin inhibits bacterial cell wall peptidoglycan synthesis but has little effect on host cells because they lack cell walls; therefore penicillin’s therapeutic index is high.

— Drugs vary considerably in their range of effectiveness.

— Many are narrow-spectrum drugs—that is, they are effective only against a limited variety of pathogens.

— Others are broad spectrum drugs and attack many different kinds of pathogens.

— Chemotherapeutic agents can be either cidal or static.

— Static agents reversibly inhibit growth; if the agent is removed, the microorganisms will recover and grow again.

— Some idea of the effectiveness of a chemotherapeutic agent against a pathogen can be obtained from the minimal inhibitory concentration (MIC). The MIC is the lowest concentration of a drug that prevents growth of a particular pathogen.

— The minimal lethal concentration (MLC) is the lowest drug concentration that kills the pathogen.

Mechanisms of Action of Antimicrobial Agents

— Antimicrobial drugs can damage pathogens in several ways.

— The most selective antibiotics are those that interfere with the synthesis of bacterial cell walls (e.g., penicillins, cephalosporins, vancomycin, and bacitracin).

— These drugs have a high therapeutic index because bacterial cell walls have a unique structure not found in eucaryotic cells.

— Streptomycin, gentamicin, spectinomycin, clindamycin, chloramphenicol, tetracyclines, erythromycin, and many other antibiotics inhibit protein synthesis by binding with the procaryotic ribosome.

— Because these drugs discriminate between procaryotic and eucaryotic ribosomes, their therapeutic index is fairly high, but not as favorable as that of cell wall synthesis inhibitors.

— Some drugs bind to the 30S (small) subunit, while others attach to the 50S (large) ribosomal subunit.

— Several different steps in the protein synthesis mechanism can be affected: aminoacyl-tRNA binding, peptide bond formation, mRNA reading, and translocation.

— The antibacterial drugs that inhibit nucleic acid synthesis or damage cell membranes often are not as selectively toxic as other antibiotics. This is because procaryotes and eucaryotes do not differ as greatly with respect to nucleic acid synthetic mechanisms or cell membrane structure.

— Several valuable drugs act as antimetabolites: they block the functioning of metabolic pathways by competitively inhibiting the use of metabolites by key enzymes.

— Sulfonamides and several other drugs inhibit folic acid metabolism. Sulfonamides (e.g., sulfanilamide, sulfamethoxazole, and sulfacetamide) have a high therapeutic index because humans cannot synthesize folic acid and must obtain it in their diet.

— Most bacterial pathogens synthesize their own folic acid and are therefore susceptible to inhibitors of folate metabolism

ANTIMICROBIAL DRUGS

— Sulfonamides or Sulfa Drugs

— Quinolones

— Penicillins

— Cephalosporins

— The Tetracyclines

— Aminoglycoside Antibiotics

— Erythromycin and Other Macrolides

— Vancomycin and Teicoplanin

— Chloramphenicol

SULPHONAMIDES

— A good way to inhibit or kill pathogens is by use of compounds that are structural analogues, molecules structurally similar to metabolic intermediates.

— These analogues compete with metabolites in metabolic processes because of their similarity, but are just different enough so that they cannot function normally in cellular metabolism.

— The first antimetabolites to be used successfully as chemotherapeutic agents were the sulfonamides, discovered by G. Domagk.

— Sulfonamides or sulfa drugs are structurally related to sulfanilamide, an analogue of p-aminobenzoic acid.

— When sulfanilamide or another sulfonamide enters a bacterial cell, it competes with p-aminobenzoic acid for the active site of an enzyme involved in folic acid synthesis, and the folate concentration decreases.

— The decline in folic acid is detrimental to the bacterium because folic acid is essential to the synthesis of purines and pyrimidines, the bases used in the construction of DNA, RNA, and other important cell constituents.

— The resulting inhibition of purine and pyrimidine synthesis leads to cessation of bacterial growth or death of the pathogen.

QUINOLINES

— A second group of synthetic antimicrobial agents are increasingly used to treat a wide variety of infections.

— The quinolones are synthetic drugs that contain the 4-quinolone ring.

— Quinolones are effective when administered orally. They sometimes cause adverse side effects, particularly gastrointestinal upset.

— Quinolones act by inhibiting the bacterial DNA gyrase or topoisomerase II, probably by binding to the DNA gyrase complex.

— This enzyme introduces negative twists in DNA and helps separate its strands.

— DNA gyrase inhibition disrupts DNA replication and repair, transcription, bacterial chromosome separation during division, and other cell processes involving DNA.

— Fluoroquinolones also inhibit topoisomerase IV, another enzyme that untangles DNA during replication.

— The quinolones are broad-spectrum drugs. They are highly effective against enteric bacteria such as E. coli and Klebsiella pneumoniae.

— They can be used with Haemophilus, Neisseria, Pseudomonas aeruginosa, and other gram-negative pathogens.

— The quinolones also are active against gram-positive bacteria such as Staphylococcus aureus, Streptococcus pyogenes, and Mycobacterium tuberculosis.

— Currently they are used in treating urinary tract infections, sexually transmitted diseases caused by Neisseria and Chlamydia, gastrointestinal infections, respiratory tract infections, skin infections, and osteomyelitis.

— More recently a family of fluoroquinolones has been produced. Three of these—ciprofloxacin, norfloxacin, and ofloxacin—are currently used.

PENCILLINS

— Penicillin G or benzylpenicillin, the first antibiotic to be widely used in medicine, has the structural properties characteristic of the penicillin family.

— Most penicillins are derivatives of 6-aminopenicillanic acid and differ from one another only with respect to the side chain attached to its amino group.

— The most crucial feature of the molecule is the β-lactam ring, which appears to be essential for activity.

— Penicillinase, the enzyme synthesized by many penicillin-resistant bacteria, destroys penicillin activity by hydrolyzing a bond in this ring.

— An increasing number of bacteria are penicillin resistant. Penicillinase-resistant penicillins such as methicillin, nafcillin, and oxacillin are frequently employed against these bacterial pathogens.

CEPHALOSPORINS

— Cephalosporins are a family of antibiotics originally isolated in 1948 from the fungus Cephalosporium, and their β-lactam structure is very similar to that of the penicillins.

— Cephalosporins resemble penicillins in inhibiting the transpeptidation reaction during peptidoglycan synthesis.

— They are broad-spectrum drugs frequently given to patients with penicillin allergies.

— Many cephalosporins are in use. There are three groups or generations of these drugs that differ in their spectrum of activity.

— First-generation cephalosporins are more effective against gram-positive than gram-negative pathogens.

— Second generation drugs act against many gram-negative as well as gram positive pathogens.

— Third-generation drugs are particularly effective against gram-negative pathogens, and often also reach the central nervous system.

— Most cephalosporins (including cephalothin, cefoxitin, ceftriaxone, and cefoperazone) are administered parenterally.

— Cefoperazone is resistant to destruction by -lactamases and effective against many gram-negative bacteria, including Pseudomonas aeruginosa.

— Cephalexine and cefixime are given orally rather than by injection.

TETRACYCLINES

— The tetracyclines are a family of antibiotics with a common four-ring structure to which a variety of side chains are attached.

— Oxytetracycline and chlortetracycline are naturally produced by some species of the actinomycete genus Streptomyces; others are semisynthetic drugs.

— These antibiotics inhibit protein synthesis by combining with the small (30S) subunit of the ribosome and inhibiting the binding of aminoacyl-tRNA molecules to the ribosomal A site.

— Because their action is only bacteriostatic, the effectiveness of treatment depends on active host resistance to the pathogen.

— Tetracyclines are broad-spectrum antibiotics active against gram-negative bacteria, gram-positive bacteria, rickettsias, chlamydiae, and mycoplasmas.

— High doses may result in nausea, diarrhea, yellowing of teeth in children, and damage to the liver and kidneys.

AMINOGLYCOSIDE

— There are several important aminoglycoside antibiotics. Streptomycin, kanamycin, neomycin, and tobramycin are synthesized by Streptomyces, whereas gentamicin comes from a related bacterium, Micromonospora purpurea.

— Although there is considerable variation in structure among the different aminoglycosides, all contain a cyclohexane ring and amino sugars.

— Aminoglycosides bind to the small ribosomal subunit and interfere with protein synthesis in at least two ways. They directly inhibit protein synthesis and also cause misreading of the genetic message carried by mRNA.

— The aminoglycosides are bactericidal and tend to be most active against gram-negative pathogens.

— Streptomycin’s usefulness has decreased greatly due to widespread drug resistance, but it is still effective against tuberculosis and plague.

— Gentamicin is used to treat Proteus, Escherichia, Klebsiella, and Serratia infections.

— Aminoglycosides are quite toxic and can cause deafness, renal damage, loss of balance, nausea, and allergic responses.

ERYTHROMYCIN AND OTHER MACROLIDES

— Erythromycin, the most frequently used macrolide antibiotic, is synthesized by Streptomyces erythraeus.

— The macrolides contain a 12- to 22-carbon lactone ring linked to one or more sugars.

— Erythromycin is usually bacteriostatic and binds with the 23S rRNA of the 50S ribosomal subunit to inhibit peptide chain elongation during protein synthesis.

— Erythromycin is a relatively broad-spectrum antibiotic effective against gram-positive bacteria, mycoplasmas, and a few gram-negative bacteria

— It is used with patients allergic to penicillins and in the treatment of whooping cough, diphtheria, diarrhea caused by Campylobacter, and pneumonia from Legionella or Mycoplasma infections.

VANCOMYCIN AND TEICOPLANIN

— Vancomycin is a glycopeptide antibiotic produced by Streptomyces orientalis.

— The antibiotic blocks peptidoglycan synthesis by inhibiting the transpeptidation step that cross-links adjacent peptidoglycan strands.

— The resulting peptidoglycan is mechanically weak and the cells osmotically lyse.

— Vancomycin’s peptide portion binds specifically to the D-alanine-D-alanine terminal sequence on the pentapeptide portion of peptidoglycan. This complex blocks transpeptidase action.

— The antibiotic is bactericidal for Staphylococcus and some members of the genera Clostridium, Bacillus, Streptococcus, and Enterococcus.

— It is given both orally and intravenously, and has been particularly important in the treatment of antibiotic resistant Staphylococcal and Enterococcal infections.

— Vancomycin-resistant strains of Enterococcus have become widespread and recently a few cases of resistant Staphylococcus aureus have appeared.

— Teicoplanin is a glycopeptide antibiotic from Actinoplanes teichomyceticus that is similar in structure and mechanism of action to vancomycin.

— It is active against staphylococci, enterococci, streptococci, clostridia, Listeria, and many other gram positive pathogens

CHLORAMPHENICAL

— Although chloramphenicol was first produced from cultures of Streptomyces venezuelae, it is now made through chemical synthesis.

— Like erythromycin, chloramphenicol binds to 23S rRNA on the 50S ribosomal subunit.

— It inhibits the peptidyl transferase and is bacteriostatic.

— This antibiotic has a very broad spectrum of activity but unfortunately is quite toxic.

— One may see allergic responses or neurotoxic reactions.

— The most common side effect is a temporary or permanent depression of bone marrow function, leading to aplastic anemia and a decreased number of blood leukocytes.

— Chloramphenicol is used only in life-threatening situations when no other drug is adequate.

ANTIFUNGAL DRUGS

— Treatment of fungal infections generally has been less successful than that of bacterial infections largely because eucaryotic fungal cells are much more similar to human cells than are bacteria.

— Many drugs that inhibit or kill fungi are therefore quite toxic for humans.

— In addition, most fungi have a detoxification system that modifies many antibiotics, probably by hydroxylation. As a result the added antibiotics are fungistatic only as long as repeated application maintains high levels of unmodified antibiotic.

— Despite their relatively low therapeutic index, a few drugs are useful in treating many major fungal diseases.

— Effective antifungal agents frequently either extract membrane sterols or prevent their synthesis.

— Similarly, because animal cells do not have cell walls, the enzyme chitin synthase is the target for fungal-active antibiotics such as polyoxin D and nikkomycin.

— Fungal infections are often subdivided into infections of superficial tissues or superficial mycoses and systemic mycoses.

— Treatment for these two types of disease is very different. Several drugs are used to treat superficial mycoses.

— Three drugs containing imidazole—miconazole, ketoconazole, and clotrimazole—are broad-spectrum agents available as creams and solutions for the treatment of dermatophyte infections such as athlete’s foot, and oral and vaginal candidiasis.

— They are thought to disrupt fungal membrane permeability and inhibit sterol synthesis.

— Tolnaftate is used topically for the treatment of cutaneous infections, but is not as effective against infections of the skin and hair.

— Nystatin, a polyene antibiotic from Streptomyces, is used to control Candida infections of the skin, vagina, or alimentary tract.

— Griseofulvin, an antibiotic formed by Penicillium, is given orally to treat chronic dermatophyte infections.

— It is thought to disrupt the mitotic spindle and inhibit cell division; it also may inhibit protein and nucleic acid synthesis.

— Side effects of griseofulvin include headaches, gastrointestinal upset, and allergic reactions.

— Systemic infections are very difficult to control and can be fatal. Three drugs commonly used against systemic mycoses are amphotericin B, 5-flucytosine, and fluconazole.

— Amphotericin B from Streptomyces spp. binds to the sterols in fungal membranes, disrupting membrane permeability and causing leakage of cell constituents.

— The synthetic oral antimycotic agent 5-flucytosine (5-fluorocytosine) is effective against most systemic fungi, although drug resistance often develops rapidly.

— The drug is converted to 5-fluorouracil by the fungi, incorporated into RNA in place of uracil, and disrupts RNA function.

— Its side effects include skin rashes, diarrhea, nausea, aplastic anemia, and liver damage.

— Fluconazole is used in the treatment of candidiasis, cryptococcal meningitis, and coccidioidal meningitis.

ANTIVIRAL DRUGS

— For many years the possibility of treating viral infections with drugs appeared remote because viruses enter host cells and make use of host cell enzymes and constituents to a large extent.

— A drug that would block virus reproduction also was thought to be toxic for the host.

— Inhibitors of virus-specific enzymes and life cycle processes have now been discovered, and several drugs are used therapeutically.

— Most antiviral drugs disrupt either critical stages in the virus life cycle or the synthesis of virus-specific nucleic acids.

— Amantadine and rimantadine can be used to prevent influenza A infections.

— When given in time, it will reduce the incidence of influenza by 50 to 70% in an exposed population.

— Amantadine blocks the penetration and uncoating of influenza virus particles.

— Adenine arabinoside or vidarabine disrupts the activity of DNA polymerase and several other enzymes involved in DNA and RNA synthesis and function. It is given intravenously or applied as an ointment to treat herpes infections.

— A third drug, acyclovir, is also used in the treatment of herpes infections. Upon phosphorylation, acyclovir resembles deoxy-GTP and inhibits the virus DNA polymerase.

— Valacyclovir is an orally administered prodrug form of acyclovir.

— Ganciclovir, penciclovir, and its oral form famciclovir are effective in treatment of herpesviruses.

— Another kind of drug, foscarnet, inhibits the virus DNA polymerase in a different way. Foscarnet is an organic analogue of pyrophosphate that binds to the polymerase active site and blocks the cleavage of pyrophosphate from nucleoside triphosphate substrates. It is used in treating herpes and cytomegalovirus infections.

— Several broad-spectrum anti-DNA virus drugs have been developed.

— A good example is the drug HPMPC or cidofovir. It is effective against papovaviruses, adenoviruses, herpesviruses, iridoviruses, and poxviruses.

— The drug acts on the viral DNA polymerase as a competitive inhibitor and alternative substrate of dCTP. It has been used primarily against cytomegalovirus but also against herpes simplex and human papillomavirus infections.

— Research on anti-HIV drugs has been particularly active. Many of the first drugs to be developed were reverse transcriptase inhibitors such as azidothymidine (AZT) or zidovudine, lamivudine (3TC), didanosine (ddI), zalcitabine (ddC), and stavudine (d4T).

— These interfere with reverse transcriptase activity and therefore block HIV reproduction.

— More recently HIV protease inhibitors have been developed. Three of the most used are saquinvir, indinavir, and ritonavir.

— These mimic the peptide bond that is normally attacked by the protease.

— The most successful treatment regimen involves a cocktail of agents given at high dosages to prevent the development of drug resistance.

— For example, the combination of AZT, 3TC, and ritonavir is very effective in reducing HIV plasma concentrations almost to zero.

— However, the treatment does not seem able to eliminate latent proviral HIV DNA that still resides in memory T cells, and possibly elsewhere.

— Probably the most publicized antiviral agents are interferons. These small proteins, produced by the host, inhibit virus replication and may be clinically useful in the treatment of influenza, hepatitis, herpes, and colds.