Antibiotics presentation.ppt

Antibiotics presentation.ppt

• 2.
  PROTEIN SYNTHESIS INHIBITORS  substancethat stops or slows the growth or proliferation of cells disrupting the processes that lead directly to the generation of new proteins.  usually refers to substances that act at the ribosome level (either the ribosome itself or the translation factor).  The bacterial ribosome is smaller (70s) than the mammalian ribosome(80s).  The mammalian mitochondrial ribosome more closely resembles the bacterial ribosomes.  Although drugs that interact with the bacterial site usually spare the host cells, high levels of drugs like chlorampenicol or the tetracyclines may cause toxic effects as a result of interaction with the mitochondrial ribosomes.
• 3.
  PROTEIN SYNTHESIS INHIBITORS TETRACYCLINES AMINOGLYCOSIDE S MACROLIDES CHLORAMPHENICO L CLINDAMYCIN Demeclocycline Doxycycline Minocycline Tetracycline Amikacin Gentamicin Neomycin Netilmicin Streptomycin Tobramycin Azithromycin ClarithromycinErythromycin
• 4.
  TETRACYCLINES Demeclomyci n Doxycyclin Minocyclin Tetracyclin
• 5.
  Group of closelyrelated compounds that consist of 4 fused rings with a system of conjugated double bonds. Small differences in clinical efficacy reflect a variation in their individual pharmacokinetics due to substitution on these rings. Generally bacteriostatic Drugs of choice for infections for:  Chlamydial infection  Rocky mountain spotted fever  Mycoplasma pneumonia  Cholera  Lyme disease I. TETRACYCLINES
• 6.
  Absorption: adequately butincompletely absorbed after oral ingestion. Taking these drugs concomitantly with dairy foods in the diet decreases absorption . Distribution: concentrate in the liver ,kidney, spleen, and skin and bind to tissues undergoing calicification, or tumors that have a high calcium content. the parent drug and/or its metabolites are secreted into the bile: most are reabsorbed in the intestine and enter the urine by glomerular filtration. PHARMACOKINETICS
• 7.
  Epigastric distress Deposition inbone and primary dentition occurs Discoloration and hypoplasia of the teeth Temporary stunting of growth Hepatotoxicity Phototoxicity Renal damage Hypersensitivity Diabetes insipidus ( with demelocycline) Teratogenecity Damage to natural gut flora Vestibular problems (dissiness, bnausea, vomiting) Pseudotumor cerebri ( benign intracranial hypertension characterized by headache and blurred vision Overgrowth of Candida or of resistant staphylococci ADVERSE EFFECTS
• 8.
  Renally impaired patientsshould not be treated with any of the tetracyclines except doxycycline. May aggravate pre-existing azotemia by interfering with protein synthesis, thus promoting amino acid degradation. Should not be employed in pregnant or breast-feeding women, or in children under 8 years of age. CONTRAINDICATIONS
• 9.
  TETRACYCLINE DRUGS
• 10.
  used to treata wide variety of bacterial infections, including those that cause acne, bronchitis and lyme disease. widely used (though off-label in many countries) in the treatment of hyponatremia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) when fluid restriction alone has been ineffective. induces nephrogenic diabetes insipidus (dehydration due to the inability to concentrate urine). drug of choice for treating SIADH contraindicated in children and pregnant ,nursing woman. interfere with bone development and may discolour teeth. DEMECLOCYCLINES
• 11.
  Acts by bindingto the 30S- and 50S-RNA, which impairs protein synthesis by bacteria. Bacteriostatic Impairs the action of antidiuretic hormone, but it is thought that it blocks the binding of the hormone to its receptor. Mode of Action
• 12.
  only tetracycline isknown to cause nephrogenic diabetes insipidus. Adverse Effects
• 13.
  Used to treat: urinarytract infections, acne, gonorrhea chlamydia, periodontitis (gum disease) Also used to treat blemishes, bumps, and acne-like lesions caused by rosacea. It will not treat facial redness caused by rosacea. May be used in combination with other medicines to treat certain amoeba infections. Can cause permanent yellowing or graying of the teeth, and it can affect a child's growth. DOXYCYCLINE
• 14.
  sold as Minocin,Dynacin, Vectrin, Solodyn and generic minocycline kills the acne bacteria more effectively than many other acne pills and has a separate "anti- inflammatory" effect safer than ibuprofen or penicillin standard treatment for severe acne MINOCYCLINE
• 15.
  hypersensitivity lupus/hepatitis, which causessevere joint pains pseudotumor cerebri (an accumulation of fluid around the brain) that causes progressively worsening headaches and vision problems Adverse Effects
• 16.
  AMINOGLYCOSIDES Tobramycin Gentamicin Amikacin Neomycin Netimicin Streptomyci n
• 17.
  mainstays of treatmentof serious infections due to aerobic gram-negative bacilli. Replaced to some extent by safer antibiotics such as the third generation drugs: Cephalosporins Fluoroquinolones Imipenem/cilastatin * Aminoglycosides that are derived from Streptomyces have “mycin” suffixes , whereas those from micromonospora end in “micin”. II. AMINOGLYCOSIDES
• 18.
  They bind tothe bacterial 30S ribosomal subunit (some work by binding to the 50S subunit)The protein synthesis inhibition of aminoglycosides does not usually produce a bactericidal effect, let alone a rapid one as is frequently observed on susceptible Gram-negative bacilli. Aminoglycosides competitively displace cell biofilm- associated Mg2+ and Ca2+ that link the polysaccharides of adjacent lipopolysaccharide molecules. "The result is shedding of cell membrane blebs, with formation of transient holes in the cell wall and disruption of the normal permeability of the cell wall. Mode of Action
• 19.
  This action alonemay be sufficient to kill most susceptible Gram-negative bacteria before the aminoglycoside has a chance to reach the 30S ribosome.The antibacterial properties of aminoglycosides were believed to result from inhibition of bacterial protein synthesis through irreversible binding to the 30S bacterial ribosome
• 20.
  Long-term treatment withhigh doses also entails the risk of irreversible inner ear lesions (imbalance, decreased hearing or deafness). According to many specialists, netilmicin is the aminoglycoside with the smallest nephrotoxic and ototoxic effect. Cutaneous and systemic hypersensitive reactions, gastrointestinal pain, and an increase of liver enzymes are rare.
• 21.
  synthetic derivative ofkanamycin. Nephrotoxic and ototoxic Many gram negative enteric bacteria are inhibited in vitro namely: Proteus Pseudomonas Anterobacter Serratia *strains of multi-drug resistant Myobacterium tuberculosis, including streptomycin-resistant strains , are usually susceptible to amikacin. AMIKACIN
• 22.
  isolated from micromonosporapurpurea Effective against both gram-positive and gram-negative organisms Inhibits in vitro many strains of staphylococci and coliforms and other gram-negative bacteria A synergistic companion with β-lactam antibiotics against: -- Pseudomonas -- Proteus -- Enterobacter -- Klebsiella -- Serratia -- Stenotrophomonas -- Other gram-negative rods that may be resistant to multiple other antibiotics GENTAMICIN
• 23.
  Intramuscular or intravenousadministration Topical: gentamicin sulfate: treatment of infected burns, wounds, or skin lesions and prevention of catheter infections. Intrarhecal: Meningitis
• 24.
   Nephrotoxicity (reversible) Ototoxicity (irreversible)  Loss of hearing ADVERSE EFFECTS
• 25.
  active against gram-positiveand gram-negative bacteria and some mycobacteria ♫The widespread use of these drugs in bowel preparation for elective surgery has resulted in the selection of resistant organisms and some outbreaks of enterocolitis in hospitals. poorly absorbed from the GI tract excreted in feces excretion of any absorbed drug is mainly through glomerular filtration in the urine. too toxic for parenteral use. NEOMYCIN
• 26.
  At higher dose,may produce systemic toxicity Topical administration : used on infected surfaces or injected into joints, the pleural cavity, tissue spaces, or abscess cavities where infection is present. Oral administration: for preparation for elective bowel surgery ADVERSE EFFECTS: ♫prolonged use may result to severe allergic reactions ♫Auditory function is more affected than vestibular
• 27.
  primarily suited forthe treatment of dangerous Gram-negative infections, whereby it demonstrates relatively good tolerance. It is particularly indicated for septicemias that have been caused by pseudomonas or gentamicin-resistant germs. can also be combined with clindamycin or metronidazole for intra-abdominal and gynecological infections. well suited for the treatment of children with Gram- negative sepsis. NETILMICIN
• 28.
  Netilmicin has proveneffective against pulmonary infections with cystic fibrosis and — in combination with other antibiotics — against several other infections (e.g. in connection with operations or traumatic wounds, Klebsiella infections). Urinary tract infections should only be treated with oral netilmicin, and only if the problems cannot be solved with better tolerated drugs.
• 29.
  binds to bacterialribosomes and blocks the protein synthesis, which has bactericidal consequences. It is an antibiotic with a broad spectrum with respect to Gram-negative bacili. All enterobacteriaceae (E. coli, Klebsiella, Enterobacter, Serratia, Proteus, etc.) are sensitive. Its activity against Pseudomonas aeruginosa is particularly useful. Netilmicin is also active against Staphylococcus aureus; however, methicillin-resistant staphylococci are often also resistant against aminoglycosides. Anaerobic germs are also resistant. causes renal damage particularly in subjects who have been administered high doses over a long period of time, as well as in patients with pre- existing renal failure, in combination with nephrotoxic drugs, and in elderly subjects. Approximately 7 to 8% of the treated subjects experience an increase of the creatinine levels, proteinuria, cylindruria, etc. If netilmicin is discontinued promptly renal damages may be reversible. PHARMACOKINETICS
• 30.
   Isolated froma strain of streptomyces griseus.  Mainly used as a second-line agent for treatment of tuberculosis, given intramuscularly or IV.  Streptomycin plus penicillin is effective for enterococcal endocarditis and 2-week therapy of viridans streptococcal endocarditis. CONTRAINDICATION -- during pregnancy, can cause deafness in the newborn. STREPTOMYCIN
• 31.
  Binds to bacterialribosomes and blocks the protein synthesis, which has bactericidal consequences with a broad spectrum with respect to Gram-negative bacili. All enterobacteriaceae (E. coli, Klebsiella, Enterobacter, Serratia, Proteus, etc.) are sensitive activity against Pseudomonas aeruginosa and Staphylococcus aureus PHARMACOKINETICS
• 32.
  vestibular toxicity (nausea,vomiting, vertigo) paresthesia of the face rash fever urticaria angioneurotic edema eosinophilia Side effects may be more likely and more severe in patients with underlying renal insufficiency. ADVERSE EFFECTS
• 33.
  antibacterial spectrum similarto gentamicin Pharmacokinetic properties are virtually identical to those of gentamicin More against pseudomonas Ototoxic and nephrotoxic Formulated in solution for inhalation for treatment of pseudomonas aeruginosa Not for patients with pre existing renal, vestibular, or hearing disorders. TOBRAMYCIN
• 34.
  MACROLIDES Azithromycin Clarithromycin Erythromycin
• 35.
  -- Group ofantibiotics with a macrocyclic lactone structure. -- Erythromycin was the first of these to find clinical application both as the drug of first choice. -- The new members of this family, clarithromycin and azithromycin have some features in common with and others that improve on, erythromycin. III. MACROLIDES
• 36.
  Binds irreversibly toa site on the 50S subunit of the bacterial ribosome, thus inhibiting the translocation steps of protein synthesis. Generally considered to be bacteriostatic, they may be cidal at higher doses. The binding site is either identical to or in close proximity to that for lindomycin, clindamycin, and chloramphenicol. A. Mode of Action
• 37.
  1. Erythromycin -- effectiveagainst the same organisms as penicillin G; it is used in patients allergic to the penicillins. -- used to treat many different types of infections caused by bacteria. It is also used to prevent bacterial endocarditis and attacks of rheumatic fever B. Antibacterial spectrum AE: Gastrointestinal disturbances, such as diarrhea, nausea, abdominal pain, and vomiting,
• 38.
  2. Clarithromycin -- effectiveagainst Haemophilus influenzae -- Its activity against intracellular pathogens such as Chlamydia, Legionella and Ureaplasm is higher than that of erythromycin -- used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia
• 39.
  3. Azithromycin -- lesseffective against streptococci and staphylococci than erythromycin -- far more active against respiratory infections due to Haemophilus influenzae and Moraxella catarrhalis -- it is now the preferred theraphy for urethritis caused by Chlamydia trachomatis -- its activity against Mycobacterium avium intracellular complex has not proven to be clinically important, except in AIDS patients with disseminated infections.
• 40.
  1. ADMINISTRATION: -- theerythromycin base is destroyed by gastric acid; thus either enteric coated tablets or esterified forms are administered. -- All are adequately absorbed on oral administration -- Clarithromycin and azithromycin are stable to stomach acid and are readily absorbed -- intravenous administration of erythromycin is associated with a high incidence of thrombophlebitis. 2. DISTRIBUTION: -- Erythromycin distributes well to all body fluids except the cerebrospinal fluid (CSF) -- Clarithromycin and azithromycin are widely distributed in tissues. PHARMACOKINETICS
• 41.
  3. METABOLISM: -- Erythromycinis extensively metabolized and is known to inhibit the oxidation of a number of drugs through its interaction with the cytochrome P-450 systems -- Clarithromycin is oxidized to the 14-hydroxy derivative, which retains antibiotic activity -- Azithromycin does not undergo metabolism 4. EXCRETION -- Erythromycin and azithromycin are primarily concentrated and excreted in an active form in the bile. -- Clarithromycin and its metabolites are eliminated by the kidney as well as the liver.
• 42.
  1. Epigastric distress 2.Cholestatic jaundice 3. Ototoxicity CONTRAINDICATIONS: Patients with hepatic dysfunction should not be treated with erythromycin, since the drug accumulates in the liver. E. Adverse Effects
• 43.
  -- active againsta wide range of gram-positive and gram- negative organisms, but because of its toxicity, its use is restricted to life-threatening infections in which there are no alternatives IV. CHLORAMPHENICOL
• 44.
  The drug bindsto the bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction. Because of the similarity of mammalian mitochondrial ribosomes to those of bacteria, protein synthesis in these organelles may be inhibited at high circulating chloramphenicol levels, producing bone marrow toxicity. A. Mode of action
• 45.
  CHLORAMPHENICOL -- a broadspectrum antibiotic -- active not only against bacteria but also against other microorganisms such as rickettsiae. -- has excellent activity against anaerobes -- either bactericidal or bacteriostatic, depending on the organism B. Antimicrobial spectrum
• 46.
  -- it maybe administered either intravenously or orally -- completely absorbed via the oral route because of its lipophilic nature and is widely distributed throughout the body. -- excretion of the drug depend on its conversion in the liver to a glucuronide that is then secreted by the renal tubule. D. Pharmacokinetics
• 47.
  The clinical useof Chloramphenicol is limited because of the serious adverse effects associated with its administration. In addition to gastrointestinal upsets, overgrowth of Candida may appear on the mucous membrane. 1. Anemias 2. Gray baby syndrome 3. Interactions: Chloramphenicol is able to inhibit some of the hepatic mixed function oxidases and thus can block the metabolism of suc drugs as warfarin, phenytoin, tolbutamide and chlorpropamide. E. Adverse Effect
• 48.
  -- has amechanism of action that is the same as that of erythromycin. -- employed primarily in the treatment of infections caused by anaerobic bacteria, such as Bacteroides fragilis. -- significantly active against nonenterococcal, gram-positive cocci. -- well absorbed by oral route -- In addition to skin rashes, the most serious adverse effect is potentially fatal pseudomembranous colitis caused by overgrowth of Clostridium difficile. V. Clindamycin