Se ha denunciado esta presentación.
Se está descargando tu SlideShare. ×

Pharmacology-Antibiotic drugs

Anuncio
Anuncio
Anuncio
Anuncio
Anuncio
Anuncio
Anuncio
Anuncio
Anuncio
Anuncio
Anuncio
Anuncio
Cargando en…3
×

Eche un vistazo a continuación

1 de 4 Anuncio
Anuncio

Más Contenido Relacionado

Presentaciones para usted (20)

Similares a Pharmacology-Antibiotic drugs (20)

Anuncio

Más reciente (20)

Anuncio

Pharmacology-Antibiotic drugs

  1. 1. M.A.A.Al-Maqrashi Antibiotic MOA & Resistance mechanism Pharmacokinetics & Uses A.E InhibitorsofCellWallSynthesis β-Lactam [Penicillins] Natural penicillin G penicillin V ± cidial interfere with the last step of bacterial cell wall synthesis (transpeptidation or cross- linkage), resulting in less stable membrane: - covalently bind to the active site of PBPs → inhibit the transpeptidation reaction and stop peptidoglycan synthesis. Penicillin-binding proteins [PBP]: - are membrane proteins that cross-link peptidoglycan. - removes the terminal alanine in the process of forming a cross-link with a nearby peptide. Resistance: - β lactamase - modification of PBP [MRSA+MRSE] - Impaired penetration of drug to target PBPs [G- ] - antibiotic efflux - Penicillin G: - inactivated by gastric juice & low oral absorbtion. - IV - Depot forms: IM [e.g. Procaine penicillin G and benzathine penicillin G] - Penicillin V: orally - incompletely absorbed after oral administration, and they reach the intestine in sufficient amounts to affect the composition of the intestinal flora. - cross the placental barrier - no penetration into bone or CSF [unless they are inflamed] - Penicillin levels in the prostate & eye are insufficient - excreted in urine & breast milk - effective against rapidly growing organisms that synthesize a peptidoglycan cell wall. - hypersensitivity [maculopapular rash, angioedema, anaphylactic shock etc.] - GIT upsets [nausea, vomiting, diarrhea, pseudomembranous colitis.] - Nephritis - Neurotoxicity [even epilepsy] - Hematologic toxicities [neutropenia] Anti-staphyl.C penicillins methicilli, cloxacillin + - IM or IV - Penicillinase-producing S. aureus. - Penicillinase-producing S. epidermis. Broad spectrum Aminopenicillins (e.g. amoxicillin) - - Orally - Similar to that of penicillin G – e.g. Haemophilus influenzae, Escherichia coli, and Proteus mirabilis Anti- pseudomonal piperacillin - - IM or IV - against Pseudomonas aeruginosa [Bacilli] [Cephalosporins] 1st g.: cephalexin ± cidial - have same mode of action as penicillins and they are affected by same resistant methods. - IV or IM - Higher generations increase efficiency against gram -ve - Ceftaroline: 5th gen. against MRSA (S. aureus) - Allergy - Thrombophlebitis [after IV injection] - Renal toxicity. - Hypo-prothrombinemia and bleeding disorders 2nd g.: cefoxitin 3rd g.: Cefotaxime 4th g.: Cefopime [β-lactamase inhibitors] Clavulanic acid tazobactam - Resemble β-lactam molecules but very weak antibacterial action. - Available only in a fixed-dose combination with penicillins and cephalosporins. - potent inhibitors of most of bacterial β lactamases → protect hydrolyzable penicillins from inactivation Penicillin-β-lactamase inhibitor combinations: - empiric therapy for infections caused by a wide range of potential pathogens. - treatment of mixed aerobic and anaerobic infections, such as intra-abdominal infections. - Amoxicillin + clavulanic acid [o-amoxiclav] - Piperacillin + Tazobactam: the combination is must
  2. 2. M.A.A.Al-Maqrashi Cont.ICWS [Glycopeptides] Vancomycine + cidial - Binds to the terminal two D- alanine residues of pentapeptide → inhibiting peptidoglycan backbone elongations. Resistance: - Replacement of D-Ala by D- lactate in resistant organisms. - Given by slow IV infusion (not absorbed orally) for systemic infections - Oral vancomycin is limited to treatment for antibiotic-associated colitis by Clostridium difficile [anaerobic bacteria] - Used in the treatment of MRSA, MRSE, enterococcal infections - Red Man Syndrome - shock from histamine release associate with rapid infusion. - Ototoxicity - Nephrotoxicity Inhibitorsofproteinsynthesis [Macrolides] Erythromycin + static - Bind irreversibly to a site on the 50S subunit of the bacterial ribosome → inhibits the translocation step - against many of the same organisms as penicillin G - An alternative to penicillin in allergic individuals - GIT disturbance. - Cholestatic jaundice. - Ototoxicity. [Aminoglycosides] Gentamycin - cidial - irreversible inhibitors of protein synthesis. - Passive diffusion via porin channels across the outer membrane. - Actively transported across the cell membrane into the cytoplasm by an oxygen- dependent process. - they bind the 30S subunit: - interfere with assembly of the functional ribosomal - misread the genetic code - Block of translocation on mRNA. - Concentration dependent. - has postantibiotic effect. - mostly used against aerobic G- bacteria including Pseudomonas aeruginosa. - Their structure prevents adequate oral absorption. - Must be given parenterally to achieve adequate serum levels. - Mostly, Combined with a β-lactam antibiotic to: - extend coverage to include potential gram-positive pathogens. - take advantage of the synergism between these two classes of drugs. - Streptomycin is used as a second-line agent for treatment of tuberculosis. - Ototoxicity: - deafness. - vertigo and loss of balance. - Nephrotoxicity. - Neuromuscular paralysis [decrease in release of Ach.] [Tetracyclines] Tetracycline ± static - Bind reversibly to the 30S subunit: - Blocking the binding of aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex. - This prevents addition of amino acids to the growing peptide. - broad-spectrum antibiotics - Against Rickettsia, Chlamydia, Mycoplasma. - used in combination regimens to treat gastric and duodenal ulcer disease caused by Helicobacter pylori - GIT upsets [nausea, vomiting and diarrhea.] - Discoloration of teeth in growing children. - Phototoxicity [sunburn occurs when a patient receiving a tetracycline is exposed to sun.] - Nephrotoxicity. - Superinfections [overgrowth with Candida or resistant staphylococci]
  3. 3. M.A.A.Al-Maqrashi Cont.IPS [Chloramphenicol] ± static - potent inhibitor of microbial protein -synthesis. - binds reversibly to the 50S subunit of the bacterial ribosome and inhibits peptide bond formation (step 2). - broad-spectrum antibiotic: against both aerobic and anaerobic - Against Rickettsiae - toxic: it is restrictly used. - GIT upset: [nausea, vomiting, diarrhea.] - Anemia: [aplastic anemia.] - Gray baby syndrome in neonates: [newborn infants lack an effective glucuronic acid conjugation mechanism for the degradation and detoxification of chloramphenicol.] - Inhibits hepatic microsomal enzymes. ActingonNucleicAcid [Fluoroquinolones] 1st g.: Nalidixic acid ± cidial - Enter the bacteria by passive diffusion through porins in the outer membrane. - They inhibit the replication of bacterial DNA by interfering with the action of DNA gyrase (topoisomerase II) and topoisomerase IV during bacterial growth and reproduction. - Binding of the quinolone to both enzymes and the DNA forms a complex that can cause cell death by inducing cleavage of the DNA. Resistance: - mutation of the target - ↓porin molecules - active transport out. - Higher generations increase efficiency against gram +ve - GIT upset: [nausea, vomiting, diarrhea.] - CNS: [headache, dizziness, light- headedness.] - Phototoxicity. - Connective tissue problems: [tendinitis or tendon rupture.] 2nd g.: Ciprofloxacin Norflaxacin Oflaxicin 3rd g.: Cefotaxime 4th g.: Cefopime [Sulfonamides] Sulfadiazine ± static - inhibit the synthesis of bacterial dihydrofolic Acid ← compete with PABA for dihydropteroate synthase. - synthetic analogs of PABA. - Only organisms that synthetize their folate requirements de novo are sensitive to the sulfonamides. - inhibit Nocardia sp, Chlamydia trachomatis, and some protozoa. - Crystalluria: [sulfonamides can precipitate in urine, especially at neutral or acid pH. ] - Hypersensitivity. - Hemopoietic disturbances: [hemolytic anemia in G6PD deficiency.] - Kernicterus: [occur in newborns, sulfonamides can displace bilirubin from binding sites on serum albumin → Bilirubin pass into the CNS (BBB is not fully developed) ]
  4. 4. M.A.A.Al-Maqrashi Cont.ANA [Trimethoprim] static - Selectively inhibits bacterial dihydrofolic acid reductase - less efficient inhibitor of mammalian dihydrofolic acid reductase. - Sulfonamide (PABA competitor) + Trimethoprim (dihydrofolate reductase inhibitor) = bactericidal synergistic activity: treating UTI and respiratory tract infections. [Metronidazole] cidial - inflicts breaks in the DNA itself. - active against a wide range of anaerobes. [e.g. Clostridium difficile] - a second antimicrobial (eg, β-lactam) is usually added to cover aerobic and facultative bacteria. [Rifampin] ± cidial - Inhibits the synthesis of RNA from DNA by inhibiting RNA polymerase. - Active against most Gram-positive bacteria and selected Gram-negative organisms. - Used to treat tuberculosis.

×