Macrolide and Polypeptide Antibiotics Skin/skin structure infections: Furunculosis, pyoderma and impetigo due to Staphylococcus aureus, S pyogenes or S agalactiae Adverse reactions include vomiting, dyspepsia, flatulence, jaundice, palpitations, chest pain Allergic reactions include rash, photosensitivity and angioedema CNS side effects are headache, dizziness, vertigo and fatigue CLARITHROMYCIN It is a macrolide antibiotic obtained by substitution of hydroxyl group by a CH3O group in the erythromycin lactone ring It is found to be to 10 times more active than erythromycin Clarithromycin is readily and rapidly absorbed after oral administration and is metabolized significantly in liver Active metabolite is excreted by kidney and other routes It is indicated in the treatment of lower respiratory tract infection e.g bronchitis and pneumonia, upper respiratory tract infections e.g pharyngitis and sinusitis, infections due to chlamydia, legionella and mycoplasma, skin and soft tissue infections and eradication of H pylori with acid suppressants The most frequently reported side effects are GI-related complaints i.e nausea, dyspepsia, abdominal pain and diarrhoea Other side effects include headache, skin rash and transient elevation of liver enzymes, hepatic dysfunction with or without jaundice and psychosis 333 bosomes and hence suppresses protein synthesis It is 7-chloro-7-deoxylincomycin, a semisynthetic derivative of lincomycin It inhibits most of the gram positive cocci e.g streptococci, staphylococci and pneumococci, C diphtheriae, Actinomyces, Nocardia and Toxoplasma It is used in the treatment of severe anaerobic infections caused by bacteroides and other anaerobes It is also used in combination with aminoglycoside in the treatment of abdomen and GIT wounds, infections of female genital tract, pelvic abscesses, aspiration pneumonia and septic abortion It is also used for prophylaxis of endocarditis It is also used along with primaquine in Pneumocystis carinii pneumonia in AIDS patients and with pyrimethamine for toxoplasmosis Oral absorption is good It is largely metabolized and metabolites are excreted in urine and bile Adverse effects include pain at injection site, stomatitis, glossitis, angioneurotic edema, serum sickness, vertigo, tinnitus, aplastic anaemia Hypotension and cardiac arrest after rapid IV use Anorexia, metallic taste, oesophagitis, abdominal pain LINCOMYCIN CLINDAMYCIN It is mainly bacteriostatic and inhibits the growth of gram positive organisms which includes staphylococci, streptococci, pneumococci, C diphtheriae and B anthracis Like erythromycin it act by interfering with protein synthesis It is a lincosamide and act by binding exclusively to 50S submit of the bacterial ri- Adverse effects include nausea, vomiting, diarrhoea, abdominal pain, Section 9/ Chemotherapy 334 pseudomembranous colitis, dizziness, rash, headache, pruritus, jaundice, leucopenia etc POLYPEPTIDE ANTIBIOTICS It is indicated in upper and lower respiratory tract infections, skin infections, septicaemia, bone and joint infection including acute haematogenous osteomyelitis They have bactericidal activity against gram negative bacteria only and are low molecular cationic polypeptide antibiotics VANCOMYCIN POLYMYXIN B It is a glycopeptide antibiotic and primarily active against gram positive bacteria, strains of Staph aureus which are resistant to methicillin are inhibited by vancomycin It is also effective against Strep viridans, enterococcus, Clostridium difficile and diphtheroids Has detergent like action on cell membrane and have high affinity for phospholipids They penetrate into and disrupt the structure of cell membranes, as a result of which amino acids and ions leak out It is bactericidal drug and it exerts it action by inhibiting the synthesis of the cell wall in sensitive bacteria After oral administration negligible or no absorption occurs After oral administration it is poorly absorbed It is given by parenteral route and high concentration of drug may accumulate when renal function is impaired It is indicated in serious life threatening staphylococcal infections resistant to other antibiotics, in severe staphylococcal infections in patients who are allergic to penicillin and cephalosporin Adverse effects include skin rash, anaphylaxis, nephrotoxicity, ototoxicity like other aminoglycosides Other side effects are local pain and phlebitis at the site of injection, fever, eosinophilia and hypotension They are listed in table 9.5.2 It is used systemically in enteric infections caused by gram negative organisms and topically for pseudomonal infections of conjunctiva and cornea, burns and skin Adverse effects include nausea, vomiting, diarrhoea after oral administration Parenteral administration (IM) cause pain, flushing, ototoxicity, nephrotoxicity and neurotoxicity COLISTIN Also known as polymyxin E, is also a cationic detergent used only orally Side effects and uses are similar to polymyxin B Table 9.5.2: Classification of polypeptide antibiotics Polymyxin B (AEROSPORIN) Colistin (as sulphate) (WALAMYCIN) Bacitracin Tyrothricin 15,000-25,000 U/kg daily for 7-10 days 25-100 mg TDS 250 µ/g powder, skin/eye ointment (0.5 mg/kg skin cream, 0.2 mg/ml solution (topical), 0.05% as otic solution with benzocaine Macrolide and Polypeptide Antibiotics 335 BACITRACIN TYROTHRICIN This antibiotic is obtained from Bacillus subtilis It is effective against gram positive (cocci and bacilli), Neisseria and H influenzae It is used only topically as antibacterial powder, skin and eye ointment and acts by inhibiting the cell wall synthesis It is bactericidal It is obtained from Bacillus bravis and effective against gram positive and some gram negative organisms It acts on bacterial cell membrane causing leakage and uncoupling of oxidative phosphorylation Used topically as skin cream and solution This page intentionally left blank r r e e t t p p a CChh 9.6 1.4 Pharmacodynamics Antiviral Agents (Mode of Action of Drugs) Viruses have no cell wall and made up of nucleic acid core enclosed in a protein coat which consists of identical subunits Viruses are of two types, DNA (deoxyribonucleic acid) viruses and RNA (ribonucleic acid) viruses DNA viruses are herpes simplex, small pox, hepatitis B, varicellazoster etc and RNA viruses are rabies, measles, dengue, rubella, yellow fever, poliomyelitis and HIV etc In viral infections, replication of viruses are at peak, at or before the manifestation of clinical symptoms So, the treatment generally depends either on early initiation of therapy or prevention of infection i.e chemoprophylaxis It prevents the replication of DNA viruses and its clinical use is limited to herpes simplex keratitis Toxicity includes alopecia, leucopenia, thrombocytopenia and liver damage It is used in herpes simplex keratoconjunctivitis in 0.1 to 0.5% solution/eye ointment applied one to two hourly ACYCLOVIR Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against human herpes viruses The various antiviral agents are classified as under (the doses for specific infections is given in text) in table 9.6.1 Acyclovir triphosphate interferes with the viral DNA polymerase and inhibits viral DNA replication with resultant chain termination following its incorporation into the viral DNA ANTI-HERPES AGENTS Acyclovir is only partially (20%) absorbed from the gut IDOXURIDINE It is chemically related to thymidine and acts by competing with it in the synthesis of DNA and ultimately preventing the utilization of thymidine Most of the drug is excreted unchanged by the kidney by tubular secretion and glomerular filtration.9Carboxymethoxymethylguanine is the only significant metabolite of acyclovir recovered from the urine ... Clostridium difficile and diphtheroids Has detergent like action on cell membrane and have high affinity for phospholipids They penetrate into and disrupt the structure of cell membranes, as a result of... 9.5.2 It is used systemically in enteric infections caused by gram negative organisms and topically for pseudomonal infections of conjunctiva and cornea, burns and skin Adverse effects include nausea,... (AEROSPORIN) Colistin (as sulphate) (WALAMYCIN) Bacitracin Tyrothricin 15,000-25,000 U/kg daily for 7-10 days 25-100 mg TDS 250 µ/g powder, skin/eye ointment (0.5 mg/kg skin cream, 0.2 mg/ml solution