- Slides: 12
Chemotherapy as a science began in the first decade of the 20 th century with understanding of the principles of selective toxicity, the specific chemical relationships between microbial pathogens and drugs, the development of drug resistance, and the role of combined therapy.
Range of action of antibiotics Antibiotics can be divided into 3 main categories : - a – Action mainly against G+ve organisms like : penicillin , erythromycin & lincomycin. b – Action mainly against G-ve organisms like : polymyxin & nalidixic acid . (the above groups called narrow spectrum) c – Action against both G+ve & G-ve organisms ( broad spectrum activity ) ampicillin & ciprofloxacin.
Mechanisms of action of chemotherapeutic agents � � 1 – Inhibition of cell wall synthesis : - such as ß-lactams that include penicillins & cephalosporins interfere with cell wall synthesis and use bacteriolysis. 2 – Inhibition of cytoplasmic membrane function : - for example polymyxins & nystatin. 3 – Inhibition of protein synthesis : - such as : tetracyclines , erythromycin and noglycosides e. g. tobramycin & gentamycin . 4 – Inhibition of nucleic acid synthesis : - Such as : quinolone , refampicin , novobiocin & sulfonamide. . 5 – Competitive inhibition : - In which the drugs compete with an essential metabolite for the same enzyme e. g. Such as sulfonamide resemble to p – aminobenzoic acid ( PABA ) is an essential metabolite for DNA synthesis.
Mechanisms of resistance � to antimicrobial agents
1 – The organism produced enzymes that destroy the drug e. g. production of ß – lactamases that destroy penicillin by penicillin resistant staphylococci & acetyltransferase which produced by gram negative bacilli destroy chloramphenecol. 2 – The organism change its permeability to the drug by modification of protein in the outer cell membranes , thus impairing its active transport into ymyxins. 3 – The organism develop an altered receptor site for the drug e. g. resistance to aminoglycosides is associated with alteration of a specific protein in the 30 s subunit of the bacterial ribosome that serve as a binding site in susceptible organisms. 4 – The organism develop an altered metabolic pathway that by passes the reaction inhibited by the drug e. g. sulfonamide-resistant bacteria acquire the ability to use performed folic acid with no need for extracellular PABA
Origin of resistance to � antimicrobial agents
A – Non genetic drug resistance : - this include 1 – Metabolic inactivity : - Most antimicrobial agents act effectively on replicating cells , non multiplying organisms are phenotypically resistant to drugs such as M. tuberculosis which survive for years in tissues & their resistance is due to metabolic inactivity but if they start multiply after suppression of cellular immunity of the e drugs. 2 – Loss of target structure : - Protoplast or Lforms of bacteria are penicillin resistant because they lost their cell wall which is a structural target site of the drug. 3 – Bacteria may infect the host in the sites where antimicrobial are exclude or not active e. g. amino glycosides such as gentamycin are not effect in treating of enteric fever because of the Salmonellae are intracellular & aminoglycosides do not inter to the cells
Genetic drug resistance : - this include 1 – Plasmid mediated resistance : - Plasmid is an extrachromosomal genetic elements associated with bacterial resistance to antibiotics , plasmids frequently carry many genes that code for the production of enzymes that inactivate or destroy the antibiotics e. g. ß- lactamases which destroys the ß- lactam ring in penicillin & cephalosporin , plasmids may result in epidemic resistance among bacteria by moving from one to the other by conjugation , transduction or transformation. 2 - Transposon-mediated resistance : - Many transposons carry genes that code for drug resistance , as they move between plasmids & chromosomes they can transfer this property to bacteria. the process called transposition. 3 – Chromosomal drug resistance : - This develop as a result of spontaneous mutation in a genes that controls susceptibility to an antimicrobial agents
What are the side-effects of antibiotics? � Below is a list of the most common side-effects of antibiotics: � Diarrhea - researchers from Stanford University School of Medicine found that a rise in sugars in the gut following antibiotic treatment allows harmful bacteria to get a foothold and cause infection. Harmful bacteria thrive on sugar. � Feeling and being sick. � Fungal infections of the mouth, digestive tract and vagina. Below is a list of rare side-effects of antibiotics: � � Formation of kidney stones (when taking sulphonamides). � Abnormal blood clotting (when taking some cephalosporins). � Sensitivity to sun (when taking tetracyclines). � Blood disorders (when taking trimethoprim). � Deafness (when taking erythromycin and the aminoglycosides). �
Some patients, especially elderly ones, may experience inflamed � bowels (a type of colitis) which can lead to severe diarrhea. Clindamycin, an antibiotic used for the most serious infections, commonly has this side effect. However, although much less common, penicillins, cephalosporins and erythromycin might do too. In August 2012, Scientists from the NY School of Medicine found � that babies who are exposed to antibiotics have a greater risk of becoming overweight or obese children. Their study was published in the International Journal of Obesity. Allergic reactions to antibiotics � Some patients may develop an allergic reaction to antibiotics - � especially penicillins. Side effects might include a rash, swelling of the tongue and face, and difficulty breathing. Allergic reactions to antibiotics may be immediate or delayed � hypersensitivity reactions 2. If you have ever had an allergic reaction to an antibiotic you must � tell your doctor and/or pharmacist. Reactions to antibiotics can be very serious, and sometimes fatal - they are called anaphylactic reactions.
Complications of antibacterial chemotherapy 1 – Development of drug resistance 2 – Drug toxicity (nephrotoxicity and ototoxicity) 3 – Superinfection 4 – Hypersensitivity 5 - Diarrhea and some cases lead to bowl (colitis) inflammation of 6 - babies who are exposed to antibiotics have a greater risk of becoming overweight or obese children