Antibiotics and cytotoxics Flashcards
Tell me about penicillin
Penicillin can be a sensitizing agent that triggers a hypersensitive exaggerated allergic immune response (e.g. anaphylaxis) in some people. There is no established safe level of penicillin in non-penicillin drug products, therefore, preventing cross-contamination of other drugs with penicillin via complete and comprehensive separation (i.e. dedicated facilities) is required by current good manufacturing practice (cGMP) regulations.
Because of the potential health risks associated with cross-reactivity of beta-lactams, regulators expect manufacturers to treat all beta-lactam products, whether antibacterial or not, similarly to penicillin.
Less stringent cross-contamination prevention is only justifiable with extensive data demonstrating no or exceedingly low potential for severe adverse reactions.
Definitions:
Beta-lactam: an organic compound containing a four-membered lactam (cyclic amide). Examples opposite.
Cross-reactivity: The process by which a compound induces a hypersensitivity immune response, such as an allergic reaction, due to the sensitizing effects of a prior exposure to a different, but chemically related, antigen.
Can you name some antibiotics?
The main types of antibiotics include: Penicillins - for example, phenoxymethylpenicillin, flucloxacillin and amoxicillin. Cephalosporins - for example, cefaclor, cefadroxil and cefalexin. Tetracyclines - for example, tetracycline, doxycycline and lymecycline.
Explain the meaning of bactericidal and bacteriostatic?
“bacteriostatic” means that the agent prevents the growth of bacteria (i.e., it keeps them in the stationary phase of growth), and “bactericidal” means that it kills bacteria
Is Penicillin bactericidal or bacteriostatic?
Bactericidal antibiotics that inhibit cell wall synthesis: the beta-lactam antibiotics (penicillin derivatives (penams), cephalosporins (cephems), monobactams, and carbapenems) and vancomycin. Also bactericidal are daptomycin, fluoroquinolones, metronidazole, nitrofurantoin, co-trimoxazole, telithromycin.
How do Antibiotics work?
Antibiotics work by blocking vital processes in bacteria. They kill the bacteria or stop it from spreading. This helps the body’s natural immune system to fight the infection.
What is special about carbapenems?
Carbapenems exhibit unique pharmacological properties and are typically used to treat complicated bacterial infections. A carbapenem is often combined with an antibiotic that targets Gram-positive bacteria when used for the empirical treatment of patients with serious nosocomial infections of unidentified origin. Their unique molecular structure is due to the presence of a carbapenem together with the beta-lactam ring. Activity is maintained against most strains of E. coli and K. pneumoniae that are resistant to cephalosporins due to the production of extended spectrum beta-lactamases. Imipenem, doripenem, and meropenem also exhibit good activity against most strains of Pseudomonas aeruginosa and Acinetobacter species. Carbapenems, such as meropenem, are a group of vital often ‘last-resort’ antibiotics used to treat serious, multi-drug resistant infections when other antibiotics, such as penicillin, have failed.
Adverse effects (−) include increased resistance to one of the drugs used in the combination, as well as lack of synergy or additivity and strain dependence. VRSA, vancomycin-resistant S. aureus; ESBL, extended-spectrum β-lactamase producing; MBL, metallo-β-lactamase producing
Carbapenems have a safety profile similar to that of other beta lactam antibiotics such as the cephalosporins and the penicillins. The most common adverse effects are injection site reactions, diarrhea, nausea, vomiting, skin rash and pruritus
Contraindications. The carbapenems are contraindicated in those who are hypersensitive to them and, because of an increased risk of seizures, in pediatric patients with central nervous system infections.
What is a Beta Lactam?
Beta-lactams are antibiotics that have a beta-lactam ring nucleus.
β-Lactam antibiotics act by binding to penicillin-binding proteins (PBPs) and disrupting peptidoglycan cross-linking during cell wall synthesis, resulting in bacterial lysis and cell death
β-Lactam antibiotics are bactericidal agents that interrupt bacterial cell-wall formation as a result of covalent binding to essential penicillin-binding proteins (PBPs), enzymes that are involved in the terminal steps of peptidoglycan cross-linking in both Gram-negative and Gram-positive bacteria.
Can you handle antibiotics in a multi product facility
A risk assessment should be carried out but it is recommended that any product that is highly potent or hypersensitive should be manufactured in its own dedicated facility due to unknown hypersensitivity, risk anaphylaxis.
How do you prevent cross contamination with the rest of your site?
Dedicated facility, Procedural control e.g. once been in dedicated facility must not enter elsewhere on site before taking a shower or within a given timescale, facility and HVAC controls, dedicated equipment and personnel, dedicated clothing, dedicated warehousing and QC testing labs
How do you control and monitor these controls as QP?
PQS, training, Quality management review, self-inspections, PQR, deviations
Manufacture of antibiotics is segregated, controlled and you are happy as QP … where do you store the retained samples of this product ?
In a dedicated archive
is there any ‘problem’ with Erythromycin? Does that have the same effect as B-lactam type?
Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This is not a penicillin and can be taken by patients that are allergic to penicillin
What is the protein name within the cell wall of the bacteria that the penicillins interfere with?
Penicillin interferes with the production of a molecule called peptidoglycan. Peptidoglycan molecules form strong links that give the bacterial cell strength as well as preventing leakage from the cytoplasm. Nearly every bacterium has a peptidoglycan cell wall
Your company are about to start manufacturing a cephalosporin cream. Describe the manufacturing process and any concerns you may have.
Normal cream manufacturing process oil, water, mix together etc. Concern is more around the type of product as it contains a beta lactam ring so I would suggest manufacturing in a dedicated facility
What groups of antibiotics are cephalosporin?
Cephalosporins are beta-lactam antimicrobials used to manage a wide range of infections from gram-positive and gram-negative bacteria
