Antibiotics Flashcards
What do antimicrobials target
An infectious disease
Describe how beta lactam antibiotics work
Act by inhibiting penicilin binding protein (PBP). PBP causes crosslinking of the peptidoglycan in the cell wall, therefore inhibiting this action weakens the cell wall
What are examples of beta lactam antibiotics
Penicillins and cephalosporins
Which bacteria can’t be targeted by synthesis inhibitors
Bacteria that don’t have a cell wall e.g. mycoplasma and urea plasma
Describe gram +ve bacteria
Bacteria that only have one plasma membrane surrounded by a thick cell wall which is made up of peptidoglycan which acts as a sort of exo-skeleton
Describe gram -ve bacteria
Have two cell membranes: the inner membrane and the outer membrane. Between the inner and outer membrane is a much thinner cell wall made of peptidoglycan
What are the 5 targets for antimicrobials
Cell wall synthesis, protein synthesis, nucleic acid synthesis, folate metabolism, cell membrane
Describe cell wall synthesis inhibitors
They inhibit synthesis of the cell wall. Beta lactam antibiotics characterised by the beta lactam ring and all inhibit transpeptidase by binding to the PBP
Why is nucleic acid synthesis a target for antibitoics
Bacteria divide every 20 minutes which means that they have to unwind their DNA, unwound DNA is a target for antibiotics
How do fluroquinolones (target nucleic acid synthesis) work
Inhibits topooisomerase II resulting in the strand breaking
How do fluroquinolones enter the cell
Through pores working synergistically with beta-lactams
What are side effects of fluroquinolones
Cartilage erosion and tenditis (therefore avoided in pregnancy and children).
What are examples of antimicrobials that target nucleic acid synthesis and how do they work
Nitrofurantoin directly damages DNA, Methronidazole interferes with DNA and protein interaction (anaerobic bacteria and amoebes), Rifampicin is an alternative fluoroquinolone which can be used if people suffer ADRs with the other types of fluoroquinolones. Rifampicin inhibits mRNA synthesis.
Why are there so many different antibiotics
Bacteria don’t react the same way to antibiotics in a test tube as they do in the human body. ADRs in patients. Superinfection. Bacteria can be resistant to antibiotics
What are examples of cell wall synthesis inhibitors
Benzylpenicillin, penicillin V, amoxicillin, flucloxacillin, co-amoxiclav, cefotaxime, vancomycin
What are examples of protein synthesis inhibitors
Clarithromycin, gentamicin, oxytetracyline
What are examples of DNA/ RNA synthesis inhibitors
Ciprofoxacin, nitrofuratoin, metronidazole
What are examples of metabolism inhibitors
Trimethoprim
Describe how antibiotics possess a degree of selective toxicity
They can have effects on bacteria without major effects on host mammalian cells, related to differences in structure (e.g. cell wall) and metabolic function of the two types of cell
What are the two things you have to consider when selecting an antibiotic
Infectious agent e.g. what it it and is it susceptible to the antimicrobial/ antibiotic. Patient- site of infection, patient factors, safety of agent, costs (pharmacokinetics/ pharmacodynamics, from uptake, everything that happens in between and secretion
How is identification of an infectious agent done
Taking a sample fro the patient, culture grown then studied by microscopic visualisation for the detection of microbial antigens. DNA/ RNA detection, antibody detection or mass spectrometry.
How do you chose the right antimicrobial
Suseptibility, antibiotic resistance, minimal inhibitory concentration- minimal drug concentration where no bacterial growth is detected
What can be used to assess is a respiratory infection is caused by bacteria or a virus
The biomarker C-reactive protein (CRP)
What are the key aspects to consider in differential diagnosis/ empiric therapy
Clinical symptoms, site of infection, patient’s history, where acquired, known association in clinical setting, antibiotic resistance
What is the most important cause for toxicity in children
Impaired hepatic function, especially in neonates
What can tetracyclines interfere with in children
Bone and teeth staining
What can fluorosquinolones interfere with
Cartilage
What is the most important factor in elderly
Reduced renal function- gentamycin contraindicated.
Who are commonly affected by poor circulation and what does this mean
Common in diabetics, may need to use a topical application and change of dose and dosage
What is the most common cause of antimicrobial allergies
Beta lactam antibiotics
Why is compliance important regarding antibiotics
Important to finish the course, otherwise the infection may come back, it creates antibiotic resistance
Why is a properly working immune system still very important even when taking antibiotics
Helps the antibiotics in clearing the infection, and also takes care of removing dead bacteria and initiate and accomplish an adaptive immune response
What are several factors that can affect the immune system
Primary (neutropenia, C-deficiencies) and secondary deficiencies (T-cell depletion in HIV) and other conditions like alcoholism and malnutrition, age (optimal at 20y), immunosuppressive drugs after e.g. transplantation, or viral infection
What do drugs that show bacteriostatic characteristics do
Stops growth. Host immune system will help eradicate microorganism: neutrophils, macrophages, complement system
What do drugs that show bactericidal characteristics do
Kills
What type of drug do you use in immunecompressed or immuneprivileged areas
Bactericidal
What are the different routes of antimicrobial administration
Oral, topical, intravenous (quick), intramuscular, intrathecal (not preferred as results on fits)
How long does it take antibiotics to reach maximal plasma levels after oral administration and what effect does food have
Takes 1-2 hours for antibiotics to reach maximal plasma levels after oral administration. Further delayed when ingested with food
What route of administration should you use if someone is critically ill
Not oral, quicker administration needed therefore IV antibiotics required
How can drugs be used to treat GI infections
Some drugs now come in a special coating meaning that the drug is only released after the stomach
Describe chemical properties that effect distribution of the drug
Lipid-soluble, polar, protein binding
How does being lipid soluble effect distribution of the drug
Well absorbed, general wide distribution (including cells, fat, CSF) as they can go through cell membranes
How does being polar effect distribution of the drug
Extracellular, low volume of distrubution, pKa/ pH dependent. Usually just distributed in the plasma bu when pH changes occur uptake is sometimes possible
How does protein binding effect distribution of the drug
Limits distribution, displaces other drugs. Best known carrier is albumin, this can cause displacement of other drugs or metabolic products
What are difficult drug targets in the body
Blood brain barrier, prostate, eye, intracellular bacteria. Poor circulation in diabetes can also be an issue.
What is one of the few antibiotics that can penetrate the blood brain barrier and enter the CSF under normal conditions
Chloramphenicol (only used in serious cases due to toxicity)
Describe how penicillins and cephalosporins are effective in treating bacterial meningitis
Normally cannot penetrate, But during this type of infection the meninges are inflammed and the blood brain barrier is broken down (tight junctions aren’t so tight) so these antibiotics can enter the CSF and reach therapeutic levels
What does the fact that some microorganisms can survive intracellularly mean
Can only use agents that penetrate the cell of the infected cells
Why is the fact that some antibiotics are metabolised important
You have to consider hepatic function
What occurs in liver disease
Drugs contraindicated- erythromycin and tetracyline that are concentrated or eliminated by the liver.
What effect does competition for the same pathway of metabolism have on the liver
Shortage of enzymes, slower metabolism, longer half life
What effect does inhibition of metabolism have on the liver
Caused by several antibiotics. Longer half-life e.g. warfarin- bleeding
What effect does enhancement of metabolism have on the liver
Caused by drugs e.g. rifampicin. Shorter half life of other drugs e.g. warfarin, oral contraceptives
What impact do drugs that cause gut disturbances have on the efficacy of the oral contraceptive
Less uptake
Describe elimination of antibiotics
Nearly all antibiotics eliminated via the kidneys (renally impaired, course of treatments for UTIs)
Why are combinations of antibiotics used
TB- only one antibiotic used= quick resistance. Serious infection- need less of each individual, less toxicity, more effiacy. Infection more than one microorganism- differences in sensitivites/ resistance. Unknown microorganism- use broad spectrum. Enhance effiacy
Describe when synergism is most favourable
Cell wall synthesis inhibitors weaken cell wall and so facilitate the entry of aminoglycosides and fluoroquinolones that normally cannot penetrate the cell wall. Each on their own would not be able to kill bacteria, combination does
Example of agent that has no antibiotic activity itself
Clavulanic acid, but mimics the structure of b-lactam antibiotics and so fools the b-lactamase: not synergism but a very useful combination: co-amoxyclav: combination of amoxicillin and clavulanic acid. The use of cell wall weakening antibiotics facilitates other antibiotics resulting in effective killing.
How do inhibitors of folate synthesis work
Bacteria cannot take up folate from the environment so have to make it themselves. Folate is important building block for the synthesis of amino acids and nucleotides
Describe how sulfonamides and trimethroprim work synergistically
Sulfonamides inhibit folate synthesis. Trimethoprim acts on the next metabolic step= act synergistically
What is the advantage of using two drugs in the way sulfonamides and trimethroprim work
You get an enhanced effect but you used the drugs at a lower dose and thus have less chance of toxicity
Describe a type A ADR
Toxicity- predictable, concentration dependent
Describe a type B ADR
Allergy- unpredictable, dose dependent
Describe a superinfection
Interference with commensal bacterial flora
What do you do in the case of resistance
Stop treatment, change treatment, treat side effect
