Antibiotics Flashcards
What can’t give macrolides alongside?
Statins - can increase risk of statin induced myopathy
How does Metronidazole work?
Damages DNA by forming reactive intermediates to inhibit DNA synthesis
Examples of glycopeptides
Vancomycin, Teicoplanin
When treating staphylococcus - what do you need to consider in terms of resistance?
90% of staphylococcus produces B-lactamase
What are plasmids?
Extrachromosomal genetic elements that exist in the cytoplasm and can replicate independently. Not known how they develop but can contain genes for antibiotic resistance. Can transfer between bacteria.
Problems with targeting Class I biochemical reactions?
Similar to human cells and pathogens can use alternative energy sources.
How does Rifampicin work?
Inhibits RNA polymerase to prevent mRNA transcription.
Key elimination routes for drugs
Usually liver metabolism and renal excretion but can be just renal.Other route - lungs, breast milk, sweat, tears, faeces.
How do tetracyclines work?
Bind 30S subunit. Competitive inhibition of tRNA.
How should time-dependent drugs be prescribed?
Need to maintain minimum inhibitory concentration for as long as possible. Give multiple doses throughout the day.
What is membrane permeability?
How well a drug can cross membranes to reach the site of action.
What is a B-lactam ring
Part of structure of penicillin that patients can develop an allergy to. Can then develop further allergies to other antibiotics that have the same structure.
How to remember quinolones
Ends floxacin
Examples of quinolones
CiprofloxacinLevofloxacin
Blood brain barrier and drug permeability
Drugs normally cannot cross. In meningitis the blood-brain barrier swells so there are larger gaps between the cells. Allows drugs through
What are Gram positive bacteria?
Bacteria can be classified on the basis of their cell wall.Gram positive bacteria have a cell wall made of multiple peptidoglycan layers.
What does Tazocin contain?
Piperacillin and TazobactimAntibiotic + B-lactamase inhibitor
How to B-lactamase inhibitors work and why are they used?
Irreversibly binds to B-lactamases. Broadens spectrum of antibiotics that contain B-lactam rings.
What is empiric antibiotic choice?
Choose antibiotic based on available information rather than the actual organism present. Allows to start treating right away instead of waiting for microbiology.
What is a steady state of drugs
When [drug] in plasma remains constant. Same amount entering as leaving.
How does chloramphenicol work
Inhibits transpeptidation (transfer of growing peptide chain to the amino acid attached to tRNA_
How do sulphonamides target antimetabolite activity
Targets enzyme required for folate synthesis
What is selective toxicity and what does it rely on?
Chemotherapy should be toxic to pathogens but leave host unharmed. Relies on exploiting biochemical differences between host and pathogen.
3 general classes of biochemical reactions that can be targeted.What is class III?
Pathways converting small molecules into macromolecules.
4 mechanisms of action in antibiotics
- Disruption of cell wall* Inhibition of nucleic acid synthesis* Inhibition of protein synthesis* Antimetabolite activity
What are transposons?Why are they important?
Stretches of DNA that can be easily transferred from plasmid to chromosome as transfer can occur outside of mitosis. Can inset even if host is unable to replicate. Likely cause of widespread distribution of antibiotic resistance between unrelated bacteria.
How do bacteriostatic antibiotics work?
Stops further growth of bacteria but won’t kill bacteria already present.
What does co-amoxiclav contain?
Amoxycillin and clavulanic acidAntibiotic + B-lactamase inhibitor
Adverse affects of glycopeptides
Red man syndrome. Generalised erythema and poss hypotension/bronchospasmNephrotoxicity
How should concentration dependent drugs be prescribed
Higher concentrations of these drugs are most effective.. Give a high dose to reach a large peak which is allowed to drop before the next dose is given. Once a day dosage.
3 general classes of biochemical reactions that can be targeted.What is class I?
Reactions to produce ATP
What are the 3 key differences between bacteria and human cells?
Bacterial cell wall - no counterpart in eukaryotes.No nucleus in bacteria - have a single chromosome in the cytoplasm.No mitochondria in bacteria - generate energy by enzyme systems in plasma membrane.
What is an antibiotic?
A drug used to treat infections caused by bacteria. Most commonly prescribed drug in primary care.
How can antibiotics target formation of the peptidoglycan cell wall?
Peptidoglycan are formed inside the bacterial cell, transported outside by a lipid carrier and cross-linked to form a strong lattice with other amino acids. Target either release of peptidoglycan or cross-linking.
How do spontaneous mutations cause antibiotic resistance?
Spontaneous mutations - low rate for a given gene but as so many cells with short generation time, rate of mutation is reasonably high.
Side Effect of rifampicin
Stains body secretions orange
How do aminoglycosides work
Bind to 30S subunit and cause misreading of mRNA - production of non-functional proteins.
How do antibiotics target antimetabolite activity?
Folate is essential for DNA synthesis. Bacteria need to synthesise folate while humans get it from their diet. Either inhibit mechanism of synthesis or inhibit folate usage.
How do antibiotics target nucleic acid synthesis
Inhibit the enzymes involved in various stages of nucleic acid synthesis.
Use of vancomycin
Last resort drug for MRSA
When choosing empiric antibiotics need to consider:
- Active against likely organisms* Reaches site of infection - appropriate route?* Low toxicity - not taken if poorly tolerated* Suitable for patient
Resistance in staphylococci
Many strains now resistant to almost all antibiotics. One of commonest causes of hospital acquired infections.
How does trimethoprim target antimetabolite activity
Targets enzyme required to metabolise folate into useful metabolites
How to remember aminoglycides
Ends in cin (not thromycin)
Adverse effects with tetracyclies
Concentrates in tissues undergoing calcification. Can stain teeth. Not used in children/pregnancy.Also causes phototoxicity - like sunburn.
How to remember Cephalosporins
Starts Cef
What are patients with penicillin allergies often also allergic to?
Cephalosporin - 2.5% of those with penicillin allergies are also allergic to this.
Lipophilic drugs - what needs to be considered when prescribing?
Accumulate in adipose tissue.
Use of Trimethoprim
First line treatment for uncomplicated UTIs
3 general classes of biochemical reactions that can be targeted.What is class II?
Pathways using energy and class I compounds to produce small molecules.
What are macrolides useful alternatives to
Penicillins
When to avoid quinolines
Epileptics - reduces seizure threshold
How do glycopeptides work?
Disrupt cell membrane - Inhibit release of building block for peptidoglycan layer from the lipid carrier.
What is a pro drug
Drug given in inactive form and converted to active form in body
What is chemotherapy?
Use of drugs selectively toxic to pathogens with minimal effects on the host.
2 key methods of transfer of resistance genes:
Conjugation - Cell-cell contact. Main method.Transduction - Plasmid DNA enclosed in bacteriophage.
Examples of Beta lactams
Penicillins, Cephalosporins, Carbapenems.
How to remember tetracyclines
Ends cyclone
Patient experienced diarrhoea when taking antibiotic previously - how to consider for future prescriptions
Intolerance not a side effect. Doesn’t stop giving antibiotics if needed.
How could gene amplification cause antibiotic resistance?
Theory that antibiotic use can increase the number of copies of preexisting resistance genes.
Example Cephalosporins
Cefadrine, Cefaclor, Cefotaximine
How to extend spectrum of penicillins
Mix with clavulnic acid
What are Gram negative bacteria?
Bacteria can be classified on basis of cell wall.Gram negative bacteria have a single peptidoglycan layer in their cell wall.
Example aminoglycosides
Gentamicin, Amikacin
Example tetracyclines
TetracyclineDoxycycline
How do Beta lactams work?
Disrupt cell membrane - Inhibit cross linking of bacterial peptidoglycan wall by forming covalent bonds with penicillin-binding proteins.
Examples of macrolides
ClarithromycinErythromycin
What are the most important class of biochemical reactions for drug targets?
Class III. Act to inhibit nucleic acid synthesis, protein synthesis or peptidoglycan synthesis.
What does B-lactamase do?
Bacterial enzyme that breaks the B-lactam ring and inactivates the antibiotic.
Recent changes to vancomycin resistance
Resistance seems to have developed spontaneously. Potential for major clinical implications.
How to remember penicillins
End cillin
How to remember macrolides
Ends thromycin
Examples of B-lactamase inhibitors
Clavulanic acidTazobactam
What bacteria doesn’t penicillin work on
Mycoplasma as no cell walls. No use for pseudomonas.
How are Class II biochemical reactions targeted?
Bacteria have to synthesise folate but humans get it through diet. Target folate synthesis/usage to stop DNA synthesis.
What drug to use for anaerobic bacteria?
Metronidazole
How do quinolones work
Inhibit DNA gyrase enzyme to prevent DNA supercoiling
How to Cephalosporins work
B-Lactam antibiotics - target cell wall
Advantages and side effects of flucoxacillin
Good penetration of soft tissueSide effects include liver damage esp if taken on long term basis.
How do antibiotics inhibit protein synthesis
Protein synthesis occurs in ribosomes. Bacterial ribosomes are 30S/50S compared to 40S/60S in humans so can specifically target the bacterial ribosome.
What is the minimum inhibitory concentration of an antibiotic
The lowest concentration of antibiotic that will inhibit visible growth of a microorganism.
What is drug clearance
Volume of blood cleared of drug per unit time
Side effects of metronidazole
Metallic taste (awful)Vomiting and rashesInstant, severe hangover if mixed with alcohol
3 ways of spread of antibiotic resistance
Transfer of resistant bacteria between peoplePlasmidsTransposons
How do macrolides work?
Binds to 50S subunit and inhibits translocation.
Why should care be taken when prescribing antibiotics?
Multi-drug resistance increasing
Loss of antibiotics would be devastating - would make routine operations impossible.
Gaining resistance may make bacteria stronger.
4 common conditions where antibiotics should not be used routinely?
Upper respiratory tract infection
Acute sinusitis
Acute conjunctivitis
Acute otitis media
What to consider before prescribing antibiotics?
Patients life in danger? Infection could cause permanent damage? Will infection resolve fully? Will antibiotics shorten illness? Will antibiotics reduce symptoms Patient's ICE - managing
What is a self-limiting illness
Resolves without treatment. Minimal change in course of illness if antibiotics take. May reduce symptoms and shorten course of illness.
