Week 2 Antibiotics: DNA + Protein Synthesis ✅ Flashcards
What are the 4 targets for DNA antibiotics?
DNA base synthesis
DNA strand breaking
DNA supercoiling
RNA polymerase
Which group of antibiotics work on DNA base synthesis?
Sulfonamides
Which antibiotics work on DNA strand breaking?
Metronidazole
Which group of antibiotics work on DNA supercoiling?
Quinolones
Which group of antibiotics work on RNA polymerase?
Rifampicin
Which are the 2 most important Sulfonomides to remember?
Trimethoprim and Nitrofurantoin
How does Trimethoprim work?
Inhibits dihydrofolate reductase
What kind of bacteria is Trimethoprim used for?
Broad spec (not Pseudomonas A)
Aerobic +ve staphylococcus, aerobic -ve E. coli, enterobacter, Klebsiella pneumoniae
What conditions can Trimethoprim be used for?
Uncomplicated UTIs e.g. cystitis
Why is Trimethoprim good for UTIs?
Excreted mainly unchanged
What are the adverse effects of Trimethoprim?
GI upset, rash, hyperkalaemia, haematological disorders
How does Nitrofurantoin work?
Damages RNA, DNA and proteins - free radical generated
Why is Nitrofurantoin good for resistance?
Multiple mechanism of action
What condition can Nitrofurantoin be used to treat?
UTIs - broad spec
Which UTI treating antibiotic is a pro drug?
Nitrofurantoin
Which drug is important to remember for DNA strand breaking?
Metronidazole
How does Metronidazole work?
Generates free radical which breaks down DNA
What type of bacteria does Metronidazole treat?
Anaerobic bacteria
What conditions can Metronidazole be used to treat?
GI tract infections, duodenal ulcers, C. diff
Which drug can be used to treat C Diff?
Metronidazole
Which antibiotic can cause C Diff?
Amoxicillin
Why is Metronidazole contraindicated with alcohol?
Metronidazole inhibits acetaldehyde dehydrogenase involved in alcohol metabolism
What symptoms can you get with alcohol and Metronidazole?
Flushing, headache, vomitting
Due to increase of acetaldehyde in body
Which important antibiotics are important to remember for inhibition of unwinding DNA supercoils?
Ciprofloxacin
Levofloxacin
Moxifloxacin
What are fluoroquinolones?
Active against -ve pseudomonas and anthrax
How do Fluoroquinolones work?
Helicase enzymes break H bonds in double helix
Gyrase and topoisomerase enzymes cut DNA strand during replication - INHIBITED
Why are Fluoroquinolones used as 2nd line antibiotics?
Resistance is easier
What bacteria are Fluoroquinolones used for?
Aerobic -ve
Which conditions are Fluoroquinolones used for?
UTI/severe GI
What is the only oral antibiotic for Pseudomonas A
Fluoroquinolones (Ciprofloxacin)
What is the important Fluoroquinolone antibiotic to remember?
Ciprofloxacin
What are respiratory quinolones?
Active against strep. pneumoniae
What are the 2 respiratory quinolones to remember?
Levofloxacin
Moxifloxacin
What are the differences between Levofloxacin and Moxifloxacin?
They are both active against MRSA (Levofloxain less so)
Both have enhanced gram +ve activity - Strep pseudomonae
What are the adverse effects of Fluoroquinolones?
Promote C Diff, colitis, nausea and diarrhoea
Increase arrhythmias (prolong QT interval)
Lower seizure threshold
Tendinitis -> rupture muscle tendons
What are the interactions of Fluoroquinolones?
Drugs/conditions that prolong the QT interval
NSAIDS - increases seizures
How are proteins made by bacteria?
RNA polymerase in nucleus
Transcription - makes mRNA from DNA using bases
mRNA goes to ribosome and binds
Ribosome reads mRNA and makes amino acid chain
tRNA carries amino acids to ribosome
mRNA read 3 bases at a time (codon)
Once finished, amino acids fold into 3D protein
What is Rafampicin?
Inhibits RNA polymerase
What is Rafampicin used to treat?
TB - 6-12m treatment as slow growing!
Also effective against leprosy
What is adverse effect of Rafampicin?
Induces CYP enzymes which decrease effect of liver metabolised drugs
What kind of bacteria is TB?
Mycobacteria
What are the symptoms of TB?
Cough, haemoptysis, fever, night sweats, weight loss
How does Isoniazid work?
Inhibits fatty acid synthase 2 (FAS-2) which polymerases fatty acids
What are the adverse effects of Isoniazid?
Causes hepatitis, peripheral neuropathy, increase plasma concentration of anti-epileptic drugs
How does Ethambutol work?
Inhibits arabinosyl transferase which prevents chains from attaching
What are the adverse effects of Ethambutol?
Optic neuritis, haemorrhaging, blue-yellow abnormalities, loss of visual field
Reversible
What is Pyrazinamide used for?
TB persisters - reduces treatment from 12m to 6m
How do tetracyclines work?
Block tRNA binding
What are examples of tetracyclines?
Aminoglycosides
Macrolides
Chloramphenicol
Doxycycline
What is Doxycycline used to treat?
Acne vulgaris, COPD, pneumonia, chlamydia, malaria, anthrax, lyme disease
What are the adverse effects of Doxycycline?
Nausea, vomitting, diarrhoea, oesophageal irritation/ulceration, photosensitivity
What is adverse effect of Doxycycline?
Binds to calcium (teeth and bones) - avoid in children
Which antibiotic is least likely to cause C diff/colitis?
Doxycycline
How are aminoglycosides adminstered?
IV/IM, narrow therapeutic index
How do aminoglycosides get into bacteria?
Water soluble so enter cells via O2-dependent pathway (absent in anaerobic bacteria)
What is an example of aminoglycosides?
Gentamicin
What is Gentamicin used for?
Severe sepsis, complicated UTI, endocarditis
What other antibiotics does Gentamicin work well with?
Penicillins as they weaken the cell wall to enhance aminoglycoside uptake
What bacteria is Gentamicin ineffective at treating?
Anaerobic
What are the adverse effects of Gentamicin?
Ototoxicity (permanent - auditory hair cells)
Nephrotoxicity
What bacteria can Chloramphenicol not be used to treat?
Pseudomonas
What is an adverse effect of Chloramphenicol?
Suppresses bone marrow (panocytopenia)
How is Chloramphenicol adminstered?
Topically e.g. eye ointment
Can Chloramphenicol penetrate CNS? How?
Yes - lipid soluble
How do Macrolides work?
Uptake by phagocytes to infection site
What is an example of a Macrolide?
Erythromycin
Clarithromycin
How do Macrolides work?
CYP3A4 inhibitor
What bacteria can Erythromycin treat?
Broad spec gram +ve and some -ve (similar to Penicillin)
What conditions can Erythromycin be used to treat?
Respiratory, skin and soft tissue infections
Penicillin allergies
H. Pylori and severe pneumonia (Legionaire’s)
What is the adverse effects of macrolides?
Oral irritation, colitis, QT interval prolong, increases drugs that are metabolised by liverH
How does Linezoid work?
Prevents tRNA initiating transcription
Which is the last new antibiotic?
Linezoid