Anti-bacterial Flashcards
Which antibiotics target cell wall?
Penicillins
Cephalosporins
Carbapenems
Glycopeptides (vancomycin)
Which antibiotics target DNA synthesis?
Fluoroquinolones
Which antibiotics target DNA polymerase?
rifampin
Which antibiotics binds ribos and inhibit protein synth?
Aminoglycosides
tetracyclines
macrolides
Clindamycin
Chloramphenicol
Linezolid
What antibiotic classes are bacteriostatic?
Sulfonamides
Tetracyclines
Macrolides
Lincosamides
Stop growth
What antibiotics are bacteriocidal?
Cell wall inhibitors (penicillins, cabapenems, monobactams, glycopeptides)
Aminoglycosides (irreversibly inhibit protein synth)
Quinolones (prevent DNA replication through inhibition of DNA uncoiling)
Describe what an antagonistic antibiotic combination is
When combined drug has less effect than either of the agents alone
Describe an additive antibiotic combination
When combined effect of both drugs is equal to the sum of the individual drug’s independent effects
Describe an synergistic antibiotic combination
When the combined effect is greater than the sum of the independent effects
Describe an indifferent antibiotic combination
When combined effect is similar to the greater effects produced by either of the drugs alone
What are some examples of synergistic antibiotic combinations?
beta-lactam abx + aminoglycosides
glycopeptide abx + aminoglycoside
Sulfamethoxazole + trimethoprim
Amphotericin B + flucytosine
What are some examples of antagonistic antibiotic combinations?
Beta-lactamabs + tetracycline OR chloramphenicol
Penicillin + macrolide
Aminoglycoside + chloramphenicol
Which antibiotics have a time-dependent mechanism?
Penicillins
Cephalosporins
Glycopeptides
Macrolides
Lincosamides
Tetracyclines
AUC/MIC
Which antibiotics have a concentration-dependent mechanism?
Aminoglycosides
Fluoroquinolones
Cmax/MIC
What are the simple penicillins?
Benzylepenicillin (PenG), acid labile (destroyed by stomach acid, IV only)
Phenoxymethylpenicillin (PenV), acid stabile (when high [tissue] not required
What are the repository forms of penicillin?
Benzathine penicillin
procaine penicillin (more soluble)
*both forms are IM only, IV will kill
What are the anti-staph penicillin?
Dicloxacillin, Flucloxacillin = similar pharmacokinetics, antibacterial action, indication
Methicillin
Oxacillin
What are the aminopenicillins?
Amoxycillin
Ampicillin
Unable to protect against b-lactamase
What are the antipseudomonal penicillin?
Piperacillin, ticarcillin = alone, not resistant to beta lactamase
b-lactamase resistant = piperacillin w/ tazobactam, ticarcillin w/ clavulanic acid
*example of pharmaco-enhancement
What are the common ADRs of penicillin?
Diarrhoea, nausea, Superinfections (inc candidiasis = dec lactobacilli)
erythema, exfoliative dermatitis, angioedema
Anaphylactic shock, bronchospasm, serum sickness, electrolyte disturbances (sodium or potassium concentration), steven johnson syndrome, toxic epidermal necrolysis
What are the ADRs of di/flucloxacillin?
inc liver enz and bilirubin
Cholestatic hepatitis
Fluclox more hepatic ADRs
What are the ADRs for aminopenicillins?
Vomiting, diarrhoea = ampicillin
Pseudo-allergy
What are some antipseudomonal ADRs?
Rare = transient inc in liver enz bilirubin
Bleeding abnormalities w/ high dose = prolonged bleeding, altered platelet aggregation
Hypokalaemia
List penicillin precautions
Pregnancy/BF = safe
Renal impairment = dose reduced in renal impaired
Penicillin is incompatible with many substances (inc aminoglycosides), give separately
Describe how pharmacoenhancement is used with penicillin?
The use of probenecid to inhibit renal secretion and inc serum levels of penicillin
What are the class A beta-lactamase enz?
Clavulanate/ clavulanic acid
What are the class B beta-lactamase enz?
Tazobactam
sulbactam
What are the first generation cephalosporins?
Cephazolin, cephalexin, cefalotin
What are the second generation cephalosporins?
cefaclor, cefoxitin, cefuroxime
What do the first and second generation cephalosporins have in common?
Moderate spectrum drugs
What are the 3rd generation cephalosporins?
cefotaxime, ceftriaxone, ceftazidime
Extremely good at penetrating the BBB
What are the 4th generation cephalosporins?
cefepime
What do the 3rd and 4th generation cephalosporins have in common?
they’re all broad spectrum
What are the ADRs of cephalosporins?
Diarrhoea, nausea, rash, electrolyte dist
Vom, headache, dizziness, oral/vaginal candidiasis, c. diff associated disease (antibiotic induced pseudomembranous c.diff)
Anaphylactic shock, bronchial obstruction, urticaria, haemolytic anaemia, angioedema, steven johnson syndome
What are the cephalosporins precautions?
Allergy to cephalosporins due to penicillin allergy (urticaria, anaphylaxis or intestinal nephritis)
List the relevant carbapenems
Imipenem (given 6 hrs, high seizure risk)
meropenem (given 8hrly)
ertapenem (given once daily)
What inactivates imipenem? How prevent?
Renal dehydropeptidase I inactivates
Prevent = cilastin –> inhibits renal dehydropeptidase
What are the ADRs of carbapenems?
Imipenem = Neurotoxicity –> myoclonic activity, confusion, seizures (esp in hx of CNS disorders, renal impairment)
Meropenem = less neurotoxic
Ertapenem = seizures with CNS disorders or renal disorders
Name the monobactams and relevant facts
Aztreonam = less toxic than aminoglycosides, more stable than cephalosporins to AMP c beta-lactamase produced by G-ve organisms
susceptible to extended spectrum beta-lactamases (made by Klebsiella, E. coli, Enterobacter species
What are the relevant glycopeptides and their MOA?
Vancomycin, teicoplanin
MOA = prevent transpeptidase from snipping terminal transpeptidase on glycopeptide of bacteria preventing final stage of bacterial cell wall synthesis
Time dependent inhibition of bacterial cell wall cross linking
What are the ADRs of glycopeptides?
Reversible ototoxicity = vestibular and cochlear
Excessive infusion = erythematous rash on face and upper body
0% oral absorption, thus IV administration
Name the relevant macrolide antibiotics and a unique characteristic of the class
Erythromycin (prokinetic –> inc GI motility)
Clarithromycin, azithromycin (anti-inflammatory)
roxithromycin, telithromycin
What are the ADRs of macrolides?
N/V, diarrhoea, abdominal cramps, pain
Rash, fixed drug reaction
Anaphylaxis, acute resp distress, Stevens-Johnson’s syndrome, psychiatric disturbance, hearing loss, seizures
Clostridium C.diff associated disease, hepatitis, pancreatitis
What drugs do macrolides interact with?
Erythromycin = Cytochrome P450 inhibitor, inc serum levels (theophylline, carbamazepine, cyclosporine, diazepam, warfarin, lovastatin
Azithromycin, not a sig P450 inhibitor
List the lincosamides and their ADRs
Clindamycin (freq dosing), lincomycin
ADRs = antibiotic pseudomembranous colitis (there’s more)
Name the relevant tetracyclines
Doxycycline, minocycline, tetracycline
List some ADRs of tetracyclines
N/V, diarrhoea, epigastric burning, tooth discolouration, enamel dysplasia, reduced bone growth
Stomatitis, fungal overgrowth
nail discolouration, oesophageal ulcers, C. diff associated disease, hepatitis, fatty liver degeneration, allergic reactions
List some tetracycline precautions
Systemic lupus erythematosus
Treatment w/ oral retinoids = inc risk of benign intracranial HTN
Mindful of co-treatment w/ other hepatotoxic drugs
Renal impairment = doxycycline + minocycline can be dose adjusted
Hepatic impairment = hepatotoxicity more likely
Discuss the use of tetracyclines in children
Children <8 = discolour teeth, cause enamel dysplasia –> inc risk of dental carries
Deposits into bone –> deformities and growth inhibition
Discuss the use of tetracyclines in pregnancy and breastfeeding
Preg = safe in first 18 wks (16wks post conception) –>C/I after this
BF = courses of 7-10 days –> safe
List the relevant aminoglycosides and their route of administration
Gentamicin, tobramycin, amikacin, streptomycin
Parenteral only (no oral absorption)
List ADRs of aminoglycosides
Nephrotoxicity = treatment >7-10 days, gradual non-oliguric renal failure (acute tubular necrosis –> reversible)
Ototoxicity = vestibular ototoxicity (n/v, vertigo, nystagmus
Cochlea toxicity (hearing loss,= hearing loss, tinnitus, fullness in ear
List some aminoglycoside precautions
Allergic reactions, hx of treatment w/ nephrotoxic/ototoxic drugs (inc risk of toxicity)
Inc risk of toxicity = tinnitus, vertigo, hearing impairment, abnormal audiogram
Neuromuscular disease (e.g. myasthinea gravis)= inc muscle weakness/resp depression
Inc risk of neuromuscular ADRs = hypocalcaemia, hypermagnesemia, general anaesthesia, large transfusion of citrate blood
Dehydration = inc tox risk/nephrotox + ototox risk
List the relevant quinolones
Ciprofloxacin, ofloxacin, gatifloxacin, moxifloxacin
Norfloxacin = poor systemic F, reserved for UTI
List quinolone ADRs
rash, itch, n/v, diarrhoea, abdominal pain, dyspepsia
What are some precautions w/ quinolones?
Serious allergic reactions
Elderly = inc risk of tendon damage
What drugs interact w/ quinolones?
dairy productions, antacids, iron, zinc, or calcium = influence absorption
Inc effects of caffeine = reduce intake
Ciprofloxacin = inhibits CYP3A4
Gati/moxifloxacin = do not interact w/ hepatically metabolised drugs
List the relevant folate inhibitors
Trimethoprim = inhibits tetrahydropholic acid by inhibiting dihydrofolate reductase
Sulfamethoxazole = inhibits conversion of PBA to dihydrofolic acid by inhibiting dihydrotetrasynthase
What are some ADRs of folate inhibitors?
thrombocytopenia, n/v, fever, hyperkalaemia
photosensitivity, blood dyscrasias
Megaloblastic anaemia, erythema, crystalluria, urinary obstruction, hypoglycaemia, c. diff associated infection
Discuss sulfonamide/sulfur allergies
Allergic to sulfonamide functional group
Present as = fever, dyspnoea, cough, rash, eosinophilia
serious = anaphylaxis, steven johnson syndrome, serum sickness, hepatitis, vasculitis, pancytopenia
What other drugs may someone w/ a sulfur allergy be allergic to?
Sulfonyureas
thiazides
frusemide
celecoxib
List some precautions for folate inhibitor antibiotics
Check G6PD def –> inc risk of haemolysis w/ sulfonamides
Slow acetylator phenotype = greater risk of ADRs
Low urine pH = risk of crystalluria (esp w/ sulfamethoxazole)
Drugs which cause K+ retention = trimethoprim –> hyperkalaemia
Renal impairment = inc hyperkalaemia or hyperglycaemia, reduce sulfamethox dose
What are some C/I for folate inhibitors?
Pre-term infants and neonates <4wks = inc risk of kernicterus –> sulphonamides displace bilirubin from plasma
Late pregnancy = neonatal kernicterus, haemolytic anaemia, and jaundice
List the relevant nitroimidazole antibiotics
Mentronidazole (anaerobic bacteria)
Tinidazole (not in Aus) –> once daily
What are some ADRs with nitroimidazole?
N/V, anorexia, abdominal pain, metallic taste, CNS effect
Furry tongue, glossitis
Hypersensitivity reaction, dark urine, Stevens Johnson syndrome, seizure
What are some precautions with nitroimidazole?
Avoid alcohol –> disulfiram effect
Avoid use w/ disulfiram –> psychotic reactions
Nitroimidazole = neurotoxic, can aggravate existing neurological disease
Can cause leucopenia –> those w/ hx of blood dyscrasias
Increases fluorouracil toxicity –> avoid w/ fluorouracil
Renal impairment = metabolites accumulate in severe impairment, don’t need to adjust dose
Hepatic impairment = risk of accumulation and tox, reduce dose
