Treatment of infections Flashcards
describe the mode of action of penicillins
Target: Bacterial penicillin-binding proteins/transpeptidase enzymes
Action: Inhibitor
Effect: Inhibit cross-linking of NAMA/NAG peptide chains in the peptidoglycan bacterial cell wall
Overall effect: Weakening of bacterial cell wall leading to lysis (bacteriocidal)
list some types of penicillin
change R side chain
Benzylpenicillin (poor GI absorption and susceptible to β-Lactamases)
Broader spectrum – Amoxicillin
(combined with β-Lactamase inhibitor clavulinic acid- Co-Amoxiclav) – rope-a-dope*
β-Lactamase resistant - Flucloxacillin
Extended spectrum – Piperacillin /Ticarcillin
(combined with β-Lactamase inhibitors (e.g. Tazobactam) to make Tazocin / Timentin)
briefly describe the pharmacokinetics of penicillins
Oral absorption variable
Widely distributed in body fluids - likely to reach infection no matter where it is
Mainly renal excretion (tubular secretion)
Short plasma half-life
describe the uses of some penicillins
Benzylpenicillin
- Bacterial meningitis
Amoxicillin
- Resp Infections
- UTI
- Otitis media
- (most widely used)
Flucloxacillin
- Cellulitis
Piperacillin
- Severe infection / pseudomonas
- can be used in septic shock
describe some adverse effects of penicillins
Generally very few adverse effects
- Hypersensitivity
- Skin rash / fever
- Anaphylaxis
- Oral – antibiotic associated diarrhoea
describe the mode of action of Cephalosporins
smilier to penicillins
Target: Bacterial penicillin-binding proteins/transpeptidase enzymes
Action: Inhibitor
Effect: Inhibit cross-linking of NAMA/NAG peptide chains in the peptidoglycan bacterial cell wall
Overall effect: Weakening of bacterial cell wall leading to lysis (bacteriocidal)
list some of the uses of cephalosporins
Use has decreased in last few years
Cefotaxime / Ceftriaxone
- Meningitis
Ceftazidime
- Bronchiectasis infections (depending on organism)
briefly describe the pharmacokinetics of Cephalosporins
Most need to be given parenterally
Excreted by the kidney (ceftriaxone 40% bile)
“10%” (probably <1%) cross-sensitivity with penicillins
- This figure is being re-analysed and is probably a lot lower for 2nd and 3rd generation cephalosporins
Occassional nephrotoxicity / alcohol intolerance
name some macrolides
Erythromycin
Clarithromycin
Azithromycin
describe the mode of action of macrolides
protein synthesis inhibitor
Target: 50s subunit of bacterial ribosome
Action: Reversibly bind
Effect: Prevent transfer of bacterial tRNA from A-site to P-site on the ribosome, thus preventing elongation of the polypeptide chain (bacteriostatic)
Overall effect: Inhibit bacterial protein synthesis
list some adverse effects of macrolides
Common:
- GI upset (nausea, vomiting, abdominal discomfort, diarrhoea)
- Taste/smell disturbance
- hypersensitivity reactions
Important:
- QT interval prolongation - arrhythmias
Contra-indications and cautions
- Caution in hepatic and renal impairment (avoid if severe) (due to effect on cytochrome P450 system) and in patients with predisposition to QT interval prolongation
name some quinolones and what are their endings
-floxacin
Ciprofloxacin
Levofloxacin
Moxifloxacin
describe the mode of action of Quinolones
Target: Bacterial DNA gyrase (topoisomerase II)
Action: Inhibitor
Effect: Inhibit supercoiling of the bacterial DNA double helix
Overall effect: Prevent bacterial DNA replication, transcription, repair and recombination
describe some clinical indications of Quinolones
Quinolones are active against gram –ve and gram +ve bacteria, particularly gram –ve enteric coliforms.
Urinary tract infection
describe some adverse effects of Quinolones
GI upset – Caution re c. diff risk
Hypersensitivity
Rarely convulsions – caution in epilepsy (or if on theophylline / NSAIDs)
Caution QT prolongation
Inhibits CYP450 increasing theophylline toxicity
FDA July 2016 re: possible temporary or permanent disability added to SPC
name two aminoglycosides
Gentamicin
Tobramycin
describe the mode of action of aminoglycosides
Target: Bacterial 30s ribosomal subunit
Action: Inhibits normal ribosomal functioning in 3 ways:
Effect: Interfere with the initiation complex of peptide formation, induce misreading of mRNA, break up ribosomal clusters (polysomes)
Overall effect: Block bacterial protein synthesis leading to cell death (bacteriocidal)
NB. Aminogylcosides require oxygen-dependent transport to enter the bacterial cell and are
therefore ineffective against anaerobes.
describe the uses of aminoglycosides
Effective against aerobic Gm-ve and some Gm+ve organisms
Especially in Gm-ve sepsis (Gent) in combination with a penicillin (synergy)
Tobramycin for Pseudomonas infections often in combination with another anti-pseudomonal antibiotic
briefly describe the pharmacokinetics of aminoglycosides
Highly polar molecules – therefore IV admin
Variable penetration into body fluids
Eliminated by kidney T1/2 2-3 hours
Elimination mirrors eGFR
MUST reduce dose and frequency in renal impairment to prevent dose dependent side effects
describe the adverse effects and interactions of aminoglycosides
Important:
> Nephrotoxicity (usually reversible when drug stopped)
> Ototoxicity (usually irreversible) (rare before 2 weeks of treatment)
- damage of sensory cells in the vestibulo-cochlear apparatus
- Deafness and/or vertigo/ataxia
Contra-indications and cautions:
- Caution in renal impairment and extremes of age
- Avoid in pregnancy and in patients with myasthenia gravis
Interactions:
- Loop diuretics e.g. Furosemide (increased risk of ototoxicity – do not co-prescribe)
- Vancomycin (increased risk of ototoxicity)
- NSAIDs (increased risk of nephrotoxicity)
describe Therapeutic drug monitoring in aminoglycosides
Safety: Renal function should be measured at baseline, re-check U+E regularly during treatment; ask
patient to report any changes in hearing or balance to detect ototoxicity
Serum aminoglycoside levels should be checked regularly – scheduling of monitoring varies depending on single-dose or multiple dose regimens. Blood samples should be taken 1 hour after IV or IM administration (peak concentration) and just before the next dose (trough concentration).
If peak is high, reduce dose. If trough is high, increase dosage interval (+/- reduce dose).
name two tetracyclines
Tetracycline
Doxycycline