Lecture 6 - Antimicrobials 2 Flashcards
Aminoglycosides
Give 2 Examples
- Gentaminicin
- Tobramycin
Aminoglycosides
Class of Drug
Mode of Action
Dont work with?
- Bactericidal antibiotic
- Inhibits bacterial protein synthesis
- Require oxygen dependent transport mechanisms in order to enter cell, thus not too effective with anerobes
- However, work synergestically well with beta-lactam inhibitors and vancomycin
Aminoglycosides
Target
Mode of action
- Bind to the 30-s subunit
- Protein synthesis is inhibited in 3 ways:
- Interfere with the initiation complex of peptide formation
- Induce mis-reading of mRNA
- Break up polysomes (clusters of ribosomes)
Aminoglcysosides
Uses
Treatment regimen for sepsis, which type of sepsis?
Which to use for Pseudomonas Infections?
Effective:
- Aerobic Gram -ve
- Some aerobic Gram +ve
Gram -ve sepsis
- Use Gentamicin and Penicilin
- Synergy
Pseudomonas Infection
- Use Tobramycin
- Often in combination with another anti-pseudomanal treatment via. nebuliser
Aminoglycosides
Pharmacokinetics
- Highly polar
- IV administration recommended
- Variable penetration in body fluids
- Elimintated by the kidney
- Half life = 2/3 hours
- Elimination is mirrored through the patients eGFR
- Lower eGFR = slower rate of elimination thus administer a lower dose to the patient
- MUST REDUCE FREQUENCY AND DOSE in patients with renal failure as the levels of drug will become toxic fast due to the decreased rate of elimination
Aminoglycosides
Adverse Effects
Further explain each
Higher risk if…
Ototoxicity
- Progressive
- Usually reversible
- Damage to the sensory cells of the vestibulo-cochlear apparatus
- Deafness/and or vertigo, ataxia
Higher Risk
- Can occur especially if the patient is on the drug for >2/52 weeks??
- Can also occur if patient is on another ototoxic drug such as a loop diuretic
Nephrotoxicity
- Damage to the tubules is usually reversible if the drug is stopped
Higher Risk…
- Previous renal impairment
- If using concamitantly with other drugs that are Nephrotoxic
- Cephalosporins
- NSAIDS
- Anti-fungals
Aminoglycosides
Explain the vicous circle
How can we minimise the effects?
- The vicous circle refers to nephrotoxicity occuring due to high levels of the drug circulating and this then leading to reduced clearnace which furthers the levels of nephrtoxixcity thus leading to renal failur
- AVOID BY MONITORING
Monitoring
- Endocarditis: 8 Hours
- Other conditions: daily
- Should measure serum trough levels after the 1st dose (prior to the administration of the 2nd dose)
- Peak: 5-10mg/L (3-5mg/L if TDS - three times daily)
- Trough: <1-2mg/L
- Monitor Urea + Electrolyte !!!!!!
Severe Sepsis and Septic Shock
Define
Severe Sepsis and Septic Shock is diagnosed in the presence of ALL 3 of the listed below
- Strong clinical impression of severe infection
-
2 of the following:
- Temp >38 or <36
- HR > 90 bpm
- RR > 20 breaths per min or PaCO2 is < 4.3 kPa
- White cell count > 12 or <4
-
Signs and symptoms of organ failure or shock
- Systolic BP <90mmHg or fall of >40mmHg from baseline
Tetracylcines
Give 2 Examples
Class of Drug
Mode of Action
Target
Effect
Use
AE - Specific?
DONT GIVE TO?
Examples
- Doxycycline
- Tetracycline
Class of Drug: Broad spectrum bacteriostatic AB
MOA: Inhibits protein synthesis
Target: Bacterial 30s ribosomal subunit
Action: Reversibly binds to the 30s ribosomal subunit blocking tRNA binding
Use: Given as an alternative for community aquired pneumonia or cellulitis
AE:
- Oesophageal Irritation
- Tetracycline teeth –> yellow/brown colour to the teet
- weakens bone and teeth, causes discolouration
- never give to young children, breast feeding mothers or women of child bearing age
Carbapenems
Examples
MOA
Target
Action
Effect
Overall Effect
Spectrum?
Use
Examples:
- Meropenem
- Imipenem
MOA
- Inhibit cross-linking of NAMA/NAG peptide chains in the peptidoglycan bacterial cell wall
- Inhibits the transpeptidase enzyme
Spectrum
- Very broad
- Aerobic and anerobic gram -ve and gram +ve
Use:
- Severe resistant infection under ID guidance
AE:
- GI upset
- Hypersensitivity reactions (fever, rash)
- AB associated colitis
- Neurotoxicity - seizures (with high doses)
Monobactum
Example
What is resistant to?
Method of administration?
Effective against?
AE
Examples: Aztreonam
- Resistant to most beta lactamases
- Only given IV
- Gram -ve aerobic rods ex. Pseudomonas Aeurginosa
AE:
- GI upset
- Similar to beta-lactams
- rare cross sensitivity reactions
Vancomycin
Class of drug
MOA
Pharmacokinetics: Cant go where?
Oral Use
IV use
Target
Effect
Overall Effect
AE:
- Cannot cross the gut wall
- ORAL: severe c.difficile collitis (locatl
- IV: MRSA - effective in systemic infections
Effect:
- Inhibits cell wall synthesis
- Does not allow the addition of NAMA and NAG to the peptidoglycan chain
AE:
- Nausea/Vomitting
- Rash
- Ototoxicity
- Nephrotoxicity
Metronidazole
Class
Spectrum
MOA
Use
AE/Warnings
- Anti-protozoal agent
- ACTS on nucleic acid synthesis
- Good anaerobic cover and activity against clostridia
MOA:
- Exact mechanism is unclear
- Bacterial DNA damage and cell death.
Use:
- 1st line against c. difficle colitis
- Anaerobic cover in intra-abdominal sepsis
AE/Warnings:
- Metallic taste on tongue
- Minor GI disturbance – diarrhoea
- Dizziness / headache
- WARNING: * reaction when taken with alcohol*
Trimethoprim
What does it act on?
MOA
Target
Action
Effect
Overall Effect
Use
AE
MOA: Bacterial dihydrofolate reductase inhibitor
- Same as methotrexate (Anti-rheumatoid)
Effect:
- Inhibits reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF)
- inhibits bacterial DNA synthesis
Use: Commonly used for simple UTI
AE:
- GI disturbance (nausea, vomiting)
-
Important:
- Hyperkalaemia
- Hypersensitivity reactions
- Anaphylaxis
Nitrofurantoin
What does it act on?
MOA
AE
Cautions
MOA:
- Poor understanding
- Inhibits protein syntheisis
- DNA toxic
AE:
-
Common:
- GI disturbance (nausea, vomiting, diarrhoea)
-
Important:
- Peripheral neuropathy
- Pulmonary fibrosis
- Hypersensitivity reactions involving skin and bone marrow
Caution:
- Anaemia
- Diabetes mellitus
- Vitamin B12 and folate deficiency
