Bacteriostatic vs bacteriocidal.
Can you use these two classes together? Why?
Static = prevents microbe replication
Cidal - kills microbes
No, often bactericidal drugs work on actively replicating cells therefore bacteriostatic antagonises their action.
Metaphylaxis vs Prophylaxis
Meta - control treatment - treat a partially infected group to reduce/prevent spread.
Pro - Preventative treatment - treat individuals/group before clinica signs show.
Outline the principles of the cascade.
Legislation which allows vets to prescribe unauthorised medicines to prevent suffering.
Order:
- Vet med authorised in the UK in another animal species or for a different condition in the same species.
- Med authorised in the UK for human use
- Vet med (VMP) not authorised in the UK but authorised in another Member State (MS) for use in any animal species/ food producing in accordance with an import certificate issued by the VMD.
What are the withdrawal periods specified under the cascade for food-producing animals?
- Eggs and milk - minimum of 7 days
- Meat from poultry and mammals - minimum of 28 days
What are MRL’s?
Describe the classification used for this system
Maximum residue limits - used in food producing animals to prevent AB’s getting into the food chain.
Four classifications:
- Annexe 1 - MRLs have been fixed
- Annexe 2 - MRLs not required
- Annexe 3 - provisional MRL fixed
- Annexe 4 - no MRL can be fixed
MIC vs MBC
- MIC = Minimal Inhibitory Concentration
- defined as the minimum concentration of the chemical that prevents the growth of bacteria.
- MBC = Minimum bactericidal concentration
- 99% reduction in the bacterial inoculum in a given time.
What is a biofilm?
Give two examples of bacteria which can form them?
- Impermeable barrier to the immune system or drug penetration
- Contain more resistant phenotypes
- Slow growth rates prevent antimicrobial action
- Hyper-mutability state reported in some bacteria
S. pseudointermedius and Pseudomonas spp.
PAE
Post-antibiotic effect
The ability of a drug to suppress or kill bacteria after the drug concentration has dropped below the MIC (PAE).
A drug with a high PAE should need less frequent dosing.
Concentration dependent vs Concentration independent (time dependent) antibiotics.
- Conc dependent - Rate of killing increases with increased drug concentration (long post antibiotic effects)
- Aminoglycosides, fluoroquinolones and metronidazole
- Conc independent - Related to the amount of time the drug is above the MIC, once the dose > MIC no increased killing rate, maintenance at this level is key
Advantages and disadvantages of injectable route of administration.
(x8)
- Advantages
- Can be used for drugs poorly absorbed, inactive or ineffective if given orally
- IV route provides immediate onset of action
- IM and SC routes for slow or delayed onset of action
- Client compliance
- Disadvantages
- Can be painful
- Cost
- Aseptic technique maybe required
- Side effects
What is the main advantage of IV drug administration?
And disadvantages?
- = Total drug reaches systemic circulation
- -ve = quick decline in conc, salt form requires slow dose/ infusion
What volume should never be exceeded when giving IM/SC antibiotics?
20mL
Why are the shoulder and neck preferred for IM AB administration in horses/cows?
Increased vascularity for intramuscular injection.
Why would a IM be preferred over SC for AB administration?
Drugs are administered subcutaneously when a slower, more prolonged effect is desired. Intramuscular injections are best for larger volumes of medication and when faster absorption of the medicine is desired.
What effects should you be aware of when administering a drug IM?
Intramuscularly may cause local tissue damage, may lead to persistence of drug residues, also hide and carcass damage.
What factors must be considered when considering oral adiministration of AB’s?
This is influenced by which characteristics of the drug? (x5)
- Fraction of the dose which reaches systemic circulation unchanged- bioavailability
- Influenced by:
- Stability in gastric contents
- Susceptibility to inactivation (GI bacteria)
- Physicochemical properties
- Passive diffusion across the epithelial barrier
- High solubility in lipids is important!
This polar organic base antibiotic is poorly absorbed orally and therefore is never given via this route.
Aminoglycosides
Describe the absorption of orally administered AB’s.
- Absorption through the gut epithelium
- Drugs then go into the hepatic portal venous blood to the liver which is the main organ for drug metabolism
- Presystemic metabolism = first pass effect
- Metabolism of the drug before it reaches systemic circulation - enterohepatic circulation
- Gut lumen (bacterial) - deconjugation
- Mucosal epithelium
- Liver
The two AB’s require activation via enterohepatic circulation to promote efficacy.
- Pivampicillin, bacampicillin -hydrolysis of ester in intestinal mucosa
- Enrofloxacin to ciprofloxacin - N-dealkylation
How can food effect the absorption of particular orally administered AB’s?
- Decreases systemic availability for the following drugs:
- Most penicillins (not amoxicillin/ampicillin prodrugs)
- Oral cephalosporins
- Trimethroprim/sulpha combinations
- Tetracyclines (except doxycycline)
- Increased availability
- Doxy and erythromycin systemic availability after food in dogs.
- In horses, systemic availability for drugs by feeding, no feeding for up to two hours.
Factors affecting systemic districution of AB’s.
- Determined by blood flow to tissues
- Penetration cellular barriers
- Rate is dependent upon:
- Perfusion - lipophilic
- Diffusion (ionised or polar drugs)
- Binding of drug to plasma protein also limits immediate availability
- Selective binding eg aminoglycosides to phospholipid rich inner ear and kidney cortex tissues = small fraction of total drug, but can result in toxicity
Define the volume of distribution.
Reflection of the amount left in the blood stream after all the drug has been absorbed.
- High = more in tissues
- Low = more in circulation
PPB
Plasma protein binding
- Affects -
- Tissue penetration
- Volume of distribution
- Half-life
- Elimination - Reduces the free fraction of drug available for bacterial killing
- Allows them to be long acting - good for B-lactams
- Cefovecin ~97% PP binding in dogs and 99% in cats
- Excreted unchanged in urine- but only unbound
Half life
Time required to divide the plasma concentration by two after reaching pseudo-equilibrium distribution
