2a/2b. Penicillins, Monob, Carb. Flashcards
B-lactam antibiotics
- Penicillins,
- Cephalosporins,
- Lactamase-inhibitors,
- Monobactams,
- Carbapenems
Penicillins
- structure
B-lactam ring + thiazolidine ring
R1: pharmacokinetics
R2: change the antimicrobial spectrum, eg amoxicillin
Se bilde i notater
Penicillins
- mechanism of action
- Peptidoglycan cell wall consists of: N-acetyl-muramic acid + N-acetyl-glucose-amine chain
- Transpeptide bonds –> transpeptidase, carboxipeptidase (PBP) produced by enzymes
- PBP: Penicillin Binding Protein, target of penicillin, inhibited by penicillin
- inhibition of cell wall synthesis
- bacterolysis
Penicillins
- Mode of action
Bactericidal: only kills dividing bacterias
- Time dependent (kills bacteria but very slowly, min. duration of treatment is 3-5 days)
- PAE (postantibiotic effect): helps us to lengthen the duration of treatment
Penicillins:
- resistance
1. Ab ovo (primary)
- from the egg
- eg: mycoplasma are always resistant because they dont have cell wall
2. B-lactamase production: clinically most important
- eg. Gram + taphylococcus produces B-lactamase that destroy the Lactam ring. SAM= skin infection, Cow: mastitis
3. PBP-gene mutation (Eg. MRSA, MRSP strains)
= methicillin resistant Staphylococcus aureus and Staph. pseudointermedius
Penicillins:
- antibacterial spectrum
- narrrow spctrum penicillins
- penicillinase stable penicillins
- borad spectrum penicillins (aminopenicillins)
- penicillins acting against Pseudomonas spp.
Narrow spectrum penicillins
- Active substances
3 main substances: difference is the absorption rate
1. Benzylpenicillin - Na, K = R1
- fast absorption.
- only water soluble, can be given IV (and IM)
- 2-4hr duration of action
2. Benzylpenicillin - procaine = R1
- slow absorption
- slow elimination
- duration of action is longer, ca 24hr
3. Benzylpenicillin - benzathine = R1
- slowest absorption
- very slow elimination
- can last for 3-4 days
4. In vet.med we use combined 2 and 3.
- Above MIC for 3 days, given IM or SC
None of them absorbed orally!
Phenoxymethyl-penicillin
- mainly used in poultry for necrotic enteritis (clostridium perforingens)
- ONLY orally!
Narrow spectrum penicillins
- antibacterial spectrum and pharmacokinetics
Antibacterial spectrum:
- Most of the Gram+ bacteria
- Gram - fastidious organisms (Pasteurella, mannheimia, hitophilus, bibersteinia =resp. tract infection) + Leptospira, Borrelia spp.
Pharmacokinetics:
- Absorption: Give IV
- oral: phenoxymethypenicillin. Short half life: 3-4hr. give in continous drinking water.
- parenteral
- Distribution: bad-moderalte
- it can not cross barriers like blood-brain, blood-milk, blood-prostate. = not usefull for treatment of meningitis, mastitis and prostatis
- Can not enter the cell = not effective against intra-cellular organisms like Chlamydia etc.
- Metabolism: minimal
- two consequences: safe for liver patients.
- Excretion: kidney
- The drug is excreted unchanged in the urine = usefull in UTI, eg: amoxicillin is 1st choice in treatment of UTI
Narrow spectrum penicillins
- Side effects
Almost nontoxic - very safe
- allergy: 5% incidences in humans, less frequent in animals
- dysbacteriosis
Procaine-penicillin
- metabolised by penicillin
- local anasthetic = tremors, astma, movement disorders can happen. Piglet is most sensitive!
- should not be given to horses as it is an doping listed drugs. dont give 2 weeks before competition
Narrow spectrum penicillins
- Indications
1st choice:
- respiratory infections
- swine erysipelas: dimond skin disease, very sensitive to penicillin
- anthrax: highly sensitive to penicillin
- Tetanus: highly sensitive to penicillin
- Necrotic enteritis: clostridum perferingens
- (Mastitis, metritis)
- Streptococcosis: horses (strangles), SAM (skin disease), Human (pharyngigits), Cattle (mastitis), swine (septicaemia in piglets)
Narrow spectrum penicillins
- combinations
Procaine-penicillin + benzathine-penicillin + dihydro-streptomycin
Pencillinase stable penicillins
- active substances
= same as B-lactamase. Can only be used in Gram+.
Active substances:
- Acid sensitive:
- Methicillin
- Acid resistant:
- Oxacillin
- Cloxacillin: contains 2 Cl-
- Dicloxacillin
- Flucloxacillin: contains Fl and Cl-
Broad spectrum penicillins
- antibacterial spectrum
Most of the Gram + bacteria
Several Gram - bacteria
Broad spectrum penicillins
- active substancs, pharmacokinetics
Disadvantage: sensitive to B-lactamase enzyme, not used alone with staph, strept. Needs to be used in combinations (se table)
Ampicillin: do not use orally!
Amoxicillin: abosprtion
- in humans: 100%, Dogs+cats: 80%, poultry: 60%, Swine: 30%, Horse: 1%
- therefore prohibited in oral treatment in horses!
Broad spectrum penicillins
- indication
- se above + everything in narrow spectrum
- UTI
- combination, but we dont
- = primary choice is Amoxicillin! because it is excreted in the urine
- there is not enough B-lactamase to be destroyed therefore we use Amoxicillin alone
- Gastrointesinal infections??
- very often resistant bacteria in GI tract, therefore these drugs are not used
- ONLY in clostridium
- Dermatitis, soft tissue infections
- = combination treament
- Lyme-disease
- do not use B-lactamase
- can use Amoxicillin alone
- Osteomyelitis: combination
- Oral cavity infections - bite wounds
- gram - anaerobic bacteria
- = combinations
