27)Penicillin, Protected penicillin's. Carbapenems. Monobactams Flashcards
Penicillin’s
Are a subclass of the Beta-lactams ⇢ Have 4-membered lactam ring structure
Classified into 3 groups:
- Narrow spectrum - B-lactamase sensitive ⇢ Penicillin G + V
- Broad spectrum - B-lactamase sensitive ⇢ Ampicillin + Amoxicillin
- Narrow spectrum - B-lactamase resistant ⇢ Oxacillin, Cloxacillin + Dicloxacillin
Penicillin G
Is the first drug of choice ⇢ pneumococcal, streptococcus, meningococci + others
- Has a narrow spectra + B-lactamase sensitive
- Not active against Gram -ve bacteria
- Penicillin V is ⇣ potent + only indicated in more minor infections
- Ampicillin + amoxicillin ⇢ wider spectrum of activity ⇢ Given to treat respiratory infection
- Effective against gram -ve bacteria
Mechanism + Action
Bactericidal in growing bacteria
- Attach to specific penicillin binding proteins
- Inhibit bacterial cell wall peptidoglycan synthesis
- Inactivate inhibitor of autolytic enzymes in cell wall ⇢ initiates bacterial cell lysis + death
Resistance
Occurs due to a number of causes
Beta-Lactamase production
- Inactivate most penicillin’s by breaking B-lactam ring
- Most s. Aureus, some H.influenzae + N.gonorrhoeae have this feature
Modified penicillin binding sites ⇢ MRSA are modified in this way
Tolerance ⇢ Bacteria such as listeria are inhibited but not killed by penicillin
Lack of Cell Wall ⇢ Mycoplasma, L-forms ⇢ do not synthesize peptidoglycans so are immune
Pharmacokinetics
- Different absorption depending on acid stability in stomach ⇢ Benzylpenicillin + Ureidopenicillins poorly absorbed + administered parenterally rather than orally
- Widely distributed in body fluids + tissues
- Cross BBB + placental barriers
Excretion
- Benzylpenicillin ⇢ rapidly excreted by kidney
- Nafcillin ⇢ via biliary excretion
- Oxacillin, Cloxacillin + Dicloxacillin ⇢ excreted by both urine + bile
Clinical uses - Benzylpenicillin + Phenoxymethylpenicillin
Streptococcal infections
Pneumococcal infections
Meningococcal infections
Anthrax
Lyme disease
Syphillis
Clinical uses - Ampicillin + Amoxicillin
Upper respiratory tract infections
Gram -ve urinary tract infections
H.pilory infections
Clinical uses - Cloxacillin, Dicloxacillin, Nafcillin + Methicillin
Systemic staphylococcal infections
Staphylococcal skin + soft tissue injection
Staphylococcal scalded skin syndrome
Side effects
- ⇣ toxic effects, safe in pregnancy
- Hypersensitivity reactions are common adverse reactions
- Steven johnson syndrome + toxic epidermal necrolysis are most severe skin reactions one can have
- Methicillin, Nafcillin, Oxacillin ⇢ Reversible neutropenia
- Methicillin ⇢ interstitial nephritis
- Oxacillin ⇢ Toxic hepatitis
Carbapenems
A group of B-lactam antibiotics used in severe infections
- More resistant to action of beta-lactamases
- Have a wider spectrum
- Classified into 3 groups
Group 1
Broad-spectrum w/limited activity against non fermentive Gram-ve bacilli
Used for community acquired infections
Eg: Ertapenem
Group 2
Broad spec w/activity against non-fermentive gram-ve bacilli
Suitable for nosocomial/hospital acquired infections
Eg: Imipenem + Meropenem
Group 3
clinical activity against MRS
Non are currently licensed
A ‘future’ group
Mechanism
Exert bactericidal action by interrupting formation of cell wall
Inhibits enzymes for peptidoglycan synthesis
Clinical use
Meropenem ⇢ Meningitis
Imipenem ⇢ Endocarditis
Pelvic infections
Upper airway infections
Complicated urinary tract infections
Intra-abdominal infections
Skin & soft tissue + bone & joint infections
