Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic category: ophthalmologicals;anti-infectives
ATC code: S01 CA 01
Mechanism of Action
MAXITROL ophthalmic ointment has a dual effect: suppression of inflammation symptoms by the corticosteroidal component dexamethasone, and an anti-infective effect due to the presence of two antibiotics, polymyxin B and neomycin.

5 MAX OIN API SEP20 V4                                                     UK SPC -JUN2020 Dexamethasone is a synthetic glucorticoid with potent anti-inflammatory activity. Polymyxin B is a cyclic lipopeptide that penetrates the cell wall of gram-negative bacilli to destabilize the cytoplasmic membrane. It is generally less active against gram-positive bacteria.
Neomycin is an aminoglycoside antibiotic that primarily exerts its effect on bacterial cells by inhibiting polypeptide assembly and synthesis on the ribosome.

Mechanism of Resistance
Resistance of bacteria to polymyxin B is of chromosomal origin and is uncommon. A modification of the phospholipids of the cytoplasmic membrane appears to play a role.
Resistance to neomycin occurs by several different mechanisms including (1) alterations of the ribosomal subunit within the bacterial cell; (2) interference with the transport of neomycin into the cell, and (3) inactivation by an array of adenylating, phosphorylating, and acetylating enzymes. Genetic information for production of inactivating enzymes may be carried on the bacterial chromosome or on plasmids.
Breakpoints
Each gram of MAXITROL eye ointment contains 6000 IU polymyxin B sulphate and 3500 IU neomycin sulphate. The breakpoints and the in vitro spectrum as mentioned below are based on the dual activity of either polymyxin B or neomycin. The breakpoints listed here are based upon acquired resistance for specific species found in ocular infections and the ratio in International Units of polymyxin B to neomycin in MAXITROL ophthalmic ointment: Resistance breakpoints: >5:2.5 to >40:20 depending upon the bacterial species 
Susceptibility
The information listed below provides guidance on the approximate probabilities on the susceptibility of microorganisms to polymyxin B or neomycin in MAXITROL ophthalmic ointment. The presentation below lists bacterial species recovered from external ocular infections of the eye.
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the combination of polymyxin B or neomycin as in MAXITROL ophthalmic ointment in at least some types of infections is questionable.

COMMONLY SUSCEPTIBLE SPECIES
Aerobic Gram-positive microorganisms
Bacillus cereus
Bacillus megaterium
Bacillus pumilus
Bacillus simplex
Corynebacterium accolens
Corynebacterium bovis
Corynebacterium macginleyi
Corynebacterium propinquum
Corynebacterium pseudodiphtheriticum
Staphylococcus aureus (methicillin susceptible - MSSA)
Staphylococcus capitis
Staphylococcus epidermidis (methicillin susceptible - MSSE)
Staphylococcus pasteuri
Staphylococcus warneri
Streptococcus mutans
6 MAX OIN API SEP20 V4                                                     UK SPC -JUN2020 Aerobic Gram-negative microorganisms
Haemophilus influenzae
Klebsiella pneumoniae
Moraxella catarrhalis
Moraxella lacunata
Pseudomonas aeruginosa
Serratia species

SPECIES FOR WHICH ACQUIRED RESISTANCE MIGHT BE A PROBLEM
Staphylococcus epidermidis (methicillin resistant - MRSE)
Staphylococcus hominis
Staphylococcus lugdunensis

INHERENTLY RESISTANT ORGANISMS
Aerobic Gram-positive microorganisms
Enterococci faecalis
Staphylococcus aureus (methicillin resistant - MRSA)
Streptococcus mitis
Streptococcus pneumonia
Aerobic Gram-negative microorganisms
Serratia species
Anaerobic Bacteria
Propionibacterium acnes

Dexamethasone is a moderately powerful corticosteroid having good penetration in ocular tissue. Corticosteroids have an anti-inflammatory as well as a vasoconstrictive effect. They suppress the inflammatory response and symptoms in various disorders without basically curing these disorders.

Pharmacokinetic Properties