Elizabeth Davis; Week 12 MED1011; Pharmacology
Ideal chemotherapeutic agent has selective toxicity. Pharmacokinetics are measured by volume of distribution, maximum peak concentration, time to maximum concentration and half life. Minimum inhibitory concentration is load that stops proliferation of infection, minimum bacteriocidal concentration is level that starts to decrease levels of organism, time dependent killing and concentration dependent killing also are relevant. Post antibiotic effect is level of killing bacteria that remains after removal of antibiotics. Targets for selective toxicity are unique or similar but not identical. Bacteria synthesise folate from pABA which makes it a good target for antibiotics (sulfonamides). Dihydrofolate to tetrahydrofolate is inhibited by DHF reductase inhibitors. Different drugs have different DHF specificity; methotrexate good for humans, trimethoprim good for bacteria and pyrimethamine good for protozoa.
Antibacterial action of a drug may be concentration or time dependant. Superinfection can occur after using antimicrobials due to upset between pathogenic and non-pathogenic organisms. Combination chemotherapy may be required if concomitant infection, if unsure of organism, to reduce toxicity, to achieve potentiating effect. Antimicrobial creed is MINDME: microbiology guides therapy where possible; indications should be evidence-based; narrowest spectrum required; dosage appropriate to site and type of infection; minimise duration of therapy; ensure monotherapy in most situations. Duration should not exceed 7 days unless there is proof this duration is inadequate.