Top 100 Drugs: Cephalosporins and carbapenems, Glycopeptide antibiotics, Metronidazole, Quinolones

MOA of cephalosporins and carbapenems?

-derived from naturally occurring antimicrobials produced by fungi and bacteria

-their bactericidal effect is due to their B-lactam ring

-during bacterial cell growth, cephalosporins and carbapenems inhibit enzymes responsible for cross-linking peptidoglycan in bacterial cell walls

-this weakens cell walls, preventing them from maintaining an osmotic gradient, resulting in bacterial cell swelling, lysis and death

important adverse effects with cephalosporins and carbapenems?

-GI upset

-antibiotic associated colitis

warnings with cephalosporins and carbapenems?

-cephalosporins and carbapenems should be used with caution in people at risk of C. difficile infection, particularly older people and those in hospital

-main contraindication is allergy to a b-lactam antibiotic

monitoring with carbapenems and cephalosporins?

-check that infection resolves by symptoms, signs and blood tests

-the duration of antibiotic therapy is a balance between ensuring effective treatment of infection and reducing adverse reactions

MOA of metronidazole?

-metro enters bacteria by passive diffusion

-in anaerobic bacteria, reduction of metronidazole generates a nitroso free radical that binds to DNA, reducing synthesis and causing widespread damage, DNA degradation and cell death

-as aerobic bacteria are not able to reduce metronidazole in this manner, they are not susceptible to its effects

warnings with metronidazole?

-metro is metabolised by hepatic CYP450 enzymes, so the dose should be reduced in severe liver disease

-metronidazole inhibits the enzyme acetaldehyde dehydrogenase, which is responsible for clearing the intermediate alcohol metabolite acetaldehyde from the body

-alchohol should be avoided while taking metronidazole as the combination causes an unpleasant reaction including flushing, headache, nausea and vomiting

important interactions with metronidazole?

metronidazole has some inhibitory effect on CYP enzymes, reducing metabolism of warfarin and phenytoin

-the reverse reaction can occur with CYP inducers which increases metronidazole metabolism resulting in reduced plasma concentrations and impaired antimicrobial efficacy.

-metronidazole also increases the risk of toxicity with lithium

MOA of glycopeptide antibiotics?

-inhibits growth and cross-linking of peptidoglycan chains

-this inhibits synthesis of the cell wall in gram-positive bacteria, causing cell lysis

-they are inactive against most gram-negative bacteria which have a diff cell wall structure

important adverse effects with glycopeptide antibiotics?

-pain and thrombophlebitis from vancomycin infusion are common

-rapid infusion of vancomycin may cause vancomycin flushing syndrome due to direct, non-immune release of histamine

-this presents with a pruritic erythematous rash over the upper body, occasionally with hypotension

warnings with glycopeptide antibiotics?

-use in caution in people with immune-mediated hypersensitivity (there is cross sensitivity between vancomycin and teicoplanin) and those with hearing impairment who are at increased risk of ototoxicity

-people with reduced renal function, including neonates and older adults are also at risk of nephrotoxicity

-glycopeptide antibiotics are renally excreted and may accumulate in renal impairment

important interactions with glycopeptide antibiotics?

-increased risk of ototoxicity and/or nephrotoxicity when prescribed with other drugs that cause these effects, particularly loop diuretics, aminoglycosides, NSAIDs and ciclosporin

monitoring with glycopeptide antibiotics?

-in parenteral therapy, pre-dose plasma drug concentrations should be measured. dosage should be adjusted to keep trough concentrations high enough for therapeutic effect

MOA of quinolones ?

-quinolones kill bacteria (bactericidal) by inhibiting DNA synthesis

-however, resistance is problematic - some bacteria prevent intracellular accumulation of the drug by reducing permeability and/or increasing efflux

-others develop protective mutations in target enzymes

-quinolone resistance genes are spread horizontally between bacteria by plasmids, accelerating acquisition of resistance

important adverse effects with quinolones?

-quinolones are generally well tolerated although they can cause GI upset and immediate and delayed type hypersensitivity reactions

-quinolones and cephalosporins are the antibiotics most commonly associated with c. diff infections

warnings with quinolones?

-use with caution in pregnancy and in children and young adults who are growing (risk of arthropathy) and in adults >60 due to risk of tendon damage

Important interactions with quinolones?

-drugs containing divalent cations (eg calcium, iron, antacids) reduce absorption and efficacy of quinolones

-ciprofloxacin inhibits certain cytochrome P450 enzymes, increasing risk of toxicity from some drugs, notably theophylline.

-co-prescription of NSAIDS increases risk of seizuresand prednisolone increases risk of tendon rupture

-caution is required in people taking other drugs that prolong the QT interval or that cause arrythmias eg amiodarone, antipsychotics, quinine, macrolide antibiotics and SSRIs.