29 Antibacterial drugs Flashcards
29.01 BETA-LACTAM ANTIBIOTICS
Penicillins - actions
bactericidal
interfere with cell wall synthesis in dividing bacteria
29.01 BETA-LACTAM ANTIBIOTICS
Penicillins - MOA
bind to and inhibit the enzyme that cross-links the peptide chain of the newly formed ‘building block’ to the peptidoglycan cell wall backbone
29.01 BETA-LACTAM ANTIBIOTICS
Penicillins - types of penicillins
beta-lactamase resistant (methicillin, flucloxacillin, temocillin), broad spectrum (ampicillin, amoxicillin), extended spectrum (piperacillin, ticarcillin)
29.01 BETA-LACTAM ANTIBIOTICS
Penicillins - abs/distrib/elim
oral absorption varies
can also be given IM or IV
pass into all body fluids
cross the placenta but not the blood-brain barrier unless the meninges are inflamed
excreted in the urine (blocked by probenecid)
29.01 BETA-LACTAM ANTIBIOTICS
Penicillins - clinical uses
bacterial meningitis - benzylpenicillin
skin, bone and joint infections - flucloxacillin
animal bites - co-amoxiclav
pharyngitis - phenoxymethylpenicillin
otitis media, bronchitis, pneumonia - amoxicillin
syphilis - procaine, or benzathine penicillin
endocarditis - benzylpenicillin (with aminoglycoside)
infections with Pseudomonas aeruginosa - piperacillin, ticarcillin
29.01 BETA-LACTAM ANTIBIOTICS
Penicillins - adverse effects
hypersensitivity reactions (rashes, urticaria, angioedema, fever, arthralgia, anaphylaxis)
29.02 BETA-LACTAM ANTIBIOTICS
Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - actions
bactericidal
interfere with cell wall synthesis in dividing bacteria
29.02 BETA-LACTAM ANTIBIOTICS
Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - MOA
bind to and inhibit the enzyme that cross-links the peptide chain of the newly formed ‘building blocks’ to the peptidoglycan cell wall backbone
29.02 BETA-LACTAM ANTIBIOTICS
Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - abs/distrib/elim
some cephalosporins given orally, but most given IM or IV
pass into all body fluids
excreted in the urine (blocked by probenecid)
excretion mostly via kidneys, but 40% of ceftriaxone is eliminated in the bile
29.02 BETA-LACTAM ANTIBIOTICS
Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - clinical use
septicaemia - cefotaxime, cefuroxime
pneumonia caused by susceptible organisms, meningitis - ceftriaxone, cefotaxime
biliary tract infections, urinary tract infections, sinusitis - cefadroxil
29.02 BETA-LACTAM ANTIBIOTICS
Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - resistance
some pneumococci, meningococci and gonococci have decreased sensitivity
29.02 BETA-LACTAM ANTIBIOTICS
Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - adverse effects
hypersensitivity reactions (rashes, urticaria, angioedema, fever, arthralgia, anaphylaxis)
GIT disturbances
rarely: hepatitis and cholestatic jaundice
29.03 BETA-LACTAM ANTIBIOTICS
Carbapenems: imipenem, meropenem, ertapenem - actions
bactericidal
interfere with cell wall synthesis in dividing bacteria
29.03 BETA-LACTAM ANTIBIOTICS
Carbapenems: imipenem, meropenem, ertapenem - MOA
bind to and inhibit the enzyme that cross-links the peptide chain of the newly formed ‘building blocks’ to the peptidoglycan cell wall backbone
29.03 BETA-LACTAM ANTIBIOTICS
Carbapenems: imipenem, meropenem, ertapenem - abs/distrib/elim
given by IV infusion
pass into all body fluids including the CSF
inactivated by renal enzymes so must be given with cilastatin which inhibits the relevant enzymes
29.03 BETA-LACTAM ANTIBIOTICS
Carbapenems: imipenem, meropenem, ertapenem - clinical use
broad spectrum: active against Gram-positive, Gram-negative and anaerobic bacteria
not active against MRSA
used to treat severe polymicrobial hospital-acquired infections, e.g. septicaemia, pneumonia, complicated urinary infections
29.03 BETA-LACTAM ANTIBIOTICS
Carbapenems: imipenem, meropenem, ertapenem - adverse effects
GIT disturbances, rashes, injection site reactions
29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS
Glycopeptides: vancomycin, teicoplanin - actions
inhibits bacterial cell wall peptidoglycan synthesis
29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS
Glycopeptides: vancomycin, teicoplanin - MOA
inhibit the synthesis of the cell wall in sensitive bacteria
these drugs are slowly bactericidal for dividing microorganisms
impair the permeability of the bacterial cell membrane and RNA synthesis
29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS
Glycopeptides: vancomycin, teicoplanin - abs/distrib/elim
given IV
vancomycin plasma half-life ~8h
vancomycin given orally for treatment of Clostridium difficile
29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS
Glycopeptides: vancomycin, teicoplanin - clinical use
vancomycin used in a wide range of serious infections, including septicaemia, and treatment of MRSA
29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS
Glycopeptides: vancomycin, teicoplanin - adverse effects
hypersensitivity reactions, ototoxicity and nephrotoxicity
phlebitis at infusion site
29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS
Glycopeptides: vancomycin, teicoplanin - special notes
daptomycin is a relatively new lipopeptide antibacterial with similar spectrum to vancomycin
used for treatment of MRSA
telavancin is also active against MRSA with longer duration of action than vancomycin
29.05 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Tetracyclines: doxycycline, tetracycline, oxytetracycline - actions and MOA
interfere with bacterial protein synthesis by competing with tRNA for the A site of the ribosome and reversibly inhibiting its binding to the mRNA codons in the 30S subunit
29.05 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Tetracyclines: doxycycline, tetracycline, oxytetracycline - abs/distrib/elim
given orally, absorption impaired by milk and by calcium, magnesium and iron preparations
29.05 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Tetracyclines: doxycycline, tetracycline, oxytetracycline - clinical use
doxycycline is drug of choice for chlamydial, rickettsial and brucella infections
effective in most chest infections, including mycoplasma and Haemophilus influenzae
used in acne, sinusitis, prostatitis, syphilis, Lyme disease and prevention/treatment of malaria
demeclocycline is used in inappropriate secretion of antidiuretic hormone causing hyponatraemia (different action from its antibacterial effect)
29.05 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Tetracyclines: doxycycline, tetracycline, oxytetracycline - adverse effects
staining of the teeth, GIT disturbances, anorexia, flushing, tinnitus
rare: hepatotoxicity, pancreatitis, hypersensitivity reactions
29.05 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Tetracyclines: doxycycline, tetracycline, oxytetracycline - special notes
tetracyclines should not be given to children or pregnant or breastfeeding women
29.06 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Aminoglycosides: gentamicin, streptomycin, amikacin, tobramycin, neomycin - actions
inhibit bacterial protein synthesis
29.06 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Aminoglycosides: gentamicin, streptomycin, amikacin, tobramycin, neomycin - MOA
cause misreading of the mRNA message due to abnormal codon:anticodon recognition with the production of abnormal proteins
29.06 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Aminoglycosides: gentamicin, streptomycin, amikacin, tobramycin, neomycin - abs/distrib/elim
given IM or by slow IV injection or infusion
can be given intrathecally
renal excretion
29.06 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Aminoglycosides: gentamicin, streptomycin, amikacin, tobramycin, neomycin - clinical use
infections with staphylococci (with a beta-lactam antibiotic), streptococci, enterococci, Gram-negative bacilli (including Pseudomonas aeruginosa)
used for septicaemia, meningitis, pyelonephritis, endocarditis, pneumonia
29.06 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Aminoglycosides: gentamicin, streptomycin, amikacin, tobramycin, neomycin - adverse effects
dose-related ototoxicity and nephrotoxicity
GIT disturbances, rash, blood disorders can occur
↑ototoxicity with loop diuretics
↑effect of neuromuscular blockers
29.07 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Amphenicols: chloramphenicol - actions
inhibit bacterial protein synthesis
29.07 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Amphenicols: chloramphenicol - MOA
inhibit transpeptidation
29.07 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Amphenicols: chloramphenicol - abs/distrib/elim
given orally or by IV injection or infusion
enters CSF and CNS
inactivated in the liver
excreted in the urine
also available as eye drops
29.07 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Amphenicols: chloramphenicol - clinical use
used mainly for life-threatening Haemophilus influenzae infections, for meningitis resistant to penicillin (or patients with severe penicillin allergy) and for typhoid
used topically for bacterial eye infections
29.07 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Amphenicols: chloramphenicol - adverse effects
dose-related bone marrow depression
‘grey baby’ syndrome in neonates who lack the relevant inactivating enzyme: circulatory collapse, flaccidity, vomiting
aplastic anaemia in a few genetically predisposed individuals
29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Macrolides: erythromycin, clarithromycin, azithromycin - actions
inhibit bacterial protein synthesis
29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Macrolides: erythromycin, clarithromycin, azithromycin - MOA
macrolides inhibit bacterial protein synthesis by an effect on ribosomal translocation
they bind to the same 50S subunit of the bacterial ribosome as chloramphenicol and clindamycin and any of these drugs may compete if given concurrently
29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Macrolides: erythromycin, clarithromycin, azithromycin - abs/distrib/elim
given orally or by IV infusion (IV injection can cause thrombophlebitis)
erythromycin half-life 1.5h
widely distributed but does not enter brain or CSF
29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Macrolides: erythromycin, clarithromycin, azithromycin - clinical use
for pneumococcal and streptococcal infections in patients allergic to penicillin
for chlamydial and mycoplasma infections
for infections of the skin and respiratory tract (syphilis, diphtheria, prostatitis, whooping cough, campylobacter enteritis)
azithromycin is more effective against Haemophilus influenzae and may be more active against Legionella
clarithromycin is effective against H. influenzae and Mycobacterium avium-intracellulare and may also be useful in leprosy and against Helicobacter pylori
29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Macrolides: erythromycin, clarithromycin, azithromycin - adverse effects
GIT disturbances
less frequent: allergic reactions, cholestatic jaundice
29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Macrolides: erythromycin, clarithromycin, azithromycin - special notes
concomitant use of statins with clarithromycin is contraindicated
statins are extensively metabolised by CYP3A4 and concomitant treatment with clarithromycin increases their plasma concentration, which increases the risk of myopathy, including rhabdomyolysis
29.09 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Lincosamide: clindamycin - actions
inhibit bacterial protein synthesis
29.09 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Lincosamide: clindamycin - MOA
inhibits the translocation of the tRNA (with its attached peptide) from the A site to the P site
29.09 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Lincosamide: clindamycin - abs/distrib/elim
given orally or by IM injection or IV infusion
half-life 2.5h
widely distributed, entering abscesses but does not penetrate brain or CSF
concentrated in bone
metabolised in liver to give active metabolite, excreted in urine
29.09 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Lincosamide: clindamycin - clinical use
effective against streptococci, penicillin-resistant staphylococci and many anaerobes (except Clostridium difficile)
used for lung abscesses, and for bone, joint, skin and soft tissue infections
29.09 BACTERIAL PROTEIN SYNTHESIS BLOCKERS
Lincosamide: clindamycin - adverse effects
GIT disturbances, skin rashes, jaundice, pseudomembranous colitis
29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE
Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - actions
interfere with bacteria DNA function
29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE
Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - MOA
inhibits DNA gyrase (aka topoisomerase II) - the enzyme that produces the supercoil in the chromosome that is essential for transcription and replication
29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE
Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - abs/distrib/elim
given orally, well absorbed
accumulate in several tissues, concentrated in phagocytes
aluminium and magnesium antacids interfere with absorption
only ofloxacin crosses blood-brain barrier
ciprofloxacin and norfloxacin eliminated partly by hepatic P450 metabolism and partly by renal excretion
ofloxacin is excreted in urine
29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE
Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - clinical use
active against Gram-positive organisms, particularly effective against Gram-negative bacteria
used for: infections of the urinary tract, GIT and bones and joints, respiratory tract infections not caused by pneumococci, gonorrhoea and septicaemia caused by sensitive organisms
29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE
Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - adverse effects
major safety concerns regarding tendon damage, aortic dissection, gait disturbance, neuropathies
infection with Clostridium difficile, GIT upsets, headache, dizziness, rashes
clinically important interaction between ciprofloxacin and theophylline which can lead to theophylline toxicity in asthmatics
29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE
Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - special notes
avoid them in older patients, patients with renal damage/impairment or organ transplant
risk of tendon injury increased if also on steroids - avoid combined use of these agents
29.11 BLOCKERS OF FOLATE SYNTHESIS/ACTION
Sulfonamides and trimethoprim - actions
bacteriostatic
both sulfonamides and trimethoprim interfere with bacterial folate metabolism and thus with DNA synthesis
29.11 BLOCKERS OF FOLATE SYNTHESIS/ACTION
Sulfonamides and trimethoprim - MOA
sulfonamides competitively inhibit the enzyme dihydropteroate synthetase
trimethoprim inhibits dihydrofolate reductase and thus the conversion of folate to tetrahydrofolate
29.11 BLOCKERS OF FOLATE SYNTHESIS/ACTION
Sulfonamides and trimethoprim - abs/distrib/elim
given orally or by IV infusion
sulfa drugs pass into inflammatory exudates, but are inactive in the presence of pus
29.11 BLOCKERS OF FOLATE SYNTHESIS/ACTION
Sulfonamides and trimethoprim - clinical use
co-trimoxazole (sulfamethoxazole and trimethoprim combined) is used for pneumocystis pneumonia, toxoplasmosis and nocardiasis, urinary infections, acute exacerbations of chronic bronchitis
trimethoprim is alone used for prostatitis, and for urinary and respiratory infections
sulfonamides with pyrimethamine are used for drug-resistant malaria and toxoplasmosis
29.11 BLOCKERS OF FOLATE SYNTHESIS/ACTION
Sulfonamides and trimethoprim - adverse effects
GIT upsets, rashes
very rare but serious: Stevens-Johnson syndrome, blood dyscrasias, toxic epidermal necrolysis, photosensitivity, hepatitis, crystalluria
trimethoprim - folate deficiency with resultant megaloblastic anaemia is possible with long-term treatment
29.12 OTHER ANTIBACTERIAL DRUGS
Metronidazole
antiprotozoal agent, but also active against anaerobic bacteria and some streptococci
effective in the treatment of pseudomembranous colitis and serious anaerobic infections
avoid alcohol, due to dilsulfiram-like action
29.12 OTHER ANTIBACTERIAL DRUGS
Nitrofurantoin
synthetic compound active against range of Gram-positive and Gram-negative organisms
damages bacterial DNA
given orally, rapidly absorbed from GIT, rapidly excreted by kidneys
clinical use in treatment of urinary tract infections
29.12 OTHER ANTIBACTERIAL DRUGS
Quinupristin and dalfopristin - actions
streptogramins - inhibit bacterial protein synthesis
individually, exhibit only modest bacteriostatic activity, but combined as an IV injection they are active against many Gram-positive bacteria
29.12 OTHER ANTIBACTERIAL DRUGS
Quinupristin and dalfopristin - clinical use
combination used to treat serious Gram-positive infections unresponsive to other antibacterials, e.g. MRSA, skin and soft tissue infections, hospital-acquired pneumonia, vancomycin-resistant Enterococcus faecium
29.12 OTHER ANTIBACTERIAL DRUGS
Aztreonam
monobactam - resistant to most beta-lactamases
given by injection with plasma half-life 2h
effective only against Gram-negative aerobic bacilli (Pseudomonas species, Neisseria meningitidis and Haemophilus influenzae)
29.12 OTHER ANTIBACTERIAL DRUGS
Polymyxin B, colistimethate
polymyxins - cationic detergent properties and disrupt bacterial outer cell membrane
selective bactericidal action on Gram-negative bacilli, especially Pseudomonas and coliform organisms
29.12 OTHER ANTIBACTERIAL DRUGS
Fosfomycin
phosphonic acid
acts against many Gram-positive and Gram-negative organisms
used for treatment of urinary tract infections
29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS
Isoniazid
nicotinic acid derivative
given orally, well absorbed
passes into CSF and tuberculous lesions
acetylated in liver
adverse effects: GIT disturbances, hypersensitivity reactions, peripheral neuritis (with high doses, pyridoxine prophylaxis required)
29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS
Rifampicin - actions
bactericidal
effective against most Gram-positive and many Gram-negative bacteria
29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS
Rifampicin - abs/distrib/elim
given orally, widely distributed
excreted in urine and bile
29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS
Rifampicin - clinical use
apart from tuberculosis - leprosy, prophylaxis for meningococcal meningitis, and Haemophilus influenzae
also used (combined with other drugs) for brucellosis, endocarditis, legionnaires’ disease, serious staphylococcal infections
29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS
Rifampicin - adverse effects
GIT disturbances, skin eruptions, liver damage
orange tint to saliva, sweat and tears
29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS
Ethambutol
bacteriostatic
given orally, well absorbed
adverse effects: optic neuritis (dose-related) - colour vision should be monitored before and during prolonged treatment
29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS
Pyrazinamide
bacteriocidal
given orally, well absorbed
adverse effects: GIT disturbances, increases plasma urate, malaise, liver damage
29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS
Capreomycin
inhibits protein synthesis
given IM
adverse effects include renal and auditory nerve damage
29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS
Cycloserine
broad-spectrum antibiotic - inhibits bacterial cell wall synthesis
given orally, penetrates CSF
adverse effects mainly on CNS
29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS
Streptomycin
aminoglycoside antibiotic - inhibits bacterial protein synthesis
given IM
adverse effects: ototoxicity and nephrotoxicity
29.14 ANTIMYCOBACTERIALS FOR LEPROSY
Dapsone - action and MOA
sulfonamide-like, may inhibit folate synthesis
29.14 ANTIMYCOBACTERIALS FOR LEPROSY
Dapsone - abs/distrib/elim
given orally
plasma half-life 24-48h
29.14 ANTIMYCOBACTERIALS FOR LEPROSY
Dapsone - clinical use
tuberculoid leprosy (and dermatitis herpetiformis)
resistance increasing
29.14 ANTIMYCOBACTERIALS FOR LEPROSY
Dapsone - adverse effects
haemolysis of red blood cells, methaemoglobinaemia, anorexia, nausea and vomiting, fever, allergic dermatitis, neuropathy
29.14 ANTIMYCOBACTERIALS FOR LEPROSY
Clofazimine - action and MOA
a dye
MOA thought to involve action on DNA of leprosy bacilli
anti-inflammatory activity
29.14 ANTIMYCOBACTERIALS FOR LEPROSY
Clofazimine - abs/distrib/elim
given orally
plasma half-life can be 8 weeks
29.14 ANTIMYCOBACTERIALS FOR LEPROSY
Clofazimine - adverse effects
skin and urine can develop a reddish colour and leprosy lesions a blue-black discolouration
GIT disturbances, headaches
