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Pharmacology > 29 Antibacterial drugs > Flashcards

29 Antibacterial drugs Flashcards

1
Q

29.01 BETA-LACTAM ANTIBIOTICS

Penicillins - actions

A

bactericidal
interfere with cell wall synthesis in dividing bacteria

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2
Q

29.01 BETA-LACTAM ANTIBIOTICS

Penicillins - MOA

A

bind to and inhibit the enzyme that cross-links the peptide chain of the newly formed ‘building block’ to the peptidoglycan cell wall backbone

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3
Q

29.01 BETA-LACTAM ANTIBIOTICS

Penicillins - types of penicillins

A

beta-lactamase resistant (methicillin, flucloxacillin, temocillin), broad spectrum (ampicillin, amoxicillin), extended spectrum (piperacillin, ticarcillin)

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4
Q

29.01 BETA-LACTAM ANTIBIOTICS

Penicillins - abs/distrib/elim

A

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)

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5
Q

29.01 BETA-LACTAM ANTIBIOTICS

Penicillins - clinical uses

A

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

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6
Q

29.01 BETA-LACTAM ANTIBIOTICS

Penicillins - adverse effects

A

hypersensitivity reactions (rashes, urticaria, angioedema, fever, arthralgia, anaphylaxis)

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7
Q

29.02 BETA-LACTAM ANTIBIOTICS

Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - actions

A

bactericidal
interfere with cell wall synthesis in dividing bacteria

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8
Q

29.02 BETA-LACTAM ANTIBIOTICS

Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - MOA

A

bind to and inhibit the enzyme that cross-links the peptide chain of the newly formed ‘building blocks’ to the peptidoglycan cell wall backbone

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9
Q

29.02 BETA-LACTAM ANTIBIOTICS

Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - abs/distrib/elim

A

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

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10
Q

29.02 BETA-LACTAM ANTIBIOTICS

Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - clinical use

A

septicaemia - cefotaxime, cefuroxime
pneumonia caused by susceptible organisms, meningitis - ceftriaxone, cefotaxime
biliary tract infections, urinary tract infections, sinusitis - cefadroxil

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11
Q

29.02 BETA-LACTAM ANTIBIOTICS

Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - resistance

A

some pneumococci, meningococci and gonococci have decreased sensitivity

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12
Q

29.02 BETA-LACTAM ANTIBIOTICS

Cephalosporins and cephamycins: ceftriaxone, cefotaxime, cefuroxime - adverse effects

A

hypersensitivity reactions (rashes, urticaria, angioedema, fever, arthralgia, anaphylaxis)
GIT disturbances
rarely: hepatitis and cholestatic jaundice

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13
Q

29.03 BETA-LACTAM ANTIBIOTICS

Carbapenems: imipenem, meropenem, ertapenem - actions

A

bactericidal
interfere with cell wall synthesis in dividing bacteria

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14
Q

29.03 BETA-LACTAM ANTIBIOTICS

Carbapenems: imipenem, meropenem, ertapenem - MOA

A

bind to and inhibit the enzyme that cross-links the peptide chain of the newly formed ‘building blocks’ to the peptidoglycan cell wall backbone

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15
Q

29.03 BETA-LACTAM ANTIBIOTICS

Carbapenems: imipenem, meropenem, ertapenem - abs/distrib/elim

A

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

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16
Q

29.03 BETA-LACTAM ANTIBIOTICS

Carbapenems: imipenem, meropenem, ertapenem - clinical use

A

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

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17
Q

29.03 BETA-LACTAM ANTIBIOTICS

Carbapenems: imipenem, meropenem, ertapenem - adverse effects

A

GIT disturbances, rashes, injection site reactions

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18
Q

29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS

Glycopeptides: vancomycin, teicoplanin - actions

A

inhibits bacterial cell wall peptidoglycan synthesis

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19
Q

29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS

Glycopeptides: vancomycin, teicoplanin - MOA

A

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

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20
Q

29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS

Glycopeptides: vancomycin, teicoplanin - abs/distrib/elim

A

given IV
vancomycin plasma half-life ~8h
vancomycin given orally for treatment of Clostridium difficile

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21
Q

29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS

Glycopeptides: vancomycin, teicoplanin - clinical use

A

vancomycin used in a wide range of serious infections, including septicaemia, and treatment of MRSA

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22
Q

29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS

Glycopeptides: vancomycin, teicoplanin - adverse effects

A

hypersensitivity reactions, ototoxicity and nephrotoxicity
phlebitis at infusion site

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23
Q

29.04 BLOCKERS OF PEPTIDOGLYCAN SYNTHESIS

Glycopeptides: vancomycin, teicoplanin - special notes

A

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

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24
Q

29.05 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Tetracyclines: doxycycline, tetracycline, oxytetracycline - actions and MOA

A

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

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25
Q

29.05 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Tetracyclines: doxycycline, tetracycline, oxytetracycline - abs/distrib/elim

A

given orally, absorption impaired by milk and by calcium, magnesium and iron preparations

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26
Q

29.05 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Tetracyclines: doxycycline, tetracycline, oxytetracycline - clinical use

A

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)

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27
Q

29.05 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Tetracyclines: doxycycline, tetracycline, oxytetracycline - adverse effects

A

staining of the teeth, GIT disturbances, anorexia, flushing, tinnitus
rare: hepatotoxicity, pancreatitis, hypersensitivity reactions

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28
Q

29.05 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Tetracyclines: doxycycline, tetracycline, oxytetracycline - special notes

A

tetracyclines should not be given to children or pregnant or breastfeeding women

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29
Q

29.06 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Aminoglycosides: gentamicin, streptomycin, amikacin, tobramycin, neomycin - actions

A

inhibit bacterial protein synthesis

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30
Q

29.06 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Aminoglycosides: gentamicin, streptomycin, amikacin, tobramycin, neomycin - MOA

A

cause misreading of the mRNA message due to abnormal codon:anticodon recognition with the production of abnormal proteins

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31
Q

29.06 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Aminoglycosides: gentamicin, streptomycin, amikacin, tobramycin, neomycin - abs/distrib/elim

A

given IM or by slow IV injection or infusion
can be given intrathecally
renal excretion

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32
Q

29.06 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Aminoglycosides: gentamicin, streptomycin, amikacin, tobramycin, neomycin - clinical use

A

infections with staphylococci (with a beta-lactam antibiotic), streptococci, enterococci, Gram-negative bacilli (including Pseudomonas aeruginosa)
used for septicaemia, meningitis, pyelonephritis, endocarditis, pneumonia

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33
Q

29.06 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Aminoglycosides: gentamicin, streptomycin, amikacin, tobramycin, neomycin - adverse effects

A

dose-related ototoxicity and nephrotoxicity
GIT disturbances, rash, blood disorders can occur
↑ototoxicity with loop diuretics
↑effect of neuromuscular blockers

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34
Q

29.07 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Amphenicols: chloramphenicol - actions

A

inhibit bacterial protein synthesis

35
Q

29.07 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Amphenicols: chloramphenicol - MOA

A

inhibit transpeptidation

36
Q

29.07 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Amphenicols: chloramphenicol - abs/distrib/elim

A

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

37
Q

29.07 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Amphenicols: chloramphenicol - clinical use

A

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

38
Q

29.07 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Amphenicols: chloramphenicol - adverse effects

A

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

39
Q

29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Macrolides: erythromycin, clarithromycin, azithromycin - actions

A

inhibit bacterial protein synthesis

40
Q

29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Macrolides: erythromycin, clarithromycin, azithromycin - MOA

A

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

41
Q

29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Macrolides: erythromycin, clarithromycin, azithromycin - abs/distrib/elim

A

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

42
Q

29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Macrolides: erythromycin, clarithromycin, azithromycin - clinical use

A

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

43
Q

29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Macrolides: erythromycin, clarithromycin, azithromycin - adverse effects

A

GIT disturbances
less frequent: allergic reactions, cholestatic jaundice

44
Q

29.08 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Macrolides: erythromycin, clarithromycin, azithromycin - special notes

A

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

45
Q

29.09 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Lincosamide: clindamycin - actions

A

inhibit bacterial protein synthesis

46
Q

29.09 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Lincosamide: clindamycin - MOA

A

inhibits the translocation of the tRNA (with its attached peptide) from the A site to the P site

47
Q

29.09 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Lincosamide: clindamycin - abs/distrib/elim

A

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

48
Q

29.09 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Lincosamide: clindamycin - clinical use

A

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

49
Q

29.09 BACTERIAL PROTEIN SYNTHESIS BLOCKERS

Lincosamide: clindamycin - adverse effects

A

GIT disturbances, skin rashes, jaundice, pseudomembranous colitis

50
Q

29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE

Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - actions

A

interfere with bacteria DNA function

51
Q

29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE

Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - MOA

A

inhibits DNA gyrase (aka topoisomerase II) - the enzyme that produces the supercoil in the chromosome that is essential for transcription and replication

52
Q

29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE

Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - abs/distrib/elim

A

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

53
Q

29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE

Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - clinical use

A

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

54
Q

29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE

Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - adverse effects

A

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

55
Q

29.10 ANTIBIOTICS AFFECTING TOPOISOMERASE

Quinolones: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin, nalidixic acid - special notes

A

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

56
Q

29.11 BLOCKERS OF FOLATE SYNTHESIS/ACTION

Sulfonamides and trimethoprim - actions

A

bacteriostatic
both sulfonamides and trimethoprim interfere with bacterial folate metabolism and thus with DNA synthesis

57
Q

29.11 BLOCKERS OF FOLATE SYNTHESIS/ACTION

Sulfonamides and trimethoprim - MOA

A

sulfonamides competitively inhibit the enzyme dihydropteroate synthetase
trimethoprim inhibits dihydrofolate reductase and thus the conversion of folate to tetrahydrofolate

58
Q

29.11 BLOCKERS OF FOLATE SYNTHESIS/ACTION

Sulfonamides and trimethoprim - abs/distrib/elim

A

given orally or by IV infusion
sulfa drugs pass into inflammatory exudates, but are inactive in the presence of pus

59
Q

29.11 BLOCKERS OF FOLATE SYNTHESIS/ACTION

Sulfonamides and trimethoprim - clinical use

A

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

60
Q

29.11 BLOCKERS OF FOLATE SYNTHESIS/ACTION

Sulfonamides and trimethoprim - adverse effects

A

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

61
Q

29.12 OTHER ANTIBACTERIAL DRUGS

Metronidazole

A

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

62
Q

29.12 OTHER ANTIBACTERIAL DRUGS

Nitrofurantoin

A

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

63
Q

29.12 OTHER ANTIBACTERIAL DRUGS

Quinupristin and dalfopristin - actions

A

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

64
Q

29.12 OTHER ANTIBACTERIAL DRUGS

Quinupristin and dalfopristin - clinical use

A

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

65
Q

29.12 OTHER ANTIBACTERIAL DRUGS

Aztreonam

A

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)

66
Q

29.12 OTHER ANTIBACTERIAL DRUGS

Polymyxin B, colistimethate

A

polymyxins - cationic detergent properties and disrupt bacterial outer cell membrane
selective bactericidal action on Gram-negative bacilli, especially Pseudomonas and coliform organisms

67
Q

29.12 OTHER ANTIBACTERIAL DRUGS

Fosfomycin

A

phosphonic acid
acts against many Gram-positive and Gram-negative organisms
used for treatment of urinary tract infections

68
Q

29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS

Isoniazid

A

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)

69
Q

29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS

Rifampicin - actions

A

bactericidal
effective against most Gram-positive and many Gram-negative bacteria

70
Q

29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS

Rifampicin - abs/distrib/elim

A

given orally, widely distributed
excreted in urine and bile

71
Q

29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS

Rifampicin - clinical use

A

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

72
Q

29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS

Rifampicin - adverse effects

A

GIT disturbances, skin eruptions, liver damage
orange tint to saliva, sweat and tears

73
Q

29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS

Ethambutol

A

bacteriostatic
given orally, well absorbed
adverse effects: optic neuritis (dose-related) - colour vision should be monitored before and during prolonged treatment

74
Q

29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS

Pyrazinamide

A

bacteriocidal
given orally, well absorbed
adverse effects: GIT disturbances, increases plasma urate, malaise, liver damage

75
Q

29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS

Capreomycin

A

inhibits protein synthesis
given IM
adverse effects include renal and auditory nerve damage

76
Q

29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS

Cycloserine

A

broad-spectrum antibiotic - inhibits bacterial cell wall synthesis
given orally, penetrates CSF
adverse effects mainly on CNS

77
Q

29.13 ANTIMYCOBACTERIALS FOR TUBERCULOSIS

Streptomycin

A

aminoglycoside antibiotic - inhibits bacterial protein synthesis
given IM
adverse effects: ototoxicity and nephrotoxicity

78
Q

29.14 ANTIMYCOBACTERIALS FOR LEPROSY

Dapsone - action and MOA

A

sulfonamide-like, may inhibit folate synthesis

79
Q

29.14 ANTIMYCOBACTERIALS FOR LEPROSY

Dapsone - abs/distrib/elim

A

given orally
plasma half-life 24-48h

80
Q

29.14 ANTIMYCOBACTERIALS FOR LEPROSY

Dapsone - clinical use

A

tuberculoid leprosy (and dermatitis herpetiformis)
resistance increasing

81
Q

29.14 ANTIMYCOBACTERIALS FOR LEPROSY

Dapsone - adverse effects

A

haemolysis of red blood cells, methaemoglobinaemia, anorexia, nausea and vomiting, fever, allergic dermatitis, neuropathy

82
Q

29.14 ANTIMYCOBACTERIALS FOR LEPROSY

Clofazimine - action and MOA

A

a dye
MOA thought to involve action on DNA of leprosy bacilli
anti-inflammatory activity

83
Q

29.14 ANTIMYCOBACTERIALS FOR LEPROSY

Clofazimine - abs/distrib/elim

A

given orally
plasma half-life can be 8 weeks

84
Q

29.14 ANTIMYCOBACTERIALS FOR LEPROSY

Clofazimine - adverse effects

A

skin and urine can develop a reddish colour and leprosy lesions a blue-black discolouration
GIT disturbances, headaches

Pharmacology (34 decks)

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