Infectious Disease Pharmacology Flashcards

Question

How do quinolones work?

Answer 1

Inhibition of alpha subunit of DNA gyrase causing inhibition of nucleic acid synthesis Petkov blue

Answer 2

Inhibition of alpha subunit of DNA gyrase causing inhibition of nucleic acid synthesis Petkov blue

Answer 3

Quinolones, nitroimidazoles Petkov blue

Answer 4

Inhibition of alpha subunit of DNA gyrase causing inhibition of nucleic acid synthesis Petkov blue

Answer 5

Sulphonamides Trimethoprim Petkov blue

Answer 6

Mimic folic acid by acting as false substrates Petkov blue

Answer 7

Competitive inhibition of bacterial Di-hydro-folate reductase - inhibiting folic acid synthesis Petkov blue

Answer 8

Petkov blue

Answer 9

Lincosamides Tetracycline Sulphonamides Macrolides at low plasma concentrationsPetkov blue Petkov blue

Answer 10

Bacteria have cell walls, membranes and are prokaryotes that rapidly replicate, asexually with DNA arranged in single circular chromosme in the cytoplasm. Bacterial ribosomes are structurally different from mammaliana nd non membran eassociated Fungi are eukaryoytes ith nuclear material enclosed in a membrane, replicate slowlyt and have intracelular organelles . Most antifungals therefore target fungal cell membrane where erogsterol replaces cholesterol

Answer 11

Pencillins Cephalosporins Carbapenams Monobactams

Answer 12

Beta lactams Glycopeptides

Answer 13

Both have acyl side chains connecting to a beta lactam ring, however the side chain may have different offshoots, and pencillins have a thiazolidine ring whereas cephalosporins have a dihydrothiazine ring

Answer 14

Suscepatability to acid degredation in the stomach Spectrum of acitivty

Answer 15

Pencillin V and pencillin G

Answer 16

Bacteriocidal, inhibit celll wall synthesis by prevenitng peptidoglycan cross linkage weakening cell walls - the beta lactam ring resembles the natural substrate D-ala-D-ala on the side chain of peptidoglycan where cross linkage occurs. Penicillins bind to several pencillin binding proteins in the cel wall that act as transpeptidase enzymes responsible for forming the cross links. Binding is irreversible due to acelyation of active serine site after cleavage of the beta lactam ring. Growth continues in the baceria but with reduced cross linkage of peptidoglycan until the cell wall weakens to the point at which it lyses

Answer 17

hydrlyses the beta lactam ring

Answer 18

Gram negative are encoded in bacterial chromosomes and plasmids which may be disseminated leading to acquired resistance

Answer 19

Yes However rarely does complete eradication occur, a significant number of beta lactam sesntiive cells known as persistors remain dormant until the antibiotic is removed. Complete erradication required addition of synthergistic antibiotic e.g. gentamicin Synergistic antibiotics have increased potency when cell wall damage has occured giving better intracellular access

Answer 20

The peptidoglycan layer to start with is thin, and although if weakened it weakens the cell wall the thicker lipopolysaccharide outer layer remains intact such that the cell doesn't lyse generally. Internal hydrostatic pressure forces the bacteria to become spherical, in cells with high intracellular osmolality the pressure may be sufficient to lyse.

Answer 21

Phenoxymethypenicillin

Answer 22

Benzylpenicillin

Answer 23

reistsance to beta lactamase in staph

Answer 24

Ampicillin, amoxicillin

Answer 25

whether it is susceptible to acid induced degradation in the stomach (hydrolysis) - if it is then it has reduced oral absorption

Answer 26

Amoxicllin has better oral absorption as it is less susceptable to acid induced degredation

Answer 27

30 minutes

Answer 28

Generally good, inflammation necessary for pencillins to pass into bone and through the BBB.

Answer 29

Kidneys unchanged 60-90% Mainly by renal tubular secretion Bile 10% 20% metabolised

Answer 30

Probenicid

Answer 31

Tazobactam clavulinic acid

Answer 32

clavulanic acid does Tazobactam does not

Answer 33

Inactivation by lactamases Altered permeability of porins in gram negative bacterial outer membrane Altered pencillin binding proteins

Answer 34

Beta lactam ring is fused with a dihydrothiazine ring to produce cephem nucleus

Answer 35

Gram positive cover is maintained, gram negative cover improved

Answer 36

Bactericidal Disrupt peptidoglycan cell wall integrity Modified beta alctam ring is more stable making them less susceptable to beta lactamases

Answer 37

Widely Readily cross placenta Third generation cephalosporins penetrated the CSF especially if meningeal inflammation occurs (10% penetration)

Answer 38

1-1.5 hours with exception of ceftriaxone which has a half life of 5.5-11 hours (R+D) (8hrs Smith)

Answer 39

Cepradine, cefuroxime, ceftazidime

Answer 40

Liver - 10% acitvity of metabolites compared to parent drug (desacetyl cefotaxime) 50% unchanged in urine

Answer 41

Urine unchanged, except for ceftriaxone which is 50% metaboised iin the liver Renal excretion both filtration and tubular secretion Probenicid increases peak concentration and plasma half life but to a lesser extent than penicillin

Answer 42

Hypersensitivity GI - C diff, especially third generation Transient positive coombs test LFT abnormalities

Answer 43

Cefalexin, cefaclor, cefradine Gram positive cocci

Answer 44

Cefuroxime, cefaclor, cefoxitin Gram positive cocci Cefuoxime also covers H influenzae

Answer 45

Cefotaxime, ceftazidime, Ceftriaxone Broader spectrum, enahanced resistance to beta lactamse Less potent against gram + Pseudomonas sensitvie Cross BBB

Answer 46

Cefepime, cefpirome Enterobacter and pseudomonas

Answer 47

Ceftaroline, ceftobipole MRSA, VRSA

Answer 48

Aminopenicllin derivitve of ampicillin (Scarth and smith)

Answer 49

Vials, sachets, capsules, suspension and syrup

Answer 50

Bactericidal - Some strains of haemophilus influenzae - Some strains of E Coli - Proteus, bordatellla pertussis, neiseria, salmonella, shigella - Strep and Clostridium (not difficile) Ineffective against - Pseudomonas, klebsiella and pencillinase producing organisms - 90%of Staph are resistance

Answer 51

Reduces the MIC againt staph aureus, E Coli, H influenza and Klebsiella

Answer 52

Allergy GI Intersisital nephritis haemopoietic disturbances Cholestatic jaundice late with clavulanic acid use

Answer 53

Absorption - rapidly absobed, 70-90% bioavailability Distribution 20% protein bound in plasma, to labumin Vd 0.3 - 0.4L/kg Metabolism - 30% by liver Excretion 250-350 ml/min Eliminiation half life 60 minutes 40% renal elimination (20-35% unchanged) Removed by haemodialysis

Answer 54

Clavulinic acid 60% bioavailability (marked variability) Clavulinic acid 20% protein bound Vd 0.2L/kg Clavulanic acid 50-70% hepatically metabolised Excretion 250-350ml/min Elimination half life 60 minutes Removed by haemodialysis

Answer 55

1st and 2nd generation - oral and IV 3rd generation IV only

Answer 56

Cefradine - 8-17% Cefuroxime/cefotaxime 35-50% Ceftazidime <10% Ceftriaxone 95%

Answer 57

They are haemodialysed

Answer 58

Semisynthetic isoxazolyl penicillin

Answer 59

Yes because it has good oral bioavailability

Answer 60

Staph auerues Beta haemolytic strep Pneumococci

Answer 61

GIT CNS Rashes Glossitis Jaundice in the critically ill Pseudomembranous colits

Answer 62

Absorption - 50-70% orally absorbed Distribution - 95% protein bound, Vd 6.8-9.4 L Metabolism - 8-13% metabolised to active form 5 hydroxy-methyl-flucoxacilin 4% hdyrolused in liver to penicilloic acid which is inactvie, the rest is excreted uncahnged Excretion - filtration and secretion, 35-75% of dose appear in the urine Clearance 3ml/min/kg Elimination half life 45 minutes

Answer 63

Not dialysed

Answer 64

aminoglycosides cause precipitation

Answer 65

- Streptpcoccus - yes - Staphylococcus - variable - Oral anaerobes - yes - Enterococcus - no - Bacillus - yes - Clostridium - yes - Listeria - yes - Trepnoma palladium - yes - E Coli - variable - Pseudomonas - variable - Bacteriodes - variable

Answer 66

Transpeptidase Carboxypeptidase

Answer 67

Hypernatraemia, hypokalaemia Allergy GIT Haemolytic anaemia Neuropathy/nephropathy

Answer 68

A - 15-30% of oral dose of benpen , unstable under acid. 60% of oral phenoxymethylpenicillin D - 60% protein bound, albumin. Vd 0.3 - 0.9 L/kg Metbaolism - penicilloic acid which is inactive, further transformation Excretion - 60-90% in urine, 25% unchanged, by active tubular secretion Elimination half life 0.7 hours Ben Pen is removed by haemodialysis

Answer 69

semi synthetic penicillin

Answer 70

Gram negatives including - E coli, H influenzae, Klebsiella, neisseria, preoteus, shigella, serratia Anaerobes including bacteriodes and clostridium Gram postiive enterooccci stpah and streo Pseudomonas Indole positive proteus Strep faecalis Serratia

Answer 71

Lower sodium content Serum potassium may decrease after administration

Answer 72

GIT LFTs Allergic reaction Transient leucopenia Transient neutorpenia

Answer 73

Absorption - not acid stable, poor absorption, hydrolysed by acids Distribution - 16% protein bound, Vd 0.32L/kg, hihg concentrations found in most tissues and body fluids Metabolism - nil Excretion - 20% in bile, remainder in urine by filtration and tubular secretion Eliminatino half life 36 - 72 minutes Dose reduction in renal impairement 30-50% removal by haemodialysis

Answer 74

Gram positive - not MRSA or enterococcus faecalis Gram negative aerobic - not stenotrophomonas maltophilia Anaerobic ESBL Do not cover MRSA or E faecalis If used in isolation cause psuedomonas resisatnce Imipenam - resistance to Beta lactamse, but only moderately effective against clostridium perfringens. Imipenam induces resisatnce to beta lactam agents in pseudomonas

Answer 75

IMipenam is metabolised by renal dehydropeptidsae I so is ocmbined with inhibitor cilastatin Meropenam is not metabolised in this way so not combined with cilastatin

Answer 76

Bind to penicillin binding proteins on the bacterial cytoplkasmic membrane blocking peptidoglycan synthesis and cell wall formation

Answer 77

Hypersiensitivity Diarrhoea/vomiting Pseudomomebranous colitis positive coombs test Can develop CNS side effects in those with pre-existing CNS disease

Answer 78

Absorption - nil orally Distribution - 12.5-20L 2% bound to plasma proteins Metabolism - metabolised to inactive metabolite Excretion - clearance equivalent to creatinine clearance, half life 60 minutes, 70% excreted unchanged in urine

Answer 79

Unaffected

Answer 80

Reduce sodium valproate levls

Answer 81

Klebsiella pneumonia - CPE

Answer 82

gram negative aeorbic e.g. enterobacter and speudomonas

Answer 83

Vancomycin Teicoplanin

Answer 84

Aerobic and anaerobic gram positive - bacteriocidal (Staph, MRSA, enterococci, C difficile) Bacteriostatic against enterococci and streptococci All gram negatives are resistant Due to large molecular weight and lack of penetratioun through gram negative cell membranes

Answer 85

inhibit cell wall syntheiss Large rigid structure binds to peptidoglycan precursers (peptidoglycan pentapeptide) hindering cross linkage and reduces cell wall rigidity - specifically binding to D-alanyl-D-alanine residues no Competition between penicillins and glycopeptides for active activ peptide binding site

Answer 86

Oral IV Intrathecal powder for reconstitution

Answer 87

Absorption - no oral bioavailability Distribution - 0.4-1L/kg, poor CNS penetration even with inflamed meninges, higher levels required for this. 50% protein bound. Widely distributed including in adpiose tissue. CSF level 7-30% of serum concentration in context of meningeal inflammation Metabolism - very minimial hepatic metabolism Excretion - 90% excreted unchanged in urine Half life 6 hours

Answer 88

Peak - dose Trough - dose and interval

Answer 89

similar acitvity Longer duration of action 2-4x potency Bone and CSF penetration more reliable (CNS penetration less reliable as per Smith) Increased resistance to teicoplanin Peck and Hill

Answer 90

Renal - nephrotoxicity 5-14%, usually seen with concurrent aminoglycosides, or with pre-existing renal impairmenet, usually resolves on withdrawal of vancomycin. Risk factors: dose >4g/day, trough levels >15, AUC >800/ 3% require dilaysis Ototoxicity - discontinue if tinnitis occurs (1% and more seen with long duration and concurrent aminoglycosides Phlebitis Histamine release - if administered too rapidly, hypotension tachycardia and a widespread rash Dose administration should not exceed 10mg/min Haematological - neutropenia, thrombocytopenia 2% and reversible - more associated with prolonge duse

Answer 91

Rash Eosinophilia Thrombocytopenia Fever

Answer 92

duration fo time where substance level is higher than the MIC

Answer 93

not dialysed

Answer 94

Cross hypersensitivtiy with vancomycin Cutaneous reactions LFTs increase Infusion reactions Cr increase

Answer 95

Absorption - nil oral absorption, IM absorption 90% Distribution - mostly serum albumin bound, 90% Vd 0.7-1.4L/kg Distributed mainly in lungs, myocardium, bone Metabolism - minimal 2 metabolites formed from hydroxylation representating 2-3% of adminsitered dose Excretion - unchanged in urine 80%, 3% to faeces Elimintation half life 100-170 hours Low clearance at 10-4ml/kg/hr

Answer 96

Aerobic gram negative organisms - pseudomonas rapidly aquires resistance in monotherapy legionella,. mycoplasma, ricketssia, chlamydia Neisseria Anaeorboes Emerging resistance from E COli, shigella, neisseria gonorrhoea, acinetobacter and pseudomonas

Answer 97

Moxifloaxacin has greater pneumococcal activity

Answer 98

Bactericidal Block DNA replication by blocking topoisomerase enzymes and DNA gyrase essential for supercoiling, replication and separation of circular bacteria DNA

Answer 99

Absorption - readily absorbed 80%, with first pass metabolism occuring Distribution - widely, protein binding 30-40%, 2-3L/kg Vd, high CSF and tissue penetration Metabolism - limited hepatic metabolism Excretion - urine and faeces in unchanged form, active tubular secretion of ciprofloaxicin 500ml/min excretion, half life 3-7 hours

Answer 100

CNS - use with caution in epilepsy, especialy in coexistent use of NSAIDs; anxiety, insomnias and hallucinations Tendon damage - rupture, especially with concurrent corticosteriods CV - prolong QT Haematological - haemolytic especially with G6PD Photosensitivity Allergy Transient LFT elevations Increased MRSA and C diff

Answer 101

nalidixic acid - fluorinated

Answer 102

Oral - tablet and pwoder for suspension IV Eye drops Eye ointment

Answer 103

25-30% removed

Answer 104

25-30% removed

Answer 105

Gram positive bacteria Limited gram negative - legionella, neisseria, H influenza

Answer 106

Bactercidal Binds ot the beta subunit of DNA dependent RNA polymerase preventing DNA transcription into RNA

Answer 107

ciprofloxacin

Answer 108

Absorption - Distribution - very lipid soluble, penetrates CNS, abscesses and heart valves Metabolism - liver mirosomes Excretion - bile, active transport into bile can become saturated, additional drug then excreted uncahined in the urine imparting red colour

Answer 109

CYP450 reducing plasma concentrations of anticonvulsants, OCP and warfarin

Answer 110

obligate anaerobes and protozoe e.g. trichomaonas, clostridia, abcteriodes, trepnoma pallidum, campylobacter Resisatnce in streptococci, lactobacilli

Answer 111

passive diffusion entry into cells Metronidazole is reduced by pyruvate:ferridoxin oxidoreductase system in obligate anaeroboes and the nitro group of reduce metronidazole acts as an electron sink capturing electrons that would usually be transferred to hydrogen ions in the metabolic cycle as a result cytotoxic intermediates accumulate with free radicals inducing DNA strand breakage and cell death Acts via a reactive intermediate which reacts with bacteria DNA so the resultant DNA complex can no longer function as an effective primer for DNA and RNA polymerases so all nucleic acid synthesis si thus blocked

Answer 112

Absorption - almost 80-100% bioavailability orally, 75% rectally Distribution - Widely distributed, CSF, cerebreal absecesses, prostate and pleural fluid half life 8 hours 10% rpotein bound Vd 0.75L/kg Metabolism - completely in liver with active hydroxy metabolite eliminated slowl form the plasma (oxidation and glucuronidation) Excretion - through kidney - 60% unchanged, does not accumulate in renal failure. Clearance is 1.22 ml/kg/min Elimination half life is 6-10 hours

Answer 113

Nausea Metallic taste Not be consumed with alcohol as severe disulfiram like reaction Prolonged use - peripheral neuropathy, leucopenia

Answer 114

Aminoacyl site (A) Peptidyl (P) Exit (E)

Answer 115

Gram positive, some gram negative (esp azithro) Anaerobes gram positive and negative Obligate intracellular parasites -mycoplasma and legionella sensitive

Answer 116

erythromycin

Answer 117

Less GI upset Better coverage for streptococci, listeria and legionella

Answer 118

Better gram negative cover e.g. moraxela catarrhalis, neisseria, H influenzae Improved bioavailabiliy and longer half life than erythromycin

Answer 119

Depends on plasma concentration

Answer 120

Halt bacterial protein synthesis by binding to 50S ribosomal subunit after formation of the initiation complex - subsequent prevention of peptidyltransferase activity and or movement of tRNA from A to the P site prevents elongation of the peptide chain

Answer 121

Absorption - Orally or parenterally; erythromycin 10-60% absorption, clarithromycin 50%, azithromycin 37% Distribution - CSF penetration poor, sputum and lung penetration good. Vd for erythromycin 0.34 - 1.22L/kg Azithromycin 0.44 L/kg 12-50% azithromycinbound to plasma proteins Metabolised - liver - erythromycin --> demethylation, clarithromycin --> 14-hydroxyclarithromycin, azithromycin via hepatic N and O demethylation to inactive metaboliutes Excretion - Erythromycin and clarithromycin renally, erythromycin half life 1.6 hours, 2-15% unchanged in urine. CLarithromycin non linear, half life 5-6 hours, 33% excreted unchanged Azithromycin - clearance 10ml/kg/min, 68 hour half life, 12% excreted uncahnged in urine but predominantly excreted in bile

Answer 122

erythromycin and clarithromycin strong inhibitors of hepatic cytochrome CYP3A4 and p glycoprotein (the transport portein responsible for limiting enteral uptake of many drugs) Simvastatin, warfarin, methylprednisone, phenytoin, ciclosporin, theophulline, sodium valproate, tacrolimus, midazolam, digoxin and carbamazepine levels are increased

Answer 123

GIT - common, prokinetic, avoid erythromycin in porphyria CV - prolonged QT associated with erythromycin and clarithromycin Ototoxicity has been reported Heptic dysfunction Allergy rare

Answer 124

Macrocyclic lactone ring to which deoxy sugars are attached

Answer 125

prolonged QT Porphyria Digoxin toxicity Caution if on warfarin, antiepileptics. immunosuppressants

Answer 126

synthetic imidazole derivitive

Answer 127

Increased anticoagulant effect of warfarin Disulfuram reaction whe alcohol is consumed Prolongs vecuronium

Answer 128

removed by dialysis

Answer 129

Gram negative aerobes - E Coli, speudomonas, enterobacter, proteus, klebsiella, serratia Staphylococcus Strep limited No anaerobic activity

Answer 130

With Vanc or Beta lactams it will be synergistic

Answer 131

Amikacin has less resistance to enzyme inactivation

Answer 132

bactericidal - concentration dependent killing, post antibiotic effect Block protein synthesis by irreversibly binding to bacterial 30S ribosome subunit - interfering with tRNA attachment and mRNA is either not transcribed or misread Large polar molecules need active transport to gain entry into bacterial cells - passive diffusion into cell via porin channels, then oxygen dependent active transport into cytoplasm. Active transport enhanced by cell wall active drugs. Low pH and anaerobic conditions inhibit transport by reducing gradient. Transport is inhibited by divalent cations calcium, magnesium, acidosis and low oxygen tension

Answer 133

Large polar molecules need active transport to gain entry into bacterial cells Transport is inhibited by divalent cations calcium, magnesium, acidosis and low oxygen tension

Answer 134

Absorption - No significantly absorbed when administrered orally as not lipid soluble, given parenterally only. NOT Inactivated in the GIT Distribution - Low protein binding for other aminoglycosides (amikacin 20%), but 70-85% for gentamicin, distribute in extracellular fluid and penetrate cells, CSF and sputum poorly. Vd 0.14-0.7 L/kg for gentamicin. Hihg concentrations in the renal cortex Metabolism - Not metabolised Excretion - Excreted unchanged in urine by filtration, gentamicin clearance 1.18 - 1.32 ml/kg/min Half life 2-3 hours with normal renal fucntion, 24-48 hours with severe renal impairment

Answer 135

Ototoxicity - vestibular and rarely auditory dysfunction occurs when significant amount accumulates in the inner ear perilymph - 1-5% receiving for >5 days. Effects permanent. Risk is increased in renal failure and with simultaneous furosemide use Nephrotoxcity - 37% of ICU patients, reversible on discontinuing treatment. ATN as accumulates in renal cortex, manifests within a week of Tx, synergistic toxicity with cephalosporins Both above are associated with high TROUGH concentrations Muscle weakness - decrease prejunctional release of acetylcholine, reduce post junctional sensitivty to acetylcholine and increase non depolarisng muscle relaxant potency. i.e. avoid in myasthenia gravis

Answer 136

aminocyclitol ring derivative bound to amino sugars

Answer 137

Liquid form for topical use IV form IM Suitable for intrathecal or Intraventricular administrtion

Answer 138

plasmid translocation Transferase enzyme inactviating drug Impaired entry into cell Alteration or delation of 30S ribosomal subunit receptor protein

Answer 139

Trough - immediately prior Peak -1 hour post

Answer 140

Both removed - in both haemofiltration and dialysis

Answer 141

Proong non depolarising muscle relaxants by inhibiting pre synaptic acetylcholine release and stabilising the post synaptic membrane at the neuromuscular junction Can be partially reversed by IV calcium

Answer 142

clindamycin

Answer 143

Gram positive Anaerobic very little gram negative aerobic cover

Answer 144

inhibits bacterial protein synthesis through disruption of 50s ribosomal subunit Bacteriostatic or bactercidial depending on concentration and organism Resistance is inducible in gram postivie organisms - imparts resisatnce to macrolides also

Answer 145

Pseudomoembranous colitis and diarrhoea common Fever Rash Eosinophilia

Answer 146

,minoclycine, doxycycline

Answer 147

INhibiting attachment of tRNA amino acid complex to ribosome inhibiting codon-anticodon interaction Binds to bacteria 30S ribosome preventing acces to amminoacyl transfer RNA (tRNA) to the mRNA-ribosome complex preventing elongation of polypeptide chain

Answer 148

Chelated by milk, calcium and magnesium

Answer 149

Avoid in renal and hepatic failure Raised ICP Increase muscle weakness in myasthenia gravis Exacerbate SLE - photosensitivty Deposited in growing teeth and bones so dont use in children Prengant and lactating women should not receive

Answer 150

Staph auerues MRSA Staph epidermitis Strep and pneumococci resistant Some gram negatives are sensitive but most resistant

Answer 151

Forms a complex with elongation factor and GTP blocking protein translocation and incorporation of amino acid residuals prevenitng protein syntheiss --> cell death

Answer 152

Well distirbuted, penetrates abscesses well No active in CSF Bone penetration si good Excreted uncahnged in bile, but little active durg in faeces Minimal renal excretion

Answer 153

GIT Otherwise well tolerated

Answer 154

napthacenecarboxamide deriviative

Answer 155

tablets Syrup for IM injection IV injection with ascorbic acid Ointment

Answer 156

Bacteriosttic Active against gram positive and gram negative - Clostridium - Streptococcus - Neisseria - Brucella - Vibrio - H influenzae - Yersinia pestis - Ricketsiae - Mycoplasma - Chlamydia - Leptospira - Treponoma

Answer 157

Absorption - incompletely absorbed, chelates with iron, calcium and aluminium. Theoretical bioavailability 77% Distribution - widely, good tissue penetration,. 65% protein bound, Vd 0.75-1.37 L/kg Metbaolism - 5% is metabolised to epitetracycline ootherwise unchanged Excretion - 95% unchanined, 60% in urine via filtration and remainder inf aeces. Clearance 1.5 ml/min/kg Half life 10-16 hours

Answer 158

Raised ICP Increased duration fo action of non depolarising muscle relaxants Incompatible with many drugs pharmaceutically

Answer 159

Ciprofloxacin Metronidazole Azole antifungals Penicillins apart from benzypenicillin (reduced by 30%) Azithromycin less commmon - Rifampicin Fusidic acid

Answer 160

aztreonam, acyclovir,zidovudine

Answer 161

Cephalosporins, teicoplanin, macrolides erythromycin and clarithromycin

Answer 162

Oxazolidinone

Answer 163

Gram postiive organisms - enterococcus, streptococcus, staph, gram postiive anaerobes inclduign clostridium perfingens

Answer 164

Inhibits bacterial protein synthesis by bidning to 50S binding subunit preventing initiation complex formation

Answer 165

Headache LFTs taste alteration GIT Fertility reversibly affected Skina nd bleeding disorders Phelbitis pancreatitis

Answer 166

Absorption - rapidly absorbed after oral administration and has oral bioavailabiltuy close to 100% Distribution - drug is 31% protein bound, Vd 0.64L/kg Metabolism - oxidised in liver to inactive carboxylic acid metbaolites Excretion - 30% unchanged in urine, metabolites in urine and faeces Eliminationhalf life 5 hours Clearance 120ml/min

Answer 167

Reversible non selective MAOI

Answer 168

antifolate antibiotic

Answer 169

Synergistic combinatino of folate antagonists blocking purine production and nucleaic acid synthesis Trimethoprim in combination wit sulphonamides becomes bactercidal due to blockade of sequential steps in folate synthesis - sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid, trimtheoprim blocks production of tetrahydrofolic acid

Answer 170

Absorption - PO or IV 5:1 sulphamethoxazole:trimethoprime Half life 8 hours Renal clearance - 30-50% sulphonamide and 50-60% of trimethoprim excreted in urine within 24 hours

Answer 171

Staph aureus Haemophilus Moraxella Klebsiella Pneumocytstis pneumonia

Answer 172

GI Fever, skin rashes - photosensivitiy, rarely SJS Urinary tract disturbances - can precipitate haematological - haemolytic or asplatic anaemia, thrombocytopenia (with diuretics) Warfarin increases INR CNS effects

Answer 173

Hypersensitivty Blood dyscrasia Marked renal or hepatic impairment Megaloblastic bone marrow

Answer 174

Concentration time curve describiong the relationship between antibiotic concentration and their killing power Anitbiotic which kill over time are those which kill according to time spent over MIC Antibiotics which kill be concentration kill according to the highest peak

Answer 175

Concentration time curve describiong the relationship between antibiotic concentration and their killing power Anitbiotic which kill over time are those which kill according to time spent over MIC Antibiotics which kill be concentration kill according to the highest peak Some kill by both

Answer 176

Beta lactams Carbepenams Monobactams Linezolid Clindamycin Macrolides

Answer 177

Aminoglycosides Metronidazole Daptomycin Fluoroquinolones

Answer 178

Fluoroquinolones, azithromycin, tetracyclines, vancomycin, tigecycline, linezolid

Answer 179

- Those which kill bacteria most effectively at some specific event e.g. when about to divide - Those which do not have much post antibiotic effect i.e. the kill characteristic only occurs when the drug concentration remains high

Answer 180

Cephalosporins even with 40-50% of dosing interval above MIC killing efficacy close to maximal and cephalosporins have the hgihest requirement for time above MIC - beta lactams the next most frequency and carbepenams less (30% with early kill characterstics)

Answer 181

Areas of poor penetration e.g osteomyelitis, CNS ifnection

Answer 182

Is a property of antibiotics which disable some sort of crucial steps in bacterial metabolism or protein synthesis - the higher the concentration reach the more synthetic enzyme molecules are inhibited e.g. aminoglycosides, metronidazole, daptomycin

Answer 183

8-10x MIC at peak levels

Answer 184

Initially related to passive ionic binding of the drug to the bacterial lipopolysaccharide coat but later becomes more reliant on active uptake into the bacterial cell. Being exposed to aminoglycosides causes bacteria to downregulate this uptake and thus the first exposure to the drug increases subsequent MIC. The forst dose better be the bigger one as it will carry out the bulk of the killing. Once daily dosing allows enough time for this effect to dissapate somewhat between doses

Answer 185

Inhibits steps in DNA synthesis or replication, or components crucial for cellular division Time is important because inhibited enzymes are most active durnig division and therefore time immersed in the drug is necessary to catch a large portion of the bacteria attempting this Concentrationsi important to disable more of target cell components

Answer 186

Stenotrophomonas maltophila Pseudomonas cepacia Enterococcus faecium MRSA

Answer 187

Lactobacillis casei Pediococcus pentosaceus Leuconostoc mesenteriods

Answer 188

Persistent of effect long after serum concentration has fallen below MIC

Answer 189

Inhibit some life sustaining enzyme or bind tightly to cell wall components Usually concentration dependent kill characteristics

Answer 190

Aminoglycosides Clindamycin Macrolide antibiotics Tetracyclines Rifampicin Quinupristin/dalfopristin

Answer 191

Carbapenems Fluoroquinolones Glycopeptides Linezolid

Answer 192

Factors which decrease the antibiotic peak dose: - Poor gut absorption - Increased volume of distribution - fluid overloaded - Poor penetration to the site of action - ischaemic gut, oedamatous lung, poor tissue perfusion Factors which increase the antibiotic peak dose: - Decreased protein binding - increased fraction unbound - Diminished clearance mechanisms - Improved penetration into inflamed tissues (eg. meningitis) Factors which increase the antibiotic half-life - Decreased renal clearance - Decreased hepatic clearance - blood flow diminished in shock and synthetic function may be poor if liver injury - Decreased overall metabolism (eg. hypothermia) Factors which decrease the antibiotic half-life - Renal replacement therapy - e.g. fluconazole it totally removes -Increased hepatic clearance, eg. enzymes induced by drug interactions; hyperdynamic circulation - Increased glomerular filtration if hyperdynamic - Hypermetabolic state

Answer 193

Factors which decrease the antibiotic peak dose: - Poor gut absorption - Increased volume of distribution - fluid overloaded - Poor penetration to the site of action - ischaemic gut, oedamatous lung, poor tissue perfusion

Answer 194

Factors which increase the antibiotic peak dose: - Decreased protein binding - increased fraction unbound - Diminished clearance mechanisms - Improved penetration into inflamed tissues (eg. meningitis)

Answer 195

- Decreased renal clearance - Decreased hepatic clearance - blood flow diminished in shock and synthetic function may be poor if liver injury - Decreased overall metabolism (eg. hypothermia)

Answer 196

Factors which decrease the antibiotic half-life - Renal replacement therapy - e.g. fluconazole it totally removes -Increased hepatic clearance, eg. enzymes induced by drug interactions; hyperdynamic circulation - Increased glomerular filtration if hyperdynamic - Hypermetabolic state

Answer 197

Enhanced organ toxicity Antibiotic toxicity will increase not only because clearance might be impaired, but because the organs themselves are likely damaged, and are therefore relatively defenceless. Toxicity may develop at drug levels which might otherwise be viewed as safe. Examples of this may include: Increased nephrotoxicity from aminoglycosides, if the renal function is already impaired Increased cardiotoxicity from bleomycin and vancomycin Increased risk of QT prolongation and arrhythmia with fluoroquinolones in the context of cardiac ischaemia, profound hypothermia, or extreme electrolyte derangement Increased bone marrow toxicity from linezolid, cotrimoxazole, gancyclovir, chloramphenicol, beta-lactams of all sorts... With a disrupted blood-brain barrier, an increased risk of seizures from high-dose beta-lactams, due to enhanced penetration. Worsening shock due to dapsone-induced methaemoglobinaemia and thus diminished oxygen-carrying capacity.

Answer 198

MIC is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. The results are usually reported as µg/mL.

Answer 199

Easily performed Frequently, an automated method is available Simplicity and automation of the test enhances reproducibility Rapid return of results

Answer 200

Minor variations in methodology can result in large variations of the MIC. For example, extended incubation will make the MIC appear higher Lower inoculum concentrations will make the MIC appear lower Interlaboratory variation in technique makes comparison problematic MIC is inhibition of visible growth: the microorganisms weren't necessarily killed! MIC may not be related to in vivo efficacy, which is a complex parameter determined by numerous factors among which the MIC is only one. An antibiotic with a low MIC may have no effect if it does not penetrate into the infected tissue. An antibiotic with a high MIC will still be effective if it happens to be concentrated in the infected tissue (eg. gentamicin in urine).

Answer 201

Tobramycin is marginally more active than gentamicin against P. aeruginosa, but not against other aerobic Gram-negative bacteria. It is inactivated by a similar range of bacterial enzymes as gentamicin. Amikacin is more resistant to bacterial enzymatic inactivation than gentamicin or tobramycin, so it should generally be reserved for treating infections resistant to other aminoglycosides. Kanamycin, along with amikacin, has largely replaced streptomycin in the treatment of resistant mycobacterial infections, because of higher rates of susceptibility and better availability. However, kanamycin is inferior to other aminoglycosides against aerobic Gram-negative bacteria. Capreomycin has also been used for multidrug-resistant tuberculosis.

Answer 202

However, widespread use of carbapenems is linked to an increasing prevalence of infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Gram-negative bacteria and Clostridioides difficile (formerly known as Clostridium difficile). Furthermore, carbapenem resistance is emerging worldwide

Answer 203

Imipenem has activity against Enterococcus faecalis, which meropenem lacks.

Answer 204

Imipenem is formulated in combination with the renal dipeptidase enzyme inhibitor, cilastatin, to prevent inactivation.

Answer 205

High-dose meropenem achieves adequate concentrations in the cerebrospinal fluid and has a lower incidence of seizures than imipenem.

Answer 206

Imipenem and meropenem have broad activity against Enterobacteriaceae (enteric Gram-negative bacilli), including isolates that produce extended-spectrum beta-lactamase enzymes (ESBLs), and Pseudomonas aeruginosa; this activity is comparable to that of aminoglycosides. They also have excellent activity against anaerobic Gram-negative bacteria (including Bacteroides fragilis), and many Gram-positive bacteria (including Nocardia species). Imipenem has activity against Enterococcus faecalis, which meropenem lacks.

Answer 207

Carbapenems are inactive against MRSA, VRE, Enterococcus faecium, Mycoplasma species, Chlamydia species and Stenotrophomonas maltophilia.

Answer 208

In terms of Gram-positive activity, they are active against streptococci and staphylococci, including beta-lactamase–producing (penicillin-resistant) staphylococci, but inactive against methicillin-resistant Staphylococcus aureus (MRSA), enterococci and Listeria monocytogenes. They are active against a narrow range of aerobic Gram-negative bacteria, including wild-type Escherichia coli and some Klebsiella species, but have no activity against anaerobic Gram-negative bacteria, including Bacteroides fragilis.

Answer 209

For oral treatment of respiratory tract infections, cefuroxime is preferred to cefalexin because of its superior activity against S. pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.

Answer 210

Enteric gram negative bacilli

Answer 211

Activity against majority of community associated enterobacteriaceae No active against pseudonomas Less active against staphyloccci than cefazolin Inactive against MRSA Cefotax > ceftriaxone for staph but for both is dose depednent Nil enteroccocus acitvity Serratia, citrobacter and enterobacter have chromosomal resiatnce and ESBL inactive them

Answer 212

Highly protein bound Kicks bilirubin off albumin increasing the risk of kernicterus

Answer 213

Extended spectrum including pseudomonal activity Both inactivated by ESBL

Answer 214

Extended spectrum including pseudomonal activity Both inactivated by ESBL Cefepime is bettyer for gram positive than ceftazidime

Answer 215

Acts against MRSA

Answer 216

Less intrinsically active Same spectrum

Answer 217

Food impairs the absorption of of dicloxacillin and flucloxacillin. Ideally, they should be dosed at 6-hourly intervals, but for practical purposes (eg in children) four-times-daily dosing, evenly spaced during waking hours, is often used.

Answer 218

Cholestatic jaundice, more likely if old or polonged use . Can occur as long as 6 weeks after

Answer 219

Less cholestatic jaundice - less irreversible hepatotoxicity More interstitial nephriits

Answer 220

Orally - Longer half life so longer time above MIC and reduced faily dosing

Answer 221

Same spectrum of acitivty, same pharmacodynamics Orally has a better absorption, less affected by food IV they are equivalent

Answer 222

Staphylococcus aureus, Bacteroides fragilis and Haemophilus influenzae, and some of the beta-lactamase enzymes produced by Escherichia coli and Klebsiella species.

Answer 223

6 hourly dosing

Answer 224

Daptomycin is only active against Gram-positive bacteria, including most strains of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). It has a similar spectrum of activity to the glycopeptides.

Answer 225

Lungs - inactvativated by pulmonary surfactant

Answer 226

Myopathy is an adverse effect of daptomycin. In patients treated with daptomycin, measure plasma creatine kinase concentration at least once weekly, or more frequently if the patient has renal impairment (creatinine clearance less than 30 mL/minute) or is receiving concomitant drugs associated with myopathy (eg statins).

Answer 227

Avoid trimethoprim+sulfamethoxazole in neonates (up to 1 month old) because of the risk of kernicterus (precipitated by the displacement of bilirubin from albumin by sulfonamides).

Answer 228

Trimethoprim inhibits tubular secretion of creatinine, which can elevate serum creatinine without any true decrease in glomerular filtration rate. Trimethoprim also inhibits tubular excretion of potassium and can cause hyperkalaemia. Monitor serum potassium after 3 days of treatment with trimethoprim in patients at increased risk of hyperkalaemia (eg patients with renal impairment, patients who are taking a high dose of trimethoprim or other drugs that can cause hyperkalaemia).

Answer 229

Oral vancomycin is used to treat Clostridioides difficile infection. In patients with severe disease, particularly in the presence of ileus, vancomycin can be given as a retention enema in addition to oral therapy. Intravenous vancomycin is not effective against C. difficile infection because of inadequate penetration of the drug into the lumen of the colon.

Answer 230

Linezolid is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative staphylococci, vancomycin-resistant enterococci (VRE), and penicillin-resistant strains of Streptococcus pneumoniae

Answer 231

Bone marrow suppression and peripheral neuropathy can occur in patients taking linezolid for longer than 14 days, so haematological and neurological monitoring is required. A protocol for monitoring patients for linezolid toxicity has been proposed [Note 2]. Linezolid is a weak monoamine oxidase inhibitor, so it significantly interacts with some foods and drugs. Consult an appropriate resource on drug interactions if starting or stopping linezolid in patients taking other drugs.

Answer 232

The macrolides, azithromycin, clarithromycin, erythromycin and roxithromycin, have a broad spectrum of activity, including activity against Gram-positive cocci, Corynebacterium species, Gram-negative cocci, and Legionella, Mycoplasma and Chlamydia species, as well as some Gram-positive and Gram-negative anaerobic bacteria. Erythromycin, azithromycin and clarithromycin are also active against Bordetella pertussis.

Answer 233

Unlike other macrolides, clarithromycin has a microbiologically active metabolite. Clarithromycin is active against nontuberculous mycobacteria, including Mycobacterium avium complex (MAC), and is used in combination with other drugs for this indication. It is also used in combination with other drugs for eradication of Helicobacter pylori.

Answer 234

Azithromycin is less active than erythromycin against Gram-positive bacteria, but has a broader range of Gram-negative activity (eg Salmonella species). Azithromycin is also active against nontuberculous mycobacteria (including MAC), Rickettsia species and some parasites (eg Toxoplasma gondii).

Answer 235

The nitroimidazoles, metronidazole and tinidazole [Note 3], have activity against almost all Gram-negative anaerobic bacteria (eg Bacteroides fragilis) and most Gram-positive anaerobic bacteria (eg Clostridium species, but not Cutibacterium acnes [formerly Propionibacterium acnes]). It is also active against protozoa, including Trichomonas vaginalis, Giardia intestinalis and Entamoeba histolytica. Helicobacter pylori resistance to metronidazole is common in Australia (about 50% of H. pylori infections, reflecting high community exposure to nitroimidazole drugs).

Answer 236

Resistance to quinolones is now widespread, particularly in Enterobacteriaceae (enteric Gram-negative bacilli), Pseudomonas aeruginosa, Campylobacter species and Neisseria gonorrhoeae.

Answer 237

Ciprofloxacin has a broad spectrum of activity, which includes activity against aerobic Gram-negative bacteria (including Haemophilus influenzae, Enterobacteriaceae [enteric Gram-negative bacilli], P. aeruginosa and Gram-negative cocci) and some aerobic Gram-positive cocci. It is also active against intracellular bacteria, including Legionella species and some mycobacteria. Ciprofloxacin has poor activity against anaerobic bacteria and streptococci.

Answer 238

Moxifloxacin, an extended-spectrum quinolone, has increased activity against Gram-positive aerobic bacteria (including staphylococci and streptococci) compared to ciprofloxacin. Susceptibility among strains of methicillin-resistant Staphylococcus aureus (MRSA) is variable. Moxifloxacin is active against many Gram-negative aerobic bacteria, but has poor activity against P. aeruginosa. Moxifloxacin has good activity against anaerobic bacteria and most atypical bacteria that cause pneumonia. It is also used for the management of some mycobacterial infections.

Answer 239

Multidrug resistant cystitis and acute ifnectious diarrhoea

Answer 240

adverse ffect in cartilage development based on animal studies - if required can be used

Answer 241

Synergistic action of cell wall active drugs and aminoglycosides - Higher rates of cure - Shorter duration

Answer 242

Toxicity previously - vestibular or auditory Hypersensitivty (rare) Myasthenia gravis

Answer 243

Post antibiotic effect

Answer 244

Enterococcal Streptococcal

Answer 245

Generally yes

Answer 246

3-5 minutes slow IV injection safe

Answer 247

The appropriate aminoglycoside dosage is determined by the patient’s weight and kidney function. Adjusted body weight is used for children who are obese and adults who are obese class I (BMI 30 to 34.9 kg/m2). Expert advice is required for adults who are obese class II or III (BMI 35 kg/m2 or more). Generally lean body weight is ideal due to dosage being dependent on renal clearance and Vd

Answer 248

>60 = 7mg/kg 24 hourly 40-60 5mg/kg 36 hourly <40 is 4mg/kg single dose

Answer 249

NB4: If actual body weight (for patients who are not obese) or adjusted body weight (for patients who are obese) is greater than 100 kg, use a weight of 100 kg to calculate the dose.

Answer 250

when treatment is expected to continue for >48 hours - if so commence from the first dose

Answer 251

Once daily dosing - clinical efficiacy related to AUC< toxicity minimised by undetectable trough plasma concentration. MIC is required for AUC calculations Timing of tetsing - 30 minutes after infusion completed, 6-8hrs after the dose

Answer 252

ANything >1 dose per day increases the risk Prolonged Tx >5 days

Answer 253

Not predicted by p;lasma concentration Can occur early or weeks after

Answer 254

Gait ataxia/imbalance Oscillopsia - bouncing vision Blurring vision with ehad movement Hearing loss

Answer 255

No Pharmacologically it makes sense 7mg/kg may have benefit for pathogens with a high MIC e.g. pseudomonas However there is no published study showing clinical advantage

Answer 256

10mg/min 1g dose takes 1 hour 1.5g 90minutes

Answer 257

Histmaine mediated non allergic reaction

Answer 258

Loading dose achieves therapeutic concentration more quickly b 12 hours - no evidence it improves clinical or microbiological outcomes

Answer 259

actual body weight

Answer 260

Similar rates of clincial success Reduced nephrotoxicity Lower daily doses Lower trough concentrations

Answer 261

Higher daily doses realtive to kidney function High trough concentration Prolonged therapy Co-committant nephrotoxins (Tazosin concurrent therapy 3-4x risk) Vasopressors

Answer 262

85% renal unchanged

Answer 263

Rapid absorption 90% bioavailable Food does not affect absorption Does not penetrate CSF but widely distributed Oxidised by CYP3A4 wtih 10% unchanged in urine, 5% in faeces and the rest as metabolites

Answer 264

Absorption 100%- PO or IV Vd 1.6L/kg + PPB 40% for trimethoprim, 0.3L/kg and 50% PPB for sulfamethoxazole. Trimethorpim 30% metabolism in CYP450, some metabolites active. Sulfamethox 80% liver metabolism Renal clearance - 30-50% sulphonamide and 50-60% of trimethoprim excreted in urine within 24 hours. Filtration + secretion

Answer 265

The bactericidal action of aztreonam results from the inhibition of bacterial cell wall synthesis due to its binding to Penicillin Binding Protein 3 (PBP3). Aztreonam is resistant to hydrolysis by many beta-lactamases (i.e. penicillinases and cephalosporinases) produced by gram-negative and gram-positive pathogens

Answer 266

Generally well tolerated

Answer 267

Nil absorption 50% protein bound Minimally metabolised

Infectious Disease Pharmacology Flashcards

(307 cards)