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Antibiotics Flashcards

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1
Q

Name 2 penecillins

A

Benzylpenecillin (IV/IM) phenoxylmethopenecillin

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2
Q

What are the mechansims by which penicillins work?

A
  • Blocks transpeptidase enzyme responsible for cross linking peptidoglycans in bacterial cell wall
  • Weakens walls and reduces ability to maintain osmotic gradient
  • Swelling, lysis, and cell death
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3
Q

What component of the penicillin is responsible for their microbial action

A
  • Beta-lactam ring- side chains attached which determines in microbrial spectrum and properties
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4
Q

What are the resistance mechanisms against penicillins?

A

Beta lactamase - break down B-lactam rings
Reduces permeability to penecillins and increased extrusion
Change target enzyme

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5
Q

What are the indications for penicillins?

A

Streptococcal infections - tonsillitis, middle ear infection, pneumonia (+ macrolide), endocarditis, soft tissue/skin infection (+fluclox if severe),

Clostridium infection e.g. tetanus

Meningococcal infection e.g. meningitis, septicaemia

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6
Q

What are the CIs for penicillins?

A
  • usually well tolerated and safe
  • Dose reduction in renal impairment
  • Current C Diff infection
  • Penecillin allergy
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7
Q

What are the SEs for penicillin?

A

Allergic reaction (1-10% population)

  • Skin rash - subacute (delayed) IgG mediated reaction - occurs 7-10 days post 1st exposure and after 1-2days repeated exposure
  • Anaphylactic reaction - immediate life threatening IgE reaction - mins-hours after exposure - hypotension, brochospasm/oedema, angioedema
  • High doses/renal impairment - CNS toxicity - convulsions/coma
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8
Q

What are the interactions of penicillin?

A

Reduces renal excretion of methotrexate - increased toxicity

Warfarin - enhances anticoagulation

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9
Q

Name one penicillinase/beta-lactamase resistant penicillin?

A

Flucloxacillin

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10
Q

What is the mechanism by which fluxcloxacillin resists Beta lactamase

A

Contains acyl side chain which protects flucloxacillin from beta lactamase - effective against beta lactamase producing staphylococcal infections

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11
Q

What are the indications for flucloxaccillin

A
  1. Skin and soft tissue infections e.g. cellulitis (+ benzylpenecillin if severe)
  2. Osteomyelitis/septic arthritis
  3. Other e.g. endocarditis
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12
Q

What 2 antibiotics make up Tazocin?

A

Tazobactam + piperacillin

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13
Q

What is Tazocin indicated for?

A
  • Anti-pseudomonal
  • Hopsital acquired pneumonia
  • Urinary tract infection (complicated)
  • Septicaemia
  • Peritonitis
  • Soft tissue and skin infection (Staph aureus)
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14
Q

What are the SEs of tazocin?

A
  • GI upset
  • ABx associated colitis (C Diff)
  • Hypersensitivity
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15
Q

What are the broad spectrum penecillins?

A
  • Amoxicillin

- Co-amoxiclav

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16
Q

What is co-amoxiclav made up of?

A

amoxicillin + clavulanic acid (increases spectrum to include beta lactamase producing bacteria e.g. staphylcoccus aureus, gram- anaerobes )

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17
Q

What are the indications for the broad spectrum penecillins (co-amoxiclav/amoxicillin)

A
  1. Empirical Tx for community acquired pneumonia (e.g. strep pneu) or gram- (e.g. H influ) bacteria
  2. Empirical Tx for urinary tract infections e.g. E Coli
  3. Tx for hospital acquired infection or intra-abdominal sepsis, caused by gram-, anaerobic pathogens, or ABx resistant
  4. Combo Tx for H Pylori peptic ulcer
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18
Q

Name 2 cephalosporins and carbapenems

A

Cephradine, Cefalexin

Meropenem, Ertapenem

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19
Q

What is the mechanism by which cephalosporins/carbapenems exert their action?

A

BROAD SPECTRUM

  • Inhibit transpeptidase responsible for the cross-linking of peptidoglycan in bacterial cell wall
  • Weakens cell wall and reduces cell ability to maintain osmotic gradient
  • Cell swelling > lysis > cell death
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20
Q

What structural properties make cephalosporins and carbapenems more resistant to beta lactamases than vs penecillin?

A

Cephalosporin - Dihydrothiazine ring on beta lactam ring

Carbapenem -Hydroxyethyl side chain on beta lactam ring

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21
Q

What are the indications for cepahlosporins/carbapenems?

A

Oral cephalosporins - 2nd line and 3rd line for UTIs and respiratory tract infection

IV carbapenems and cephalosporins - reserved for severe, hospital acquired infections, complicated UTIs, septicaemia, intraabdominal sepsis, soft and skin infections

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22
Q

What are the SEs of cephalosporins/carbapenems?

A
  • GI upset
  • Hypersensitivity
  • CNS toxicity - seizures/coma - high doses or with renal impairment
  • ABx associated colitis (C Diff)
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23
Q

What are the CIs for carbapenems/cephalosporins?

A
  • Risk of C Diff infection
  • Caution in epilepsy
  • Hypersensitivity (beta lactam ring)
  • Renal impairment - reduce dose
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24
Q

What are the potential interactions of cephalosporins/carbapenems?

A
  • Reduce efficacy and plasma concentration of sodium valporate
  • Enhanced anticoagulative effect of warfarin- Kills of floral bacteria responsible for synthesising vitamin K -
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25
What is the mechanism by which trimethoprime exerts its action?
- inhibits bacterial folate metabolism - slows bacterial growth (bacteriostatic) - Broad spectrum - gram +/- bacteria (especially enterobacteria e.g. E Coli) - however, widespread resistance
26
What are the indications for trimethoprine?
1st line for uncomplicated UTI infection (nitrofurantoin/amoxicillin = alternatives)
27
What are the CI for trimethoprine?
- 1st trimester in pregnancy - folate antagonist - results in neural tube/cranial defect - Folate deficiency - may worsen haematological defects - Renal impairment - excreted unchanged = good for UTI, not so good for renal impairment - Adverse effects more in neonates, elderly and HIV sufferers
28
What are the SEs for trimethoprine?
- GI upset - Skin rash/hypersensitivity reactions e.g. anaphylaxis, drug fever, erythema multiform - Haematological defects - folate antagonist (leucopenia, thrombocytopenia) - Hyperkalaemia and increased serum creatine
29
What are the potential interactions for trimethoprine?
- K+ elevating drugs e.g. aldosterone antagonists, ACEi, AT1 blockers could precipitate hyperk+ - Enhances anti-coagulation of warfarin by killing off Vit K synthesising bacteria - Drugs that antagonise folate (e.g. methotrexate) or increase folate metabolism (e.g. phenytoin) increase susceptibility to haematological disorders
30
What is the mechanism by which nitrofurantoin exerts its action?
Metabolised by nitrofuran reductase. Active metabolites damage bacterial cell DNA - bacteriocidal
31
What bacteria is nitrofuratoin active against?
Gram- (E Coli) and gram+ (Staph caprophyticus) - commonly cause UTI
32
What are the resistance mechanisms against nitrofurantoin?
Lower nitrofuran reductase
33
What are the indications for nitrofurantoin?
1. 1st line for uncomplicated UTI (alternative = trimethoprin, amoxicillin)
34
What are the CIs for nitrofurantoin?
- Pregnant women coming towards term - Babies <3 months old - Renal impairment - reduces efficacy and increases risk of SE - Long term prevention of UTI - increases risk of SE, especially elderly
35
What are the SEs of nitrofurantoin?
- GI upset - Hypersensitivity - delayed/immediate - Turn urine green/yellow/brown - temporary - Pulmonary (fibrosis, pneumonitis), hepatic and peripheral neuropathy - Haemolytic anaemia in neonates - immature RBCs damaged by nitrofuratoin produced superoxides
36
Name 2 tetracyclines
Doxycycline, lymecycline
37
What is the mechanism by which tetracyclines work?
Prevents bacterial protein synthesis Bind to 30S subunit of ribosome. Prevents binding of tRNA to mRNA - prevents AA binding to polypeptide chain
38
What are the indications for tetracycline?
1. Acne vulgaris 2. LRTI - COPD exacerbation, pneumonia, atypical pneumonia 3. Chlamydial infection and inflammatory pelvic disease 4. Others: malaria prophylaxis, lyme disease, anthrax, typhoid
39
What are the CIs for tetracyclines?
- Binds to developing bones and teeth. Contraindicated in pregnancy, breastfeeding and children <12 yrs - Renal impairment - reduces efficacy and increases risk of toxicity
40
What are the SEs of tetracyclines?
- GI upset - Hypersensitivity - delayed/immediate Tetracycline specific: - Oesophageal irritation, ulceration, dysphagia - Discolouration and hypoplasia of tooth enamel - Photosensitivity - Cranial hypertension (rare - headache/visual disturbance)
41
What are the Interactions of tetracyclines?
- binds to divalent cations - take 2hrs after ingesting calcium, anatacids and iron - otherwise, absorption impaired - Kills off Vit K synthesising bacteria - enhance anticoagulant effect of warfarin
42
Name one aminoglycoside
Gentamicin
43
What is the mechanism by which aminoglycosides/gentamicin works?
- Blocks ribosome subunit 30S (reduces bacterial protein synthesis) and bacteriocidal by unknown mechanism - Dependent on O2 dependent transport system - Effective against gram - aerobes and staphylococcal but NOT anaerobes/streptococcus
44
What are the indications for gentamicin?
Severe life threatening infection - mainly by gram- aerobic species e.g. Pseduo. aeruginosa 1. Severe sepsis 2. Pyelopheritis/complicated UTI (e.g. prostatis) 3. Biliary/intra-abdominal sepsis 4. Endocarditis 5
45
What are the SEs of gentimicin?
- BInd to tubular epithelial cells in kidney and vestibular/cochlear hair cells - Nephrotoxic - increased serum urea and creatinine, reduced urine - Ototoxic - hearing loss, tinnitus, vertigo
46
What are the CIs for gentamicin?
- Monitor plasma levels of gentamicin to prevent damage to kidney/cochlear/vestibular system, particularly if: - renal impaired - elderly - neonates - Avoid in myasthenia gravis - reduces neurotransmission
47
What are the interactions of gentamicin?
- Ototoxicity - increased in combo with vancomycin and loop diuretics - Nephrotoxicity - increased in combo with nephrotoxic drugs
48
How is gentamicin administered?
IV - dose dependent on patient weight and renal function
49
Name 2 macrolides
ErythromYcin, clarithromYcin
50
what is the mechanism by which clarithromycin/erythromycin (macrolides) exert their action?
Inhibit bacterial protein synthesis - block 50S of ribosome, preventing translocation Broad spectrum against gram-/+ bacteria - especially H Infu
51
What are the indications for erythromycin/clarithromycin? (macrolides)
Alternative to penicillin allergy - Respiratory Infection - soft tissue/skin infection (alternative to patient with penicillin allergy) - Severe pneumonia by atypical organism (+ penicillin) - Eradication Tx for H pylori (+ PPI & metronidazole/amoxicillin)
52
What are the CIs for macrolides (erythromycin/clarithromycin?
- Hepatic or renal impairment - Hypersensitivity - Existing arrhythmias - prolongs QT interval
53
What are the SEs of macrolides (clarithromycin/erythromycin?)
- GI upset - Hypersensitivity - Ototoxicity (in high doses) - Hepatic abnormalities (cholestatic jaundice) - Prolong QT interval - ABx associated colitis (C Diff)
54
What are the potential drug interactions of macrolides (erythromycin/clarithromycin)
- PY450 inhibitors - increases drug concentration/toxicity of drugs broken down by PY450) - Prolong QT interval - caution in other drugs that prolong QT interval (e.g. SSRIs, amiodarone, antipsychotics)
55
Name 3 quinolones
Ciprofloxacin, mexofloxacin, levofloxacin
56
What is the mechanism by which quinolones work?
Inhibit DNA synthesis | Active against gram- bacteria (newer ones e.g. levoflox, mexoflox - increased activity to gram+)
57
What is the main problem with quinolones?
Bacteria gain rapid resistance against quinolones (therefore, reserved 2nd to 3rd line for most indications) Associated with C Diff
58
What are the indications for quinolones?
2nd - 3rd line for most interactions - resistance/C Diff association 1. UTI - particularly men (2 weeks, 4 weeks if prostatis) 2. Severe GI infection e.g. cympobacter, shigella 3. Atypical pneumonia 4. Ciprofloxacin - only oral ABx with activity against pseudo auerginosa
59
What are the CI of quinolones?
- People who are still growing (increased risk of arthropathy) - People at risk of seizures (lowers seizure threshold) - People with risk factors to increases QT interval (e.g. CV disease, arrythmias)
60
What are the SEs of quinolones?
- GI upset/hypersensitivity - Reduces seizure threshold - Prolongs QT interval - Inflammation and muscle tendon rupture - Associated with C Diff colitis
61
What are the interactions of quinolones?
- CYP450 inhibitor - increases concentration and toxicity of drugs broken down by CYP450 - Prolong QT interval - avoid combination with other QT interval prolonging drugs e.g. SSRIs, antipsyhotics, tricyclic antidepressants - Do not take in combo with drugs/food containing divalent cations - binds to them and reduces absorption into gut
62
Name one anaerobic antimicrobrial
Metronidazole
63
What is the mechanism by which metronidazole works?
Only for anaerobic bacteria or protozoa infections (aerobic bacteria cannot reduce metronidazole) - Enters bacterium/protozoa by passive diffusion > reduced > nitroso free radical > causes DNA degeneration and cell death
64
What are the indications for metronidazole?
1. ABx associated colitis (C Diff) 2. Oral infections or aspiration pneumonia caused by gram- infections of mouth 3. Surgical or gynaecological infections caused by gram- anaerobes of colon 4 Protozoal infections
65
What are the CI for metronidazole?
- Metabolised by CYP450 - inhibitors/inducers/reduce with hepatic impairment - DO NOT DRINK WITH ALCOHOL - inhibits alcetyaldehyde dehydrogenase - breaks down alcohol metabolite acetyladehyde (causes hangover)
66
What are the SEs of metronidazole?
- Hypersensitivity - GI upset - CNS toxicity with high dose/prolonged causes - peripheral/optic neuropathy, seizures etc
67
What are the interactions of metronidazole
- CYP450 inhibitor | - Metabolised by CYP450 too
68
Name one glycopeptide
Vancomycin
69
What is the mechanism by which vancomycin/glycopeptide exerts its action?
Inhibits synthesis and crosslinking of peptidoglycans, preventing growth and synthesis of bacterial cell walls Effective specifically against gram + bacteria and anaerobes (not gram- which have a different lipoopolypeptide wall structure)
70
What are the indications for vancomycin/glycopeptide?
1. Gram+ aerobic infections where infection is SEVERE or where penecillin cannot be used e.g. MRSA 2. 2nd line for C Diff (where metronidazole is CI/not tolerated)
71
What are the CIs for +vancomycin/glycopeptide?
Low theurapetuic index | Dose reduction in elderly/renal impairment (increased risk of side effects)
72
What are the SEs of vancomycin/glycopeptides?
- Thrombophlebitis at infusion site - Hypersensitivity reaction - if infusion too quick, red man syndrome - generalised erythema with hypotension and bronchospasm (not allergic reaction but caused by degranulation of eosinophils) - Ototoxicity - Nephrotoxicity - Blood disorders (e.g. neutropenia, thrombocytopenia)
73
What are the potential interactions of glycopeptides/vancomycin?
- Higher risk of ototoxicty/nephrotoxicity if given in combo with aminoglycosides, loop diuretics or ciclosporin
74
How is vancomycin administered?
Oral - C Diff | IV - systemic infections

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