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Year 3 Drugs > Antibiotics > Flashcards

Antibiotics Flashcards

1
Q

Penicillin indication

A
  1. Streptococcal infections, including tonsillitis, pneumonia (combined with macrolide if severe), endocarditis, and skin and soft tissue infection (combined with flucloxacillin if severe)
  2. Clostridial infection e.g. tetanus
  3. Meningococcal infection e.g. meningitis and septicaemia
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2
Q

Penicillin MOA

A
  • Inhibits enzymes responsible for cross-linking peptidoglycan in bacterial call wall
  • Weakens cell walls and makes them unable to maintain osmotic gradient, allowing water to enter causes cell lysis
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3
Q

Mechanisms of resistance to penicillin

A
  • Contain beta-lactam ring - bacteria can produce beta-lactamase enzyme to prevent antimicrobial activity
  • Limiting intracellular penicillin by increased excretion / decreased bacterial permeability,
  • Changes in target enzyme to prevent penicillin binding
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4
Q

Penicillin administration

A
  1. Benzylpenicillin: for severe infection. Can only be given iV or IM as hydrolysed by gastric acid. High dose: 1.2g 4-6 hourly
  2. Penicillin V: for milder infection e.g. tonsilitis. Given orally - usually 2 tablets QDS for 10 days.
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5
Q

Penicillin contraindications

A
  1. Penicillin allergy

2. Dose reduction in renal impairment

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6
Q

Penicillin side effects

A
  1. Allergy: affects 1-10% people. Usually skin rash 7-10 days after first exposure or 1-2 days after repeat exposure. = delayed IgG mediated reaction.
  2. Immediate IgE mediated anaphylactiv reaction: hypotension, bronchial and laryngeal spasm / oedema and angioedma.
  3. High doses / renal excretion impaired: CNS toxicity including convulsions and coma
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7
Q

Penicillin interactions

A

Reduces renal excretion of methotrexate, increasing risk of toxicity

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8
Q

Anti-pseudomonal penicillin examples

A

Tazocin = piperacillin with tazobactam

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9
Q

Anti-pseudomonal penicillin indications

A

Reserved for severe infection where there is a broad spectrum of potential pathogens, resistance is likely, or patient is immunocompromised:

  • LRTI
  • UTI
  • Intra-abdominal sepsis
  • Skin and soft tissue infection
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10
Q

Anti-pseudomonal penicillin mechanism of action

A
  • Same as penicillin
  • Side chain attached to beta-lactam ring converted to form of urea which improves affinity to penicillin binding proteins therefore increases spectrum to pseudomonas
  • Tazobactam is a beta-lactamase inhibitor
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11
Q

Anti-pseudomonal penicillin administration

A

IV: 5 - 14 days, 4.5g every 6-8 hours

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12
Q

Anti-pseudomonal penicillin contraindications

A
  1. Penicillin allergy
  2. Risk of C. diff e.g. in hospital, elderly
  3. Dose reduction required in renal impairment
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13
Q

Anti-pseudomonal penicillin side effects

A
  1. GI upset - common
  2. Antibiotic-associated colitis
  3. Delayed / immediate hypersensitivity
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14
Q

Anti-pseudomonal penicillin interactions

A
  1. Methotrexate: reduce renal excretion increasing risk of toxicity
  2. Warfarin: enhance anti-coagulant effects by killing normal GI flora that synthesise vitamin K
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15
Q

Broad Spectrum Penicillins examples

A

Amoxicillin, co-amoxiclav

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16
Q

Broad Spectrum Penicillins indications

A
  1. Empirical treatment of pneumonia which may be caused by gram positive (S. pneumoniae) or Gram-negative (H. influenzae) pathogens
  2. Empirical treatment of UTI (commonly caused by E. Coli).
  3. As part of combination treatment as co-amoxiclav for hospital acquired infection or intra-abdominal sepsis which may be caused by gram-negative, anaerobic or antibiotic resistant pathogens
  4. As part of combination treatment for H. Pylori associated peptic ulcers
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17
Q

Broad Spectrum Penicillins MOA

A
  • Amoxicillin: amino group added to side chain increases activity against aerobic gram-negatives
  • Clavulanic acid: beta-lactamase inhibitor, increases spectrum to inclide beta-lactamsase producing bacteria (S. aureus, gram negative anaerobes).
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18
Q

Broad Spectrum Penicillins administration

A
  • Severe: amoxicillin IV 1g 8 hourly. Oral switch ASAP (after 48 hours if clinically indicated e.g. resolution of pyrexia, tachycardia)
  • Mild-moderate, without systemic features: amoxicillin oral 250-500mg 8 hourly
  • Co-amoxiclav: 500/125
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19
Q

Broad Spectrum Penicillins contraindications

A
  • Penicillin allergy
  • Caution in those susceptible to C. diff
  • Dose reduction in renal impairment
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20
Q

Broad Spectrum Penicillins side effects

A
  • Common: GI upset
  • Less common: antibiotic-associated colitis - can be complicated by colonic perforation
  • Delayed / intermediate hypersensitivity
  • Cholestatic jaundice is a rare complication of co-amoxiclav
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21
Q

Broad Spectrum Penicillins interactions

A
  1. Methotrexate: reduce renal excretion increasing risk of toxicity
  2. Warfarin: enhance anti-coagulant effects by killing normal GI flora that synthesise vitamin K
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22
Q

Cephalosporins and carbapenems examples

A

Cephalexin, cefotaxime, meropenem, ertapenem

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23
Q

Cephalosporins and carbapenems indications

A
  1. Oral cephalosporins: second and third line treatments for urinary and respiratory tract infections
  2. IV cephalosporins or carbapenems: reserved for treatment of severe / complicated infections or those caused by antibiotic resistant organisms
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24
Q

Cephalosporins and carbapenems MOA

A
  • Antimicrobial effect due to beta-lactam ring
  • Cephalosporins: progressive structural modification has led to successive generations with increasing activity against GNB
  • Both drugs have natural resistance to beta-lactamase
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25
Q

Cephalosporins and carbapenems administration

A

Cephalosporins: IV 6-12 hourly. Only cephalexin is orally active.
Carbapenems: only IV e.g. 1-2g 8 hourly

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26
Q

Cephalosporins and carbapenems contraindications

A
  • Penicillin or Cephalosporins and carbapenem allergy
  • Susceptibility to C. diff
  • Renal impairment
  • Carbapenems should be used with caution in epileptics
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27
Q

Cephalosporins and carbapenems side effects

A
  • GI upset
  • Antibiotic-associated colitis
  • Delayed / intermediate hypersensitivity reactions
  • Similar structure = cross-reactivity with penicillin allergy
  • Risk of CNS toxicity including seizures, especially high-dose carbapenems
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28
Q

Cephalosporins and carbapenems interactions

A
  1. Methotrexate: reduce renal excretion increasing risk of toxicity
  2. Warfarin: enhance anti-coagulant effects by killing normal GI flora that synthesise vitamin K
  3. Aminoglycosides: cephalosporins increase nephrotoxicity
  4. Valproate: carbapenems reduce plasma concentration and efficacy
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29
Q

Trimethoprim class and other example

A
  • Folate synthesis inhibitors

- Trimethoprim and co-trimoxazole

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30
Q

Trimethoprim inidactions

A
  1. 1st line for uncomplicated UTI - alternatives include nitrofurantoin and amoxicillin
  2. Co-trimoxazole (trimethoprim + sulfamethoxazole): treats / prevents pneumocystis pneumonia in immunosuppression e.g. due to HIV
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31
Q

Trimethoprim MOA

A
  • Inhibits bacterial folate synthesis, slowing growth (bacteriostatic)
  • Sulfamethoxazole inhibits folate synthesis in a different step, causing a more complete inhibition. Co-trimoxazole is therefore bactericidal
  • Broad spectrum against gram positive and negative, particularly enterobacteriaceae e.g. E. Coli
  • Clinical utility reduced by widespread bacterial resistance through reduced intracellular antibiotic accumulation and reduced sensitivity of target enzymes.
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32
Q

Trimethoprim administration

A

Trimethoprim: Oral. Acute UTI = 200mg 12 hourly. Prophylaxis for recurrent UTI = 100mg for prolonged period.

Co-trimoxazole: oral of IV. pneumocystis infection = 120mg / kg for 14-21 days.

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33
Q

Trimethoprim contraindications

A
  • 1st trimester of pregnancy = increased risk of foetal abnormality.
  • Used cautiously in patients with folate deficiency - more susceptible to haematological events
  • Dose reduction in renal impaimet
  • Neonates, elderly and HIV all t greater risk of adverse effects
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34
Q

Trimethoprim side effects

A
  • GI upset: including mouth sores and skin rash
  • Hypersensitivity rare with trimethoprim but common in sulphonamides which limits use
  • Haematological disorders: impaired haematopoiesis. e.g. megaloblastic anaemia, leukopenia and thrombocytopenia.
  • Hyperkalaemia
  • Raised creatinine
35
Q

Trimethoprim interactions

A
  • Potassium elevating drugs: aldosterone agonists, ACEi, ARBS. pre-disposes to hyperkalaemia.
  • Other folate antagonists (methotrexate) and dugs that increase folate metabolism (phenytoin): increased risk of haematological events.
  • Warfarin: enhance anti-coagulation by killing normal GI flora that synthesise vit K.
36
Q

Nitrofurantoin indications

A

Uncomplicated UTI. Particularly suited as effective against common causative agents, reaches therapeutic concentrations in urine through renal excretion, and is most bactericidal in acidic environments such as urine

37
Q

Nitrofurantoin MOA

A
  • Metabolised in bacterial cells by nitrofuran reductase to active metabolite which damages DNA and causes cell death (bactericidal).
  • Active against E. coli and GP organisms that normally cause UTI.
  • Resistance: bacteria with reduced nitrofuran reductase activity e.g. klebsiella and proteus
38
Q

Nitrofurantoin aministration

A

Oral

  • Acute: 50-100mg 6 hourly. 3 days for uncomplicated women, 7 days for men.
  • Prevention of recurrent: single nightly dose of 50-100mg for up to 6 months
39
Q

Nitrofurantoin contraindications

A
  • Pregnant women towards term
  • Babies < 3months
  • Chronic use increases risk of adverse effects
40
Q

Nitrofurantoin side effects

A
  • GI upset
  • Delayed / immediate hypersensitivity
  • Less common = pulmonary reactions (inflammation= pneumonitis and fibrosis), hepatitis and peripheral neuropathy.
  • Neonates: haemolytic anaemia as immature red blood cells are unable to clear nitrofurantoin simulated superoxides which damage RBCs
41
Q

Tetracyclines examples

A

Doxycycline, lymecycline

42
Q

Tetracyclines indications

A
  1. Acne vulgaris: particularly where there are inflamed papules, pustules ± cysts (propionibacterium acnes).
  2. LRTI: including infective COPD exacerbations and pneumonia
  3. Chlamydial infection including PID
  4. Other infections: typhoid, anthrax, malaria and Lyme disease
43
Q

Tetracyclines MOA

A
  • Bind ribosomal 30s subunit which prevents binding of tRNA to mRNA meaning new amino acids cannot be added - bacteriostatic
  • Relatively broad spectrum
  • Resistance by acquisition of efflux pump which pumps tetracyclines out
44
Q

Tetracyclines administration

A

Oral

-Doxycycline: 100-200mg daily

45
Q

Tetracyclines contraindications

A
  • Bind to teeth and bones: contraindicated in pregnancy, breastfeeding and children <12
  • Avoid in renal impairment: anabolic effects can raise plasma urea and reduced excretion increase adverse effects
46
Q

Tetracyclines side effects

A
  • GI upset
  • Hypersensitivity in around 1% but no cross-reactivity with penicillin
  • Oesophageal irritation, ulceration and dysphagia
  • Discolouration and hypoplasia of tooth enamel in children
  • Intracranial hypertension is a rare adverse effect causing headache / visual disturbance
47
Q

Tetracyclines interactions

A
  • Binds divalent cations. Do not give within 2 hours of calcium, antacids or iron - prevents tetracycline absorption
  • Warfarin: enhance anti-coagulation by killing normal gut flora that synthesise vitamin K
48
Q

Tetracyclines patient info

A

Swallow whole with plenty of water whilst standing to prevent oesophageal irritation

49
Q

Aminoglycosides examples

A

Gentamicin, amikacin

50
Q

Aminoglycosides indications

A

Severe infections, particularly those caused by gram-negative aerobes e.g. pseudomonas:

  1. Severe sepsis including where unidentified source
  2. Pyelonephritis and complicated UTI
  3. Biliary and other intra-abdominal sepsis
  4. Endocarditis

Lack activity against streptococci and anaerobes, so should be combined with penicillin and metronidazole when organism unknown.

51
Q

Aminoglycosides MOA

A
  • Bind ribosomal 30s unit and inhibit protein synthesis
  • Bactericidal due to other mechanisms poorly understood
  • Spectrum: GN aerobes, staphylococci and mycobacteria
  • Enter bacteria through oxygen dependent transport system - strep and anaerobic bacteria do not have this, so innately resistance
  • Acquired resistance: reduced cell membrane permeability, acquisition of enzymes which modify aminoglycosides to prevent them reaching ribosome
  • Penicillins enhance aminoglycoside activity as they weaken cell walls to allow easier entry
52
Q

Aminoglycosides administration

A
  • Highly polarised so do not cross lipid membranes - cannot be taken orally.
  • In severe infection given once daily IV infusion - 5mg/kg
53
Q

Aminoglycosides contraindications

A
  • Neonates / elderly / renally impaired at greater risk of toxicity - dose monitoring and adjustment
  • Impair NM transmission - do not give in myasthenia gravis
54
Q

Aminoglycosides side effects

A
  • Ototoxicity: accumulate in cochlear and vestibular hair cells and trigger apoptosis. CAuses hearing loss, tinnitus and vertigo (may be irreversible)
  • Nephrotoxicity: accumulate in renal tubular epithelial cells and trigger apoptosis, causing reduced urine output and increased creatinine and urea
55
Q

Aminoglycosides interaction

A
  • Ototoxicity: loop diuretics, vancomycin

- Nephrotoxicity: ciclosporin, platinum chemotherapy, cephalosporins or vancomycin

56
Q

Macrolides eaxmples

A

Erythromycin, Clarithromycin, azithromycin

57
Q

Macrolides indications

A
  1. Treatment of respiratory and skin / soft tissue infection as penicillin alternative in penicillin allergy
  2. Added to penicillin in severe pneumonia to cover atypical organisms e.g. legionella pneumophila and mycoplasma pneumoniae
  3. Eradication of H. Pylori in combination with PPI and either amoxicillin or metronidazole
58
Q

Macrolides MOA

A
  • Bind 50s subunit and block translocation = Bacteriostatic
  • Erythromycin first, has broad spec activity against gram-positive and some gram-negative
  • Clarithromycin and azithromycin are synthetic - increased activity against gram-negative, particularly H. influenzae.
  • Resistance is common - ribosomal mutations to prevent binding
59
Q

Macrolides administration

A

Clarithromycin most common: more stable, fewer side effects, cheaper.

  • Oral / IV if not tolerated
  • 200-500mg twice daily for 7-14 days.
60
Q

Macrolides contrainidcations

A
  • History of macrolide allergy - no cross-sensitivity

- Dose reduction in hepatic or renal impairment

61
Q

Macrolides side effects

A
  • Most common and severe with erythromycin. Acts as irritant:
  • Oral: nausea, vomiting, abdominal pain and diarrhoea
  • IV: thrombophlebitis
  • Allergy
  • Anti-biotic-associated colitis
  • Cholestatic jaundice
  • Prolonged QT interval
  • Ototoxicity at high doses
62
Q

Macrolides interactions

A
  • Erythromycin and clarithromycin (not azi) inhibit cytochrome P450 enzymes
  • Other drugs that prolong QT interval or cause arrhythmias: amiodarone, antipsychotics, quinine, quinolone abx and SSRIs
63
Q

Quinolones examples

A

Ciprofloxacin, moxifloxacin, levofloxacin

64
Q

Quinolones indiciations

A

Reserved as 2nd / 3rd line treatment due to potential for rapid emergence of resistance and C. diff infection. Used in:

  1. UTI
  2. Severe GI infection e.g. shigella, campylobacter
  3. LRTI (moxifloxacin and levofloxacin)

Ciprofloxacin is the only oral antibiotic with antipseudomonal activity

65
Q

Quinolones MOA

A
  • Bactericidal: inhibit DNA synthesis
  • Particularly active against gram-negative bacteria
  • Moxi/levofloxacin are newer with enhanced gram-positive activity and can be used for LRTI
66
Q

Mechanisms of resistnace to quinolones

A

Bacteria rapidly develop resistnace to quinolones:

  • prevent cellular accumulation by reducing cell permeability
  • increase efflux
  • modify target enzymes
  • horizontal gene transmission which speeds up rate of resistance
67
Q

Quinolones administration

A

Oral or IV where not tolerated.

  • Ciprofloxacin: 250-750mg orally 12 hourly
  • Moxifloxacin: 400mg oral daily
  • Levofloxacin: 500mg oral daily
68
Q

Quinolones contraindications

A

Use in caution in patients with risk of adverse effects:

  • seizures
  • children still growing = arthropathy
  • risk factors for QT prolongation: cardiac disease, electrolyte disturbance
69
Q

Quinolones side effects

A
  • Generally well tolerated
  • GI upset including C. diff
  • Immediate / delayed hypersensitivity
  • Lowering of seizure threshold
  • Hallucinations
  • Inflammation and rupture of muscle tendons
  • Prolong QT interval = increased risk of arryhtmias
70
Q

Quinolones interactions

A
  • Drugs containing divalent cations e.g. calcium and antacids: reduce absorption and efficacy
  • Ciprofloxacin inhibits some cP450 enzymes
  • Prednisolone: increased risk of tendon rupture
  • NSAIDs: increased risk of seizures
  • Other drugs that prolong the QT interval: amiodarone, SSRIs, antipsychotics, quinine and macrolides - increased risk of arrhythmias
71
Q

Metronidazole class

A

Anaerobic antimicrobials

72
Q

Metronidazole indications

A

Treatment of infections caused by bacteria in

  1. Antibiotic associated colitis caused by C. difficile (gram-positive anaerobe)
  2. Oral infection: dental abscess, aspiration pneumonia caused by gram-negative organisms from the mouth
  3. Surgical and gynaecological infections caused by gram-negative anaerobes from colon
  4. Protozoal infections including trichomonal vaginal infection, amoebic dysentery, giardiasis
73
Q

Metronidazole MOA

A
  • Diffuse into bacterial cell
  • Reduced to form nitroso free radical, which binds to DNA
  • Reduces DNA synthesis and causes cell death
  • Spectrum restricted to anaerobic bacteria and protozoa for this reason
  • Resistance low (+increasing) but includes reduced uptake and reduced generation of nitroso free radicals
74
Q

Metronidazole administration

A
  • Oral: GI infection or where patient not systemically ill
  • IV for severe infection
  • Rectal
  • Gel for topical treatment of vagina or skin
75
Q

Metronidazole contraindications

A
  • Dose reduction in hepatic impairment

- Alcohol: inhibits acetaldehyde dehydrogenase - can cause disulfiram like reaction (flushing, headache, N&V)

76
Q

Metronidazole side effects

A
  • GI upset
  • Delayed / immediate hypersensitivity
  • Neurological effects when used at high doses for long periods: peripheral and optic neuropathy, seizures, encephalopathy
77
Q

Metronidazole interactions

A
  • Inhibits cP450 enzymes

- Increases risk of lithium toxicity

78
Q

Glycopeptides examples

A

Vancomycin

79
Q

Glycopeptides indications

A
  1. Treatment of gram-positive infection e.g. endocarditis, where infection is severe ± penicillin cannot be used due to resistance or allergy
  2. 2nd line treatment of antibiotic-associated colitis where metronidazole is ineffective or poorly tolerated
80
Q

Glycopeptides MOA

A
  • Inhibits growth and cross-linking of peptidoglycan chains, inhibiting synthesis of cell wall of gram-postivie bacteria
  • Specific to GP as GN have lipopolysaccharide cell wall
81
Q

Glycopeptides administration

A

Systemic: IV

C. diff: oral, 125mg 6 hourly for 10-14 days

82
Q

Glycopeptides contraindications

A

-Careful monitoring to avoid toxicity, especially in renal impairment and the elderly

83
Q

Glycopeptides side effects

A
  • Thrombophelbitis at infusion site. If rapid infusion = ‘red man syndrome’, characterised by erythema, hypotension and bronchospasm.
  • Non-specific degranulation of mast cells causing anaphylactoid reaction
  • True delayed and immediate hypersensitivity reactions can also occur
  • Nephrotoxicity: renal failure, interstitial nephritis
  • Ototoxicity: tinnitus and hearing loss
  • Blood disorders: neutropenia and thrombocytopenia
84
Q

Glycopeptides interactions

A

Increased risk of ototoxicity and nephrotoxicity when prescribed with aminoglycosides, loop diuretics or ciclosporin

Year 3 Drugs (9 decks)

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