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Anaesthetic FRCA Primary - eLFH Pharmacology > eLFH - Antimicrobial agents > Flashcards

eLFH - Antimicrobial agents Flashcards

1
Q

Classification of bacteria

A

Gram stain

Morphology (shape)

Relationship with oxygen (aerobes or anaerobes)

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2
Q

Gram positive bacteria features and appearance

A

Retain crystal violet stain in their thicker outer peptidoglycan cell wall

Appear blue / violet

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3
Q

Gram negative bacteria features and appearance

A

Do not have outer peptidoglycan wall so thinner cell wall

Therefore don’t stain with crystal violet

Instead stain with safarin red counter stain and appear red / pink

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4
Q

Bacterial morphology classification

A

Cocci - spheres

Bacilli - rods

Spirilla - spirals

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5
Q

Gram positive bacteria tree

A
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6
Q

Gram negative bacteria tree

A
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7
Q

Bacteria responsible for Diphtheria

A

Corynebacterium

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8
Q

Aerobic bacteria definition

A

Use O2 for metabolism

Obligate anaerobes can only survive if O2 present

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9
Q

Anaerobic bacteria definition

A

Metabolise in absence of O2

Obligate anaerobes cannot survive in presence of O2
(lack enzymes to detoxify O2)

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10
Q

Facultative anaerobic bacteria definition

A

Can survive with or without O2

If given choice, prefer O2 as more efficient metabolism

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11
Q

Obligate anaerobic bacteria examples

A

Bacteroides

Clostridium

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12
Q

Three mechanisms of action of antibacterials

A

Actions on cell wall synthesis

Inhibition of protein synthesis

Inhibition of nucleic acid synthesis

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13
Q

Actions on cell wall synthesis mechanisms

A

Cell wall synthesis inhibitors

Cell wall integrity inhibitors

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14
Q

Cell wall synthesis inhibitor examples

A

Glycopeptides

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15
Q

Cell wall integrity inhibitor examples

A

Beta lactams

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16
Q

Inhibition of protein synthesis mechanisms

A

Ribosome 50s subunit inhibitors

Ribosome 30s subunit inhibitors

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17
Q

Ribosome 50s subunit inhibitor examples

A

Macrolides

Lincosamides

Chloramphenicol

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18
Q

Ribosome 30s subunit inhibitor examples

A

Tetracyclines

Aminoglycosides

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19
Q

Inhibition of nucleic acid synthesis mechanisms

A

DNA synthesis inhibitor

DNA gyrase inhibitor

DNA dependent RNA polymerase inhibitor

Folic acid metabolism inhibitor

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20
Q

DNA synthesis inhibitor examples

A

Nitroimidazoles

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21
Q

DNA gyrase inhibitor examples

A

Quinolones

Aka Fluoroquinolones

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22
Q

DNA dependent RNA polymerase inhibitor examples

A

Rifampicin

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23
Q

Folic acid metabolism inhibitor examples

A

Diaminopyrimidines (e.g. trimethoprim)

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24
Q

Mechanism by which beta lactams reduce cell wall integrity

A

Inhibit enzymes which cross link the peptidoglycan chains of the cell wall

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25
Q

Beta lactam abx examples

A

Penicillins

Cephalosporins

Carbapenems

Monobactems

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26
Q

Mechanism by which glycopeptides inhibit cell wall synthesis

A

Bind to terminal residues of growing peptidoglycan chains - prevents formation of cross links

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27
Q

Glycopeptide abx examples

A

Vancomycin

Teicoplanin

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28
Q

Which abx classes are bacteriostatic rather than bactericidal

A

All abx which inhibit protein synthesis

Trimethoprim

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29
Q

Macrolides specific mechanism of action

A

Bind to 50s ribosome subunit and inhibits peptide chain translocation

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30
Q

Macrolide abx examples

A

Erythromycin

Clarithromycin

Azithromycin

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31
Q

Lincosamide specific mechanism of action

A

Disrupts 50s subunit to inhibit protein synthesis

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32
Q

Lincosamide abx examples

A

Clindamycin

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33
Q

Chloramphenicol specific mechanism of action

A

Inhibits peptidyl transferase activity of 50s subunit

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34
Q

Tetracycline specific mechanism of action

A

Binds to 30s subunit
Inhibits binding of aminoacyl-tRNA

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35
Q

Tetracycline abx examples

A

Doxycycline

Lymecycline

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36
Q

Aminoglycoside specific mechanism of action

A

Binds to 30s subunit
Causes misreading of mRNA

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37
Q

Aminoglycoside abx examples

A

Gentamicin

Amikacin

Neomycin

Streptomycin

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38
Q

Diaminopyrimidines specific mechanism of action

A

Inhibitor of dihydrofolate reductase

Needed for purine / pyrimidine synthesis

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39
Q

Diaminopyrimidine abx examples

A

Trimethoprim

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40
Q

Quinolones specific mechanism of action

A

Inhibits DNA gyrase

This enzyme usually compresses DNA into super coils

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41
Q

Quinolone abx examples

A

Ciprofloxacin

Levofloxacin

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42
Q

Nitroimidazoles specific mechanism of action

A

Inhibits and damages DNA synthesis

Exact mechanism is unclear

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43
Q

Nitroimidazole abx examples

A

Metronidazole

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44
Q

Rifampicin specific mechanism of action

A

Inhibits DNA dependent RNA polymerase

Prevents RNA transcription

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45
Q

Only clinical situation where choice of a bactericidal abx should be used rather than bacteriostatic abx

A

Immunocompromised patient

Otherwise bacteriostatic vs bactericidal is irrelevant clinically

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46
Q

Categories of penicillin abx

A

Narrow spectrum

Broad spectrum

Antipseudomonal

Beta lactamase resistant

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47
Q

Narrow spectrum penicillin examples

A

Benzylpenicillin

Flucloxacillin

48
Q

Broad spectrum penicillin examples

A

Amoxicillin

Piperacillin

Ampicillin

49
Q

Antipseudomonal penicillin examples

A

Piperacillin (hence use of Tazocin)

Ticarcillin

50
Q

Beta lactamase resistant penicillin examples

A

Flucloxacillin

51
Q

Features of narrow spectrum penicillins

A

Little Gram negative activity

Gram negative bacteria have outer phospholipid membrane hindering access of penicillins to cell wall beneath

52
Q

Features of broad spectrum penicillins

A

Hydrophobic - pass through phospholipid membrane pores
Therefore have more Gram negative activity

More inactivated by beta lactamases
Overcome this by combining broad spectrum penicillin with beta lactamase inhibitor

53
Q

Beta lactamase inhibitor examples

A

Clavulanic acid

Tazobactam

54
Q

Features of antipseudomonal penicillins

A

Particularly broad spectrum - gram negative, gram positive, anaerobes

Beta lactamase sensitive
Therefore presented with beta lactamase inhibitor

55
Q

Organisms which commonly produce penicillinase (a beta lactamase)

A

Staphylococci

Hence flucloxacillin use as it is penicillinase resistant

56
Q

MRSA mechanism of resistance

A

Increased resistance via changes in its penicillin binding proteins

Therefore different class of antibiotic needed

57
Q

Penicillin pharmacokinetics

A

Short half life

Renal excretion

Good tissue penetration but meninges must be inflamed to cross blood brain barrier

58
Q

Side effects of penicillins

A

Encephalopathy
Diarrhoea

Low toxicity

59
Q

Cephalosporin features compared to penicillins

A

Similar structure to penicillins but broader spectrum

Beta lactam ring is less susceptible to beta lactamases

60
Q

Cephalosporin pharmacokinetics

A

Most excreted unchanged in urine

Exceptions of Cefotaxime and Ceftriaxone

61
Q

Cefotaxime pharmacokinetics

A

50% metabolised in the liver

62
Q

Ceftriaxone pharmacokinetics

A

Highly protein bound (95%)

Long half life so given once daily

63
Q

Cephalosporin indications

A

Pneumonia

Septicaemia

Meningitis

Surgical prophylaxis

64
Q

Cephalosporin classification and relevance

A

First generation

Second generation

Third generation

With each successive generation, gram positive cover maintained while gram negative cover increases

65
Q

First generation cephalosporin examples

66
Q

First generation cephalosporin uses

A

Surgical prophylaxis with gram positive organisms

E.g. orthopaedic

67
Q

Second generation cephalosporin examples

A

Cefuroxime

68
Q

Second generation cephalosporin uses

A

More stable beta lactam ring and more gran negative cover

Prophylaxis in bowel surgery but lacks sufficient anaerobic cover so metronidazole often added

69
Q

Third generation cephalosporin examples

A

Cefotaxime

Ceftriaxone

Ceftazidime

70
Q

Disadvantages of third generation cephalosporins

A

Highly broad spectrum which can encourage superinfection

71
Q

Carbapenem abx examples

A

Meropenem

Imipenem

72
Q

Carbapenem spectrum

A

Covers gram positive, gram negative, aerobic and anaerobic bacteria

Highly beta lactamase resistant

73
Q

Organisms against which carbapenems are ineffective

A

MRSA

E faecalis

Some pseudomonas strains

74
Q

Carbapenem pharmacokinetics

A

Excreted unchanged in kidneys

Imipenem is combined with cilastatin to prevent renal metabolism and increase plasma concentration

75
Q

Potential side effect of carbapenems

A

Can cause convulsions

(Imipenem more than Meropenem)

76
Q

Monobactam abx example

A

Aztreonam

This is the only available monobactam

77
Q

Monobactam coverage

A

Spectrum limited to Gram negative aerobic bacteria

78
Q

Glycopeptide spectrum

A

Broad Gram positive spectrum

Limited Gram negative cover as large polar molecules unable to penetrate outer lipid layer of these bacteria

79
Q

Glycopeptide indications

A

MRSA

Endocarditis

80
Q

Teicoplanin features compared to Vancomycin

A

Teicoplanin is:
More potent with longer duration of action (OD dosing)

Better tissue penetration

Better tolerated

Demonstrates more resistance

81
Q

Glycopeptide pharmacokinetics

A

Elimination unchanged in urine

Minimal systemic absorption absorption from healthy gut

82
Q

Side effects of glycopeptides

A

Reversible toxicity is common so plasma level monitoring needed:

Nephrotoxicity
Ototoxicity
Thrombocytopenia
Neutropenia

Red man syndrome with Vancomycin

83
Q

Red man syndrome

A

Risk with Vancomycin use so must be given slowly IV

Caused by phlebitis and histamine release

84
Q

Macrolide spectrum

A

Similar spectrum to penicillin but broader spectrum
(Hence their use in penicillin allergy)

Cover Gram positive, Mycoplasma and Legionella

85
Q

Azithromycin use and why

A

Increased Gram negative cover and longer half life

Therefore single dose will treat chlamydial urethritis

86
Q

Macrolide pharmacokinetics

A

Metabolised and excreted mainly by liver

Generally well tolerated

87
Q

Macrolide side effects

A

Potent cP450 inhibitor - multiple interactions

GI upset / Prokinetic

Prolong QT interval

88
Q

Aminoglycoside spectrum

A

Gram negative including pseudomonas

Some Gram positive activity

89
Q

Aminoglycoside indications

A

First line for Gram negative infections

Urological surgery prophylaxis - Gram negative organisms predominate

90
Q

Why aminoglycosides work synergistically with penicillins and glycopeptides

A

Aminoglycosides are large polar molecules that require active transport into the cell

Penicillins and glycopeptides break down cell wall allowing the aminoglycosides better cellular access

91
Q

Aminoglycoside pharmacokinetics

A

Renal excretion

Low lipid solubility so IV administration

Narrow therapeutic range

92
Q

Side effects of Aminoglycosides

A

Reversible toxicity to kidneys

Permanent toxicity to cranial nerve VIII

Prolongs non-depolarising neuromuscular blocker effects

93
Q

How do aminoglycosides prolong effects of non-depolarising neuromuscular blockers

A

Aminoglycosides impair neuromuscular transmission by decreasing prejunctional release and reducing junctional sensitivity to ACh

94
Q

Quinolone spectrum

A

Broad

Mainly towards gram negatives but some Gram positive cover

Levofloxacin has increased pneumococcal cover

95
Q

Quinolone pharmacokinetics

A

Good oral absorption

Widely distributed with excellent CNS penetration

Excreted unchanged in urine and faeces

96
Q

Side effects of Quinolones

A

Risk of C diff / MRSA colonisation

Prolonged QT interval

Lowers seizure threshold via GABA antagonism

GI upset

Inhibits cP450

97
Q

Nitroimidazole spectrum

A

Anaerobes (Bacteroides, gut flora, Clostridia)

Protozoa

98
Q

Nitroimidazole pharmacokinetics

A

Excreted unchanged in urine

Distributes widely in CSF, cerebral abscesses, prostate and pleural fluid

Well tolerated generally

99
Q

Side effects of Nitroimidazoles

A

Rash

Pancreatitis

Peripheral neuropathy

100
Q

Side effects of nitroimidazoles when combined with alcohol

A

Flushing

Hypotension

101
Q

Differences between bacterial cells vs human cells

A

Single celled organisms

Cell walls

No nucleus - just loop of DNA in middle

Replicate by dividing

102
Q

Why do abx affecting ribosomes not affect human cells

A

Human ribosomes have different sized subunits

103
Q

Definition of antibiotics

A

Pharmacological agents which target bacteria without damaging mammalian host cells

Act by either killing bacteria of preventing replication which relies on host immune system

104
Q

Minimum inhibitory concentration

A

Minimum concentration required to prevent ongoing growth of bacteria

If peak antibiotic levels fall below this concentration then bacteria will start to grow again

105
Q

Virus definition

A

Segment of DNA or RNA code surrounded by protein

Target host cells infecting them and promoting replication

106
Q

Aciclovir mechanism of action

A

Inhibits nucleic acid synthesis

Only affects infected cells

107
Q

Main subgroups of fungi

A

Moulds - e.g. aspergillus

Yeasts - e.g. candida

108
Q

3 major sub-classes of antifungals

A

Azoles

Polyenes

Echinocandins

109
Q

Ergosterol

A

Predominant component of fungal cell membrane and main target of antifungals

110
Q

Examples of Azoles

A

Fluconazole

Voriconazole

Ketoconazole

111
Q

Examples of Polyenes

A

Amphotericin B

Nystatin

112
Q

Examples of Echinocandins

A

Caspofungin

Micafungin

113
Q

Azoles mechanism of action

A

Inhibit Lanosterol 14 alpha-demethylase enzyme

Prevents conversion of Lanosterol to Ergosterol

114
Q

Polyenes mechanism of action

A

Binds to ergosterol in fungal cell membrane - creates pores disrupting electrochemical gradient and leads to fungal cell death

115
Q

Echinocandins mechanism of action

A

Inhibit B-1,3-glucan synthase

Inhibits B-1,3-glucan synthesis with is required for fungal cell wall integrity

Anaesthetic FRCA Primary - eLFH Pharmacology (11 decks)

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