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Pharmacology > Anti-bacterial > Flashcards

Anti-bacterial Flashcards

1
Q

Explain concentration dependent killing

A

The rate and extent of killing is proportional to the drug concentration.

Drugs of this type (aminoglycosides, quinolones) have a post-antibiotic effect (persistent growth suppression) after levels drug below MIC because the drug binds to the receptor for a long time.

Optimal response when concentrations are >10x MIC at infection site

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2
Q

Explain time-dependent killing

A

Drug is only effective while levels are higher than the MIC (no post-antibiotic effect) so rate and extent of killing not affected once higher than MIC.

Drugs of this type (beta lactams, vancomycin) don’t bind to receptors for long, so the amount of drug depends on the serum level of drug.

Optimal response when drug remains above MIC for >50% of the dosing interval

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3
Q

Explain Resistance mechanisms

A
  1. Production of an enzyme by the bacteria that inactivates the drug
  2. Alteration of drug-sensitive or drug binding sites (can’t bind because it doesn’t fit)
  3. Decreased drug accumulation in bacterium (drug pumped out of bacteria by active efflux pump)
  4. Development of a pathway that bypasses the reaction inhibited by the antibiotic (e.g. produce new enzyme insensitive to drug)
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4
Q

Causes of resistance

A
  1. Sub-optimal doses & duration
  2. Prolonged treatment
  3. Late initiation of therapy
  4. Unnecessary prescription
  5. Inappropriate combinations
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5
Q

What is classified as prolonged antibiotic treatment

A

> 5 days for most infections

> 4 weeks for endocarditis and bone infections

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6
Q

Name cell wall synthesis inhibitors

A

Beta lactams:

  1. penicillins
  2. cephalosporins
  3. Transpeptidase inhibitors

Other:

  1. peptides
  2. bacitracin
  3. Glycopeptides
  4. fosfomycin
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7
Q

Are penicillins bacteriostatic or bactericidal?

A

bactericidal

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8
Q

Name natural penicillins

A 
Penicillin G (Benzylpenicillin)
Penicillin V (phenoxymethyl penicillin)
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9
Q

General MoA of penicillin

A

Causes lysis in growing cells by inhibiting transpeptidase

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10
Q

General reasons of resistance to penicillin

A
  1. No cell wall
  2. Metabolically inactive bacteria
  3. Produce beta-lactamase
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11
Q

Explain Penicillin G kinetics

A

Limited liver metabolism (remains unchanged on excretion), with excretion in urine

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12
Q

Limitations of Penicillin G

A
  1. Narrow spectrum
  2. Acid labile (destroyed in acid e.g. stomach)
  3. Beta-lactamase sensitive
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13
Q

Penicillin G spectrum

A
  1. Gram-positive cocci
  2. Neisseria species (where not resistant)
  3. Anaerobes
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14
Q

Penicillin G side effects

A
  1. Hypersensitivity reactions
  2. Neurotoxicity (high [])
  3. Diarrhea
  4. Neutropenia & agranulocytosis
  5. Cross-hypersensitivity between penicillins
  6. Antibiotic-associated colitis (ampicillin) & infectious mononucleosis (amoxicillin)
  7. Reduced oral contraceptive pill efficacy
  8. Bleeding (reduced platelet aggregation)
  9. Fluid retention and hypokalaemia in renal/cardiac disease patients
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15
Q

Penicillin G drug interactions

A
  1. Aminoglycosides (never combine)
  2. Allopurinol (increase rash chance)
  3. Oral contraceptive Pill
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16
Q

Penicillin G admin

A

IV, IM

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17
Q

Penicillin V kinetics

A

Limited liver metabolism

Urine excretion mostly unchanged

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18
Q

Penicillin V use

A
  1. Less serious streptococcal infections

2. Followup antibiotic treatment after serious infection

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19
Q

Penicillin V drug interactions

A
  1. Aminoglycosides (never combine)
  2. Allopurinol (increase rash chance)
  3. Oral contraceptive Pill
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20
Q

Penicillin V side effects

A
  1. Hypersensitivity reactions
  2. Neurotoxicity (high [])
  3. Diarrhea
  4. Neutropenia & agranulocytosis
  5. Cross-hypersensitivity between penicillins
  6. Antibiotic-associated colitis (ampicillin) & infectious mononucleosis (amoxicillin)
  7. Reduced oral contraceptive pill efficacy
  8. Bleeding (reduced platelet aggregation)
  9. Fluid retention and hypokalaemia in renal/cardiac disease patients
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21
Q

Name Beta-lactamase resistant penicillins

A

Cloxacillin

Flucloxacillin

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22
Q

Beta-lactamase resistant penicillin kinetics

A

Limited liver metabolism

Excreted unchanged in urine

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23
Q

Use of beta-lactamase resistant penicillins

A

Mild Gram-positive Staphylococcal infections (>90% S. aureus isolates produce beta-lactamase so are resistant to Penicillin G)

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24
Q

Side effects of cloxacillin

A
  1. Hypersensitivity reactions
  2. Neurotoxicity (high [])
  3. Diarrhea
  4. Neutropenia & agranulocytosis
  5. Cross-hypersensitivity between penicillins
  6. Antibiotic-associated colitis (ampicillin) & infectious mononucleosis (amoxicillin)
  7. Reduced oral contraceptive pill efficacy
  8. Bleeding (reduced platelet aggregation)
  9. Fluid retention and hypokalaemia in renal/cardiac disease patients
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25
Q

Side effects of flucloxacillin

A
  1. Hypersensitivity reactions
  2. Neurotoxicity (high [])
  3. Diarrhea
  4. Neutropenia & agranulocytosis
  5. Cross-hypersensitivity between penicillins
  6. Antibiotic-associated colitis (ampicillin) & infectious mononucleosis (amoxicillin)
  7. Reduced oral contraceptive pill efficacy
  8. Bleeding (reduced platelet aggregation)
  9. Fluid retention and hypokalaemia in renal/cardiac disease patients
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26
Q

Cloxacillin admin

A

Oral, IV, IM

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27
Q

Flucloxacillin admin

A

Oral

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28
Q

Name aminopenicillins

A

Ampicillin
Amoxicillin
Clavulanic acid

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29
Q

Ampicillin kinetics

A

Beta-lactamase sensitive
Food lowers bio-availability
Limited liver metabolism
Excreted unchanged in urine

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30
Q

Ampicillin spectrum

A

(Broad spectrum)

Gram-positive
Gram-negative (mostly resistant)
Aerobic
Anaerobic

Mostly used for H. influenzae

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31
Q

Ampicillin side effects

A
  1. Hypersensitivity reactions
  2. Neurotoxicity (high [])
  3. Diarrhea
  4. Neutropenia & agranulocytosis
  5. Cross-hypersensitivity between penicillins
  6. Antibiotic-associated colitis (ampicillin) & infectious mononucleosis (amoxicillin)
  7. Reduced oral contraceptive pill efficacy
  8. Bleeding (reduced platelet aggregation)
  9. Fluid retention and hypokalaemia in renal/cardiac disease patients
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32
Q

Ampicillin admin

A

Oral, IM, IV, parenteral

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33
Q

Amoxicillin kinetics

A

Acid labile
Beta-lactamase sensitive
Limited liver metabolism
Excreted unchanged in urine

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34
Q

What is Augmentin?

A

Beta-lactamase resistant penicillin

Combination of amoxicillin and clavulanic acid

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35
Q

What is Ampiclox?

A

Combination of ampicillin and cloxacillin with extended spectrum

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36
Q

Amoxicillin spectrum

A 
(Broad spectrum)
Gram-positive
Gram-negative
Aerobic
Anaerobic
Otitis media
sinusitis
Pneumonia (& other lower RTIs)
Cholecystitis
GIT infections
UTIs
Prevent infective endocarditis (prophylaxis)
Soft tissue infection
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37
Q

MoA of clavulanic acid

A

Beta-lactamase inhibitor
No antibiotic effect
Binds covalently to active site of beta-lactamase

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38
Q

Clavulanic acid spectrum

A

Gram-positive

Gram-negative

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39
Q

Clavulanic acid resistant species

A 
Kiebsella
Proteus spp
Enterobacter
Serratia
Pseudomonas
Actinobacteria
B. fragilis
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40
Q

Clavulanic acid use

A 
RTI
Soft tissue infection
Cholecystitis
GIT infection
UTI
Infective endocarditis prophylaxis
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41
Q

Clavulanic acid side effects

A
  1. Hypersensitivity reactions
  2. Neurotoxicity (high [])
  3. Diarrhea
  4. Neutropenia & agranulocytosis
  5. Cross-hypersensitivity between penicillins
  6. Antibiotic-associated colitis (ampicillin) & infectious mononucleosis (amoxicillin)
  7. Reduced oral contraceptive pill efficacy
  8. Bleeding (reduced platelet aggregation)
  9. Fluid retention and hypokalaemia in renal/cardiac disease patients
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42
Q

Clavulanic acid admin

A

Oral, IV

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43
Q

Amoxicillin admin

A

Oral

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44
Q

Name antipseudomonal penicillins

A

Piperacillin

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45
Q

Piperacillin MoA

A

Beta-lactamase inhibitor synergistic with tazobactam

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46
Q

Piperacillin kinetics

A 
Limited liver metabolism
Urine excretion (unchanged)
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47
Q

Piperacillin spectrum

A

(extended spectrum)
P. aeruginosa

Synergistic with aminoglycosides against gram-negative

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48
Q

Piperacillin side effects

A
  1. Hypersensitivity reactions
  2. Neurotoxicity (high [])
  3. Diarrhea
  4. Neutropenia & agranulocytosis
  5. Cross-hypersensitivity between penicillins
  6. Antibiotic-associated colitis (ampicillin) & infectious mononucleosis (amoxicillin)
  7. Reduced oral contraceptive pill efficacy
  8. Bleeding (reduced platelet aggregation)
  9. Fluid retention and hypokalaemia in renal/cardiac disease patients
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49
Q

Piperacillin admin

A

IV, parenteral

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50
Q

Piperacillin precautions

A 
Elderly
Neonates (extend dose interval)
Flucloxacillin use (risks porphyric attacks)
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51
Q

Piperacillin contraindications

A

Penicillin allergy

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52
Q

Cephalosporin kinetics

A

Urine excretion

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53
Q

Methods of cephalosporin resistance

A

Cell wall impermeability
Drug Cephalosporinase sensitivity
Altered binding site

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54
Q

Name first generation cephalosporins

A

Cefalexin
Cefadroxil
Cefazolin

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55
Q

What species is completely resistant to all cephalosporins

A

Enterococci

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56
Q

Spectrum of cefalexin/cefadroxil/cefazolin

A

(Gram-positive cocci)
Streptococci
Staphylococci

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57
Q

Cephalosporin cautions

A 
Penicillin allergy (some may tolerate it)
Anaphylactic shock
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58
Q

Cephalosporin contraindication

A

Hyperbilirubinaemic neonate

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59
Q

Cepahlosporin side effects

A
  1. Hypersensitivity
  2. Cross-hypersensitivity
  3. Reduced oral contraception efficacy
  4. Nephrotoxicity (especially in combination with aminoglycosides/vancomycin)
  5. Neurotoxicity (high [])
  6. Phlebitis
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60
Q

First gen cephalosporin admin

A

Oral

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61
Q

Name second gen cephalosporins

A

cefuroxime
cefprozil
cefamandole
cefoxitin

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62
Q

Second gen cephalosporin spectrum

A 
Streptococci
Staphylococci
E. coli
Kiebsella
Proteus
H. influenzae
Enterobacter
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63
Q

Second gen cephalosporin side effects

A
  1. Hypersensitivity reactions
  2. Neurotoxicity (high [])
  3. Diarrhea
  4. Neutropenia & agranulocytosis
  5. Cross-hypersensitivity between penicillins
  6. Antibiotic-associated colitis (ampicillin) & infectious mononucleosis (amoxicillin)
  7. Reduced oral contraceptive pill efficacy
  8. Bleeding (reduced platelet aggregation)
  9. Fluid retention and hypokalaemia in renal/cardiac disease patients
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64
Q

cefamandole side effects

A

General second gen side effects

Alcohol intolerance

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65
Q

Second gen cephalosporin drug interactions

A 
Alcohol
Warfarin
NSAIDS
Contraceptive pill
Probenicid (lowered clearance raises toxicity)
Aminoglycosides (inactivation)
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66
Q

Cefuroxime admin

A

Oral, IV, IM

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67
Q

Cefamandole admin

A

IV

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68
Q

Cefoxitin admin

A

IV, IM

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69
Q

Name 3rd gen cephalosporins

A 
Cefotaxime
Ceftriaxone
Ceftazidime
Cefixime
Cefpodoxime
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70
Q

Ceftriaxone kinetics

A

40% hepatic elimination

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71
Q

3rd gen Cephalosporin MoA

A

Penicillin-like

Penetrates CSF well

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72
Q

3rd gen cephalosporin spectru

A

H. influenzae
N. gonorrhoeae
Salmonella spp.
P. aeruginosa

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73
Q

Ceftriaxone side effects

A

Concurrent Ca admin (precipitation) especially in babies

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74
Q

3rd gen cephalosporin admin

A

IV, IM

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75
Q

Name 4th gen cephalosporins

A

Cefepime

Cefpirome

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76
Q

4th gen cephalosporin spectrum

A

Gram-positive
Gram-negative (most effective)

H. influenzae
N. gonorrhoeae
Salmonella spp.
P. aeruginosa

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77
Q

4th gen cephalosporin admin

A

IV

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78
Q

Name Carbapenems

A

Imipenem
Meropenem
Ertapenem

79
Q

Carbapenem spectrum

A

Very broad spectrum

Inactive against methicillin-resistance staphylococci

80
Q

Imipenem use

A

Severe nosocomial infections (except meningitis)

81
Q

Meropenem use

A

Alternative treatment for meningitis

82
Q

Carbapenem side effects

A

(Beta-lactam effects):
Hypersensitivity reactions, GIT effects, haematological abnormalities, CNS effects, increase liver enzymes, increase serum creatinine & blood urea

Red urine discoloration (children)
Pain, erythema (IV)
Thrombophlebitis

83
Q

Carbapenem cautions

A

Penicillin allergy
CNS disorders/seizures
Renal impairment

84
Q

Carbapenem admin

A

IV

Ertapenem is single IV/IM dose daily

85
Q

Monobactam (aztreonam) benefits

A

Beta-lactamase stability

No cross-sensitivity in penicillin or cephalosporin allergies

86
Q

Monobactam spectrum

A 
(Gram-negative bacteria)
E. coli
P. aeruginosa
Enterobacter
Citrobacter
Proteus mirabilis
H. influenzae
87
Q

Monobactam side effects

A

Skin rash

Raised serum aminotransferases

88
Q

Monobactam admin

A

IV, IM

89
Q

Name glycopeptides in cell wall synthesis inhibition

A

Vancomycin

Teicoplanin

90
Q

Glycopeptide spectrum

A

Incredibly severe, cloxacillin-resistant staphylococci and penicillin-resistant enterococci

91
Q

Glycopeptide side effects

A 
Fever
Skin rashes
Red man syndrome (histamine release)
Colitis (if given orally)
Pain (IM)
Ototoxicity
Nephrotoxicity
92
Q

Glycopeptide admin

A 
IV
Oral (Pseudomembranous colitis only)
93
Q

Glycopeptide cautions & contraindications

A 
Geriatrics
Renal impairment
Neonates
Hearing abnormalities
Pregnancy
94
Q

Glycopeptide drug interactions

A

Ototoxic and nephrotoxic drugs (aminoglycosides)

95
Q

Glycopeptide resistance

A

Enterococci

Staphylococci

96
Q

Fosfomycin MoA

A

Pro-drug that interferes with NAMA formation to inhibit early cell wall synthesis

97
Q

Fosfomycin spectrum

A

(Broad spectrum)
Gram-positive
Gram-negative

98
Q

Fosfomycin synergisms

A

Beta-lactams
Aminoglycosides
Quinolones

99
Q

Fosfomycin use

A

Acute uncomplicated UTI

Prophylaxis in diagnostic and surgical transurethral procedures in adult men

100
Q

Fosfomycin side effects

A

GIT disturbances

Skin rashes

101
Q

Fosfomycin drug interactions

A

Metoclopramide (decrease fosfomycin concentration)

102
Q

Fosfomycin contraindications

A

Renal failure

Pregnancy and lactation

103
Q

Fosfomycin resistance mechanism

A

Impermeability - no transport into cell

104
Q

Fosfomycin admin

A

Oral (2 hours before meal)

105
Q

Fosfomycin kinetics

A

Activated in bowel

Excreted in breast milk and urine

106
Q

Name inhibitors of DNA synthesis

A

Ciprofloxacin (Ofloxacin)
Moxifloxacin (Levofloxacin)
Nalidixic acid

107
Q

DNA synthesis inhibitor MoA

A

Inhibit topoisomerase II - promote supercoiling, inhibit cutting and joining of DNA

Inhibit topoisomerase IV - promote supercoiling, inhibit separation of chromosomes into daughter cells

Bactericidal

108
Q

DNA synthesis inhibitor spectrum

A 
(Gram-negative aerobic - Strong):
Enterobacteriaceae
P. aeruginosa (not oflaxacin)
Haemophilus
Neisseria
Legionellae spp.

(Gram-positive aerobic - weak):
Streptrococci
Pneumococci (now resistant)

Mycobacteria

109
Q

Ciprofloxacin use

A

Typhoid fever
Cystitis
Meningococcal prophylaxis

110
Q

Moxifloxacin spectrum

A 
(Gram-positive infections)
Lower RTIs
Acute sinusitis
Skin infections
UTIs
TB
111
Q

When is moxifloxacin used

A

When there is a beta-lactam allergy

112
Q

What is moxifloxacin useless against

A

Pseudomonas spp

113
Q

Nalidixic acid use

A

(Gram-negative)

Acute/chronic UTI (lower only)

114
Q

DNA synthesis inhibitor side effects

A
  1. GIT disturbances
  2. Skin rash
  3. Seizures
  4. Headache, dizziness, restlessness
  5. Drowsiness, insomnia, tremor, agitation, confusion
  6. Hallucinations
  7. Photosensitivity (lomefloxacin)
  8. QT interval prolongation
  9. Hypo/hyperglycaemia (oral hypoglycaemic agents/diabetics)
  10. Arthropathy (damage growing cartilage)
  11. Tendinitis
115
Q

Nalidixic acid side effects

A

Photosensitivity
Seizures
Neurotoxicity

116
Q

DNA synthesis inhibitor contraindications

A 
Epilepsy (nalidixic acid)
Hepatic failure
Pregnancy/lactation
Children
Renal failure
Porphyria
Elderly
Allargy
G6PD deficiency
117
Q

DNA synthesis inhibitor resistant organisms

A

Staphylococci
Pseudomonas
Serratia

118
Q

Causes of DNA synthesis inhibitor resistance

A

1+ point mutations in quinolone
Change in binding region of target enzyme
Change in permeability

119
Q

Admin of DNA synthesis inhibitors

A

Oral, IV

Ciprofloxacin is best taken on empty stomach, but with lots of water

120
Q

What foods should be avoided when using DNA synthesis inhibitors and why?

A

Milk, yogurt, and antacids’

Cations can form cholate and impair absorption

121
Q

DNA synthesis inhibitor kinetics

A

Metabolized by Cytochrome P450 enzymes in liver, with 40-50% excreted unchanged in urine

122
Q

Name fluoroquinolones

A 
Ciprofloxacin
Ofloxacin
Norfloxacin
Levofloxacin
Moxifoxacin
Gemifloxacin
123
Q

What is the quinolone mother substance?

A

Nalidixic acid (defluorinated)

124
Q

Fluoroquinolone drug interactions

A
  1. Theophylline (with ciprofloxacin) causes theophylline toxicity due to CytP450 enzyme inhibition
  2. Warfarin (bleeding)
  3. NSAIDs (Seizure threshold reduced)
  4. Oral hypoglycemic agents (glibenclamide) inhibited metabolism
  5. Agents prolonging QT interval (some)
  6. Antacids/minerals
125
Q

Metronizadole MoA

A

Bactericidal

Selectively toxic against anaerobic protozoa

126
Q

How is Metronizadole selectively toxic?

A
  1. Reactions between reactive intermediates and
  2. Macromolecules like DNA cause alterations in DNA helix and break DNA chain
  3. When activated, the nitro group receives electrons from the electron transport protein, ferredoxin
  4. 4 electron reduction of nitro group = hydroxylamine, chemical reactive intermediate molecules are formed
127
Q

Metronizadole Spectrum

A

Antiprotozoal:
Entamoeba histolytica
Trichoonas vaginalis
Giardiasis

Gram-positive and negative anaerobic (except actinomycetes):
H. pylori now requires combo therapy)

128
Q

Metronizadole Use

A
  1. Protozoa-induced vaginitis and urethritis
  2. Pseudomembranous colitis
  3. Peptic ulcer
  4. Acute necrotizing ulcerative gingivitis
129
Q

Metronizadole side effects

A
  1. Nausea
  2. Headache
  3. Dry mouth
  4. Metallic taste
  5. Inhibits alcohol metabolism (disulfiram-like effect)
  6. CNS effects
130
Q

Metronizadole contraindications

A 
Alcohol
Epileps
Porphyria
CNS disease
Impaired liver function
1st trimester pregnancy (teratogenic)
Lactation
131
Q

Metronizadole admin

A

Oral
Rectal
IV
Topical

132
Q

Metronizadole kinetics

A

Liver clearance, with 10-20% renal unchanged excretion

133
Q

Metronizadole drug interactions

A
  1. Cimetidine (Reduce metronizadole metabolism)
  2. Phenobarbitone (increase metronizadole metabolism)
  3. Phenytoin (increase phenytoin plasma level)
  4. Warfarin (bleeding)
  5. Alcohol (reduced alcohol metabolism)
  6. Lithium (increased lithium level)
134
Q

Name bacterial protein synthesis inhibitor types

A 
Aminoglycosides
Tetracyclines
Macrolides
Chloramphenicol
Clindamycin
135
Q

Name aminoglycosides

A

Gentamycin
Streptomycin
Amikacin
Neomycin

136
Q

How do aminoglycosides inhibit protein synthesis?

A
  1. Attach to 30S ribosomal subunit
  2. Prevent formation of initiation complex
  3. Cause incorrect amino acid insertion
137
Q

Aminoglycoside spectrum

A

(narrow spectrum)
Aerobic gram-negative:
P. aeruginosa
M. tuberculosis

Some gram-positive bacteria

138
Q

Aminoglycoside side effects

A

Narrow therapeutic index: toxicity is dependent on:
• Plasma concentration (therapeutic peak and non-toxic trough levels)
• The duration of exposure to the drugs
• Dosages are in accordance with age, body weight and renal function

All are nephrotoxic and ototoxic (therapy > 5 days, ↑ doses, in elderly, renal insufficiency)
• Nephrotoxicity  The tubular cells are very sensitive and can be easily damaged  Neomycin, tobramycin & gentamicin are most nephrotoxic  Generally reversible
• Ototoxicity  In the inner-ear sensory cells of the vestibular apparatus and the organ of Corti can be damaged (partly irreversible)
o Vestibular damage → vertigo, ataxia & loss of balance
o Cochlear damage → deafness
o Streptomycin & gentamicin → most vestibulotoxic
o Streptomycin given during pregnancy cause deafness in the child
o Often irreversible

Neuromuscular blockage 
•	(very high doses -
•	respiratory paralysis) 
•	↓ prejunctional Ach release
•	and ↓ postsynaptic sensitivity
•	antidotes: calcium gluconate, neostigmine)

Electrolyte disturbance
Liver damage

139
Q

Aminoglycoside admin

A

IM

Topical

140
Q

Aminoglycoside kinetics

A

Mainly excreted unchanged in urine

141
Q

Are aminoglycosides concentration or time dependent?

A

Concentration dependent

Therefore, post-antibiotic effect

142
Q

Aminoglycoside synergies

A

Penicillin: against staphylococci, streptococci & enterococci

Metronizadole/Clindamycin: anaerobes

143
Q

Aminoglycoside resistance

A
  • Intrinsic: enterococci, M. tuberculosis (16S rRNA mutation)
  • Acquired: cell permeability, efflux pumps, enzymatic modification, mutation of binding site (streptomycin only), inhibition of transport into the cell, inactivation via enzymes produced by bacteria
144
Q

Aminoglycoside drug interactions

A
  1. General anaesthetics
  2. Neuromuscular blocking agents
  3. Oto- or nephrotoxic agents (vancomycin,
    amphotericin)
  4. Loop diuretics (higher risk of ototoxicity
145
Q

Aminoglycoside contraindications

A
  • Pregnancy (streptomycin)
  • Myasthenia gravis
  • Caution in the elderly, patients with renal insufficiency and neonates
146
Q

Name macrolides

A

Erythromycin
Clarithromycin
Azithromycin

147
Q

Macrolide MoA

A

Attach to 50S ribosomal subunit

148
Q

Macrolide spectrum

A

Erythromycin has similar small antibacterial spectrum as penicillin G

  • Erythromycin is used in patients that have an allergy to penicillin
  • Corynebacterial diphtheriae infections (erythromycin is drug of choice as its highly active)
  • Erythromycin/azithromycin NOT TO BE USED for syphilis in pregnant women allergic to penicillins (a greater effect has never been observed)
  • Azithromycin/clarithromycin → rickettsia infections (2nd line agent)
149
Q

Macrolide use

A 
Effective in resp infections:
o	Legionnaires disease
o	Whooping cough
o	Mycoplasma pneumoniae
o	Diphtheria
  • Erythromycin can be used in acne (2nd line agent)
  • Also used in resp, neonatal, ocular, genital, chlamydial infections
  • Treatment of community acquired pneumonia (resistance has developed here)
  • Prophylaxis against endocarditis during dental procedures (also used in case of allergy to penicillin)
  • Peptic ulcers (Clarithromycin + Omeprazole)
  • Erythromycin/azithromycin NOT TO BE USED for syphilis in pregnant women allergic to penicillins (a greater effect has never been observed)
  • Azithromycin/clarithromycin → rickettsia infections (2nd line agent)
150
Q

Macrolide side effects

A

• GIT intolerance (↓ in clari + azith) → (abdominal pain, cramping, nausea, vomiting, diarrheoa)
• Allergy (rare)
• Hepatotoxicity (cholestatic jaundice if estolate taken for more than 10 days →(adults & neonates
→ immunological) – Benign elevation of serum transaminase)
• Metabolites of erythromycin and clarithromycin inhibit CYP 450 (increase levels of other drugs in blood)

151
Q

Macrolide drug interactions

A
  • Warfarin
  • Oral contraceptive
  • Serum concentrations of different drugs ↑ Carbamazepine, theophylline, ciclosporin, alfentanil, midazolam, ebastine, ergot alkaloids, colchicine and the oral anticoagulants
152
Q

Macrolide cautions

A
  • Liver disease

* Impaired biliary function

153
Q

Macrolide contraindications

A

Porphyria

154
Q

Macrolide admin

A

Oral

stearate salt or esterified (estolate) form (estolate = best absorption)

155
Q

Macrolide kinetics

A
  • Distributes readily into all tissues, including prostate fluid
  • Crosses the placenta, but not the blood-brain barrier
  • High protein binding occurs
  • Partially metabolised by the liver and excreted in the bile, 2-5% unaltered in urine
156
Q

Macrolide resistance

A
  • Intrinsic: Enterobacteriaceae, P. aeruginosa, Acinetobacter baumanni (↓perm.)
  • Acquired: efflux pumps/permeability, target site alterations, enzymatic drug inactivation (esterases)
  • Reduced cell membrane permeability or active efflux
  • Production of esterases (Enterobacteriaceae) that hydrolyze macrolides
  • Modification of the ribosomal binding site
157
Q

Name tetracyclines

A

Tetracycline
Doxycycline
Minocycline

158
Q

Tetracycline MoA

A

Bind to 30S ribosomal subunit and prevent formation of initiation complex

159
Q

Tetracycline resistance

A
  • Efflux pumps
  • Decreased intracellular accumulation (low influx or active efflux) [NB!]
  • Production of protein that acts in ribosomal protection (prevent binding)
  • ↓porins (normally moves in actively/passively)
  • Enzymatic inactivation
160
Q

Tetracycline spectrum

A

(Broad)
Streptococci, staphylococci, pseudomonas + proteus are resistant

Used for
Rickettsia
Chlamydia
Brucellosis
Mycoplasma
Spirochetes
161
Q

Tetracycline use

A

Acne
Chronic bronchitis
Malaria
Zoonotic infections

162
Q

Tetracycline side effects

A
  • GIT disruptions (nausea, vomiting, diarrhea)
  • Superinfections (destruction of normal gut flora)
  • Pseudomembranous colitis -> clostridium difficile can also occur
  • Elderly – hepatotoxicity
  • Photosensitivity
  • Minocycline – blue-grey pigmentation of skin, pigmentation of acne scars, vestibular toxicity
  • Deposited in bones and teeth -> Bone growth retardation in children = Discoloration of nails and teeth + occasional enamel hyperplasia (in children)
  • Hepatotoxic and nephrotoxic
  • Reduced efficacy of oral contraceptive pill
163
Q

Tetracycline contraindications

A 
•	Systemic lupus erythematosus
•	Myasthenia gravis
•	Hepatic impairment
•	Porphyria
•	Elderly
•	Pregnancy 
•	Children (<8-12)
o	Deposited into bone so any growing child = bad effects
164
Q

Tetracycline admin

A

Oral with lots of water

165
Q

Do tetracycline users need to avoid milk and antacids?

A

Yes

166
Q

Tetracycline kinetics

A

• “Newer generation” tetracyclines e.g. doxycycline and minocycline are more lipid soluble → nearly completely absorbed in the presence of food so less inclined to chelate (minocycline)

  • Cross placenta, excreted in breast milk
  • Doxycycline and Minocycline – Excreted mainly in bile (safer in renal impairment)
167
Q

Tetracycline drug interactions

A
  1. Carbamazepine, phenytoin, barbiturates, rifampicin (serum levels of doxycycline ↓)  all liver enzyme inducers induce metabolism so lower conc. of doxycycline
  2. Vit A (high dosages) & other retinoids → enhanced risk of ↑ intracranial pressure
  3. Combined oral contraceptive pill
168
Q

Chloramphenicol MoA

A

Attaches reversibly to 50S ribosomal subunit

169
Q

Why is chloramphenicol not used anymore?

A

Extreme toxicity

170
Q

Chloramphenicol spectrum

A 
(Broad)
Rickettsia
Bacterial meningitis
Typhoid fever
Bacterial eye infections
171
Q

Chloramphenicol use

A 
Chlamydia
Mycoplasma
Streptococci
Staphylococci
Haemophilus
Anaerobes
172
Q

Chloramphenicol side effects

A
  • Serious irreversible bone marrow depression → idiosyncratic → fatal aplastic anaemia (topical use)
  • Dose-related reversible bone marrow toxicity
  • Efficacy of the combined oral contraceptive pill → reduced
  • Use with great care → babies → ineffective conjugation with glucuronic acid and excretion of the drug causes severe bone marrow depression → “grey baby syndrome” (approximately 40% mortality) – Abdominal distension, cyanosis, vasomotor collapse, failure to feed
  • GIT effects, optic or peripheral neuritis
  • Hypersensitivity reactions and jaundice
  • Inhibit liver enzymes
173
Q

Chloramphenicol contraindications

A
  • Allergy
  • Porphyria
  • Third trimester of pregnancy
  • Neonates
  • Lactation
174
Q

Chloramphenicol cautions

A
  • Impaired hepatic function

* Bone marrow depression

175
Q

Chloramphenicol admin

A

Oral

176
Q

Chloramphenicol kinetics

A

Metabolized in liver after glucouronide formation

177
Q

Chloramphenicol drug interactions

A
  • Cause hepatic enzyme inhibition: – ↑ concentrations of phenytoin, warfarin, sulphonylurea antidiabetic agents
  • Used with hepatic enzyme inducers (phenobarbital, rifampicin) → efficacy of chloramphenicol ↓
  • Vit B, folic acid & iron → chloramphenicol may
  • interfere with haematological response
  • Combined oral contraceptive pill
178
Q

Chloramphenicol resistance

A

• Production of chloramphenicol acetyltransferase that inactivates the drug

179
Q

Clindamycin MoA

A

Bind with 50S ribosomal subunits

180
Q

Clindamycin kinetics

A

Clindamycin is excreted in bile mostly

181
Q

Clindamycin resistance mechanisms

A

Mutation of ribosomal binding site

2. Enzymatic inactivation

182
Q

Clindamycin spectrum

A

Gram-positive:
Staphylococci
Anaerobic
Inactive against enterococci

183
Q

Clindamycin use

A 
Patients with penicillin allergy
Soft tissue infections
Lung abscess
Quinsy
Aspiration pneumonia
Endocarditis prophylaxis
184
Q

Clindamycin side effects

A
  • Diarrheoa, nausea, skin rashes
  • Transient increase liver enzymes and bilirubin
  • Impaired liver function
  • Neutropenia, leucopenia, thrombocytopenia, agranulocytosis, eosinophilia
  • Pseudomembranous colitis (toxin created by C. difficile causes serious and potentially fatal complication)
  • Lowered efficacy of pill
185
Q

Clindamycin cautions

A
  1. GIT disease, Severe hepatic impairment
  2. Porphyria, Elderly
  3. Pregnancy/Lactation
186
Q

Clindamycin admin

A

Oral

Need lots of fluid

187
Q

Clindamycin drug interactions

A

Oral contraceptive

188
Q

Name antimicrobials for resistant infections

A 
Ketolides
Telithromycin
Streptogramins
Oxazolidinones
Lipopeptides
Glycylcyclines
189
Q

Ketolide description

A

 Belong to the macrolide group of antibiotics
 Semi-synthetic derivatives of the 14-membered macrolide erythromycin A → broader spectrum
 Active against H. influenza & erythromycin-resistant pneumococcus
 Used when resistant against macrolides

190
Q

Telithromycin description

A

 used clinically (oral)
 can bind to two sites on the bacterial ribosome
 bind with higher affinity than macrolides
 risk of potentially serious hepatotoxicity
 resp failure in patients with myasthenia gravis
 visual disturbances and loss of consciousness

191
Q

Streptogramins description

A

 Macrolide/Lincosamides/streptogramin class
 Quinupristin-dalfopristin (fixed 30/70 combination)
o Synergistic combination
o Most Gram pos. bacteria & most respiratory pathogens
o They bind to distinct sites on the 50S ribosomal subunit
o Interfere with peptidyl transferase enzyme action
o Large number of side-effects and drug interactions

192
Q

Oxazolidinone description

A

 New class of synthetic antibiotics
 Heterocyclic organic compound
 Linezolid is used clinically (oral/IV)
 Gram positive infections
 Resistant infections
 Last resort where every other antibiotic therapy has failed → should be reserved for this purpose
 Prevent formation of ribosome complex that initiates protein synthesis
 Reversible non-selective inhibitor of MAO [mono-amine oxidases  interferes with antidepressants]
 Headache, moniliasis/fungal infection, metallic taste, GIT effects, Haematological toxicity, neurotoxicity

193
Q

Lipopeptide description

A

 Daptomycin in clinical use (IV)
 Naturally occurring compound found in soil Streptomyces roseosporus
 Spectrum/Uses:
o Infections caused by multi-resistant bacteria
o Active against Gram pos. bacteria only
o S. aureus bacteraemia incl. right-sided infective endocarditis
o Disrupting bacterial cell membrane function
o Inhibition of protein, DNA and RNA synthesis
o Large number of side effects (myopathy)

194
Q

Glycylcycline description

A

 New class derived from minocycline
 Tigecycline in clinical use (IV)
 Similar to tetracycline and used in Tetracycline-resistant bacteria
 Mechanism of action: Similar to tetracyclines
 Adverse effects similar to tetracyclines
 Increased mortality and treatment failure noted

Pharmacology (4 decks)

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