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ACEM Primary VIVA > VIVA: Pharmacology - Antimicrobials > Flashcards

VIVA: Pharmacology - Antimicrobials Flashcards

1
Q

What are the indications for acyclovir in the ED?

A

HSV encephalitis*
VZV
Genital herpes
Patients with HIV

  • needed to pass
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2
Q

Describe the mechanism of action of acyclovir

A

Inhibition of viral DNA synthesis*
- Irreversible binding to viral DNA polymerase
- Incorporation into viral DNA with termination
- Specificity for virus-infected cells (virus-specific thymidine kinase)

  • needed to pass + one other
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3
Q

Describe the pharmacokinetics of acyclovir

A
  • Short half-life of 2.5hrs (5x daily dosing oral)*
  • Low oral bioavailability
  • Mostly excreted unchanged in urine
  • CSF 20-50% of plasma
  • Wide distribution
  • needed to pass + one other
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4
Q

Name some side effects of acyclovir

A

2 to pass:
- Nausea
- Vomiting
- Diarrhoea
- Headache
- Reversible renal toxicity
- Neurological: tremor, delirium, seizures

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5
Q

Name some macrolide antibiotics

A

2 to pass:
- Erythromycin
- Roxithromycin
- Azithromycin
- Clarithromycin

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6
Q

Describe the mechanism of action of macrolides

A

Inhibits bacterial protein synthesis* by binding to 50S ribosomal RNA, which blocks aminoacyl translocation reaction and formation of initiation complexes (transpeptidation)
May be inhibitory or bactericidal, particularly at higher concentrations

  • needed to pass
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7
Q

What organisms are macrolides effective against?

A

3 to pass:
- Gram positive organisms: pneumococci, streptococci, staphylococci, corynebacteria
- Atypicals: Mycoplasma, Legionella, Chlamydia sp, Listeria, some mycobacteria
- Gram negative organisms: Neisseria sp, Bordatella pertussis, Treponema pallidum, Campylobacter sp, bartonella (Haemophillus less susceptible)

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8
Q

What are the adverse effects of erythromycin?

A

Gastrointestinal*: anorexia, nausea, vomiting, diarrhoea
Liver toxicity: acute cholestatic hepatitis (particularly with estolate)
Allergic reaction: fever, eosinophilia, rash
Drug interactions: inhibits CP450

  • needed to pass + one other
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9
Q

Describe the mechanism of action of ceftriaxone

A
  • Bacteriocidal antibiotic *
  • Only kills growing bacterium
  • Binds to bacterial cell wall peptidases leading to inhibition of transpeptidation reaction of bacterial cell wall synthesis
  • Halts peptidoglycan synthesis, leading to inhibition of bacterial growth and ultimately cell death

*needed to pass

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10
Q

What is the spectrum of activity of ceftriaxone?

A
  • Not usually degraded by bacterial beta-lactamases therefore broader spectrum of activity
  • Broad spectrum third generation cephalosporin with good tissue penetration (crosses BBB) and effective against a broad range of Gram positive and Gram negative organisms * including Haemophilus, Neisseria and penicillin-resistant pneumococcus
  • Not effective against anaerobes, Pseudomonas, Listeria, and MRSA *

*Gram positive and Gram negative (name each group or one examples from each group and at least one non-susceptible organism to be at standard

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11
Q

Describe the pharmacokinetics of ceftriaxone

A

3/7 to pass:
- Administration: IV and IM, <1% bioavailability orally
- Excretion: 35-70% excreted unchanged in urine, remainder excreted in bile with some hepatic/gut metabolism
- Half-life: 6-9hrs
- Distribution: penetrates tissues and body fluids well, including CSF
- Volume of distribution: 5.8-13.5L
- Negligible protein binding
- Duration of action: 24hrs

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12
Q

List some anti-influenza agents

A

1 to pass:
- Zanamivir
- Oseltamivir
- Amantadine
- Rimantadine

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13
Q

What is the mechanism of action of zanamivir (Relenza) and oseltamivir (Tamiflu)?

A

Neuraminidase (glycoprotein) inhibitors:
- Disrupt viral replication and release
- Active against both influenza A and B

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14
Q

What is the mechanism of action of zanamivir (Relenza) and oseltamivir (Tamiflu)?

A

Neuraminidase (glycoprotein) inhibitors:
- Disrupt viral replication and release
- Active against both influenza A and B

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15
Q

What is the mechanism of action of zanamivir (Relenza) and oseltamivir (Tamiflu)?

A

Neuraminidase (glycoprotein) inhibitors:
- Disrupt viral replication and release
- Active against both influenza A and B

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16
Q

What are the indications for the use of anti-influenza agents?

A

Approved for treatment of uncomplicated influenza:
- 5 day course of therapy within 36-48 hrs of symptom onset shortens severity and duration of illness
- May decrease incidence of respiratory complications

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17
Q

What is the relevance of anti-influenza agents to emergency medicine practice?

A
  • May be of use to higher risk groups (e.g. Indigenous, pregnant women, older people, immunocompromised), however primary prevention by vaccination is preferred
  • Used preferably at early phase of influenza pandemic to limit spread and numbers infected, and limit severity of disease in those infected
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18
Q

What classes of antibiotics are used in the treatment of Staphylococcal infections?

A

3 classes to pass:
1. Beta-lactamase negative Staph:
- Penicillin
- 1st generation cephalosporin
2. Beta-lactamase positive Staph:
- Beta-lactamase resistant penicillins (methicillin, naficillin, dicloxacillin, flucloxacillin)
- 1st generation cephalosporin
- Beta-lactamase inhibitor with penicillin combination (clavulanic acid, sulbactam, tazobactam)
- Vancomycin
- Aminoglycosides
- Macrolides

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19
Q

What is the mechanism of resistance in methicillin-resistant Staph aureus?

A
  • Beta-lactam antibiotics normally bind to penicillin binding proteins (PBPs) * causing inhibition of transpeptidation, thus blocking cell wall synthesis and lead to cell wall death
  • MRSA produce PBPs that have a low affinity for binding beta-lactam antibiotics and hence render them ineffective *
  • May be overcome if used in high enough concentrations, but not clinically achievable
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20
Q

What are the adverse effects of vancomycin?

A

1 to pass:
- Local phlebitis
- Chills, fever
- Flushing due to histamine release (“red man”)
- Ototoxicity / nephrotoxicity if administered with aminoglycoside

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21
Q

In treatment of a new case of tuberculosis, what are the important principles of drug use?

A
  • Multiple drugs used initially * (usually 4) ensures efficacy
  • Prolonged course, usually 6 months
  • Close supervision to ensure compliance and detect adverse effects
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22
Q

Describe the pharmacokinetics and adverse effects of rifampicin

A

2/6 to pass:
Absorption:
- Well-absorbed orally
Distribution:
- Highly lipid soluble: widely distributed in tissues
Metabolism and excretion:
- Metabolism in liver, excreted in faeces
- Induces p450 enzymes (many drug interactions)
Adverse effects:
- Orange discolouration of body fluids
Uses:
- Can be used as prophylaxis

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23
Q

What class of antibiotic is azithromycin?

A

Macrolide

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24
Q

What is the mechanism of action of azithromycin?

A
  • Inhibits protein synthesis by reversibly binding to the 50S ribosomal RNA *
  • Blocks aminoacyl translocation and formation of initiation complexes (transpeptidation)
  • Bacteriostatic at lower does, bactericidal at high concentrations

*needed to pass

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25
Q

What organisms does azithromycin cover?

A

3 to pass:
1. Gram positives:
- Staphylococcus
- Streptococcus (including pneumococcus)
- Corynebacterium
- Mycoplasma
- Legionella
- Chlamydia sp
- Haemophilus influenza
- Mycobacterium avium complex
2. Gram negative:
- Neisseria sp
- Bordatella pertussis
- Treponema pallidum
- Campylobacter sp
- Bartonella

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26
Q

What is an important cardiac side effect of azithromycin?

A

Prolonged QT interval

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27
Q

How does azithromycin differ from other macrolides?

A
  1. Pharmacokinetic differences:
    - Absorption impeded by food
    - Higher tissue penetration (tissue concentration&raquo_space;» serum concentration)
    - Doesn’t inhibit hepatic cytochrome p450 so drug interactions are uncommon
    - Long elimination half-life * (2-4 days) vs 2-5hrs for clarithromycin and erythromycin
    - Excreted unchanged in urine
    - Single daily dosing *
  2. Pharmacodynamic differences:
    - More effective against Haemophilus, M. catarrhalis, Neisseria
    - Less active against Strep and Staph

*needed to pass + 1 other

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28
Q

What kind of antibiotic is ceftriaxone?

A

Third generation cephalosporin
Beta lactam antibiotic

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29
Q

What is ceftriaxone’s plasma half-life? How is this relevant clinically?

A

Half-life of 7-8hrs, meaning it may be administered once daily at 15-50mg/kg

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30
Q

What is the mechanism of action of cephalosporins?

A
  • Inhibit bacterial cell wall synthesis *, cell division and growth (similar to penicillins)
  • Work best in rapidly-dividing cells

*needed to pass

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31
Q

What class of antibiotics do cephalosporins belong to?

A

Beta lactams

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32
Q

How are cephalosporins classified? Give an example of each class

A

1st generation:
- Very active against GPC, E. coli, K. pneumoniae, Proteus
- No Pseudomonas coverage
- Anaerobic cocci sensitive
- E.g. cephalexin, cephazolin
2nd generation:
- Active against those by 1st generation but added Gram negative cover (Klebsiella, some anaerobe cover)
- No Pseudomonas coverage
- E.g. cefaclor, cefuroxime
3rd generation:
- Expanded Gram negative coverage and cross BBB
- Less active against Staph
- Effective against beta-lactamase-producing Haemophilus and Neisseria
- Ceftazidime has anti-Pseudomonal activity
- E.g. ceftriaxone, ceftazidime, cefotaxime
4th generation:
- More resistant to beta-lactamases
- Crosses BBB
- Extended coverage against GNR, Pseudomonas, Enterobacteriaceae, S. pneumoniae, S. aureus, Haemophilus, Neisseria
- E.g. cefipime

*4 generations to pass + concept of increasing activity against Gram negatives + example of 2 classes

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33
Q

Why are 3rd generation cephalosporins used in CNS infection?

A
  • Expanded GN activity and crosses the BBB *
  • Penetrates body fluids well *
  • Good toxicity profile

*needed to pass

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34
Q

Are there any bacteria responsible for CNS infection that cephalosporins do not cover?

A

1 example to pass:
- Listeria
- Resistant pneumococci may need vancomycin
- Resistant E. coli
- Use with aminoglycosides to cover Pseudomonas

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35
Q

What are the adverse effects of cephalosporins?

A
  1. Hypersensitivity reactions identical to penicillins *:
    - Anaphylaxis, fever, skin rashes, nephritis, granulocytopaenia, haemolytic anaemia
    - Some individuals with a history of penicillin allergy may tolerate cephalosporins
    - Frequency of cross-allergenicity uncertain, probably around 5-10%
  2. Renal:
    - Interstitial nephritis
    - Acute tubular necrosis
  3. Cephalosporins with methylthiotetrazole group (e.g. cefamandole, cefotetan) can cause:
    - Hypoprothrombinaemia and bleeding (preventable with vitamin K 10mg twice weekly)
    - Severe disulfiram-like reactions with alcohol
  4. Related to route of administration:
    - Severe pain with IM
    - Thrombophlebitis IV

*needed to pass + 2 others

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36
Q

What are the adverse effects of chloramphenicol?

A

2 to pass:
1. GIT:
- Nausea and vomiting
- Diarrhoea
2. Bone marrow suppression:
- Reversible RBC suppression
- Idiosyncratic aplastic anaemia
3. Gray baby syndrome in newborns
4. Drug interactions:
- Prolongs half-life and raises concentration of phenytoin, chlorpropamide and warfarin

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37
Q

Which bacteria are affected by chloramphenicol?

A
  • Aerobic and anaerobic Gram positive and negative
  • Includes Rickettsia but not Chlamydia
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38
Q

What is the mechanism of action of chloramphenicol?

A
  • Potent inhibitor of microbial protein synthesis: binds to 50S subunit of bacterial ribosome by inhibiting peptidyl transferase
  • Bacteriostatic
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39
Q

What is an antiseptic?

A

A chemical disinfectant applied to living tissue (skin, mucous membrane and wounds) which decreases the number of organisms by killing, removing or diluting, and has generally low toxicity to tissues

40
Q

Describe the actions and uses of chlorhexidine

A
  • Low skin sensitising or irritating capacity
  • Oral toxicity low (poorly absorbed from the alimentary tract)
  • Active against bacteria (most effective against GPC) and Mycobacteria, moderate activity against fungi and viruses
  • Not inhibited by blood or organic products
41
Q

When is chlorhexidine contraindicated?

A
  • Middle ear surgery (causes sensorineural deafness)
  • Neurosurgery (neural toxicity)
  • Allergy
42
Q

Describe the pharmacokinetics of ciprofloxacin

A
  1. Absorption:
    - PO or IV *
    - PO bioavailability >80%
  2. Distribution:
    - 20-40% protein-bound
    - Elimination half-life 3-5hrs *
  3. Metabolism and elimination:
    - Renally eliminated (dose adjustment if Cr Cl <50ml/min)
  4. Dosing:
    - PO 250-500mg BD (max 1.5g)
    - IV 200-300mg BD (max 1.2g)

*needed to pass

43
Q

Describe the mechanism of action of ciprofloxacin

A
  • Blocks DNA synthesis * by inhibiting bacterial topoisomerase II (DNA gyrase) and IV
  • Prevents normal transcription and replication

*needed to pass

*needed to pass

44
Q

What is its antimicrobial spectum?

A
  • Excellent Gram negative activity, moderate Gram positive activity *
  • Covers S. aureus, Mycoplasma, Chlamydia, Legionella, Pseudomonas, Mycobacterium, Anthrax

*needed to pass

45
Q

What is the mechanism of action of doxycycline generally, and in malaria?

A

Protein synthesis inhibitor *:
- Binds reversibly to 30S subunit of ribosome
- Bacteriostatic
In malaria:
- Inhibits protein synthesis
- Active against erythrocytic schizonts of all malaria parasites
- Used for prophylaxis
- Not used as single agent in treatment (slow and not active against liver stages)

*needed to pass

46
Q

What are the side effects of doxycycline?

A
  1. GIT:
    - Nausea and vomiting
    - Hepatotoxicity
  2. Dermatological:
    - Photosensitivity *
    - Discolouration of teeth and bones * (binds to calcium in newly forming bone/teeth; contraindicated in pregnancy and children <8yo)
    - Candidal vaginitis
  3. Neurological:
    - Intracranial HTN

*1/2 to pass + 2 others

47
Q

Other than malaria, what are other indications for doxycycline?

A

2 to pass:
- Respiratory tract infections
- STIs (e.g. Chlamydia, syphilis)
- Skin infections (e.g. acne)
- Rickettsia (e.g. Q fever)
- Vibrio species (e.g. Cholera)
- Antihelminthic
- Anthrax
- Gram negatives (rarely)
- H. pylori infections

48
Q

What is the mechanism of action of erythromycin?

A
  • Inhibits RNA-dependent protein synthesis by binding to the 50S ribosomal subunit *
  • Bacteriostatic * (at high concentration with selected organisms can be bactericidal)

*needed to pass

49
Q

What is the mechanism of the drug interactions associated with erythromycin? Give some examples

A
  • Inhibits hepatic CYP3A4 *
  • Usually inhibits metabolism of other drugs’ metabolism causing increased activity (e.g. benzodiazepines, carbamazepine, cisapride, digoxin, warfarin, theophylline, cyclosporine, tacrolimus)

*needed to pass + 1 example

50
Q

What are the adverse effects of erythromycin?

A
  1. GIT *:
    - Abdo cramp
    - Diarrhoea
    - Nausea and vomiting
    - Pancreatitis, hepatotoxicity (rarely)
  2. Dermatological:
    - Candida (oral, vaginal)
  3. Hearing loss (rarely)
  4. Hypersensitivity (rarely)
  5. Rapid IV administration may cause ventricular arrhythmias

*needed to pass + 1 other

51
Q

What is the mechanism of action of flucloxacillin?

A
  • Beta-lactam
  • Inhibits bacterial growth by binding to active site of penicillin binding proteins (PBP), interfering with transpeptidation of bacterial cell wall synthesis * -> cell death (bactericidal)

*needed to pass

52
Q

What microorganisms are susceptible to flucloxacillin?

A
  • Staphylococcal * (including beta lactamase producing)
  • Streptococcal *
  • Not active against MRSA, enterococci, anaerobes, Gram negatives

*needed to pass

53
Q

What are the important side effects of flucloxacillin?

A
  1. Hypersensitivity:
    - Allergy/anaphylaxis*
    - Serum sickness
  2. GIT:
    - Nausea and vomiting
    - Hepatic (cholestasis) *
  3. Renal:
    - Interstitial nephritis
  4. Haematological:
    - Neutropaenia
    - Thrombocytopaenia

*needed to pass + 1 other

54
Q

Why is oral flucloxacillin given before meals?

A

1/2 to pass:
- Acid labile (inactivated by gastric acid)
- Binds to food proteins (decreasing absorption)

55
Q

What is the frequency of cross-allergenicity between flucloxacillin and cephalosporins?

A

5-10%

56
Q

What is the mechanism of action of fluoroquinolones?

A

DNA gyrase inhibitor (blocks protein production)

57
Q

What are the mechanisms of resistance to fluoroquinolones?

A

Resistance is due to one or more point mutations in the quinolone-binding region of the target enzyme or to a change in the permeability of the organism

58
Q

What are the clinical uses of ciprofloxacin?

A

3 organ system uses to pass:
1. Genitourinary:
- UTI
- Gonococcal infection
- Chlamydial urethritis or cervicitis
2. Bacterial diarrhoea caused by Shigella, Salmonella, toxigenic E. coli, Campylobacter
3. Soft tissue, bone and joint infections
4. Intra-abdominal infections
5. Respiratory tract infections
6. Prophylaxis and treatment against anthrax
7. Treatment against multidrug-resistant organisms (Pseudomonas, Enterobacter)
8. TB and atypical mycobacterial infections
9. Eradication of meningococcal carrier state
10. Prophylaxis in neutropaenic patients

59
Q

What class of drug is ciprofloxacin?

A

Fluoroquinolone

60
Q

What is the antimicrobial spectrum of ciprofloxacin?

A
  • Excellent Gram negative activity and moderate Gram positive activity *
  • Methicillin-susceptible strains of S. aureus only
  • Agents of atypical pneumonia (Mycoplasma, Chlamydiae)
  • Intracellular pathogens such as Legionella and Mycobacterium
  • Drug of choice for anthrax

*needed to pass + 1 other

61
Q

What are the potential adverse effects of fluoroquinolones?

A
  • Prolonged QT * (with some)
  • Nausea, vomiting, diarrhoea (including C. difficile infection)
  • Abnormal LFTs
  • Photosensitivity
  • Growing cartilage damage (not routinely recommended in pregnancy or <18yo)
  • Tendonitis
  • Rash
  • Allergy
  • Hyperglycaemia in diabetics

*needed to pass + 2 others

62
Q

How does antibacterial activity of norfloxacin compare to that of ciprofloxacin?

A

Ciprofloxacin has greater activity * (4-8x lower MICs) against Gram negatives and much greater activity against Gram positives

*needed to pass

63
Q

Describe the antibacterial activity of norfloxacin

A
  • Gram negative bacteria *
  • Organisms of atypical pneumonia: Mycoplasma, Chlamydiae
  • Limited Gram positive activity

*needed to pass

64
Q

Describe the mechanism of action of gentamicin

A
  • Irreversible inhibitor of protein synthesis (bactericidal)
  • Concentration-dependent killing
  • Passive diffusion via porin channels then active into cytoplasm via O2 dependent process
  • Post-antibiotic effect
  • 2 mechanisms: binds 30S ribosome to inhibit protein synthesis *, and disrupts polysomal structure resulting in non-functional monosomes
  • Transport enhanced by cell wall active drugs (e.g. penicillin, vancomycin), and inhibited by low ECG pH and anaerobic conditions

*needed to pass

65
Q

Describe the pharmacokinetics of gentamicin

A

Absorption:
- Poor oral absorption
- Well-absorbed IM, usually given IV
- Can also be given topically or by inhalation
- Peak serum concentration within 30-90mins
Distribution:
- Small Vd because <10% protein bound
- Highly polar, water-soluble and thus does not enter cells well
- Variable penetration of tissue spaces (most tissues low except renal cortex): CSF 20% of plasma levels, bile 30%, pleural/synovial 50-90%
Metabolism:
- Not metabolised
- Half-life 2-3hrs
Elimination:
- Cleared by kidney *
- Dosage adjustment needed for renal impairment
Dosing:
- Dose 5-7mg/kg as single daily dose

*needed to pass + 2 others

66
Q

How do bacteria develop resistance against gentamicin?

A

1 to pass:
- Transferase that inactivates drug, carried by plasmid
- Impaired cell entry (cell wall)
- Altering ribosomal receptor protein

67
Q

What class of antibiotic is gentamicin?

A

Aminoglycoside

68
Q

What are the advantages of single daily dosing regimen for gentamicin?

A
  • Decreased toxicity time *: once-daily dosing results in less time above toxic threshold concentration
  • Concentration-dependent killing *: at increased concentration kills increased number of bacteria at a more rapid rate
  • Post-antibiotic effect: effect lasts longer than detectable serum levels
  • Can be used as outpatient therapy
  • Cost-effective

*needed to pass

69
Q

What are the adverse effects of gentamicin?

A
  • Nephrotoxic *
  • Ototoxic *
  • Prolongs neuromuscular blockade

*needed to pass

70
Q

What microorganisms is gentamicin effective against?

A
  • Gram negative bacteria * (E. coli, Pseudomonas, Proteus, Klebsiella, Serratia)
  • Gram positive bacteria (Staph and Strep with beta lactams or vancomycin)
  • No anaerobic activity

*needed to pass + 3 organisms

71
Q

How do penicillins enhance the efficacy of gentamicin?

A
  • Low ECF pH and anaerobic conditions inhibits transport
  • Transport enhanced by cell wall active drugs (e.g. penicillin)
72
Q

Name some macrolide antibiotics

A

2 to pass:
- Erythromycin
- Roxithromycin
- Azithromycin
- Clarithromycin

73
Q

By what mechanisms can bacteria be resistant to beta-lactam antibiotics?

A
  • Inactivation by beta-lactamase (commonest mechanism) *
  • Modification of target proteins (PBPs; by MRSA, pneumococci, enterococci)
  • Impaired penetration through cell wall to PBPs (Gram negatives only - outer cell wall membrane) which enhances efficacy or beta-lactamase enzymes within the cell
  • Efflux pump (Gram negatives only)

*needed to pass + 1 other

74
Q

What circumstances encourage the development of bacterial resistance to antimicrobial agents?

A

Resistance is an example of natural selection, and arises through spontaneous mutations or DNA exchange between different species of bacteria (either directly by plasmids or via bacteriophages), therefore resistance is promoted by (1 to pass):
- Dirty hospital environments within multiple species of bacteria co-existing and “exchanging” between environment, patients and staff
- A course of antibiotics that only partially treats a target population (inadequate potency, dose or duration)
- Thus paradoxically both underuse and overuse of antibiotics plays a role in the development of resistance
- Overall, however, total consumption of antibiotics within a human population is the critical factor in development of resistant strains

75
Q

Describe the pharmacokinetics of metronidazole

A

3 to pass:
Absorption:
- Well-absorbed orally with 99% oral bioavailability
- Oral/IV/suppository
Distribution:
- Low protein binding (10-20%)
Metabolism:
- Hepatic (can accumulate in hepatic insufficiency)
- Half-life 7.5hrs
Elimination:
- Via kidney
Dosage:
- 500mg TDS or single dose of 2g for vaginitis

76
Q

What are the adverse effects of metronidazole?

A

2 to pass from different systems:
1. GIT:
- Nausea
- Diarrhoea
- Dry mouth
- Metallic taste
- Hairy black tongue
2. CNS:
- Headache
- Paraesthesia
- Dizziness
- Insomnia
3. Thrombophlebitis
4. Disulfiram-like effect (avoid alcohol)
5. Drug interactions:
- Potentiates effects of warfarin, lithium

77
Q

Describe the mechanism of action of penicillins

A
  • Inhibition of cell wall synthesis * by interfering with transpeptidation
  • Structural analogue of D-Ala-D-Ala substrate, covalently binds to penicillin-binding protein, important in cross-linkage
  • Bactericidal, only kills growing cells

*needed to pass

78
Q

How does resistance to penicillins occur?

A
  • Inactivation by beta-lactamases *
  • Modification of target PBPs (pneumococcus, enterococci)
  • Impaired penetration of drug to PBP via impact on porin channels (Gram negatives)
  • Efflux pump (Gram negatives)
  • needed to pass + 1 other
79
Q

In general, what is the anti-microbial spectrum of penicillin G?

A

3 to pass:
- Streptococci
- Meningococci
- Enterococci
- Some pneumococci
- Treponema pallidum
- Clostridia
- Non-beta-lactamase producing Staphylococci

80
Q

What are the clinical manifestations of penicillin allergy?

A

2 to pass:
- Anaphylaxis
- Fever
- Skin reactions (maculopapular rash, urticaria, exfoliative dermatitis)
- Serum sickness
- Steven Johnson syndrome

81
Q

What other side effects of penicillin treatment besides allergy are there?

A

3 to pass:
- Renal failure
- Seizure at high doses
- GI disturbance
- Candidal infections
- Hepatitis (flucloxacillin, oxacillin)

82
Q

How are penicillins eliminated?

A

Renal excretion and secretion *
Biliary secretion

*needed to pass

83
Q

How does probenicid alter the elimination of some penicillins?

A

Inhibits secretion of weak acids from the proximal tubule

84
Q

Describe the mechanism of antimicrobial activity of the sulphonamides

A

Reversibly blocks folic acid synthesis thus inhibiting growth

85
Q

Why is trimethoprim commonly administered in combination with sulfamethoxazole?

A

Antibacterial synergism:
- Blocks sequential steps in folic acid dependent purine synthesis

86
Q

How do tetracyclines exert their antimicrobial activity?

A
  • Bacteriostatic
  • Enters cell by diffusion and active transport
  • Binds irreversibly to 30S subunit of the ribosome *
  • Blocks binding of tRNA to mRNA-ribosome complex, and stops addition of amino acids to peptide *

*needed to pass

87
Q

Describe the pharmacokinetics of tetracyclines

A

Absorption:
- Variable oral absorption depending on which drug
- Generally >60% absorbed *
- Absorption occurs mainly in upper small intestine
- Food, calcium, dairy products and alkaline pH impair absorption *
Distribution:
- 40-80% protein bound *
- Distributed widely to tissues except CSF *
- Crosses placenta
- Chelates to calcium and binds to growing teeth and bones *
Elimination:
- Excreted in bile and in urine *
- Concentrated in bile (up to 10x serum concentration)
- Undergoes enterohepatic circulation *
- Depending on drug 10-50% urine or biliary excretion (doxycycline is the exception: NO renal elimination)

*4/7 to pass

88
Q

Are there any group of patients where tetracyclines are contraindicated and why?

A

Pregnancy and breastfeeding
Children <8yo

89
Q

How does resistance to doxycycline develop?

A
  1. Decreased intracellular accumulation:
    - Impaired influx
    - Increased efflux by active transport protein pump
    - Encoded on plasmid (commonly encode resistance genes for other drugs: aminoglycosides, sulfonamides, chloramphenicol)
  2. Ribosome protection:
    - Proteins interfere with tetracycline binding to ribosome
  3. Enzymatic inactivation of tetracyclines
90
Q

Describe the mechanism of action of trimethoprim

A
  • Selectively inhibits bacterial enzyme * (dihydrofolic acid reductase), which is required in the conversaion of dihydrofolic acid to tetrafolic acid
  • Hence inhibits purine and DNA synthesis *
  • Less efficient in inhibiting mammalian dihydrofolic acid reductase

*needed to pass

91
Q

What is the rationale for combining trimethoprim with sulfonamides?

A

Enhanced effect * due to antibacterial synergism:
- Sulfonamides inhibit sequential steps * (acts at step before trimethoprim): inhibits dihydropteroate synthase involved in conversion of PABA to dihydrogolic acid
- As sequential steps are blocked in folate synthesis, usually bactericidal (when used alone both are bacteristatic)

*needed to pass

92
Q

How does resistance to trimethoprim occur?

A

1 to pass:
- Reduced cell permeability
- Increased production of enzyme DHF reductase
- Alteration in the enzyme with reduced binding of drug

93
Q

What is the mechanism of action of vancomycin?

A
  • Inhibits cell wall synthesis * by binding to peptidoglycan pentopeptide
  • This inhibits transglycosylase preventing cross-linking and weakening the cell membrane
  • Bactericidal *

*needed to pass

94
Q

What are the target organism ofor vancomycin?

A

2 to pass:
- Gram positive (Staph including MRSA, enterococci)
- Gram positive anaerobes (C. difficile)

95
Q

What clinical condition requires dose adjustment for vancomycin?

A

Renal impairment
Morbid obesity

96
Q

Describe the pharmacokinetics of penicillin

A

Absorption:
- Oral absorption impaired by food
Distribution:
- Wide
Elimination:
- Renal excretion and tubal secretion

ACEM Primary VIVA (45 decks)

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