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Pharmacology - Antibiotics Flashcards

1
Q

Name 4 major classes of antibiotics

A
  1. Beta lactams
  2. Aminoglycosides
  3. Fluoroquinolones
  4. Tetracyclines
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2
Q

What is empirical therapy?

A
  • Identify key elements of disease/infection
  • Make a tentative diagnosis
  • Initiate therapy –> usually broad spec (tier 1)
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3
Q

Compare empirical therapy vs evidence based therapy

A

Empirical: use clinical signs to make tentative diagnosis, usually use broad spec drugs

Evidence based: obtain diagnosis, identify bacteria, susceptibility tests. More likely to use tier 2 drugs

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4
Q

Compare time-dependent vs concentration-dependent antibiotics

A

Time-dependent: important parameter is T > MIC; aim to maintain drug conc above the MIC. Req multiple smaller doses e.g beta lactams

Conc-dependent: main parameter is Cmax:MIC ratio; aim to achieve higher plasma conc. Req one large dose e.g fluoroquinolones, aminoglycosides

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5
Q

Give two examples of aminoglycosides

A

Streptomycin, Gentamicin, Neomycin

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6
Q

Aminoglycosides have good activity against …..

A

Gram neg aerobes e.g E.coli, Pseudomonas a.

Moderate to low against gram pos aerobes, penicillinase staph

No useful activity against obligate anaerobes

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7
Q

Describe the mechanism of action of Aminoglycosides

A

Irreversible inhibition of protein synth by irreversible binding to 30S ribsomal subunit

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8
Q

Can you use Aminoglycosides for food animals?

A

No

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9
Q

Describe some of the pharmacokinetic features of aminoglycosides

A
  • Narrow therapeutic range
  • Poor oral abs if GI mucosa healthy
  • Admin parenterally or intramammary
  • Poor dist in lipophilic tissue
  • Poor CNS or eye penetration
  • Eliminated primarily by glomerular filtration
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10
Q

Are aminoglycosides conc or time dependent?

A

Conc dependent

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11
Q

Describe the common adverse effects and toxicity of Aminoglycosides

A

Accumulation in endolymph and phospholipids causing renal and ototoxicity

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12
Q

List two commonly used Fluoroquinolones

A

Enrofloxacin, Marbofloxacin

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13
Q

Describe the mechanism of action of Fluoroquinolones

A
  • Bind bacterial DNA gyrase (topoisomerase II and IV), the enzyme which controls supercoiling of bacterial DNA
  • Leads to stabilisation of DNA-DNA gyrase complex –> broken strands cannot be released –> DNA rep blocked
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14
Q

Describe the spectrum of activity of Fluoroquinolones

A
  • Very good against gram neg aerobes and penicillinase staph
  • Moderate - low against gram pos aerobes
  • No useful activity against obligate anaerobes
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15
Q

What tier of drug are Fluoroquinolones?

A

Tier 2 - not for routine non-life threatening infections

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16
Q

List some of the indications for Fluoroquinolones

A
  • Recurrent UTIs
  • Bacterial prostatitis in dogs
  • Osteomyelitis due to gram neg bacteria
  • Deep granulomatous pyoderma
  • Serious resp tract infections
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17
Q

List some of the pharmacokinetic properties of Fluoroquinolones

A
  • good to moderate oral abs but foods may slow abs
  • low protein binding, highly lipophilic
  • good dist to most tissues
  • conc-dependent w/ strong post antibiotic effect
  • bigger vol of dist in lipophilic tissue e.g prostate, skin, CSF, bone
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18
Q

Describe the most common adverse effects of Fluoroquinolones

A

Retinal degeneration and interfering with cartilage and bone development

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19
Q

Why can Metronidazole not be used for food animals?

A

Has very good distribution

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20
Q

Describe the mechanism of action of Metronidazole

A
  • Diffuse into cell and then reduced to a free radical under anaerobic conditions
  • free radicals interfere w/ DNA causing breakage, destabilisation and cell death
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21
Q

Describe the spectrum of activity of Metronidazole

A
  • Good against ANAEROBES!
  • Also effective against select parasites e.g Giardia, Entamoeba, Trichomonas
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22
Q

True or False: Metronidazole is the drug of choice for post surgical peritonitis and abscess formation due to anaerobic bacteria in dairy cattle

A

False - cannot be used for food animals

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23
Q

Name three commonly used Potentiated Sulfonamides

A

Sulfamethoxine
Sulfamethoxazole
Sulfadiazine

24
Q

Can Potentiated Sulfonamides be used for food animals?

25
Describe the mechanism of action of Potentiated Sulfonamides
Bind to active site of dihydropteroate synthetase in place of PABA which inhibits folic acid synth
26
What tier are Potentiated Sulfonamides?
Tier 1
27
Which two classes of compounds are highly synergistic with Potentiated Sulfonamides, lowering the MIC against bacterial infections several fold?
Trimethoprim and Ormetoprim
28
List some of the clinical indications for Potentiated Sulfonamides
Can be used in all animals in infections incl: - resp tract - urinary tract - wound infections - pyodermas - protozoal infection
29
Describe some of the pharmacokinetic properties of Potentiated Sulfonamides
- Oral, parenteral, topical - Well abs and dist widely
30
What are the most common adverse effects of Potentiated Sulfonamides?
Crystalluria and renal tubule blockage, keratoconjunctivitis, hematopoietic toxicity
31
Name 3 commonly used Macrolides
Erythromycin, Spiramycin, Tulathromycin
32
Describe the mechanism of action of Macrolides
Inhibit protein synth by reversibly binding to 50S subunit of bacterial ribosome. Accumulates in leukocytes and gets transported to site of infection
33
Describe the spectrum of activity of Macrolides
Gram pos plus Campy, Pastuerlla, Chlamydophila, etc
34
Which Macrolide may be used as a tier 1 drug in large animals and poultry?
Erythromycin
35
Describe some of the pharmacokinetic properties of Macrolides
- Erythromycin is destroyed by stomach acid, abs inhibited by food - Dist well into most tissues except CSF. Conc in lungs - Metabolism hepatic biliary
36
List some of the adverse effects of Macrolides
- Muscle paralysis w/ some anaesthetics - GI upset --> diarrhoea - Hypothermia - Painful IM injection - Cardiac effects in horses, pigs, primates
37
Describe the mechanism of action of Lincosamides
Inhibit bacterial synth by reversibly binding to 50S ribosomal subunit
38
Give 2 examples of Lincosamides
Clindamycin, Lincomycin
39
Describe the spectrum of activity of Lincosamides
Clindamycin has high activity against gram pos anaerobes, toxoplasma, neospora but spec similar to macrolides
40
What tier are Lincosamides? What are some of their clinical uses?
Tier 2/3 - Bone infections - Periodontal disease - Upper resp tract - Skin
41
Gram pos anaerobic infections in deep wounds, abscesses and those causing osteomyelitis are often difficult to treat. Amongst the macrolides and lincosamides which drug has excellent dist and efficacy in these types of lesions?
Clindamycin
42
True or False: Clindamycin should not be used concomitantly with chloramphenicol and macrolides as they antagonise each other at the site of action (50S ribosomal subunit)
True
43
What class of drugs are good for treating resp tract infections as they accumulate in higher conc in lungs?
Macrolides e.g Erythromycin
44
Rifampicin exhibits excellent synergy with which other drug?
Erythromycin
45
Name a synthetic long-acting and a natural short-acting Tetracycline
Doxycycline, Oxytetracycline
46
Describe the spectrum of activity of Tetracyclines
- Gram pos and neg - VERY broad spec - 1st tier in animals only
47
Describe some of the pharmacokinetic properties of Tetracyclines
- Can be admin orally, systemically, topically - Only oxytet is non-irritant to tissue and can be given IM or SC - Doxy most lipophilic - Moderate tissue dist --> can cross blood-placenta barrier - Time dependent
48
Describe the mode of action of Tetracyclines
Chelate w/ Mg --> periplasmic space --> dissociate from Mg --> diffuse across membrane --> chelate w/ Mg to enable binding to 30S ribosome (reversible) Binding to 30S subunit prevents binding of aminoacyl-tRNA to mRNA-ribosome complex
49
List 9 adverse effects of Tetracyclines
1. Dysbiosis due to being broad spec 2. Excretion in active form in urine and faeces 3. Env contamination with increased resistance in env bacteria 4. Bind to new mineral deposits in bone and enamel --> make weak 5. Unstable in light 6. IV solutions diluted to avoid cardiovascular collapse in horses 7. Photosensitisation (humans) 8. Hepatotoxicity in high doses 9. Tablets can cause oesophageal erosion in cats
50
What is the main mechanism of resistance bacteria have to tetracyclines?
Tetracycline efflux: pumps tet straight out of cell
51
What are the two types of Beta-Lactam drugs?
Penicillins, Cephalosporins
52
What is the mechanism of action of Beta-Lactam drugs?
Prevent cross-linking (transpeptidation) of peptidoglycan layer
53
Are Beta-Lactam drugs time or conc-dependent?
Time-dependent
54
How can the T1/2 of Beta-Lactam drugs be extended?
Depot or protein-bound formulations
55
What compound may often be given with Beta-Lactam drugs?
Clavulanic acid
56
List 4 adverse effect of Beta-Lactam drugs
1. Dysbiosis in GIT --> diarrhoea 2. Hypersensitivity 3. False pos urine glucose 4. Overdose can cause renal failure

TV3001 (8 decks)

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