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Pharmacology > Antibiotics > Flashcards

Antibiotics Flashcards

1
Q

Cell wall structure of:

  1. Gram negative bacteria
  2. Gram positive bacteria
A
  1. lipid bilayer (lipopolysaccharides are present), thin peptidoglycan layer
  2. no lipid bilayer (no lipopolysaccharides are present), thick peptidoglycan layer
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2
Q

Antibiotic resistance

-4 ways it can happen

A
  1. Efflux
  2. Immunity and Bypass
  3. Target modification
  4. Inactivating enzymes
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3
Q

MIC vs. MBC

A

MIC –> the lowest concentration of an anti-bactericidal agent necessary to inhibit visible growth

MBC –> the minimum concentration of an anti-bactericidal agent that results in bacterial death

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4
Q

Vertical vs. Horizontal transmission/ resistance

A

Vertical - bacteria could develop by itself a defensive mechanism due to DNA mutation.

Horizontal - bacteria could “talk” to each other and transfer plasmids (the gene which will have the protective info against a particular antibiotic)

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5
Q

Concentration dependent antibiotics

  • explanation
  • names
A
  • a much higher concentration than MIC is necessary at the binding site
  • Quinolones, Aminoglycosides, Azithromycin, Ketolides
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6
Q

Time dependent antibiotics

  • explanation
  • names
A
  • need higher amount in blood for a long period of time

- Penicillins, Cephalosporins, Macrolides, Clindamycin

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7
Q

Types of antibiotics

A

Bactericidal –> kill bacteria
-the ratio of MBC to MIC is <4

Bacteriostatic –> stop the growth, slow killing
-the ratio of MBC to MIC is >4

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8
Q

Resistance to antibiotics (6)

A 
Synthesis of beta-lactamases 
Decreased uptake by the bacterium 
Alteration of the drug-binding site 
Intra-cellular enzymatic activation 
Mutation in DNA gyrase 
Increased elimination by the bacterium
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9
Q

Beta Lactam antibiotics

-only names

A

Penicillins
Cephalosporins
Carbapenems
Monobactams

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10
Q

B-lactamase inhibitors

  • names (2)
  • characteristics (5)
A

-Clavulanic acid, Sulbactam

  • weak anti-bacterial action
  • inhibitors of many but not all bacterial b lactamases and can protect hydrolyzable penicillins from inactivation by these enzymes
  • extends the spectrum of a penicillin
  • empirical therapy
  • only in fixed combinations: ampicillin-sulbactam, amoxicillin-clavulanic acid
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11
Q

What does MRSA positive means?

A

it means that staphylococcus aures is resistant to Methicillin = do not use anti-staphyloccocal penicillins

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12
Q

Penicillin G (Penicillin V oral)

  • clinical use
  • mechanism of action
  • basis of resistance
A
  • meningitis, endocarditis, skin and soft tissue infections
  • bactericidal - inhibit bacterial growth by interfering with the transpeptidation reaction, halts peptidoglycan synthesis = cell dies
  • inactivation of antibiotic by beta lactamase –> modification of target PBPs –> impaired oenetration of drug to target PBPs –> antibiotic efflux
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13
Q

Penicillin G (Penicillin V oral)

  • pharmacokinetics (5)
  • unwanted effects (3)
A
  • activity against sexual transmitted diseases
  • absorption impaired by food
  • excreted by the kidneys
  • dont cross blood brain barrier but if meninges are inflamed readily cross and reach therapeutically concentration in the CSF
  • oxacillin excreted by the kidneys and with bile
  • hypersensitivity
  • oxacillin hepatitis
  • ampicillin pseudomembranous colitis
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14
Q

Cephalosporins

-names

A
  • more stable to many bacterial beta lactamases
  • broader spectrum of activity
  • First generation – Cefazolin
  • Second generation – Cefuroxime
  • Third generation
  • Fourth generation – Cefepime
  • Fifth generation
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15
Q

Why aren’t fourth and fifth generation cephalosporins always used?

A

because they have a really broad spectrum, they are useful in severe cases where the exact cause is unknown
they are not used all the time to prevent resistance

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16
Q

Cephalosporins

  • indications
  • mechanism of action
A

First generation - skin and soft tissue infections; prophylaxis before surgery
Second generation - respiratory infections
Third generation - meningitis, respiratory, abdominal infections

-bactericidal

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17
Q

Cephalosporins

  • pharmacokinetics
  • unwanted effects
A
  • all are excreted via the kidneys except for Ceftriaxone
  • third generation achieve sufficient levels in the cerebrospinal fluid –> useful in meningitis

-hypersensitivity

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18
Q

Carbapenems

  • name
  • mechanism of action
  • pharmacokinetics
  • unwanted effects
A
  • Imepenem
  • resistant to all beta lactamases
  • bactericidal
  • renal excretion
  • seizures, nausea, vomiting, reaction at the infusion site
  • patients allergic to penicillins may be allergic to carbapenems
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19
Q

Glycopeptides antibiotics

  • name
  • mechanism of action
  • pharmacokinetics
A
  • Vancomycin
  • bactericidal, inhibits cell wall synthesis
  • poorly absorbed from the GI tract, given orally only for the treatment of C-difficile
  • widely distributed, renal excretion
20
Q

in Immuno-supressed patients, we should start with broad spectrum antibiotics, usually 2 of them. How are they called?

A

Carbapenems

Vancomycin

21
Q

Vancomycin

-unwanted effects

A
  • nephrotoxicity
  • “red man” syndrome
  • infusion related flushing is caused by the release of histamine

Usually it is given together with high amount of glucose solution during at least 30min in order to avoid possible reactions to the blood vessel and histamine release

22
Q

Polymyxins

  • name
  • mechanism of action
  • pharmacokinetics
  • unwanted effects
A
  • Polymyxin E – Colistin
  • bactericidal, interact with bacterial outer membrane, by displacing bacterial counter ions in the lipopolysaccharide
  • eliminated by kidneys and non-renal mechanisms
  • nephrotoxicity, neurotoxicity
23
Q

Tetracyclines

  • name
  • uses (6)
A

-Doxycycline

  • good drug to be used in respiratory infections where the cause is still unknown
  • anti-malaria
  • first line for Lyme disease
  • also used for H.pylori infection
  • chlamydial infections
  • mycoplasm pneumonia
24
Q

Tetracyclines

  • mechanism of action
  • basis of resistance
  • unwanted effects
A
  • bacteriostatic, inhibit protein synthesis, bind REVERSIBLY to bacterial 30S ribosome subunit
  • common mechanisms
  • bony structures and teeth because it bound to calcium
  • should be avoided in pregnancy and in children younger than 8 years
  • sensitivity to sunlight or ultraviolet light
25
Q

Tetracyclines

  • pharmacokinetics
  • drug interations
A
  • oral absorption impaired by food (cations could form complexes and decrease drug absorption)
  • Doxycycline is not significantly affected by food and it is eliminated by non-renal mechanisms

-chronic alcohol use may shorten the 1/2 life of doxycycline

26
Q

Aminoglycosides

  • names
  • mechanism of action
  • basis of resistance
A

-Streptomycin, Amikacin, Gentamicin

  • bactericidal
  • inhibit protein synthesis, IRREVERSIBLY bind to 30s ribosomal subunit

-common mechanisms

27
Q

Aminoglycosides

-pharmacokinetics (6)

A
  • do not cross blood brain barrier
  • concentration dependent
  • single daily doses
  • kidney clearance, excretion is directly proportional to creatinine clearance
  • together with a cell wall active antibiotic exhibit synergistic killing against certain bacteria
  • post-antibiotic effect
28
Q

Aminoglycosides (6)

-unwanted effects

A
  • when given in a time dependent manner, the risk of side effects are bigger
  • nephrotoxic
  • ototoxic
  • could cause muscle paralysis
  • amikacin –> auditory damage
  • streptomycin, gentamicin –> vestibulotoxic
29
Q

Macrolides

  • names
  • use (4)
A

-Erythromycin, Clarithromycin, Azithromycin

  • first line - atypical pneumonia and h. pylori infectitons
  • chlamydial infections
  • mycoplasm pneumonia
  • Legionnaire’s disease
30
Q

Macrolides

  • mechanism of action
  • basis of resistance
A
  • bacteriostatic
  • inhibits protein synthesis –> bind to the 50s ribosome subunit

-common mechanisms

31
Q

Pharmacokinetics of:

  1. Erythromycin
  2. Clarithromycin
  3. Azithromycin
A
  1. mainly excreted in bile, food interferes with absorption
  2. eliminated in urine and metabolized in the liver, improved acid stability and oral absorption
  3. rapidly absorbed and well tolerated orally, high activity against chlamydia sp.
32
Q

Drug interactions and unwanted effects:

  1. Erythromycin
  2. Clarithromycin
  3. Azithromycin
A
  1. inhibit cytochrome p450 enzymes; increase the serum concentration of many drugs
    - direct stimulation of gut motility
  2. same as with erythromycin
  3. does not inactivate cytochrome p450 enzymes, free of the drug interactions

prolong QT interval

33
Q

Lincosamides

-name

A

-Clindamycin

34
Q

Clindamycin

  • mechanism of action
  • basis of resistance
A
  • bacteriostatic
  • inhibits bacterial protein synthesis –> 50s ribosome subunit

-common mechanisms

35
Q

Clindamycin

  • pharmacokinetics
  • unwanted effects
A
  • penetrates well into most tissues except for cerebrospinal fluid is an exception
  • metabolized by the liver
  • usually used when infection is located in the upper body parts

-C-difficile

36
Q

Oxazolidinones

  • names
  • mechanism of action
  • pharmacokinetics
  • unwanted effects
A
  • Linezolid
  • bacteriostatic, inhibits protein synthesis
  • 100% bioavailability after oral administration, metabolized by oxidative metabolism
  • optic and peripheral neuropathy
37
Q

Fluoroquinolones

-names

A
  • Second generation – Ciprofloxacin, Norfloxacin
  • Fourth generation – Moxifloxacin

from first to fourth generation –> increased activity against gram positive, gram negative and anaerobic activity

38
Q

Ciprofloxacin, Norfloxacin, Moxifloxacin

-therapeutic indications

A

Ciprofloxacin, Norfloxacin –> first line drugs for urinary tract infections

Moxifloxacin –> anaerobic infections

also –> pneumonia: atypical (Legionella)

39
Q

Fluoroquinolones

  • mechanism of action
  • basis of resistance
  • pharmacokinetics
  • unwanted effects
A
  • bactericidal
  • block bacterial DNA synthesis by inhibiting bacterial DNA gyrase

-common mechanism

  • renal clearance except for moxifloxacin
  • well absorbed, absorption can be impaired by cations, antacids, milk
  • photo-sensitivity
  • tendonitis, risk of tendon rupture
40
Q

Sulfonamides (sulfadiazine, sulfamethoxazole)

-indications

A
  • acute toxoplasmosis (first line)

- malaria

41
Q

Pyrimethamine; Trimethoprim

-indications

A
  • prostate and urinary tract infections
  • respiratory infections
  • malaria
42
Q

Sulfadiazine and Pyrimethamine, Sulfamethoxazole and Trimethoprim

  • mechanism of action
  • pharmacokinetics
  • unwanted effects
A
  • bacteriostatic, bactericidal with trimethoprim
  • bacteria cannot take folic acid, they synthesize it from aminobenzoid acid and the drugs inhibit it this process
  • excreted mainly by glomerular filtration
  • orally or topical

-hypersensitivity reacions, crystalluria, bone marrow depression

43
Q

Sulfamethoxazole and Trimethoprim

-indications

A
  • Pneumocystis Jiroveci Pneumonia
  • Respiratory infections
  • Prostate and urinary tract infections
44
Q

Trimethoprim

  • mechanism of action
  • pharmacokinetics
  • unwanted effects
A
  • bacteriostatic, bactericidal with sulfomanide
  • really useful to treat genitourinary tract infections
  • it is a weak base concentrates in prostatic fluid and in vaginal fluid, it has more anti-bacterial activity in prostatic and vaginal fluids than many other antimicrobial drugs
  • fever, rashes, leukopenia, diarrhea, hyperkalemia, hyponatremia
45
Q

Metronidazole

  • indications
  • mechanism of action
  • pharmacokinetics
  • unwanted effects
A

-amoebiasis, trichomoniasis, C. difficile

  • bactericidal
  • produces products that are toxic to anaerobic cells, metabolities are taken up into bacterial DNA
  • well absorbed after oral administration (bioavailability 90-100%)
  • should be avoided with alcohol
46
Q

Antibiotics could be used in pregnancy

A
  • Penicillin
  • Ampicillin
  • Amoxicillin
  • Clindamycin
  • Erythromycin
  • Nitrofurantoin
47
Q

Antibiotics contraindicated in pregnancy

A
  • Doxycycline
  • Streptomycin
  • Ciprofloxacin
  • Sulfonamides and trimethoprim

Pharmacology (29 decks)

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