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Pharm Exam 1 > Abx 3 > Flashcards

Abx 3 Flashcards

1
Q

What are the two families of tetracyclines and what are their members?

A
  1. Tetra-, oxytetra-, and chlortetracycline (older water soluble drugs)
  2. Doxycycline and minocycline (newer drugs; commonly used in small animal medicine)
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2
Q

Are tetracyclines time dependent or concentration dependent? How does that affect the way the drugs are dosed?

A

-Time dependent; they need to be dosed more frequently

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3
Q

Are tetracyclines considered broad spectrum or narrow spectrum?

A

-Broad spectrum

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4
Q

Are tetracyclines bactericidal or bacteriostatic?

A

Bacteriostatic (are -cidal when higher doses are used)

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5
Q

Which tetracycline member is preferred to be used in large animal because of cost and availability of FDA approved products?

A

Oyxtetracycline is preferred over tetracycline for use in food animal medicine.

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6
Q

Which tetracycline member is preferred for use in small animal medicine?

A

-Doxycycline has largely replaced tetracycline and oxyetetracycline in small animal medicine due to its broader spectrum and greater ability to penetrate barriers

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7
Q

What is the primary target for the action of tetracycline family of drugs?

What does it do there?

A

Primary Target: Bacterial ribosomes (30s unit)
•MOA:
- disrupts the binding of tRNA to the mRNA copy –> Bacterial protein synthesis is disrupted (bacteriostatic action).
- Some protein production still occurs.
- It does not disrupt it so extensively that the bacterial cell dies.–> reduced ability

Secondary Targets: Bacterial ribosomes (50s unit)
•MOA:
- drug disrupts the bacterial cell membrane integrity allowing more drug in and electrolytes out.

** At high enough concentrations, the drug can disrupt mammalian cell protein synthesis!

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8
Q

What is the mechanism by which bacteria have resistance to most tetracyclines?
How does it involve the bacterial genome?

A

-Tetracyclines enter bacteria→combine with Mg++ ion→tetracycline-Mg complex removes inhibition on gene that codes for proteins that forms an efflux pump→tetracycline is actively pumped from the bacteria (unable to significantly disrupt protein synthesis

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9
Q

What is the preferred route of administration for the older tetracyclines: tetracycline, oxytetracycline, and chlortetracycline?
What is the problem with giving these drugs PO?

A

Preferred route: IV or IM
– Can be given PO and absorbed on an empty stomach! However, don’t give PO with food.

• food –> reduce bioavailability by 50%
- the drugs chelate with polyvalent cations (Ca++, M++, Fe++, Al+++)→chelated tetracycline precipitates out of solution and is NOT absorbed!

•Ex: Dairy products (Ca++) given PO (e.g. nursing calves) will precipitate out tetracycline

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10
Q

Besides dairy products, what other drugs, compounds or products should tetracyclines (especially the older ones) NOT being given PO with?
How do they need to be given if tetracycline and any of these drugs must be used PO?

A 
Don’t give the following with tetracyclines PO:
•	Oral iron supplements (Fe++)
•	Sucralfate
•	Kaopectate
•	Pepto Bismol
•	Antacids (Ca++, Al+++, Mg++)

Alternative: if must be given together PO, give the tetracycline 1st, wait 2 hours, and then give the chelating agent

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11
Q

Why are tetracyclines used for growth promotion not simultaneously good for controlling bacterial infections?

A
  • Low dose tetracyclines are used for growth promotion in livestock and poultry.
  • Growth promotion effect is thought to be the result of local effect within the lumen of the GI tract. Lack of absorption is likely due to more ionized state of drug while IN the GI tract.
  • amount absorbed systemically is well below MIC for anything but the most susceptible bacteria found in infections.
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12
Q

How do the different families of the tetracycline class differ in their ability to be absorbed from the GI tract with or without food?

What is the mechanism by which food can decrease the bioavailability of PO administered tetracycline and oxytetracycline?

A
  • Doxycycline and Minocycline do NOT have the same degree of chelation as the older family of drugs.
  • Absorption PO of doxy- and minocycline is much better even in the presence of food or Ca++, Mg++, etc. because the drugs are not as ionized in the GI tract like tetracycline and oxytet.
  • Bioavailablity is 90-100% in humans and monogastric veterinary patients (90-100% makes it to systemic circulation)
  • Less well absorbed in diets with high fiber because fiber diets chelate more (equine)
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13
Q

List the three groups of intracellular pathogens against which tetracyclines are most commonly used.
In addition to the intracellular pathogens, what other group of bacteria (such as those found in leptospirosis) are tetracyclines used?

A

Effective against intracellular pathogens
• Mycoplasma
• Rickettsia
• Chylamydia

  • Also effective against spirochetes (leptospirosis)
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14
Q

Are tetracyclines as a group effective against Pseudomonas? Are they effective against anaerobes?

A

o Not effective against most anaerobes

o Does NOT get Pseudomonas

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15
Q

What is the agent of Lyme disease?
What kind of an organism is it?
Which tetracycline family member is one of the key drugs indicated for treatment of Lyme disease?
Why would it be better than oxytetracycline?

A

o Agent = Borrelia burgdorferi, a spirochete.
o CNS signs of Lyme disease are treated with doxycycline.
o Doxy penetrates CNS better than oxytetracycline because it is more lipophilic and can better penetrate tissue barriers.

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16
Q

Why can tetracyclines kill mycoplasma organisms when beta lactams cannot?

A
  • Mycoplasma doesn’t have a cell wall (nothing for beta lactam to disrupt!)
  • Tetracyclines are very lipophilic so readily passes into organism and accumulates
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17
Q

What is the organism that causes Rocky Mt. Spotted Fever?
What kind of organism is it?
Why are tetracyclines effective in killing this organism?

A
  • Rickettsia = intracellular organisms

- Tetracyclines penetrate cells to reach pathogen and disrupt Rickettsia life cycle.

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18
Q

What organism causes chlamydia in birds? What is the treatment of choice?

A
  • Chylamydophila psittaci = intracellular organism

- Doxycycline treats Chlamydia in birds.

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19
Q

What advantage do tetracyclines have in treating respiratory infections that beta lactams and aminoglycosides do not?

A
  • Tetracyclines accumulate in secretions

- It is delivered directly to the bacteria, while most drugs do not reach the surface of the airway.

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20
Q

Why have tetracyclines been used in the past to try to treat epiphora (red stain in white dogs)?

A
  • Tetracyclines have been used to chelate iron in tears to reduce epiphora stain. The oxidized iron in the tears stains the hair
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21
Q

Why is oxytetracycline used to treat BRD?

A

-Oxytet- accumulates at high concentrations in respiratory secretions and penetrates the lung parenchyma.
LA, Liquamycin, 200 formulation oxytet- provides 24 hours of drug concentrations above the MIC (may get 3-5 days for some pathogens).

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22
Q

What is the basis for saying that tetracyclines can reduce some inflammation?

A
  • Tetracyclines concentrate in neutrophils.
  • It reduces neutrophil chemotaxis and movement of neutrophils into area of infection or inflammation.
  • Less cellular destruction occurs, therefore, less inflammation occurs.
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23
Q

Why is doxycycline advocated by some as an adjunct treatment for heartworm disease in dogs?

A
  • Doxy is advocated to kill Wolbachia
    - an organism that lives within adult canine heartworms (Dirofilaria immitis) & needed for D. immitis to survive.
  • Wolbachia surface proteins (WSP)
    - liberated at time of adult heartworm death –> dangerous inflammatory response in the lungs.
24
Q

Why isn’t doxycycline universally accepted as a treatment adjunct for heartworm disease?

A
  • Additional 4 week doxy therapy = heartworm pathology progresses (even without the WSP) versus elimination of WSP and less inflammation at time of adulticide treatment.
25
Q

Why might tetracycline PO cause equine diarrhea?

A

-Equine + oral tetracycline –> overgrowth and proliferation of Salmonella and Clostridium perfringens –> severe enteritis.

26
Q

What is the problem with oral doxycycline and cats?

A
  • become LODGED IN THE ESOPHAGUS –> erosions.
  • As the drug interacts with saliva, it can cause perforations in the esophagus.
  • Most commonly found with DOXYCYCLINE HYCLATE formulation.
  • Must insure cats get enough water to flush medication.
27
Q

How does tetracycline produce brown teeth?
What part of the tooth is affected?
Administration of tetracycline at what age of animal is likely to cause this?

A
  • Tetracycline and oxytetracycline
  • -> bind to calcium in developing bones and teeth
  • When adult teeth are being formed the tetracycline incorporates into the dentin and turn teeth yellow/brown.
  • not a problem with doxy- and minocycline
28
Q

What animal should doxycycline never be used IV?

A
  • horses
  • Doxy is thought to chelate calcium disrupting normal cardiac rhythm.
  • -> fatal arrhythmias
    • even at fairly low doses.
  • not seen with PO doxycycline in horses.
29
Q

Why might tetracyclines be a pretty good antibiotic for treatment of a urinary tract infection?

A

-Tetra- oxy- and chlortetra- = excreted mostly by the kidney
–> achieve high concentrations in urine
– may be effective against “resistant” organisms!

30
Q

Why are oxytetracycline and tetracycline concentrations in the body affected more by renal disease or renal insufficiency than minocycline or doxycycline?

A
  • Renal failure patients or older patients may accumulate older tetracyclines to toxic levels.
  • Doxy- and minocycline = metabolized by liver and excreted into feces
    - used in patients with renal compromise.
31
Q

Name five aminoglycosides used in veterinary medicine.

A

Recognize by –micin and –mycin
• Gentamicin
• Amikacin (does not follow the –mycin rule)
• Kanamycin
• Tobramycin (ophthalmic use)
• Neomycin (large animal feed additive -topical use)

32
Q

What is the broad type of bacteria against which aminoglycosides are used?

A
  • Gram negative aerobes only
33
Q

What is the target of aminoglycoside activity against the bacteria?
How is it different than tetracyclines?

A

Target:
- 30s ribosome (same as tetracylines)
Action:
- Disrupts mRNA linking with 30s ribosome and terminates protein formation

** Aminoglycosides are BACTERICIDIAL and have a POST-ANTIBIOTIC EFFECT, while the tetracyclines are bacteriostatic and time dependent.

34
Q

Why are aminoglycosides ineffective against anaerobic bacteria?

A
  • diffuse through the outer membrane layer of gram negative through porins.
  • In PERIPLASMIC SPACE, drug is actively transported BY AN OXYGEN DEPENDENT MECHANISM in the bacterium to reach the ribosome.
35
Q

If aminoglycosides are typically ionized at body pH, how are they able to reach their target site within Gram negative bacteria?

A
  • they are totally dependent upon carriers or porins to get through barriers, like the phospholipid bilayer.
36
Q

What is the post-antibiotic effect of aminoglycosides?

Why is this a good thing?

A
  • concentration dependent.
    - must reach a high spike concentration to be effective;
    - however, you don’t have to maintain the drug above the MIC for a long time.
  • Typically, you want to reach a concentration 8-10 times the MIC –> slowly drops off!

*** can be given SID, unlike most time dependent drugs that need to be given BID or TID.

37
Q

Are aminoglycosides concentration dependent or time dependent antimicrobials?

A

-Concentration dependent

38
Q

Which is typically given more frequently, a time dependent antimicrobial or a concentration dependent antimicrobial? Which is given more frequently: beta lactams or aminoglycosides?

A

-Time dependent drugs, like the beta lactams, are given more frequently

39
Q

What 2 other classes of antimicrobials besides aminoglycosides are considered when facing a nasty Gram negative bacterial infection?

A

o Fluoroquinolones

o 3rd generation cephalosporins

40
Q

Which is the common “go to” aminoglycoside in small animal medicine?

A
  • Amikacin
  • due to its broader spectrum than gentamicin and possibly less toxicity.
  • thought to have less resistance.
41
Q

Which has a broader spectrum of activity: gentamicin or amikacin?

A

-Amikacin

42
Q

For what purpose is tobramycin mostly used for in veterinary medicine?

A
  • Ophthalmic medication
43
Q

What is the most nephrotoxic aminoglycoside?
Why doesn’t it kill more kidneys in spite of its wide-spread use?
What is it used to treat?

A
  • Neomycin
    • yet it produces the least amount of toxicosis of all of the aminoglycosides.
    • not absorbed systemically
      - very hydrophilic

It is primarily used topically as a first aide cream usually combined with bacitracin and polymyxin.

-Neomycin and oxytetracycline used in feed for calf scours.

44
Q

What is meant by a “narrow therapeutic index”?

A

-The interval between the MIC and toxic level are very narrow

45
Q

How good are aminoglycosides at penetrating the CSF or CNS? Why?

A
  • Poor! Find another drug!

- bc its hydrophilic

46
Q

Why are aminoglycosides used as aerosols or in nebulizers?

A
  • They are distributed to the bacteria on the surface of the airways faster.
  • If given systemically, they will not reach the pulmonary infections.
47
Q

What is the sole route of elimination for aminoglycosides?
What role does GFR and active transport by the renal tubule cells have to do with aminoglycoside elimination?
How great is passive diffusion as a mechanism for aminoglycoside transport across a membrane?

A
  • kidney
  • excreted unmetabolized
    - excreted in active form
  • It is primarily removed by GFR to achieve therapeutic concentration in the urine.
    • Renal tubular cells
      • take up drug by active transport
      • hydrophilic drugs –> do not easily diffuse back out of the renal tubular cells
      • Lysosomes in the tubular cells will pick up the drug, lyse, release their enzymes to kill the cells
48
Q

What clinical signs would appear in an animal with aminoglycoside ototoxicosis?

A
  • High accumulations of drug within the perilymph and endolymph of the inner ear is toxic to sensitive hair cells in cochlea and vestibular labyrinth
    • Toxicity in cochlea hair cells → deafness
    • Toxicity in vestibular labyrinth hair cells → balance issues (ataxia, staggering, head tilt, nystagmus, circling)
    • Cells don’t die quietly; discharge as die → send wrong signals to brain
49
Q

What is the physiological reason that the renal tubule cells and the cells of the inner ear are more prone to accumulation of aminoglycosides?

A
  • Cationic AG’s –> attracted to anionic cell membrane phospholipids and actively transported into cells.
    - “aminoglycoside receptor sites” or phosphatidylinositol
  • Renal cortex and cochlear tissue have disproportionately high amounts of phosphatidylinositol that can bind aminoglycosides, so these tissues accumulate more of the drug than other tissues.
50
Q

What is the “proposed” mechanism by which aminoglycosides injure the renal tubular cells?

A
  • Nephrotoxcity due to antibiotic accumulation within PCT cell’s lysosomes
  • Not entirely understood, but thought that lysosomes are damaged and begin to leak lysosomal enzymes
  • Early renal damage detected as proteinuria and presence of casts (before full loss of function to 75% when BUN and creatinine increases)
    o Can be reversible if caught early
51
Q

If we want to lower the risk for nephrotoxicosis in a patient receiving aminoglycosides, what do we do to the dose regimen? Do we decrease the dose?

A
  • extend dose interval
    • do NOT ↓ dose (even in animals w/ renal failure)

• Allow enough time b/w doses of aminoglycosides for concentration to drop low enough in blood/plasma that drug diffuses out and enters cells as slower rate
• Get [aminoglycoside] in blood low enough for passive diffusion out of cells into blood
–> will also ↓ amount going into cells

52
Q

Why is a denuded skin area different than an intact skin area when it comes to topical administration of aminoglycosides?

A

If skin not intact → very easily absorbed → like giving drug systemically
—?
o Ex: Cat abscess – necrotic tissue
• Concern about Pseudomonas infection because of dead tissue
• Aminoglycosides given systemically will NOT reach site of infection because there is no blood supply to dead tissue. The drugs do not diffuse through barriers.
• Use topical application to get drug to infection site – less systemic absorption and little risk of nephro- or ototoxic effects
• Poultice applied 12 hrs each day (like giving an infusion for 12hrs) → got ↑ BUN/creatinine after 4 days b/c skin must be intact to prevent systemic absorption

53
Q

Why is a CRI (constant rate infusion – “IV drip”) a bad idea in aminoglycosides?

A
  • narrow therapeutic range.
  • CRI will induce toxicity.

Using a low dose to avoid nephrotoxicity is ineffective because need that high spike!
o Ex: using a low dose amikacin CRI for a gram negative septicemia (from a GI perforation from a FB)
→don’t want a CRI, want a high spike!

54
Q

• Why is a goopy, cocker spaniel ear still a potential area that aminoglycosides might be ineffective even if the ear canal is still open and provides an aerobic environment?

A

-Owner treats BID but therapy fails
→ cellular debris and pus are dead cells and lysed cell parts
→ drug combines with the ribosomes of the dead cells/cellular debris (pus)
→pus accumulates the drug so it is not effective in the ear

•Need to clean ears before treating with medication

55
Q

How well, compared to beta lactams, do tetracyclines as whole penetrate body compartments?

How is the ability to penetrate membrane barriers different for the two tetracycline groups?

What two organs, beside the brain, have significant membrane barriers to drug distribution?

A

As a group tetracyclines are distributed to:
• Kidney
• Lung parenchyma, pleural fluid, bronchial secretions
• Sputum, saliva
• Synovial fluid
• Fluid within eye globe
• Prostate

  • Penetrability to CNS, prostate, and eye varies between tetracycline families
  • Tetracyline and oxytet are mostly non-ionized at body pH 7.4 = lipophilic (more than beta-lactams or aminoglycosides). This means they can get through cell membranes and penetrate tissue barriers well.
  • Doxycycline and minocycline are lipophilic and penetrate better than oxy and tet.

Pharm Exam 1 (6 decks)

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