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PY6010 > TDM - Gentamicin & Vancomycin > Flashcards

TDM - Gentamicin & Vancomycin Flashcards

1
Q

Difference between pharmacokinetics and pharmacodynamics

A

Pharmacokinetics focuses on measurement of the time course of the drug concentrations in serum and tissues (ADME).

Pharmacodynamics focuses on what the drug does to the body.

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2
Q

What is MIC?

A

The lowest concentration of an antibiotic that completely inhibits the growth of a microorganism in vitro.

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3
Q

What are the 3 pharmacodynamic properties of antibiotics that best describe killing activity?

A
  1. Time dependence
  2. Concentration dependence
  3. Persistent effects
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4
Q

Name 5 antibiotics that are concentration dependent

A
  • Aminoglycosides (gentamycin)
  • Metronidazole
  • Quinolones
  • Daptomycin
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5
Q

In concentration dependent antibiotics, which ratio on the pk/pd graph is the most important predictor in antibiotic efficacy?

A

Cmax : MIC

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6
Q

For aminoglycosides like gentamicin, what is the best Cmax:MIC ratio to prevent antibacterial resistance?

A

8 - 10

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7
Q

Name 3 time dependent antibiotics

A
  • Vancomycin
  • Beta Lactams
  • Clindamycin
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8
Q

What is the difference between time-dependent and concentration-dependent antibiotics?

A

Time dependent antibiotics exert optimal bactericidal effect when drug concentrations are maintained above the minimum inhibitory concentration (MIC).

Concentration-dependent antibiotics exert optimal bactericidal effect with increasing levels of drug.

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9
Q

In time dependent antibiotics, which ratio on the pk/pd graph is the most important predictor in antibiotic efficacy?

A

T > MIC

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10
Q

Which 2 antibiotics can be seen exerting maximum killing when their time above MIC is 70% of the dosing interval?

A

Beta lactams and erythromycin

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11
Q

Which antibiotic has mixed properties of time-dependent killing and moderate persistent effect?

A

Vancomycin

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12
Q

In practical terms, how can we avoid toxicity when giving drugs that we want at high peak levels?

A
  • Give short term of high peak levels
  • Maximise the time above MIC, so have steady levels with reduced peaks and higher troughs. This can be achieved by giving antibiotics by continues infusion.
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13
Q

List when TDM is useful

A
  • When drugs have a narrow therapeutic index
  • When multiple doses of aminoglycosides and glycopeptides are given
  • When giving itraconazole, posaconazole and voriconazole
  • TB meds if GI absorption is impairment
  • ARVs for treatment of HIV
  • Severe infection with renal impairment e.g. Daptomycin
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14
Q

For aminoglycosides like gentamicin, why is there no need for GI absorption?

A

Because it is given intravenously or intramuscularly or topically via ear drops.

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15
Q

Does Gentamicin target Gram-positive or Gram-negative bacteria?

A

Gram-negative

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16
Q

Is gentamicin water soluble?

A

yes

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17
Q
  1. Why is the volume of distribution of gentamicin less in adults than in children?
  2. Which other two groups have altered volume of distribution?
A
  1. Because children have a higher proportion of water per kg of body weight.
  2. Patients with ascites and pregnant women.
18
Q

When do we use a patient’s adjusted body weight when dealing with gentamicin?

A

For very obese patients because gentamicin does not penetrate fat well.
So when the patient’s body weight is 20-30% over their ideal body weight, we use their adjusted body weight.

19
Q

Where does gentamicin distribute?

A

Gentamicin is distributed in the biliary tract and the epithelial lining fluid which is a thin layer of fluid that covers the mucosa of the alveoli, the small airways and the large airways.

20
Q

Can you give gentamicin to a pregnant woman?

A

It should be avoided unless it is ESSENTIAL!!
This is because gentamicin crosses the placenta and cause ototoxicity (when a person develops hearing or balance problems due to a medicine) of the foetus.
If gentamicin is given to pregnant women, serum-aminoglycoside concentration monitoring is essential.

21
Q

Gentamicin is given to treat Gram-negative UTI because…

A

…they concentrate well in urine.

22
Q

What is the half-life of gentamicin in a normal renal function compared to an End-Stage Renal Failure?

A

2 - 3 hours in normal renal function

24 - 86 hours in ESRF

23
Q

Toxicity of gentamicin

A
  • Gentamicin can cause irreversible ototoxicity. It is rare (0.5 - 3% of patients develop ototoxicity).
  • Some people are more genetically prone to ototoxicity and it is thought to be due to a mitochondrial gene that confers the increased risk.
  • Patients with a family history of deafness should not be given gentamicin due to the irreversible ototoxicity even when the drug is within therapeutic range.
  • The half-life in the perilymph and endolymph of the inner ear is 5-6 times greater than in plasma and therefore progressive accumulation occurs.
  • Nephrotoxicity is usually reversible. In Acute Tubular Necrosis, there is no reduction in urinary output but creatinine clearance is reduced. Gentamicin levels will increase as the renal function decreases so if no dose adjustment is made, toxicity can worsen.
  • Gentamicin should be avoided in myasthenia gravis as it can impair neuromuscular transmission and cause clinically significant muscle weakness resulting in respiratory depression.
24
Q

Describe the administration of a single-dose or once-daily (OD) Gentamicin

A

5mg/kg infused over 60 minutes once daily

Single dose or once daily administration in patients without pre-existing renal impairment is as effective as multiple daily dosing.

A pre-dose level should be taken 18-24 hours before the next dose and aim for a trough level of < 1mg/L

25
Q

Advantages of single-dose / once daily administration of Gentamicin

A
  • High peaks are more effective in achieving bacterial kill.
  • There’s a long post-antibiotic effect and therefore it is not necessary to have levels above the MIC all day
  • There is a reduced risk of nephrotoxicity due to a wash-out period allowed by infrequent dosing.
  • There’s no greater risk of ototoxicity
  • Monitoring of levels is simpler
  • Less nursing time is required to administer the antibiotic
26
Q

What antibiotic can you give in combination with Gentamicin to treat Enterococci and Streptococci?

A

Beta-lactams

27
Q

Multiple Dose (MD) Gentamicin

A

3-5mg/kg per day every 8-12 hours intravenously infused over 20-30minutes.

Less commonly used unless given to pregnant patients, cystic fibrosis patients, patients with severe burns and patients with endocarditis.

Both pre- and post- dose levels are required.
Take a pre-dose sample which will give the trough level before giving the 3rd or 4th dose after commencement of gentamicin.
Post-dose sample which gives the peak level should be taken 1 hour after the end of the infusion.

28
Q

Who should you not give Once-daily Gentamicin to?

A
  • In significant renal impairment (CrCl < 30ml/min)
  • In burns that cover more than 15-20% of their body surface area.
  • In ascites greater than 10% of body weight.
  • In pregnancy
  • In cystic Fibrosis

Consult local guidelines for paediatrics.

29
Q

What information do you include in a protocol concerning antibiotic dosing and monitoring?

A 
When to use/not use OD 
Calculations for obese patients 
Calculating renal function 
Dosing table 
How to administer dose 
When to take levels
What levels to aim for 
What to do if levels are too low / too high 
References / Review date
30
Q

Clinical case:

Miss LC is 46 years old.
Treated for abdominal sepsis.
(Weight = 95kg, Height = 5ft 4”, SrCr = 74).
Given amoxicillin 1g IV tds, Metronidazole 500mg IV tds, gentamicin 360mg OD.
First dose was given 2pm yesterday.
No levels were taken this morning.
The nursing staff are asking whether they can give the second dose at 2pm today?

can you?

A

You can give a 2nd dose without waiting for level results in patients who are less than 65 years old with good renal function.

31
Q

What is Vancomycin?

A

Vancomycin is a glycopeptide antibiotic with activity against gram-positive infections.

32
Q

What can vancomycin treat?

A 
MRSA sepsis 
Intravascular catheter-related bloodstream infections
Skin and soft tissue infection 
Pneumonia 
Infective endocarditis

Vancomycin is also an alternative to penicillin for patients who have a history of serious penicillin allergy.

33
Q

Why is vancomycin available as capsules?

A

Oral vancomycin is used for its local effect to treat c diff infections (Clostridioides difficile-associated diarrhea (also called C diff)). C diff is a type of bacteria that causes severe diarrhea.

34
Q

Is vancomycin water soluble?

A

Yes

35
Q

Metabolism of Vancomycin?

A

Vancomycin is poorly metabolised and is primarily eliminated unchanged.

36
Q

What is the most common adverse reaction caused by rapid infusion of Vancomycin?

A

Red Man Syndrome (also known as Red Neck Syndrome)

37
Q

What should the infusion rate of Vancomycin not exceed?

A

10mg/minute

38
Q

Do you give a loading dose when giving vancomycin?

A

Yes.

A loading dose is always given to all patients who are starting on Vancomycin.

39
Q

Why is a loading dose given in vancomycin?

A

To reach the therapeutic range quicker.

40
Q

Vancomycin monitoring

A
  • Trough levels (0-60 minutes pre-dose) should be taken before giving the 3rd or 4th dose to ensure they are taken at steady state
  • The dose can be given after trough levels are taken providing serum creatinine is normal with good urine output.
  • Do not wait for levels to come back before giving dose unless it is for dialysis patient/severe renal impairment.
  • If levels are normal and patients renal function is stable, twice weekly monitoring of pre dose levels is recommended.

Routine peak level monitoring is unnecessary for vancomycin.

41
Q

What is the loading dose and maintenance dose in vancomycin based on?

A

The loading dose is based on Body weight.

The initial maintenance dose is base on renal function.

42
Q

Clinical case:

Male patient given Vancomycin for cellulitis caused by MRSA.
Age: 76
Weight: 75kg 
Height: 5ft 10
SrCl: 105 (stable)
CrCl: 56l/min
Loading dose: 1.5g two days ago
Maintenance dose : 750mg bd started yesterday.

It is now 10pm. The vancomycin levels taken this morning were 36mg/L.
The nurse says “I am not going to give the next dose. Is that okay?”

Is it okay?

A

Since the morning levels were 36mg/L, the nurse needs to contact the pharmacy.
Think it through:
- What levels being aimed for?
- Why could the level be high? Look for errors, Look for changes in the patients clinical condition.

If there has been no errors made

  • request for urgent repeat vancomycin levels to confirm if possible
  • Repeat level in morning; if the level comes back <20mg/L, we would then give a dose.

PY6010 (30 decks)

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