CD 11

Question 1

Concentration-dependent of a drug means?

Answer 1

The higher the concentration the greater the activity. Clearly, all drugs display concentration-dependent activity in the sense that no dose no concentration no activity.

Question 2

Time dependent activity of a drug means ?

Answer 2

Some drugs are threshold dependent i.e. when the concentration exceeds a threshold then higher concentrations do not provide extra benefit. These drugs are termed time-dependent.

Question 3

Minimum bactericidal concentration (MBC) means?

Answer 3

The lowest concentration of antibiotic required to kill a particular bacterium.

Question 4

Minimum inhibitory concentration (MIC)?

Answer 4

Lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation.

Question 5

Differentiate Antibiotics vs antimicrobials?

Answer 5

Originally produced by microorganisms. Vs an ANTIMICROBIAL is any substance of natural, semisynthetic, or synthetic origin

Question 6

PK Vs PD

Answer 6

PK: The change in concentration over time in the plasma after administration of the drug.
PD: The effect of the drug concentration on the body. Pharmacodynamics is essentially pharmacology – so it’s the action of the drug at the receptor site.

Question 7

What is the GFR mean ?

Answer 7

Glomerular Filtration Rate (a measure of kidney filtration ability) where normal = 120 ml/min
Since F = 0 then we know that gentamicin is not absorbed orally.

Question 8

What is Gentamicin and tobramycin?

Answer 8

Aminoglycoside.
Indication:  Against E. coli & H. influenza 
IV infusion over 30 min
Renal excretion
Half-life 2.5 hours

Gentamicin shows bacterial killing by Concentration-dependent of the medicine

Question 9

What are the Side effect of Gentamycin?

Answer 9

Prolonged use in high concentrations leads to Nephrotoxicity & autotoxicity.

Autotoxicity (can kill similar other species)

Question 10

What is IBW mean?

Answer 10

Ideal body weight.

It is used to calculate individual patient dose. Unless the person’s actual body weight is less than their IBW in which case the lower of IBW is used.

Male(kg)=50+0.9’ (HT-150) HT means Hight in centimetre)
Female(kg)=45+0.9’ (HT-150)

Question 11

What is GFR mean?

Answer 11

glomerular filtration rate
(a measure of kidney filtration ability) where normal = 120 ml/min
If (filtration) F=0 then we know that gentamicin is not absorbed orally.
Or any other orally administered dose will not be absorbed too

Question 12

When we are not able to use a nomogram for aminoglycoside patients?

Answer 12

if the patient is given
Aminoglycoside once-daily dose.
Creatinine clearance less than 1.2ml/s

then we can’t use this nomogram at all. (It is in the guidelines)

Question 13

What are the side effects of Gentamicin (Aminoglycoside)?

Answer 13

Prolong high concentration leads to 
Nephrotoxicity
Autotoxicity
Auditory damage 
(So does need to be adjusted according to liver function)

Question 14

For concentration dependent killing what is important?

Answer 14

Dose is important.

For concentration dependent killing Bigger the Cmax=greater the bacterial kill and the faster the bacterial kill.

Question 15

What type of killing occurs by gentamycin?

Answer 15

kill concentration-dependent bacterial killing

The higher the Cmax the greater the bacterial kill and the faster the bacterial kill.

The first dose is the most important. Gentamicin kills bacteria that are reproducing – it is not good when the bacterial are dormant (alive but not actively growing).

Question 16

What is Gentamicin Post antibiotic effect?

Answer 16

There is continued inhibition of the growth of the bacteria for a further period of time after the plasma concentration has decreased below the MIC. Important for aminoglycosides, as it contributed to the success of extended interval dosing regimens.

Question 17

What is Adaptive resistance?

Answer 17

Non-mutational resistance occurs for short time.
It occurs in response to certain environmental conditions.
The adaptive resistance not permanent.

Ex:
We did an experiment and In that experiment, gentamicin was given at time 0, 6h, 12h, 18h, and 24h. The first dose gives a 3 log order reduction in bacterial count. Subsequent doses provide almost no effect at all. So to get the effect again a washout of 24-36 h was needed for the bacteria to become sensitive again.

Question 18

How aminoglycosides damages kidney?

Answer 18

By damaging the kidney tubules.

Question 19

What are the risk factors we need to consider before applying aminoglycosides?

Answer 19

Duration of treatment
Dose
Liver disease
Gender: female
Another nephrotoxic drugs

Question 20

The goal of treatment by aminoglycoside?

Answer 20

To reach the highest Cmax

To ensure that a high plasma level is achieved but that drug is cleared before giving the next dose.

Question 21

What is the target Cmax & Cmin for aminoglycoside?

Answer 21

Cmax is 10mg/L & Cmin 0.5mg/L

Question 22

How to be dosed according to nomogram of the gentamicin?

Answer 22

So, for normal renal function patient’s creatinine clearance is 72 mL/min or 1.2ml/sec
If higher the concentrations, then we will need dose reduction
If Lower the concentrations we may need an increase in dose.

Question 23

What is the clinical use of Flucloxacillin?

Answer 23

Against G positive bacteria (minor or serious infections)

Question 24

Route of Administration of Flucloxacillin?

Answer 24

IM
IV
Slow push by a syringe over 3-5 mins
Dr needs to be with the patient available to monitor not a very common but severe allergic reaction.

F=0.3 means 30% absorbed orally

Question 25

Flucloxacin abosorption follow which order of process ?

Answer 25

The absorption from the gut into the body follows a first-order process

Question 26

Side effects of Flucloxacillin?

Answer 26

Nephrotoxicity
Kidney toxicity
Anaphylaxis reaction

Question 27

Flucloxacillin absorption what kind of PK follow?

Answer 27

The drug has complicated PK. First, absorb into vain than the body and then bone which is slow and takes time.

Question 28

Flucloxacillin has?

Answer 28

Time-dependent bacterial killing

Question 29

What is the goal of treatment with flucloxacillin?

Answer 29

• Choosing a dosing regimen where the concentration is above the MIC for the longest period of time.
• Current thinking is that a successful dosing regimen is where the plasma concentration is above the MIC for at least 40% of the dose interval.

Question 30

How we calculate half-lives?

Answer 30

For example:
•If the half-life is 1 hour and the dose interval is 6 hours, then only ~1.5% of the drug is left at the end of the dose interval.
o100%→50%→25%→12.5%→6.25%→3.13%→1.56%
•If you have an MIC of 1 mg/L then you need to aim for a Cmax of 66 mg/L.
o66→33→16→8→4→2→1
•An MIC of 8 mg/L requires a Cmax of 512 mg/L.
oWhich is higher than that achievable in general dosing. (Aim for the highest dose allowable or give as a constant infusion)

Question 31

What is constant infusion?

Answer 31

An alternative method to achieve more than 40% cover over a dose interval is to give the penicillin as a constant infusion – just above the MIC.
Concentration dependent: the highest Cmax to MIC ratio as possible
Aminoglycosides &
Fluoroquinolones.
Time-dependent: so we want the drug concentration to stay in the body for a certain time avobe the MIC as much as possible between the dose interval.
•Beta-lactams
•vancomycin
•macrolides
•tetracyclines

Question 32

Generally, there are two different biomarker goals?

Answer 32

• High Cmax: MIC ratio.

* Duration of time the concentration is above MIC.