Clinical Pharm Flashcards
What is half life ?
Time taken for serum drug level to fall 50% during elimnation
what can increase vd?
large size of body
sepsis (due to vasodilation and capillary leak)
changes in body composition (oedema and third space fluids)
decreased plasma protein binding, such as in liver/renal failure or drug interactions
how does plasma protein binding affect vd?
substances that are widely protein bound are NOT in the tissues and therefore will have a low Vd, whilst substances that are not widely protein bound will be able to distribute into the tissues and therefore will have HIGH vd
what are the 5 different important points for loading doses?
Loading dose required hit and run loading dose for compliance loading does not required loading dose contraindicated
example of loading dose contraindicated
Amytriptyline Oral for depression
Start low go slow, because adverse effects are greater early on (tolerance then occurs)
loading dose not required explain and example
Start on maintence dose (usually at lower end of the range). Used for most chronic conditions.
Amlodipine (CCB) oral for hypertension
Loading dose for compliance explain and example
administer enough drug to achieve sufficient concentration for time to efficacy. IM penicillin for gonorrhoea
Vd =
Volume of Distribution
Vd defintion
volume into which a drug appears to distribute with a concentration equal to that of plasma (proportionality constant, relating the total amount of drug present in the organism to its plasma concentration at the same moment)
What is the most important pharmacokinetic parameter?
Clearance
What is unit for Vd?
L
Clinically, what is the point of knowing about the drug’s Vd?
It can determine the loading dose
Ld =
Loading dose
What is the definition of loading dose?
dose of the drug that is required to FILL the volume of distribution to achieve a target plasma concentration
If no loading dose is given, how many half lives does it take to achieve >90% of steady state concentration?
If no loading dose is given, it takes 4 half lives to achieve over 90% of steady state concentrations with maintenance dosing.
what is the best index of drug exposure?
area under the concentration time curve AUC: this is because AUC is DIRECTLY proportional to total amount of unchanged drug that reaches the systemic circulation
Last week you calculated the half-life and volume of distribution of gentamicin, in a person given 400 mg intravenously (IV).
t½ = 2 hr
Vd = 24 L
The AUC for a person in this group is 50 mg/L.hr
Calculate the CL:
i) Using the given AUC
ii) Using the given values of t½ and Vd
CL = Dose/AUC
= 400mg/50
= 8L/hr
CL = 0.693 x Vd/ t1/2
= 0.693 x 24L/ 2 hr
= 8.3L/hr
What practical oral maintenance dose-rate of digoxin would you give a 60 kg man to maintain a Cpss of 1 microgram per litre?
Digoxin: F = 0.8
CL = 0.1 L/hr per kg
t½ = 36 hr
tablets: 62.5 microg and 250 microg
Dose rate X F = CL x CPss
- Work out clearance first:
CL =
2. Dose-rate = CL x CPss = 6L/Hr X 1 microgram/L = 6 microgram/her =144 microgram/day
F of Diogoxin = 0.8
DR =
- Cefalexin is used as empiric treatment for some systemic infections. The fraction excreted unchanged in urine (fe) of cefalexin is 1.0 and t½ with normal renal function = 1 h. The standard maintenance dosing orally is 500 mg twice a day. It is available as 250 mg and 500 mg capsules.
A 60-year-old woman is being started by her GP on cefalexin for cellulitis. Her renal function is about half-normal (CrCL 50 ml/min).
a) What maintenance dose-rate would you prescribe to give her a similar plasma AUC as a “healthy young adult” taking 500 mg twice a day?
b) b) Why is dose-adjustment of cefalexin for renal function usually considered inappropriate?
She has half normal renal function = so half the clearance, so half the dose so 250mg twice a day or 500mg once a day
Dose adjustment considered inappropriate as target site for action is post renal and therefore decreasing to achieve the same AUC (in plasma pre renal) can result in lower urinary cefalexin
concentrations, risking therapeutic failure.
- A 70-year-old man (180 cm, 70 kg), requires treatment for bacterial endocarditis. Intravenous benzylpenicillin is recommended. Serum creatinine 150 micromol/L (normal range 50-110), eGFR 30 mL/min/1.73m2.
Assume benzylpenicillin fe = 1.0, t½ with normal renal function = 1 h. Benzylpenicillin comes in vials of 600 mg. The maintenance dose-rate for normal renal function is 2.4 g every 4 hours (q4h).
a) Calculate the benzylpenicillin maintenance dose-rate.
b) Should this be given as a different dose amount or a different dose frequency? Why?
eGFR = 30mL/min/1.73
BSA =√kg x cm /3600
= 70 x 180/3600 = 1.87m2
eGFR = 30 x 1.87/1.73 = 32mL = 1/3 of normal
2.4g ever four hours = 14.4g over 24 hours
dose rate 14.4g over 24 hours
patients = 1/3 of 14.4g over 24 hours = 4.8 over 24 hours
should be given as 4800g over 24 hours
4800/4 = 1200mg every 6 hours
600mg x 2 = 6
problem giving 0.8g every 4 hourly is that penicillin is only in 600mg vials easy to give two vials.
- An 80-year-old woman (160 cm, 50 kg), presents with atrial fibrillation and a rapid ventricular rate. Her serum creatinine is 100 micromol/L (normal range 45-90). The decision is made to treat with oral digoxin. You prescribe a loading dose of 750 micrograms, but need to work out the maintenance dosing.
Assume digoxin F = 1, fe = 0.7 and t½ = 36 h with normal renal function. Digoxin comes in 62.5 and 250 microgram tablets. The maintenance dose-rate for normal renal function is 250 micrograms once a day.
a) Calculate the digoxin maintenance dose-rate.
b) Should this be given once daily, or a bigger dose less frequently?
eGFR = eCrCl = (140-age) x wt /[Cr] (x 1.25 if male)
= (140-80 = 60) X 50kg / 100
= 30ml/min
= 1/3 of normal
Maintenance dose-rate (patient)
Maintenance dose-rate (normal) = (1 - fe) + fe × (
GFR (patient)
100 )
= 1-fe + fe x 30/100
= 1-0.7 = 1/3 x 0.7 = 0.53
0.53 x normal dose (250)
= 0.125mg per day
once daily for copmliance and if this okay with long half life
