PK PD

Question 1

Define potency

Answer 1

Lowest EC 50 (achieves 50% of effect at lowest concentration)

Question 2

Causes for an anticlockwise hysteresis conc-effect loop

Answer 2

Distribution delay in drug reaching site of action from plasma
Or
Formation of an active metabolite

Question 3

Causes for an clockwise hysteresis conc-effect loop

Answer 3

Tolerance or tachyphylaxis (down regulation of receptor over time so same conc gives less of an effect)

Question 4

Volume of distribution

Answer 4

V = Dose/Conc at time 0

Question 5

CL (L/h)

Answer 5

CL = 0.693 X V / t0.5
CL = dose / AUC

Question 6

Loading dose (mg)

Answer 6

Loading dose =
V / F X desired conc (mg/L)

(vol of distrib = Dose/C0)
F = bioavailability - fraction absorbed

Question 7

Maint dose rate (mg/h)

Answer 7

Maintenance dose rate =

Css X CL / F

Question 8

F

Assuming linear PK

Answer 8

AUC PO / AUC IV
X
Dose IV / Dose PO

Low bioavailability means significant first pass effect, meaning less is absorbed into the systemic circ, so cirrhosis will increase plasma concentration

Question 9

Half life

Answer 9

0.693 X V / CL

In2/ Kel (elimination rate constant)

Question 10

Css when rate of input = output

Remember CL has the biggest influence on steady state drug level

Answer 10

Maintenance dose rate X F / CL

Css takes 4-5 half lives to reach steady state

Question 11

Equation for therapeutic index

Answer 11

ED 50 (dose at which 50% of pop experience toxic effect) toxic/ED 50 therapeutic

Question 12

What properties of drugs cause Higher elimination via haemodialysis?

Answer 12

Smaller (

Question 13

In what form can drugs be reabsorbed in the distal tubule?

Answer 13

Unionised will be reabsorbed
Urine pH usually between 5-8
The renal reabs of a drug depends on pka of a drug
Fraction excreted in the urine
Net reabsorption in the kidney

Renal excretion of a weak base is enhanced by acidifying urine (pH below the pkb the drug will be ionised so renal clearance increased by reduced reabsorption)

Question 14

Example of a weak base drug

Answer 14

Amphetamine
Is a weak base
So becomes ionised in alkaline urine: alkaline urine causes reduced renal CL
Renal excretion enhanced by acidic urine

Question 15

C initial (at time zero)

Answer 15

Dose / V

Question 16

What influences the extraction ratio and hepatic clearance for drugs with a LOW EXTRACTION RATIO (

Answer 16

E and CL sensitive to ENZYME activity as the rate limiting step
- CL depends here on protein binding because only unbound drug can enter the liver
So if you give an enzyme inhibitor = clearance will be reduced

Question 17

What effects E and CL in high extraction ratio (>0.7)

Answer 17

Changes in blood flow will change CL of a drug

E and CL unaffected by changes in protein binding or enzyme activity (because activity is high)