Drug Delivery

Question 1

What are all the pharma phases of drug delivery?

Answer 1

1. Pharmaceutical
2. Pharmacokinetic - ADMET
3. Pharmacodynamic

Question 2

Types of Absorption

Answer 2

1. Carrier Mediated
   - Active (against concentration gradient, need energy) and Facilitated (no energy needed - with concentration gradient)
2. Passive (Filtration(non pokar, <100 Da) and Passive Diffusion (small molecule))

Question 3

Kel - formula and what is it

Answer 3

Elimination rate constant
Kel = CL/Vd
t0.5 = 0.693 / kel
(0.693 = ln2)

Question 4

Vd - definition and formula

Answer 4

Vd = volume of distribution, fraction of drug that reaches circulation
Vd = Dd/Cp
Dd = drug dose
Cp = concentration in plasma

Question 5

t0.5

Answer 5

time at which half of drug has been lost from its MAX CONCENTRATION

Question 6

what functional groups are always considered to be neutral?

Answer 6

Aliphatic alcohols and amides

Question 7

Biliary excretion vs renal excretion

Answer 7

biliary excretion - liver and pancreas = faeces
Renal excretion - kidneys - urine

Question 8

Lipinski’s Rule of 5

Answer 8

1) 1 < Log P < 3
2) MW < 500 Da
3) No more than 10 HB Acceptors
4) No more than 5 HB donors
5) PSA < 140 A
6) No more than 10/20 rotatable bonds

Question 9

Log P vs Log DpH, ideal, values meaning

Answer 9

P = conc(octanol)/conc(water) - measure of lipophilicity.
ClogP is computer calculated value.
Ideal : 1 < logP < 5
under 1 is hydrophilic, higher values are hydrophobic

Log DpH is same thing but with buffer so you can see solubility in different pH solutions

Question 10

Extended rule of 5

Answer 10

500 Da < MW < 700 Da, PSA under 200, c Lop P can be 0 to 7.5, Non rotatable bonds < 20

Question 11

How can polarity be masked in drugs?

Answer 11

Intramolecular hydrogen bondings.

Question 12

pKaH of tertiary amine?

Answer 12

7/8 - below this pH the conjugate acid will have donate its proton so it will be neutral.

Question 13

pKaH of pyridine

Answer 13

2.8
Very basic, only under this pH value will the structure be uncharged as the conjugate acid will have been forced to give up its proton

Question 14

Extent of deprotonation/protonation - more than 2 pH units away from pKa/pKaH

Answer 14

Fully (de)protonated

Question 15

pH duodenum

Answer 15

5

Question 16

pH illeum

Answer 16

8.5

Question 17

pH stomach

Answer 17

1.5

Question 18

What is the major type/way metabolism eliminates drugs?

Answer 18

Cytochrome P450 - Non specific oxidative enzyme that oxidises non polar compounds to allow excretion.

Question 19

Inhibitor of P450?

Answer 19

Grapefruit juice - however this can be dangerous as if you take grapefruit juice with terfedine (prodrug) is problamatic as prodrug itself is cardiotoxic

Question 20

What food increases P450 activity?

Answer 20

Brussel sprouts!

Question 21

Area Under Curve - what information does it give us, what type of graph is it referring to

Answer 21

the area under the plot of plasma concentration of a drug versus time after dosage (called “area under the curve” or AUC) gives insight into the extent of exposure to a drug and its clearance rate from the body

Question 22

What is IC50

Answer 22

half maximal inhibitory concentration - how much drug is needed to inhibit a biological process by half, thus providing a measure of potency of an antagonist drug in pharmacological research - gives an indication to OVERALL DRUG EXPOSURE

Question 23

CL

Answer 23

clearance = kel / Plasma concentration
Plasma concentration can be expressed as F % (bioavailability)