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Flashcards in Solubility and partitioning of drugs Deck (42)
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1
Q

What are the barriers that a drug has to cross before it becomes effective?

A

GIT

BBB

2
Q

Why are biological membranes hydrophobic in nature?

A

Because they are composed of phospholipids containing long hydrobcarbon chains

3
Q

What must a drug do to succeed in its mission?

A

Pass from the aq solution of the EXTRACELLULAR fluid to the aq solution of the INTRACELLULAR fluid by crossing the lipid membrane

4
Q

What are the properties of some organic solvents (e.g. n-octanol, cyclohexane) thought to resemble?

A

Similar properties of a lipid bilayer membrane. This suggests that distribution of drugs into hydrophobic organic media stimulates their ability to passively diffuse across biological membranes

5
Q

What is partitioning?

A

The movement (or redistribution) of organic compounds from one liquid to another

6
Q

What happens if an excess of an organic compound is added to a mixture of two immiscible liquids?

A

It will partition itself between the two liquids so that each becomes saturated

7
Q

What happens if the amount of compound added is not enough to saturate the solutions?

A

It will be distributed between the two immiscible liquids according to a definite concentration ratio:
Corg -> Caq

8
Q

What is the partition coefficient (P)?

A

A constant, which is the ratio of concentration of compound in organic phase to the concentration in aq phase at EQUILIBRIUM

9
Q

What is the equation for P?

A

P = Corg/Caq

10
Q

What is the TRUE partition coefficient?

A

The partition coefficient of UNIONISED drug

11
Q

What does it mean if Ptrue > 1?

A

Then Corg > Caq and the compound is HYDROPHOBIC (lipophilic)

12
Q

What does it mean if Ptrue < 1?

A

then Corg < Caq and the compound is HYDROPHILIC (lipophobic/polar)

13
Q

What does LogP = 1 means?

A

P = 10 and Corg:Caq = 10:1

14
Q

What does LogP = 0 mean?

A

P=1 and Corg:Caq = 1:1

15
Q

What does P= -1 mean?

A

P= 0.1 and Corg:Caq = 1:10

16
Q

What can P be used to predict?

A

the absorption, distribution and elimination of drugs within the body

17
Q

What is the Hansch-Fujita parameter?

A

They describe the contribution of various functional groups to the lipophilicity of a compound

18
Q

What are the hydrophobic functional groups (+)?

A

Aromatic hyrdocarbons
Aliphatic hydrocarbons
Halogens

19
Q

What will happen to P if there is a predominance of hydrophobic (+) groups?

A

Increase - making molecule more lipid soluble and more able to pass through the lipid membrane

20
Q

What are the hydrophilic (-) functional groups?

A
Hydroxyl groups
Carboxyl groups
Amines
Ether
Amide
21
Q

What will happen to P if there is a predominance of hydrophilic groups (-)?

A

Decrease - making molecule less lipid soluble and less able to pass through the lipid membrane

22
Q

How does the permeability of a drug in the unionised form differ from that of the ionised form?

A

Permeability of the unionised form of a drug across a phospholipid membrane by passive diffusion is 10^8 higher

23
Q

Should a drug be in the ionised or unionised form at the membrane surface to permeate the membrane by passive diffusion?

A

Uncharges (i.e. unionised)

24
Q

What effects the concentration of the compound passing through the membrane barrier?

A

The % of the compound that is unionised

25
Q

What controls the % of the unionised compound?

A

pKa of compound and pH of solution

26
Q

For weak acids and bases, how does P vary?

A

Varies depending upon the pH at which it is measured (APPARENT P)

27
Q

Papparent is sometimes referred to as what?

A

D or Distribution coefficient

28
Q

What is Papparent dependent on?

A

the proportion of unionised form of the drug present in solution

29
Q

How is Papparent calculated?

A

Papp = Ptrue x funionised

30
Q

What is funionised?

A

The fraction of the total amount of drug unionised at a certain pH

31
Q

What does is mean if funionised = 1?

A

Then Papp = Ptrue

32
Q

What is funionised dependent upon?

A

The pH of the aq solution and the pKa of the drug

33
Q

If drug is only absorbed in the small intestine there will be a delay in onset of action. Why?

A

Because the drug has to pass through the stomach first

34
Q

When should patients take antihistamines for travel sickness?

A

At least one hour before travelling

35
Q

Drugs can be _______ in the kidneys rather than excreted.

A

reabsorbed

36
Q

How is it possible to control reabsorption of drugs from the kidney tubule and accelerate excretion?

A

If the reabsorption happens through passive diffusion via unionised drug form, the same partitioning rules can be applied

37
Q

Acidic drugs are reabsorbed best from _______ urine

A

Acidic

38
Q

If the drug taken in overdose is a weak acid then the reabsorption can be minimised by _______ the urine

A

basifying

39
Q

What happens to acidic drugs in forced base diuresis in terms of reabsorption and clearance?

A

The reabsorption decreases and the clearance is more rapid

40
Q

Basic drugs are reabsorbed best from _______ urine

A

Alkaline

41
Q

If the drug taken in overdose is a weak base reabsorption can be minimised by _______ the urine

A

acidifying

42
Q

What happens to basic drugs in forced acid diuresis in terms of reabsorption and clearance?

A

decrease in reabsorption and more rapid clearance

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