Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

The Medicine - Y3 > Drug disposition and PK > Flashcards

Drug disposition and PK Flashcards

1
Q

Why should enteric coated tablets be taken on a fasted stomach?

A

Because if taken with a heavy meal where transit time can be delayed for up to 10 hours, the coating may degrade and therefore will no longer be effective

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why should poorly soluble drugs be taken with food?

A

Food will delay gastric emptying so there will be more time for dissolution of the drug, increasing the fraction of the drug that is reabsorbed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Why are poorly permeable drugs not good candidates for extended release formulations?

A

Because permeability varies along the wall of the GIT so if most of the drug doesn’t get released until it reaches the lower regions of GIT, where permeability is significantly lower, absorption will be hindered

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Why does the extent of first pass metabolism vary along the regions of the GIT?

A

Because the expression of metabolic enzymes varies. Highest abundance being in the upper SI (duodenum), so based on where drug is released, extent of first pass will vary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the equation for bioavailability?

A

F = Fa x Fg x Fh

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are some of the implications of intestinal first pass metabolism?

A

Can result in low Fg as a result of extensive metabolism in enterocytes so will lead to a reduction in F
Transporter-metabolism interplay - additional factor leading to reduced F
Inhibition of intestinal enzymes and transporters -> DDIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which compound present in grapefruit juice causes an interaction with CYP enzymes?

A

Furanocoumarins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the interaction between grapefruit juice and CYP3A4?

A

Grapefruit juice irreversibly inhibits intestinal CYP3A4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Does grapefruit juice interact with hepatic CYP3A4?

A

A standard dose (i.e. glass of juice) does not affect hepatic CYP3A4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

In the context of CYP3A4 and grapefruit juice, what is meant by irreversible inhibition?

A

Even if the inhibitor was removed, the enzyme would be inactive. The only way to recover the enzyme would be to produce a new protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What happens if grapefruit juice is co-administered with a CYP3A4 substrate e.g. statin?

A

Metabolism and elimination of victim drug (i.e. statin) prevented so build up of victim drug and hence increased plasma levels -> toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

It is recommended that grapefruit juice isn’t consumed with all statins. True or false?

A

False - not all statins are metabolised by CYP3A4 so can be taken with statins that aren’t

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the effect of grapefruit juice on Simvastatin in terms of AUC and Cmax

A

Increased Cmax and AUC -> increased risk of adverse effects e.g. myopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Name two statins that have low oral bioavailability due to extensive first pass met

A

Atorvastatin

Simvastatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Name two drugs that are not statins that have low oral bioavailability due to extensive first pass met

A

Sildenafil

Verapamil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why do drugs with extensive first pass metabolism show higher F when formulated as MR?

A

Because drug released in distal GIT, where fewer metabolic enzymes are present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the lowest Vd you can have and why?

A

3L - because that is the volume of plasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the volume of total body water?

A

~40L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the volume of extracellular water?

A

~12L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Which PK parameter is important for determining the loading dose of a drug?

A

Volume of distribution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

In general how does the volume of distribution of acidic drugs compare to that of basic drugs?

A

Vd of acidic drugs tends to be lower than that of basic drugs because acidic drugs tend to reside in plasma as they bind to plasma proteins. Vd of basic drugs is higher because they bind to acidic phospholipids in tissues, therefore leaving the blood/plasma and distributing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the volume of distribution of digoxin?

A

40L - similar to that of total body water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What does a low Vd indicate?

A

The drug may be highly protein bound and therefore doesn’t distribute well to tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What does a high Vd indicate?

A

Drug may be well distributed around the body OR may not distribute around the body only concentrates in certain tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

When is a low Vd desirable?

A

When the drug target is vascular or extracellular

26
Q

When is a high Vd desirable?

A

When the drug target is intracellular

27
Q

At equilibrium, what determines the distribution of drug within the body?

A

Binding to plasma proteins and tissue components

28
Q

Compare the lipophilicity of parent drugs and metabolites

A

Parent drugs are more lipophilic than metabolites. Metabolites reduce the lipophilicity of parent drug so that they are more polar and therefore more water-soluble so they can be eliminated by renal excretion

29
Q

Renal clearance of metabolites is higher than than of parent drug. True or false?

A

True

30
Q

Metabolites are less water soluble than parent drugs. True or false?

A

False

31
Q

Name a pharmacologically active metabolite

A

ezetimibe glucuronide

32
Q

What are the phase I drug metabolism reactions?

A

Oxidation
Reduction
Hydrolysis

33
Q

What is the phase II metabolism reaction?

A

Conjugation

34
Q

Which of the drug metabolism reactions is the most important?

A

Oxidation

35
Q

Which group of enzymes catalyses oxidation metabolism reactions?

A

CYP450

36
Q

What are the three different oxidation reactions in phase I metabolic reactions?

A

Aliphatic
Aromatic
De-alkylation

37
Q

What are the two different mechanisms of oxidation reactions in phase I metabolic reactions?

A

Hydroxylation

Oxidative cleavage

38
Q

What are the three reactions that take place during paracetamol metabolism?

A

N-hydroxylation
Glucuronidation
Sulfation

39
Q

Excretion is only a function of the kidneys. True or false?

A

False - liver can also excrete drugs - biliary excretion

Pulmonary excretion can also take place

40
Q

Which PK parameter primarily describes drug elimination?

A

Clearance

41
Q

Would you expect two drugs with the same CL to have the same half-life?

A

Only if the two drugs have the same Vd as the 2 parameters that affect t1/2 are V and CL

42
Q

What factors effect hepatic clearance of drugs?

A

Hepatic blood flow (affects drugs with high Eh)
Plasma binding (affects drugs with low Eh)
Enzyme activity
Transporter activity - uptake and efflux
Disease status

43
Q

What can induce an increase in hepatic blood flow?

A

Bed rest
Thyrotoxicosis
Isoprenaline

44
Q

What can induce a reduction in hepatic blood flow?

A

Exercise
Heart failure
Propranolol

45
Q

What effect does liver cirrhosis have on hepatic clearance?

A

Reduced activity of metabolic enzymes
Changes in plasma protein binding as impaired albumin synthesis
hepatic clearance reduced
GFR impaired

46
Q

What is the enterohepatic cycle?

A

Drug -> liver -> excreted in bile -> SI -> reabsorbed by portal vein -> liver

47
Q

CYP3A4 is more specific to which drug it metabolises than CYP2C9. True or false?

A

False - CYP2C9 narrow specificity than 3A4

48
Q

Ecstasy has a basic functional group. Which CYP enzyme is it most likely to be metabolised by?

A

CYP2D6

49
Q

Tolbutamide has both lipophilic and hydrophilic groups. Which CYP enzyme is it most likely to be metabolised by?

A

CYP2C9

50
Q

Midazolam is a bulky drug i.e. multiple rings in its structure. Which CYP enzyme is it most likely to be metabolised by?

A

CYP3A4

51
Q

CYP3A4 only have the ability to metabolise drugs. True or false?

A

False - can metabolise endogenous compounds such as testosterone

52
Q

Why is it important to know which drugs are metabolised by which CYPs?

A

Genetic polymorphism - some people lack gene for metabolisers and so drugs will build up
Polymorphism contributes to inter-patient variability
DDI potential

53
Q

What is meant by the term ‘poor metaboliser’.

A

Lacks the gene for the CYP enzyme and so patient does not metabolise drugs that are substrates for that particular CYP enzyme

54
Q

What are the therapeutic consequences of giving a drug that is a CYP2D6 substrate to a patient who is a poor metaboliser?

A

High plasma concentrations of drug as it is not metabolised and cleared -> toxicity

55
Q

What is Ki?

A

the inhibitor-enzyme dissociation constant. It definees the affinity of an inhibitor to a particular enzyme

56
Q

What does a low Ki value indicate?

A

A potent inhibitor for a particular enzyme

57
Q

What are the two types of induction DDI?

A

Autoinduction and heteroinduction

58
Q

What are the two major families of enzyme transporters in the human genome?

A 
ATP-binding Cassette (ABC) - mainly efflux role
Solute carrier (SLC) - uptake role
59
Q

Where are the most relevant transporters expressed?

A

Epithelia of liver, kidney and intestines

Endothelium of BBB

60
Q

Where are OATPs located?

A

Sinusoidal membrane of hepatocytes

61
Q

What happens upon co-administration of OATP1B1 inhibitor with statins?

A

Increased plasma conc of statin as a result of reduced hepatocyte uptake -> increased risk of myopathy

The Medicine - Y3 (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions